In JoVE (2)

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Articles by Joy Hirsch in JoVE

 JoVE Behavior

fMRI Validation of fNIRS Measurements During a Naturalistic Task

1Department of Psychiatry, Yale School of Medicine, 2Department of Electronics and Bioinformatics, Meiji University, 3Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, 4ADAM Center, Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, 5Department of Neurobiology, Yale School of Medicine

JoVE 52116

Other articles by Joy Hirsch on PubMed

Imaging and Biological Function in Health and Disease

The Journal of Clinical Investigation. May, 2003  |  Pubmed ID: 12750390

Shared and Separate Systems in Bilingual Language Processing: Converging Evidence from Eyetracking and Brain Imaging

Brain and Language. Jul, 2003  |  Pubmed ID: 12821416

The neurological and cognitive aspects of bilingual language processing were examined in late Russian-English bilinguals using headband-mounted eyetracking and functional neuroimaging. A series of three eyetracking studies suggested that, at early stages of word recognition, bilinguals can activate both languages in parallel, even when direct linguistic input is in one language only. A functional neuroimaging study suggested that, although the same general structures are active for both languages, differences within these general structures are present across languages and across levels of processing. For example, different centers of activation were associated with first versus second language processing within the left Inferior Frontal Gyrus, but not within the Superior Temporal Gyrus. We suggest that parallel activation (as found with eyetracking) and shared cortical structures (as found with fMRI) may be characteristic of early stages of language processing (such as phonetic processing), but the two languages may be using separate structures at later stages of processing (such as lexical processing).

Real-time Magnetic Resonance Imaging for Interventional Neuroradiological Procedures

Surgical Technology International. 2003  |  Pubmed ID: 12931300

Over the last two decades, interventional neuroradiologists have developed powerful techniques for the treatment of cerebrovascular disorders and brain tumors. Current interventional neuroradiological procedures are performed under X-ray fluoroscopy, which has allowed for high temporal and spatial resolution. However, these imaging techniques do not provide the treating physician with vital anatomic and functional information regarding vessel walls and the surrounding brain tissue. Better visualization of vessel structures and real-time information about the state of perfusion and metabolism of the surrounding brain tissue (real-time magnetic resonance arteriography, diffusion and perfusion-weighted imaging, apparent diffusion coefficient maps) would enhance safety and efficacy of neuroendovascular procedures available currently. Recent advances in magnetic resonance hardware and software have permitted significant enhancements in temporal and spatial resolution, which have resulted in the capability of visualizing anatomic structures with real-time fluoroscopy and angiography. This review outlines how real-time magnetic resonance procedures may replace conventional X-ray fluoroscopy in diagnostic and interventional neuroradiology during the next decade.

FMRI Evidence for Cortical Modification During Learning of Mandarin Lexical Tone

Journal of Cognitive Neuroscience. Oct, 2003  |  Pubmed ID: 14614812

Functional magnetic resonance imaging was employed before and after six native English speakers completed lexical tone training as part of a program to learn Mandarin as a second language. Language-related areas including Broca's area, Wernicke's area, auditory cortex, and supplementary motor regions were active in all subjects before and after training and did not vary in average location. Across all subjects, improvements in performance were associated with an increase in the spatial extent of activation in left superior temporal gyrus (Brodmann's area 22, putative Wernicke's area), the emergence of activity in adjacent Brodmann's area 42, and the emergence of activity in right inferior frontal gyrus (Brodmann's area 44), a homologue of putative Broca's area. These findings demonstrate a form of enrichment plasticity in which the early cortical effects of learning a tone-based second language involve both expansion of preexisting language-related areas and recruitment of additional cortical regions specialized for functions similar to the new language functions.

Hypoperfusion Without Stroke Alters Motor Activation in the Opposite Hemisphere

Annals of Neurology. Dec, 2004  |  Pubmed ID: 15562431

To specifically investigate the effect that large-vessel disease may have on cortical reorganization, we used functional magnetic resonance imaging to study patients with unilateral hemispheric hypoperfusion and impaired vasomotor reactivity from critical internal carotid or middle cerebral artery disease but without stroke. We hypothesized that when these patients used the hand contralateral to the hypoperfused hemisphere they would show unique activation in motor-related areas of the normally perfused hemisphere, that is, ipsilateral activation. We found that normal performance of two motor tasks was associated with increased ipsilateral hemispheric activation in the patients compared with age-matched controls. In addition, although task difficulty had an effect on ipsilateral activation, the increased ipsilateral activation seen in patients was not dependent on task difficulty. Our findings demonstrate that hemodynamic compromise alone is sufficient to cause atypical ipsilateral activation. This activation may serve to maintain normal motor performance.

Individual Differences in Trait Anxiety Predict the Response of the Basolateral Amygdala to Unconsciously Processed Fearful Faces

Neuron. Dec, 2004  |  Pubmed ID: 15603746

Responses to threat-related stimuli are influenced by conscious and unconscious processes, but the neural systems underlying these processes and their relationship to anxiety have not been clearly delineated. Using fMRI, we investigated the neural responses associated with the conscious and unconscious (backwardly masked) perception of fearful faces in healthy volunteers who varied in threat sensitivity (Spielberger trait anxiety scale). Unconscious processing modulated activity only in the basolateral subregion of the amygdala, while conscious processing modulated activity only in the dorsal amygdala (containing the central nucleus). Whereas activation of the dorsal amygdala by conscious stimuli was consistent across subjects and independent of trait anxiety, activity in the basolateral amygdala to unconscious stimuli, and subjects' reaction times, were predicted by individual differences in trait anxiety. These findings provide a biological basis for the unconscious emotional vigilance characteristic of anxiety and a means for investigating the mechanisms and efficacy of treatments for anxiety.

Mindboggle: a Scatterbrained Approach to Automate Brain Labeling

NeuroImage. Jan, 2005  |  Pubmed ID: 15627570

Mindboggle ( is a fully automated, feature matching approach to label cortical structures and activity anatomically in human brain MRI data. This approach does not assume that the existence of component structures and their relative spatial relationship is preserved from brain to brain, but instead disassembles a labeled atlas and reassembles its pieces to match corresponding pieces in an unlabeled subject brain before labeling. Mindboggle: (1) converts linearly coregistered subject and atlas MRI data into sulcus pieces, (2) matches each atlas piece with a combination of subject pieces by minimizing a cost function, (3) transforms atlas label boundaries to the matching subject pieces, (4) warps atlas labels to their transformed boundaries, and (5) propagates labels to fill remaining gaps in a mask derived from the subject brain. We compared Mindboggle with four registration methods: linear registration, and nonlinear registration using SPM2, AIR, and ANIMAL. Automated labeling by all of the nonlinear methods was found to be at least comparable with linear registration. Mindboggle outperformed every other method, as measured by the agreement between overlapping atlas labels and manually assigned subject labels, with respect to the union or the intersection of voxels. After applying the same procedure that Mindboggle uses to fill a subject's segmented gray matter mask with labels (step 5), the results of the other methods improved. However, after performing a one-way ANOVA (and Tukey's honestly significant difference criterion) in a multiple comparison between the results obtained by the different methods, Mindboggle was still found to be the only nonlinear method whose labeling performance was significantly better than that of linear registration or SPM2. Further advantages to Mindboggle include a high degree of robustness against image artifacts, poor image quality, and incomplete brain data. We tested the latter hypothesis by conducting all of the tests again, this time registering the atlas to an artificially lesioned version of itself, and found that Mindboggle was the only method whose performance did not degrade significantly as the lesion size increased.

The Neural Correlates and Functional Integration of Cognitive Control in a Stroop Task

NeuroImage. Jan, 2005  |  Pubmed ID: 15627596

It is well known that performance on a given trial of a cognitive task is affected by the nature of previous trials. For example, conflict effects on interference tasks, such as the Stroop task, are reduced subsequent to high-conflict trials relative to low-conflict trials. This interaction effect between previous and current trial types is called "conflict adaptation" and thought to be due to processing adjustments in cognitive control. The current study aimed to identify the neural substrates of cognitive control during conflict adaptation by isolating neural correlates of reduced conflict from those of increased cognitive control. We expected cognitive control to be implemented by prefrontal cortex through context-specific modulation of posterior regions involved in sensory and motor aspects of task performance. We collected event-related fMRI data on a color-word naming Stroop task and found distinct fronto-parietal networks of current trial conflict detection and conflict adaptation through cognitive control. Conflict adaptation was associated with increased activity in left middle frontal gyrus (GFm) and superior frontal gyrus (GFs), consistent with increased cognitive control, and with decreased activity in bilateral prefrontal and parietal cortices, consistent with reduced response conflict. Psychophysiological interaction analysis (PPI) revealed that cognitive control activation in GFs and GFm was accompanied by increased functional integration with bilateral inferior frontal, right temporal and parietal areas, and the anterior cerebellum. These data suggest that cognitive control is implemented by medial and lateral prefrontal cortices that bias processes in regions that have been implicated in high-level perceptual and motor processes.

Intentional False Responding Shares Neural Substrates with Response Conflict and Cognitive Control

NeuroImage. Mar, 2005  |  Pubmed ID: 15734361

The ability to deceive others is a high-level social and cognitive function. It has been suggested that response conflict and cognitive control increase during deceptive acts but this hypothesis has not been evaluated directly. Using fMRI, we tested this prediction for the execution of an intentional false response. Subjects were instructed to respond truthfully or falsely to a series of yes/no questions that were also varied in autobiographical and nonautobiographical content to further examine the influence of personal relevance when lying. We observed an interference effect (longer reaction times for false versus true responses) that was accompanied by increased activation within the anterior cingulate, caudate and thalamic nuclei, and dorsolateral prefrontal cortex (DLPFC), a circuit that has been implicated in response conflict and cognitive control. Behavioral and neural effects were more robust when falsifying autobiographical responses relative to nonautobiographical responses. Furthermore, a correlation between reaction time and left caudate activity supported the presence of increased response inhibition when falsifying responses. When presented with self-relevant (autobiographical) stimuli regardless of response condition, the mesial prefrontal and posterior cingulate cortices were recruited. Neural activity within these two regions and the anterior cingulate cortex (ACC) also showed correlations with self-report personality measures from the Psychopathic Personality Inventory (PPI). Overall, we conclude that the process of interference is inherent to the act of falsifying information and that the amount of conflict induced and cognitive control needed to successfully execute false responses is greater when dealing with personal information.

Raising Consciousness

The Journal of Clinical Investigation. May, 2005  |  Pubmed ID: 15864333

The national debate over Terri Schiavo exposed a critical gap between emotional fervor about brain-injured patients and the medical science that informs standards of care for them. Some of the questions raised in the public and legal forums point to a need for research and enhanced understanding of the mechanisms of recovery from disorders of consciousness.

Human Cortical Specialization for Food: a Functional Magnetic Resonance Imaging Investigation

The Journal of Nutrition. May, 2005  |  Pubmed ID: 15867274

Although specialized cortical pathways that process specific sensory stimuli and/or execute cognitive functions have been identified, the neuro-specificity for food-related stimuli has not been clearly demonstrated. We employed functional magnetic resonance imaging (fMRI) to compare neural systems associated with the appreciation of foods and nonfoods. Healthy, normal weight, right-handed men and women (n = 12; age 29.8 +/- 1.8 y, BMI 21.8 +/- 0.8 kg/m(2)) were imaged by fMRI while fasting. Real food and nonfood items were presented to subjects both visually and tactilely, during scanning. Subjects were instructed to pay attention to the items. A randomized 2 x 2 block design consisted of 4 conditions: visual food, visual nonfood, tactile food, and tactile nonfood. Brain regions that were significantly activated to a greater extent during the presentation of foods compared with nonfood items included the anterior cingulate, superior temporal gyrus, parahippocampal gyrus, hippocampus, and the insula. These findings support the claim that the presence of food (either seen or felt) elicits a unique cortical response that is differentiated from nonfood items. This neural substrate specialized for processing of foods informs models of food-related behavior.

Functional Specialization Within the Medial Frontal Gyrus for Perceptual Go/no-go Decisions Based on "what," "when," and "where" Related Information: an FMRI Study

Journal of Cognitive Neuroscience. Jul, 2005  |  Pubmed ID: 16102231

Cortical systems engaged during executive and volitional functions receive and integrate input from multiple systems. However, these integration processes are not well understood. In particular, it is not known whether these input pathways converge or remain segregated at the executive levels of cortical information processing. If unilateral information streams are conserved within structures that serve high-level executive functions, then the functional organization within these structures would predictably be similarly organized. If, however, unilateral input information streams are integrated within executive-related structures, then activity patterns will not necessarily reflect lower organizations. In this study, subjects were imaged during the performance of a "perceptual go/no-go" task for which instructions were based on spatial ("where"), temporal ("when"), or object ("what") stimulus features known to engage unilateral processing streams, and the expected hemispheric biases were observed for early processing areas. For example, activity within the inferior and middle occipital gyri, and the middle temporal gyrus, during the what and when tasks, was biased toward the left hemisphere, and toward the right hemisphere during the "where" task. We discover a similar lateralization within the medial frontal gyrus, a region associated with high-level executive functions and decision-related processes. This lateralization was observed regardless of whether the response was executed or imagined, and was demonstrated in multiple sensory modalities. Although active during the go/no-go task, the cingulate gyrus did not show a similar lateralization. These findings further differentiate the organizations and functions of the medial frontal and cingulate executive regions, and suggest that the executive mechanisms operative within the medial frontal gyrus preserve fundamental aspects of input processing streams.

Discordance Between Functional Magnetic Resonance Imaging During Silent Speech Tasks and Intraoperative Speech Arrest

Journal of Neurosurgery. Aug, 2005  |  Pubmed ID: 16175856

The goal of this study was to investigate discordance between the location of speech arrest during awake cortical mapping, a common intraoperative indicator of hemispheric dominance, and silent speech functional magnetic resonance (fMR) imaging maps of frontal language function.

Functional Neuroimaging During Altered States of Consciousness: How and What Do We Measure?

Progress in Brain Research. 2005  |  Pubmed ID: 16186013

The emergence of functional neuroimaging has extended the doctrine of functional specificity of the brain beyond the primary stages of perception, language, and motor systems to high-level cognitive, personality, and affective systems. This chapter applies functional magnetic resonance imaging to another high-level realm of cognition and neurology to characterize cortical function in patients with disorders of consciousness. At first pass, this objective appears paradoxical because conventional investigations of a cognitive process require experimental manipulation. For example, to map the location of language-sensitive cortex, a language-related task is performed according to a temporal sequence that alternates the task with rest (no-task) periods. Application of this approach to the study of consciousness would require that levels of consciousness be similarly varied, this is an unlikely technique. Alternatively, another strategy is presented here where the focus is on functional brain activity elicited during various passive stimulations of patients who are minimally conscious. Comparisons between patients with altered states of consciousness due to brain injury and healthy subjects may be employed to infer readiness and potential to sustain awareness. As if a behavioral microscope, fMRI enables a view of occluded neural processes to inform medical practitioners about the health of the neurocircuity-mediating cognitive processes. An underlying point of view is that assessment of recovery potential can be enhanced by neuroimaging techniques that reveal the status of residual systems specialized for essential cognitive and volitional tasks for each patient. Thus, development of imaging techniques that assess the functional status of individual unresponsive patients is a primary goal. The structural integrity of injured brains is often compromised depending on the specific traumatic event, and, therefore, images cannot be grouped across patients, as is the standard practice for investigations of cognitive systems in healthy volunteers. This chapter addresses these challenges and discusses technique adaptations associated with passive stimulation, paradigm selection, and individual patient assessments, where there is "zero tolerance for error," and confidence in the results must meet the highest standards of care. Similar adaptations have been previously developed for the purpose of personalized planning for neurosurgical procedures by mapping the locations of essential functional systems such as language, perception, and sensory-motor functions for each individual patient. Rather than addressing the question of "how does the brain do consciousness" with these techniques, this chapter presents methods for assessment of neurocognitive health in specific patients with disorders of consciousness.

Mindboggle: Automated Brain Labeling with Multiple Atlases

BMC Medical Imaging. Oct, 2005  |  Pubmed ID: 16202176

To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data.

Where Memory Meets Attention: Neural Substrates of Negative Priming

Journal of Cognitive Neuroscience. Nov, 2005  |  Pubmed ID: 16269113

The negative priming (NP) effect refers to the observed increase in identification time for a current target stimulus or stimulus feature (the "probe") that has been employed as a distractor stimulus or stimulus feature on the previous trial (the "prime"), representing strong evidence that ignored information is actively processed to a high level by selective attention systems. However, theoretical accounts of NP differ in whether they attribute the effect to processes of selective inhibition or episodic memory retrieval. Here we derived neurophysiological predictions from the rival "selective inhibition" and "episodic retrieval" models of NP, and employed event-related fMRI in a color-naming Stroop task to assess neural responses to probe trials that were subject to either no priming or negative priming. Compared to no-priming probe trials, NP resulted in increased activation of the right dorsolateral prefrontal cortex, in a region which has been closely linked with episodic memory retrieval functions. NP was also accompanied by activation of the right thalamus, particularly the mediodorsal nucleus, which has been implicated in the pathophysiology of schizophrenia, a condition associated with diminished NP effects. Our results support the proposal that ignored stimulus information is fully encoded in memory, and that episodic retrieval, not selective inhibition, of such information affects selective attention performance on subsequent trials.

Cognitive Control Mechanisms Resolve Conflict Through Cortical Amplification of Task-relevant Information

Nature Neuroscience. Dec, 2005  |  Pubmed ID: 16286928

A prominent model of how the brain regulates attention proposes that the anterior cingulate cortex monitors the occurrence of conflict between incompatible response tendencies and signals this information to a cognitive control system in dorsolateral prefrontal cortex. Cognitive control is thought to resolve conflict through the attentional biasing of perceptual processing, emphasizing task-relevant stimulus information. It is not known, however, whether conflict resolution is mediated by amplifying neural representations of task-relevant information, inhibiting representations of task-irrelevant information, or both. Here we manipulated trial-by-trial levels of conflict and control during a Stroop task using face stimuli, while recording hemodynamic responses from human visual cortex specialized for face processing. We show that, in response to high conflict, cognitive control mechanisms enhance performance by transiently amplifying cortical responses to task-relevant information rather than by inhibiting responses to task-irrelevant information. These results implicate attentional target-feature amplification as the primary mechanism for conflict resolution through cognitive control.

Visual and Tactile Guidance of Dexterous Manipulation Tasks: an FMRI Study

Perceptual and Motor Skills. Aug, 2005  |  Pubmed ID: 16353365

Models of motor guidance that dynamically adjust to the availability and quality of sensory information are based on the observation that dexterous tasks are routinely performed using various combinations of visual and tactile inputs. However, a dynamic neural system that acquires and processes relevant visual and tactile information remains relatively uncharacterized in humans. In this study, whole-brain functional magnetic resonance images were acquired during a dexterous manipulation task, compression of the end caps of a slender spring prone to buckling, to investigate the neural systems associated with motor guidance under four visual and tactile guidance conditions: (1) eyes closed (no visual input), smooth end caps, (2) eyes dosed, rough end caps, (3) eyes open and watching hand, smooth end caps, and (4) eyes open and watching hand, rough end caps. Performance of the dexterous task remained constant in all conditions. Variations in the two levels of visual input resulted in modulation of activity in the middle and inferior occipital gyrii and inferior parietal lobule, and variation in the two levels of tactile input during the task resulted in modulation of activity in the precentral (primary motor) gyrus. Although significantly active in all conditions, cingulate gyrus, medial frontal gyrus, postcentral gyrus, and cerebellum activities were not modulated by levels of either visual or somatosensory input, and no interaction effects were observed. Together, these data indicate that a fine-tuned motor task guided by varying visual and tactile information engages a distributed and integrated neural complex consisting of control and executive functions and regions that process dynamic sensory information related to guidance functions.

Mistaking a House for a Face: Neural Correlates of Misperception in Healthy Humans

Cerebral Cortex (New York, N.Y. : 1991). Apr, 2006  |  Pubmed ID: 16014866

Individuals with normal vision can sometimes momentarily mistake one object for another. In this functional magnetic resonance imaging study, we investigated how extrastriate visual regions respond during these erroneous perceptual judgements. Subjects were asked to discriminate images of houses and faces that were degraded such that they were close to an individually defined threshold for perception. On correct trials, voxels localized on the inferior occipital (OFA), fusiform (FFA) and parahippocampal (PPA) gyri exhibited selectivity for face and house images as expected. On incorrect trials, no face- or place-selectivity was observed for OFA or PPA. However, consistent with 'predictive coding' accounts of perception, we observed that the FFA also responded robustly on trials where a house was misperceived as a face, and concurrent activation was observed in medio-frontal and right parietal regions previously implicated in decision making under uncertainty. We suggest that FFA responses during misperception may be driven by a predictive top-down signal from these regions.

Responsivity to Food Stimuli in Obese and Lean Binge Eaters Using Functional MRI

Appetite. Jan, 2006  |  Pubmed ID: 16364498

Functional neuroimaging was employed to study 10 obese and 10 lean healthy young right-handed women, divided equally into binge and non-binge eaters. Subjects were presented with visual and auditory stimuli of binge type foods, non-binge type foods, and non-food stimuli in the fMRI scanner. Brain areas activated by both the visual and auditory stimuli across all individual subjects within a particular group was observed only for the binge food stimuli in the obese binge eaters, in the right premotor area, involved in planning of motor behavior. For four of the five obese binge eaters, the activation was in the ventral premotor cortex adjacent to the oral region, and may reflect past or concurrent motor planning about eating binge foods. Because a random effects group analysis has not yet been completed, this should be considered a preliminary report.

Hemodynamic Impairment As a Stimulus for Functional Brain Reorganization

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Oct, 2006  |  Pubmed ID: 16421509

We used functional magnetic resonance imaging to investigate whether hemispheral hemodynamic impairment can play an independent role in the functional reorganization of motor-related activity in the brain. Fourteen patients with large vessel occlusion but no infarct performed a simple motor task with the hand contralateral to the occluded vessel. Statistical parametric maps of regional activity were generated to compare the distribution of motor-related activity among patients with that of control subjects. Patients were classified into normal or abnormal cerebral hemodynamics on the basis of intracerebral vasomotor reactivity using transcranial Doppler and carbon dioxide inhalation. Controls and patients with normal vasomotor reactivity showed typical motor activity in contralateral motor areas. When the 9 patients with abnormal vasomotor reactivity were compared with the 14 control subjects in a single analysis, unique motor activation was identified in ipsilateral motor regions in the nonhypoperfused hemisphere. In a confirmatory analysis, blood oxygen level-dependent (BOLD) signal intensity was averaged in prespecified motor regions of interest. A significant group by hemisphere interaction was identified, driven by higher ipsilateral and lower contralateral hemisphere BOLD signal in patients with abnormal vasomotor reactivity compared with controls (F=12.40, P=0.002). The average ipsilateral motor region signal intensity was also significantly higher in the subgroup of patients with abnormal vasoreactivity and no TIA compared with controls (P=0.04). Our results suggest that hemodynamic impairment in one hemisphere, even in the absence of any focal lesion or any symptoms can be associated with a functional reorganization to the opposite hemisphere.

A Neural Representation of Categorization Uncertainty in the Human Brain

Neuron. Mar, 2006  |  Pubmed ID: 16504950

The ability to classify visual objects into discrete categories ("friend" versus "foe"; "edible" versus "poisonous") is essential for survival and is a fundamental cognitive function. The cortical substrates that mediate this function, however, have not been identified in humans. To identify brain regions involved in stimulus categorization, we developed a task in which subjects classified stimuli according to a variable categorical boundary. Psychophysical functions were used to define a decision variable, categorization uncertainty, which was systematically manipulated. Using event-related functional MRI, we discovered that activity in a fronto-striatal-thalamic network, consisting of the medial frontal gyrus, anterior insula, ventral striatum, and dorsomedial thalamus, was modulated by categorization uncertainty. We found this network to be distinct from the frontoparietal attention network, consisting of the frontal and parietal eye fields, where activity was not correlated with categorization uncertainty.

Neocortical Connectivity During Episodic Memory Formation

PLoS Biology. May, 2006  |  Pubmed ID: 16605307

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face-house binding. These data support the view that during episodic encoding, "top-down" control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace.

Facial Emotion Recognition After Curative Nondominant Temporal Lobectomy in Patients with Mesial Temporal Sclerosis

Epilepsia. Aug, 2006  |  Pubmed ID: 16922878

The right (nondominant) amygdala is crucial for processing facial emotion recognition (FER). Patients with temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS) often incur right amygdalar damage, resulting in impaired FER if TLE onset occurred before age 6 years. Consequently, early right mesiotemporal insult has been hypothesized to impair plasticity, resulting in FER deficits, whereas damage after age 5 years results in no deficit. The authors performed this study to test this hypothesis in a uniformly seizure-free postsurgical population.

Resolving Emotional Conflict: a Role for the Rostral Anterior Cingulate Cortex in Modulating Activity in the Amygdala

Neuron. Sep, 2006  |  Pubmed ID: 16982430

Effective mental functioning requires that cognition be protected from emotional conflict due to interference by task-irrelevant emotionally salient stimuli. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Drawing on the classic Stroop conflict task, we developed a protocol that allowed us to dissociate the generation and monitoring of emotional conflict from its resolution. Using functional magnetic resonance imaging (fMRI), we find that activity in the amygdala and dorsomedial and dorsolateral prefrontal cortices reflects the amount of emotional conflict. By contrast, the resolution of emotional conflict is associated with activation of the rostral anterior cingulate cortex. Activation of the rostral cingulate is predicted by the amount of previous-trial conflict-related neural activity and is accompanied by a simultaneous and correlated reduction of amygdalar activity. These data suggest that emotional conflict is resolved through top-down inhibition of amygdalar activity by the rostral cingulate cortex.

Cortical Reorganization Following Intradigital Tendon Transfer

Neuroreport. Nov, 2006  |  Pubmed ID: 17047451

We distinguish between two models of adult cortical reorganization, adaptive and constant somatotopy, using functional magnetic resonance imaging maps corresponding to individual thumb and fourth-finger digits in a patient with a right-hand fourth digit tendon transfer that salvaged impaired function of the right thumb. Comparison of motor and sensory maps for both digits and both hands was consistent with a model of 'adaptive somatotopy' in which thumb control was taken over by regions adjacent to the fourth finger control cluster rather than at the presurgical lateral region as predicted by a model of 'constant somatotopy'. These findings are the first to demonstrate that rerouting of peripheral input, in the absence of brain injury, is sufficient to drive cortical reorganization resulting in recovery of lost motor function, and further suggest an adaptive mechanism associated with brain tissue engaged in intact motor functions.

Predictive Codes for Forthcoming Perception in the Frontal Cortex

Science (New York, N.Y.). Nov, 2006  |  Pubmed ID: 17124325

Incoming sensory information is often ambiguous, and the brain has to make decisions during perception. "Predictive coding" proposes that the brain resolves perceptual ambiguity by anticipating the forthcoming sensory environment, generating a template against which to match observed sensory evidence. We observed a neural representation of predicted perception in the medial frontal cortex, while human subjects decided whether visual objects were faces or not. Moreover, perceptual decisions about faces were associated with an increase in top-down connectivity from the frontal cortex to face-sensitive visual areas, consistent with the matching of predicted and observed evidence for the presence of faces.

Functional Neuroimaging Applications for Assessment and Rehabilitation Planning in Patients with Disorders of Consciousness

Archives of Physical Medicine and Rehabilitation. Dec, 2006  |  Pubmed ID: 17140882

To describe the theoretic framework, design, and potential clinical applications of functional neuroimaging protocols in patients with disorders of consciousness.

Separate Conflict-specific Cognitive Control Mechanisms in the Human Brain

NeuroImage. Apr, 2007  |  Pubmed ID: 17276088

To ensure optimal task performance, the human brain detects and resolves conflict in information processing via a cognitive control system. However, it is not known whether conflict resolution relies on a single central resource of cognitive control, or on a collection of independent control mechanisms that deal with different types of conflict. In order to address this question, we assessed behavioral and blood-oxygen-level-dependent (BOLD) responses during the simultaneous detection and resolution of two sources of conflict in a modified color-naming Stroop task: conflict stemming from incompatibility between the task-relevant and an irrelevant stimulus feature (stimulus-based or Stroop conflict), and conflict stemming from incompatibility between an irrelevant stimulus feature and response features (response-based or Simon conflict). Results show that control mechanisms recruited by stimulus-based conflict resolve stimulus-based conflict, but do not affect the resolution of response-based conflict, and vice versa. The resolution of response-based conflict was distinguished by modulation of activity in premotor cortex, whereas resolution of stimulus-based conflict was distinguished by the modulation of activity in parietal cortex. These results suggest that the human brain flexibly adopts, and independently controls, conflict-specific resolution strategies, biasing motor programming to resolve response-based conflict, and biasing stimulus representations to resolve stimulus-based conflict. We propose a non-centralized, modular architecture of cognitive control, where separate control resources operate in parallel, and are recruited in a context-sensitive manner.

Cortical Activation During Word Processing in Late Bilinguals: Similarities and Differences As Revealed by Functional Magnetic Resonance Imaging

Journal of Clinical and Experimental Neuropsychology. Apr, 2007  |  Pubmed ID: 17454346

Functional magnetic resonance imaging was used to compare cortical organization of the first (L1, Russian) and second (L2, English) languages. Six fluent Russian-English bilinguals who acquired their second language postpuberty were tested with words and nonwords presented either auditorily or visually. Results showed that both languages activated similar cortical networks, including the inferior frontal, middle frontal, superior temporal, middle temporal, angular, and supramarginal gyri. Within the inferior frontal gyrus (IFG), L2 activated a larger cortical volume than L1 during lexical and phonological processing. For both languages, the left IFG was more active than the right IFG during lexical processing. Within the left IFG, the distance between centers of activation associated with lexical processing of translation equivalents across languages was larger than the distance between centers of activation associated with lexical processing of different words in the same language. Results of phonological processing analyses revealed different centers of activation associated with the first versus the second language in the IFG, but not in the superior temporal gyrus (STG). These findings are discussed within the context of the current literature on cortical organization in bilinguals and suggest variation in bilingual cortical activation associated with lexical, phonological, and orthographic processing.

Neural Dynamics of Rejection Sensitivity

Journal of Cognitive Neuroscience. Jun, 2007  |  Pubmed ID: 17536965

Rejection sensitivity (RS) is the tendency to anxiously expect, readily perceive, and intensely react to rejection. This study used functional magnetic resonance imaging to explore whether individual differences in RS are mediated by differential recruitment of brain regions involved in emotional appraisal and/or cognitive control. High and low RS participants were scanned while viewing either representational paintings depicting themes of rejection and acceptance or nonrepresentational control paintings matched for positive or negative valence, arousal and interest level. Across all participants, rejection versus acceptance images activated regions of the brain involved in processing affective stimuli (posterior cingulate, insula), and cognitive control (dorsal anterior cingulate cortex; medial frontal cortex). Low and high RS individuals' responses to rejection versus acceptance images were not, however, identical. Low RS individuals displayed significantly more activity in left inferior and right dorsal frontal regions, and activity in these areas correlated negatively with participants' self-report distress ratings. In addition, control analyses revealed no effect of viewing negative versus positive images in any of the areas described above, suggesting that the aforementioned activations were involved in rejection-relevant processing rather than processing negatively valenced stimuli per se. Taken together, these findings suggest that responses in regions traditionally implicated in emotional processing and cognitive control are sensitive to rejection stimuli irrespective of RS, but that low RS individuals may activate prefrontal structures to regulate distress associated with viewing such images.

Preparatory Neural Activity Predicts Performance on a Conflict Task

Brain Research. Oct, 2007  |  Pubmed ID: 17889835

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

Repeated Exposure to Media Violence is Associated with Diminished Response in an Inhibitory Frontolimbic Network

PloS One. 2007  |  Pubmed ID: 18060062

Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior.

Brain Activity Associated with Stimulation Therapy of the Visual Borderzone in Hemianopic Stroke Patients

Neurorehabilitation and Neural Repair. Mar-Apr, 2008  |  Pubmed ID: 17698955

Visual restoration therapy is a home-based treatment program intended to expand visual fields of hemianopic patients through repetitive stimulation of the borderzone adjacent to the blind field. We hypothesized that the training itself would induce visual field location-specific changes in the brain's response to stimuli, a phenomenon demonstrated in animal experiments but never in humans with brain injury.

Dissociable Neural Systems Resolve Conflict from Emotional Versus Nonemotional Distracters

Cerebral Cortex (New York, N.Y. : 1991). Jun, 2008  |  Pubmed ID: 17940084

The human brain protects the processing of task-relevant stimuli from interference ("conflict") by task-irrelevant stimuli via attentional biasing mechanisms. The lateral prefrontal cortex has been implicated in resolving conflict between competing stimuli by selectively enhancing task-relevant stimulus representations in sensory cortices. Conversely, recent data suggest that conflict from emotional distracters may be resolved by an alternative route, wherein the rostral anterior cingulate cortex inhibits amygdalar responsiveness to task-irrelevant emotional stimuli. Here we tested the proposal of 2 dissociable, distracter-specific conflict resolution mechanisms, by acquiring functional magnetic resonance imaging data during resolution of conflict from either nonemotional or emotional distracters. The results revealed 2 distinct circuits: a lateral prefrontal "cognitive control" system that resolved nonemotional conflict and was associated with enhanced processing of task-relevant stimuli in sensory cortices, and a rostral anterior cingulate "emotional control" system that resolved emotional conflict and was associated with decreased amygdalar responses to emotional distracters. By contrast, activations related to both emotional and nonemotional conflict monitoring were observed in a common region of the dorsal anterior cingulate. These data suggest that the neuroanatomical networks recruited to overcome conflict vary systematically with the nature of the conflict, but that they may share a common conflict-detection mechanism.

Reproducibility of Single- and Multi-voxel 1H MRS Measurements of Intramyocellular Lipid in Overweight and Lean Subjects Under Conditions of Controlled Dietary Calorie and Fat Intake

NMR in Biomedicine. Jun, 2008  |  Pubmed ID: 17955571

The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.

A Neurology of Belief

Annals of Neurology. Feb, 2008  |  Pubmed ID: 18306392

A Case of Locked-in Syndrome Complicated by Central Deafness

Nature Clinical Practice. Neurology. Aug, 2008  |  Pubmed ID: 18506168

A 53-year-old male with a history of hypertension, diabetes mellitus, and factor V deficiency presented to an emergency room with progressively increasing headache, slurred speech, and left upper extremity weakness. Over the previous 3 months, he had been receiving warfarin for prophylaxis of deep venous thrombosis following knee surgery. After presentation and an initial period of coma, he became tetraplegic and anarthric, requiring intubation and ventilatory assistance.

Neural Integration of Top-down Spatial and Feature-based Information in Visual Search

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jun, 2008  |  Pubmed ID: 18550756

Visual search is aided by previous knowledge regarding distinguishing features and probable locations of a sought-after target. However, how the human brain represents and integrates concurrent feature-based and spatial expectancies to guide visual search is currently not well understood. Specifically, it is not clear whether spatial and feature-based search information is initially represented in anatomically segregated regions, nor at which level of processing expectancies regarding target features and locations may be integrated. To address these questions, we independently and parametrically varied the degree of spatial and feature-based (color) cue information concerning the identity of an upcoming visual search target while recording blood oxygenation level-dependent (BOLD) responses in human subjects. Search performance improved with the amount of spatial and feature-based cue information, and cue-related BOLD responses showed that, during preparation for visual search, spatial and feature cue information were represented additively in shared frontal, parietal, and cingulate regions. These data show that representations of spatial and feature-based search information are integrated in source regions of top-down biasing and oculomotor planning before search onset. The purpose of this anticipatory integration could lie with the generation of a "top-down salience map," a search template of primed target locations and features. Our results show that this role may be served by the intraparietal sulcus, which additively integrated a spatially specific activation gain in relation to spatial cue information with a spatially global activation gain in relation to feature cue information.

Leptin Reverses Weight Loss-induced Changes in Regional Neural Activity Responses to Visual Food Stimuli

The Journal of Clinical Investigation. Jul, 2008  |  Pubmed ID: 18568078

Increased hunger and food intake during attempts to maintain weight loss are a critical problem in clinical management of obesity. To determine whether reduced body weight maintenance is accompanied by leptin-sensitive changes in neural activity in brain regions affecting regulatory and hedonic aspects of energy homeostasis, we examined brain region-specific neural activity elicited by food-related visual cues using functional MRI in 6 inpatient obese subjects. Subjects were assessed at their usual weight and, following stabilization at a 10% reduced body weight, while receiving either twice daily subcutaneous injections of leptin or placebo. Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake. Specifically, following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus. There were also leptin-reversible decreases in activity in response to food cues in the hypothalamus, cingulate gyrus, and middle frontal gyrus. These data are consistent with a model of the weight-reduced state as one of relative leptin deficiency.

Detection of Time-varying Signals in Event-related FMRI Designs

NeuroImage. Nov, 2008  |  Pubmed ID: 18775784

In neuroimaging research on attention, cognitive control, decision-making, and other areas where response time (RT) is a critical variable, the temporal variability associated with the decision is often assumed to be inconsequential to the hemodynamic response (HDR) in rapid event-related designs. On this basis, the majority of published studies model brain activity lasting less than 4 s with brief impulses representing the onset of neural or cognitive events, which are then convolved with the hemodynamic impulse response function (HRF). However, electrophysiological studies have shown that decision-related neuronal activity is not instantaneous, but in fact, often lasts until the motor response. It is therefore possible that small differences in neural processing durations, similar to human RTs, will produce noticeable changes in the HDR, and therefore in the results of regression analyses. In this study we compare the effectiveness of traditional models that assume no temporal variance with a model that explicitly accounts for the duration of very brief epochs of neural activity. Using both simulations and fMRI data, we show that brief differences in duration are detectable, making it possible to dissociate the effects of stimulus intensity from stimulus duration, and that optimizing the model for the type of activity being detected improves the statistical power, consistency, and interpretability of results.

A Multiplicative Model for Spatial Interaction in the Human Visual Cortex

Journal of Vision. 2008  |  Pubmed ID: 18831627

Multifocal visual evoked potentials (mfVEP) were recorded simultaneously for both the target and the neighbor stimuli, each varying over 6 levels of contrast: 0%, 4%, 8%, 16%, 32%, and 64%. For most conditions, the relationship between the amplitude of target response and the contrast of the neighbor stimulus, as well as the amplitude of the response to the target stimulus, were described with a simple, normalization model. However, when the neighbor stimulus had a much higher contrast than the target stimulus, the amplitude of the target response was larger than the prediction from the normalization model. These results suggest that spatial interaction observed in the mfVEP requires (1) multiplicative mechanisms, (2) mutual inhibition between neighboring regions, and (3) a mechanism that saturates when the ratio between the contrasts of the target and that of the neighbor is large. A modified multiplicative model that incorporates these elements describes the results.

Neuroimaging and Disorders of Consciousness: Envisioning an Ethical Research Agenda

The American Journal of Bioethics : AJOB. Sep, 2008  |  Pubmed ID: 18853371

The application of neuroimaging technology to the study of the injured brain has transformed how neuroscientists understand disorders of consciousness, such as the vegetative and minimally conscious states, and deepened our understanding of mechanisms of recovery. This scientific progress, and its potential clinical translation, provides an opportunity for ethical reflection. It was against this scientific backdrop that we convened a conference of leading investigators in neuroimaging, disorders of consciousness and neuroethics. Our goal was to develop an ethical frame to move these investigative techniques into mature clinical tools. This paper presents the recommendations and analysis of a Working Meeting on Ethics, Neuroimaging and Limited States of Consciousness held at Stanford University during June 2007. It represents an interdisciplinary approach to the challenges posed by the emerging use of neuroimaging technologies to describe and characterize disorders of consciousness.

Comparison of Contrast-response Functions from Multifocal Visual-evoked Potentials (mfVEPs) and Functional MRI Responses

Journal of Vision. 2008  |  Pubmed ID: 19146350

Contrast response functions (CRFs) from multifocal visual-evoked potential (mfVEP) and BOLD fMRI responses were obtained using the same stimuli to test the hypothesis of a linear relationship between the mfVEP and BOLD fMRI responses. Monocular mfVEP and BOLD fMRI responses were obtained using an 8 degrees in diameter, dartboard pattern stimulus with reversing checkerboards. Six contrast conditions (4%, 8%, 16%, 32%, 64%, and 90%) were run. The mfVEP, largely generated in V1, was compared to the BOLD fMRI signal from V1 and extrastriate cortex. Retinotopic maps of each subject were acquired and used to localize the V1 area. For all subjects, the CRFs for the mfVEPs and BOLD fMRI responses showed good agreement, suggesting that they both share the same functional relationship with underlying neural activity. In particular, this result is consistent with the assumption that the relationship between the BOLD response and underlying neural activity is linear, although the particular linear model proposed by D. J. Heeger, A. C. Huk, W. S. Geisler, and D. G. Albrecht (2000) does not fit the results.

The Dynamics of Deductive Reasoning: an FMRI Investigation

Neuropsychologia. Mar, 2009  |  Pubmed ID: 18835284

Although the basis for deductive reasoning has been a traditional focus of philosophical discussion, the neural correlates and mechanisms that underlie deductive reasoning have only recently become the focus of scientific investigation. In syllogistic deductive reasoning information presented in two related sequential premises leads to a subsequent conclusion. While previous imaging studies have identified frontal, parietal, temporal, and occipital complexes that are activated during these reasoning events, there are substantive differences among the findings with respect to the specific regions engaged in reasoning and the contribution of language areas. Further, little is known about the various stages of information processing during reasoning. Using event-related fMRI and an auditory and visual conjunction technique, we identified a long-range supramodal network active during reasoning processes including areas in the left frontal and parietal regions as well as the bilateral caudate nucleus. Time courses of activation for each of these regions suggest that reasoning processes emerge during the presentation of the second premise, and remain active until the validation of the conclusion. Thus, areas within the frontal and parietal regions are differentially engaged at different time points in the reasoning process consistent with coordinated intra-network interactions.

11C-dihydrotetrabenazine PET of the Pancreas in Subjects with Long-standing Type 1 Diabetes and in Healthy Controls

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. Mar, 2009  |  Pubmed ID: 19223416

Type 2 vesicular monoamine transporter (VMAT2), found in the brain, is also expressed by beta-cells of the pancreas in association with insulin. Preclinical experiments suggested that (11)C-dihydrotetrabenazine PET-measured VMAT2 binding might serve as a biomarker of beta-cell mass. We evaluated the feasibility of (11)C-dihydrotetrabenazine PET quantification of pancreatic VMAT2 binding in healthy subjects and patients with long-standing type 1 diabetes.

Neural Mechanisms of Grief Regulation

Biological Psychiatry. Jul, 2009  |  Pubmed ID: 19249748

The death of an attachment figure triggers intrusive thoughts of the deceased, sadness, and yearning for reunion. Recovery requires reduction of symptoms. We hypothesized that symptoms might correlate with a capacity to regulate attention toward reminders of the deceased, and activity in, and functional connectivity between, prefrontal regulatory regions and the amygdala.

Reperfusion Normalizes Motor Activation Patterns in Large-vessel Disease

Annals of Neurology. Feb, 2009  |  Pubmed ID: 19259970

Hemodynamic impairment in one hemisphere has been shown to trigger ipsilateral motor activation in the opposite hemisphere on functional imaging. We hypothesized that reversing the hypoperfusion would normalize the motor activation pattern.

Neural Circuitry of Submissive Behavior in Social Anxiety Disorder: A Preliminary Study of Response to Direct Eye Gaze

Psychiatry Research. Sep, 2009  |  Pubmed ID: 19628377

Fear of eye gaze is common in social anxiety disorder (SAD) and may represent an evolutionarily conserved submissive behavior. SAD subjects and healthy volunteers who underwent functional magnetic resonance imaging showed significant differences in neural activity in amygdala, fusiform, insula, anterior cingulate and prefrontal cortex in response to direct versus averted gaze. Neural response to direct gaze may identify brain regions important in the pathophysiology of SAD.

Adipose Tissue Distribution After Weight Restoration and Weight Maintenance in Women with Anorexia Nervosa

The American Journal of Clinical Nutrition. Nov, 2009  |  Pubmed ID: 19793856

Body image distortions are a core feature of anorexia nervosa (AN). We, and others, previously reported abnormalities in adipose tissue distribution after acute weight restoration in adult women with AN compared with body mass index-matched healthy control women. Whether these abnormalities persist over time remains unknown.

Behavioral Assessment in Patients with Disorders of Consciousness: Gold Standard or Fool's Gold?

Progress in Brain Research. 2009  |  Pubmed ID: 19818893

In the absence of "hard" neurophysiologic markers, the burden of proof for establishing conscious awareness in individuals who sustain severe brain injury lies in behavioral assessment. Because behavior represents indirect evidence of consciousness, reliance on behavioral markers presents significant challenges and may lead to misdiagnosis. Detection of conscious awareness is confounded by numerous factors including fluctuations in arousal level, difficulty differentiating reflexive or involuntary movement from intentional behavior, underlying sensory and motor impairments, and medication side effects. When an ambiguous behavior is observed, the onus falls to the clinician to determine where along the continuum of unconsciousness to consciousness, it lies. This paper (1) summarizes the current diagnostic criteria for coma, the vegetative state, and the minimally conscious state, (2) describes current behavioral assessment methods, (3) discusses the limitations of behavioral assessment techniques, (4) reviews recent applications of functional neuroimaging in the assessment of patients with disorders of consciousness, and (5) concludes with a case study that illustrates the disparity between behavioral and functional neuroimaging findings that may be encountered in this population.

Functional Magnetic Resonance Imaging Guided Transcranial Magnetic Stimulation in Obsessive-compulsive Disorder

Biological Psychiatry. Apr, 2010  |  Pubmed ID: 19793582

Effects of Heartbeat and Respiration on Macaque FMRI: Implications for Functional Connectivity

Neuropsychologia. Jun, 2010  |  Pubmed ID: 19969009

The use of functional magnetic resonance imaging (fMRI) in non-human primates is on the increase. It is known that the blood-oxygen-level-dependent (BOLD) signal varies not only as a function of local neuronal energy consumption but also as a function of cardiac and respiratory activity. We mapped these cyclic cardiac and respiratory artifacts in anesthetized macaque monkeys and present an objective analysis of their impact on estimates of functional connectivity (fcMRI). Voxels with significant cardiac and respiratory artifacts were found in much the same regions as previously reported for awake humans. We show two example seeds where removing the artifacts clearly decreased the number of false positive and false negative correlations. In particular, removing the artifacts reduced correlations in the so-called resting state network. Temporal bandpass filtering or spatial smoothing may help to reduce the effects of artifacts in some cases but are not an adequate replacement for an algorithm that explicitly models and removes cyclic cardiac and respiratory artifacts.

A Translational Bridge Between Mouse and Human Models of Learned Safety

Annals of Medicine. Mar, 2010  |  Pubmed ID: 20121549

Learned safety is established by negatively correlating the occurrence of a neutral stimulus and a noxious stimulus, which renders the previously neutral stimulus a 'safety signal'. While the neurophysiological and molecular mechanisms have been characterized in mice, it is currently not known how the neural substrates involved compare between mice and people.

Energy Intake in Weight-reduced Humans

Brain Research. Sep, 2010  |  Pubmed ID: 20595050

Almost anyone who has ever lost weight can attest that it is harder to sustain weight loss than to lose weight. Maintenance of a 10% or greater reduced body weight is accompanied by decreases in energy expenditure to levels significantly below what is predicted solely on the basis of weight and body composition changes. This disproportionate decline in energy expenditure would not be sufficient to account for the over 80% recidivism rate to pre-weight loss levels of body fatness after otherwise successful weight reduction if there were a corresponding reduction in energy intake. In fact, reduced body weight maintenance is accompanied by increased energy intake above that required to maintain reduced weight. The failure to reduce energy intake in response to decreased energy output reflects decreased satiation and perception of how much food is eaten and multiple changes in neuronal signaling in response to food which conspire with the decline in energy output to keep body energy stores (fat) above a CNS-defined minimum (threshold). Much of this biological opposition to sustained weight loss is mediated by the adipocyte-derived hormone "leptin."

Self-specific Priming Effect

Consciousness and Cognition. Dec, 2010  |  Pubmed ID: 20598907

Priority of the "self" is thought to be evolutionarily advantageous. However, evidence for this priority has been sparse. In this study, subjects performed a gender categorization task on self- and non-self target faces preceded by either congruent (same gender as target) or incongruent (different gender) periliminal (33ms) or subliminal (17ms) primes. We found that subliminal primes induced a priming effect only on self target faces. This discovery of a self-specific priming effect suggests that functional specificity for faces may include timing as well as spatial adaptations.

Analysis of Clamping Versus Cutting of T3 Sympathetic Nerve for Severe Palmar Hyperhidrosis

The Journal of Thoracic and Cardiovascular Surgery. Nov, 2010  |  Pubmed ID: 20951250

Endoscopic thoracic sympathectomy can predictably eliminate the disabling symptoms of palmar hyperhidrosis. Debate has ensued over competing techniques, in particular, cutting versus clamping of the sympathetic chain. We subjectively assessed the sweat severity in different areas of the body and evaluated changes in the quality of life in patients undergoing either the cutting or clamping technique.

Self-face Enhances Processing of Immediately Preceding Invisible Faces

Neuropsychologia. Feb, 2011  |  Pubmed ID: 21168427

The self-face is thought to be an especially salient stimulus. Behavioral evidence suggests that self-face processing advantage is associated with enhanced processing of temporally adjacent subliminal stimuli. However, the neural basis of this self-related processing modulation has not been investigated. We studied self-face induced signal amplification through masked priming and repetition suppression (fMRI adaptation). Subjects performed a gender-categorization task on self- and non-self target faces preceded by subliminal (17 ms) prime faces. The relationship between prime and target was varied between task-incongruent (when prime and target belonged to a different gender) and task-congruent (when prime and target belonged to the same gender) pairs. We found that, in the presence of the visible self-face (but not of other non-self faces), a bilateral fronto-parietal network exhibited repetition suppression to subliminal prime faces belonging to the same gender (task-congruent) as the target, consistent with the notion that, in the presence of the self-face, subliminal stimuli access high-level processing systems. These results are in agreement with the notion of self-specific top-down amplification of subliminal task-relevant information, and suggest that the self-face, through its high salience, is particularly efficacious in focusing attention.

The Dorsal Medial Frontal Cortex is Sensitive to Time on Task, Not Response Conflict or Error Likelihood

NeuroImage. Jul, 2011  |  Pubmed ID: 21168515

The dorsal medial frontal cortex (dMFC) is highly active during choice behavior. Though many models have been proposed to explain dMFC function, the conflict monitoring model is the most influential. It posits that dMFC is primarily involved in detecting interference between competing responses thus signaling the need for control. It accurately predicts increased neural activity and response time (RT) for incompatible (high-interference) vs. compatible (low-interference) decisions. However, it has been shown that neural activity can increase with time on task, even when no decisions are made. Thus, the greater dMFC activity on incompatible trials may stem from longer RTs rather than response conflict. This study shows that (1) the conflict monitoring model fails to predict the relationship between error likelihood and RT, and (2) the dMFC activity is not sensitive to congruency, error likelihood, or response conflict, but is monotonically related to time on task.

Selective Reduction in Neural Responses to High Calorie Foods Following Gastric Bypass Surgery

Annals of Surgery. Mar, 2011  |  Pubmed ID: 21169809

To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity.

Conflict, Error Likelihood, and RT: Response to Brown & Yeung Et Al

NeuroImage. Jul, 2011  |  Pubmed ID: 21554960

Speech Stimulation During Functional MR Imaging As a Potential Indicator of Autism

Radiology. Aug, 2011  |  Pubmed ID: 21628495

To determine the feasibility of applying functional magnetic resonance (MR) imaging as an objective indicator of language disability in autism by using passive speech stimulation.

Brain Tissue Volume Changes Following Weight Gain in Adults with Anorexia Nervosa

The International Journal of Eating Disorders. Jul, 2011  |  Pubmed ID: 21661001

To measure brain volume deficits among underweight patients with anorexia nervosa (AN) compared to control participants and evaluate the reversibility of these deficits with short-term weight restoration.

Differences in Regional Brain Activation Patterns Assessed by Functional Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus Stratified by Disease Duration

Molecular Medicine (Cambridge, Mass.). Sep, 2011  |  Pubmed ID: 21953419

PURPOSE: The mediators of tissue damage in systemic lupus Erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will aquire tissue damage slowly and not at the same rate as other organs. Based on these assumptions, we wished to determine if duration of disease correlated with brain injury as measured with functional MRI (fMRI) and if this was independent of degree of tissue damage in other organs. RESULTS: We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short term; ST) or ≥10 years (long term; LT). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for 1 and 2 shape recall, however, both groups did poorly with 3 shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the 2 shapes retention phase of the working memory task (p<.001) and increased amygdala (p<.05) and superior parietal (p<.01) activation in response to the fearful faces paradigm. CONCLUSION: Analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggest that these observed differences are attributable to SLE effects on the central nervous system (CNS) exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the SLICC damage index.

Effects of Intensive Glucose Lowering on Brain Structure and Function in People with Type 2 Diabetes (ACCORD MIND): a Randomised Open-label Substudy

Lancet Neurology. Nov, 2011  |  Pubmed ID: 21958949

People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control.

Distinct but Overlapping Neural Networks Subserve Depression and Insecure Attachment

Social Cognitive and Affective Neuroscience. Oct, 2011  |  Pubmed ID: 22037687

Insecure attachment has been linked to depression and to outcome in psychotherapy. The neural mechanisms subserving the relationship between attachment security and depression are not well understood. We have developed a method to examine attachment-related brain activity in depression. Twenty-eight women, half depressed, viewed images of their mother, a female friend, and female strangers during fMRI scanning. The effects of depression and insecure attachment were determined with whole-brain multiple linear regression of blood-oxygen-level-dependent response against subjects' Beck Depression Inventory and Adult Attachment Interview (AAI) coherence of mind scores. Interaction effects were analyzed with ANOVA. Activity associated with depression and with insecure attachment was found in the cortico-striato-thalamic circuits of affect regulation. For early attachment (mother-friend contrast), depression scores correlated with activation of cortical and sub-cortical components of these circuits, while attachment insecurity correlated with sub-cortical activity in the same circuitry. Depression and attachment insecurity correlated with both cortical and sub-cortical activities for mother-stranger, and areas of overlap and of enhancing interactions between depression and insecure attachment were found. For late attachment (friend-stranger contrast), only cortical effects were found. Depression and attachment insecurity may be subserved by similar but distinct components of affect regulating circuits. Their interactions may explain the greater difficulty of treating depression in insecurely attached patients and suggest a contributing role for insecure attachment in depression. Further, differential sub-cortical vs cortical encoding of early vs late attachment suggests a top-down model of late attachment, potentially relevant to psychotherapeutic outcome.

Neural Response to Eye Contact and Paroxetine Treatment in Generalized Social Anxiety Disorder

Psychiatry Research. Dec, 2011  |  Pubmed ID: 22047726

Generalized social anxiety disorder (GSAD) is characterized by excessive fears of scrutiny and negative evaluation, but neural circuitry related to scrutiny in GSAD has been little studied. In this study, 16 unmedicated adults with GSAD and 16 matched healthy comparison (HC) participants underwent functional magnetic resonance imaging to assess neural response to viewed images of faces simulating movement into eye contact versus away from eye contact. GSAD patients were then treated for 8 weeks with paroxetine, and 15 patients were re-imaged. At baseline, GSAD patients had elevated neural response to eye contact in parahippocampal cortex, inferior parietal lobule, supramarginal gyrus, posterior cingulate and middle occipital cortex. During paroxetine treatment, symptomatic improvement was associated with decreased neural response to eye contact in regions including inferior and middle frontal gyri, anterior cingulate, posterior cingulate, precuneus and inferior parietal lobule. Both the magnitude of GSAD symptom reduction with paroxetine treatment and the baseline comparison of GSAD vs. HCs were associated with neural processing of eye contact in distributed networks that included regions involved in self-referential processing. These findings demonstrate that eye contact in GSAD engages neurocircuitry consistent with the heightened self-conscious emotional states known to characterize GSAD patients during scrutiny.

Can Depression Be Diagnosed by Response to Mother's Face? A Personalized Attachment-based Paradigm for Diagnostic FMRI

PloS One. 2011  |  Pubmed ID: 22180777

Objective measurement of depression remains elusive. Depression has been associated with insecure attachment, and both have been associated with changes in brain reactivity in response to viewing standard emotional and neutral faces. In this study, we developed a method to calculate predicted scores for the Beck Depression Inventory II (BDI-II) using personalized stimuli: fMRI imaging of subjects viewing pictures of their own mothers.

Neural Systems for Speech and Song in Autism

Brain : a Journal of Neurology. Feb, 2012  |  Pubmed ID: 22298195

Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal-posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls.

Sleep Restriction Leads to Increased Activation of Brain Regions Sensitive to Food Stimuli

The American Journal of Clinical Nutrition. Apr, 2012  |  Pubmed ID: 22357722

Epidemiologic evidence shows an increase in obesity concurrent with a reduction in average sleep duration among Americans. Although clinical studies propose that restricted sleep affects hormones related to appetite, neuronal activity in response to food stimuli after restricted and habitual sleep has not been investigated.

Decoding Unattended Fearful Faces with Whole-brain Correlations: an Approach to Identify Condition-dependent Large-scale Functional Connectivity

PLoS Computational Biology. 2012  |  Pubmed ID: 22479172

Processing of unattended threat-related stimuli, such as fearful faces, has been previously examined using group functional magnetic resonance (fMRI) approaches. However, the identification of features of brain activity containing sufficient information to decode, or "brain-read", unattended (implicit) fear perception remains an active research goal. Here we test the hypothesis that patterns of large-scale functional connectivity (FC) decode the emotional expression of implicitly perceived faces within single individuals using training data from separate subjects. fMRI and a blocked design were used to acquire BOLD signals during implicit (task-unrelated) presentation of fearful and neutral faces. A pattern classifier (linear kernel Support Vector Machine, or SVM) with linear filter feature selection used pair-wise FC as features to predict the emotional expression of implicitly presented faces. We plotted classification accuracy vs. number of top N selected features and observed that significantly higher than chance accuracies (between 90-100%) were achieved with 15-40 features. During fearful face presentation, the most informative and positively modulated FC was between angular gyrus and hippocampus, while the greatest overall contributing region was the thalamus, with positively modulated connections to bilateral middle temporal gyrus and insula. Other FCs that predicted fear included superior-occipital and parietal regions, cerebellum and prefrontal cortex. By comparison, patterns of spatial activity (as opposed to interactivity) were relatively uninformative in decoding implicit fear. These findings indicate that whole-brain patterns of interactivity are a sensitive and informative signature of unattended fearful emotion processing. At the same time, we demonstrate and propose a sensitive and exploratory approach for the identification of large-scale, condition-dependent FC. In contrast to model-based, group approaches, the current approach does not discount the multivariate, joint responses of multiple functional connections and is not hampered by signal loss and the need for multiple comparisons correction.

Cortical Functional Connectivity Decodes Subconscious, Task-irrelevant Threat-related Emotion Processing

NeuroImage. Jul, 2012  |  Pubmed ID: 22484206

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. 'subcortical alarm' and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing.

Frontal-occipital Connectivity During Visual Search

Brain Connectivity. 2012  |  Pubmed ID: 22708993

Although expectation- and attention-related interactions between ventral and medial prefrontal cortex and stimulus category-selective visual regions have been identified during visual detection and discrimination, it is not known if similar neural mechanisms apply to other tasks such as visual search. The current work tested the hypothesis that high-level frontal regions, previously implicated in expectation and visual imagery of object categories, interact with visual regions associated with object recognition during visual search. Using functional magnetic resonance imaging, subjects searched for a specific object that varied in size and location within a complex natural scene. A model-free, spatial-independent component analysis isolated multiple task-related components, one of which included visual cortex, as well as a cluster within ventromedial prefrontal cortex (vmPFC), consistent with the engagement of both top-down and bottom-up processes. Analyses of psychophysiological interactions showed increased functional connectivity between vmPFC and object-sensitive lateral occipital cortex (LOC), and results from dynamic causal modeling and Bayesian Model Selection suggested bidirectional connections between vmPFC and LOC that were positively modulated by the task. Using image-guided diffusion-tensor imaging, functionally seeded, probabilistic white-matter tracts between vmPFC and LOC, which presumably underlie this effective interconnectivity, were also observed. These connectivity findings extend previous models of visual search processes to include specific frontal-occipital neuronal interactions during a natural and complex search task.

Conceptual Representations of Perceptual Knowledge

Cognitive Neuropsychology. 2012  |  Pubmed ID: 22994286

Many neuroimaging studies of semantic memory have argued that knowledge of an object's perceptual properties are represented in a modality-specific manner. These studies often base their argument on finding activation in the left-hemisphere fusiform gyrus-a region assumed to be involved in perceptual processing-when the participant is verifying verbal statements about objects and properties. In this paper, we report an extension of one of these influential papers-Kan, Barsalou, Solomon, Minor, and Thompson-Schill (2003 )-and present evidence for an amodal component in the representation and processing of perceptual knowledge. Participants were required to verify object-property statements (e.g., "cat-whiskers?"; "bear-wings?") while they were being scanned by functional magnetic resonance imaging (fMRI). We replicated Kan et al.'s activation in the left fusiform gyrus, but also found activation in regions of left inferior frontal gyrus (IFG) and middle-temporal gyrus, areas known to reflect amodal processes or representations. Further, only activations in the left IFG, an amodal area, were correlated with measures of behavioural performance.

Gray Matter Abnormalities in Social Anxiety Disorder: Primary, Replication, and Specificity Studies

Biological Psychiatry. Jan, 2013  |  Pubmed ID: 22748614

Despite increasing evidence that neuroanatomical abnormalities underlie pathological anxiety, social anxiety disorder (SAD)-although among the most common of anxiety disorders-has received little attention. With magnetic resonance imaging, we: 1) examined gray matter (GM) differences between generalized SAD and healthy control groups; 2) retested the findings in an independent clinical sample; and 3) tested for specificity by contrasting the SAD group to a separate group of panic disorder (PD) subjects.

The Temporal Derivative of Expected Utility: a Neural Mechanism for Dynamic Decision-making

NeuroImage. Jan, 2013  |  Pubmed ID: 22963852

Real world tasks involving moving targets, such as driving a vehicle, are performed based on continuous decisions thought to depend upon the temporal derivative of the expected utility (∂V/∂t), where the expected utility (V) is the effective value of a future reward. However, the neural mechanisms that underlie dynamic decision-making are not well understood. This study investigates human neural correlates of both V and ∂V/∂t using fMRI and a novel experimental paradigm based on a pursuit-evasion game optimized to isolate components of dynamic decision processes. Our behavioral data show that players of the pursuit-evasion game adopt an exponential discounting function, supporting the expected utility theory. The continuous functions of V and ∂V/∂t were derived from the behavioral data and applied as regressors in fMRI analysis, enabling temporal resolution that exceeded the sampling rate of image acquisition, hyper-temporal resolution, by taking advantage of numerous trials that provide rich and independent manipulation of those variables. V and ∂V/∂t were each associated with distinct neural activity. Specifically, ∂V/∂t was associated with anterior and posterior cingulate cortices, superior parietal lobule, and ventral pallidum, whereas V was primarily associated with supplementary motor, pre and post central gyri, cerebellum, and thalamus. The association between the ∂V/∂t and brain regions previously related to decision-making is consistent with the primary role of the temporal derivative of expected utility in dynamic decision-making.

Dynamic Coupling Between the Lateral Occipital-cortex, Default-mode, and Frontoparietal Networks During Bistable Perception

Brain Connectivity. 2013  |  Pubmed ID: 23510237

The lateral occipital cortex (LOC), a visual area known to be involved in object recognition, was dynamically coupled with each of two distributed patterns of neural activity depending upon the percept (default or alternative) elicited by a bistable figure. The two distributed patterns included core nodes of the default-mode and frontoparietal networks (FPN), and they were most highly coupled to each other during the alternative percept, whereas they were less coupled during the default percept. Surprisingly, the regions associated with the nonengaged percept exhibited the highest connectivity to the LOC. Together, these findings reveal a dynamic organization between the default mode and the FPNs, and the incoming bottom-up visual stream during perceptual binding of visual images.

Effects of Reduced Weight Maintenance and Leptin Repletion on Functional Connectivity of the Hypothalamus in Obese Humans

PloS One. 2013  |  Pubmed ID: 23555620

Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown leptin-sensitive increases in activation of the right hypothalamus and reduced activation of the cingulate, medial frontal and parahippocampal gryi, following weight loss, in response to food stimuli. In the present study, we expanded our cohort of in-patient subjects and employed psychophysiological interaction (PPI) analysis to examine changes in the functional connectivity of the right hypothalamus. During reduced-weight maintenance with placebo injections, the functional connectivity of the hypothalamus increased with visual areas and the dorsal anterior cingulate (dorsal ACC) in response to food cues, consistent with higher sensitivity to food. During reduced-weight maintenance with leptin injections, however, the functional connectivity of the right hypothalamus increased with the mid-insula and the central and parietal operculae, suggesting increased coupling with the interoceptive system, and decreased with the orbital frontal cortex, frontal pole and the dorsal ACC, suggesting a down-regulated sensitivity to food. These findings reveal neural mechanisms that may underlie observed changes in sensitivity to food cues in the obese population during reduced-weight maintenance and leptin repletion.

Shared Space, Separate Processes: Neural Activation Patterns for Auditory Description and Visual Object Naming in Healthy Adults

Human Brain Mapping. Jun, 2014  |  Pubmed ID: 23918095

Historically, both clinicians and cognitive scientists have used visual object naming measures to study naming, and lesion-type studies have implicated the left posterior, temporo-parietal region as a critical component of naming circuitry. However, recent results from behavioral and cortical stimulation studies using auditory description naming as well as visual object naming in left temporal lobe epilepsy patients suggest that discrete sites in anterior temporal cortex are critical for description naming, whereas posterior temporal regions mediate both visual object naming and description naming. To determine whether this task specificity reflects normal cerebral organization and processing, 13 healthy adults performed description naming and visual naming during functional neuroimaging. In addition to standard univariate analysis, multivariate, ordinal trend analysis examined the network character of the regions involved in task-specific naming. Univariate analysis indicated posterior temporal activation for both visual naming and description naming, whereas multivariate analysis revealed broader networks for both tasks, with both overlapping and task-specific regions, as well as task-related differences in the way the tasks utilized common regions. Additionally, multivariate analysis revealed unique, task-specific, regionally covarying activation patterns that were strikingly consistent in all 13 subjects for visual naming and 12/13 subjects for description naming. Results suggest a common neural substrate, yet differentiable neural processes underlying visual naming and description naming in neurologically intact individuals. These findings support the use of both types of tasks for clinical assessment and may have application in the treatment of neurologically based naming deficits. Inc.

Learning Not to Fear: Neural Correlates of Learned Safety

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Feb, 2014  |  Pubmed ID: 23963118

The ability to recognize and properly respond to instances of protection from impending danger is critical for preventing chronic stress and anxiety-central symptoms of anxiety and affective disorders afflicting large populations of people. Learned safety encompasses learning processes, which lead to the identification of episodes of security and regulation of fear responses. On the basis of insights into the neural circuitry and molecular mechanisms involved in learned safety in mice and humans, we describe learned safety as a tool for understanding neural mechanisms involved in the pathomechanisms of specific affective disorders. This review summarizes our current knowledge on the neurobiological underpinnings of learned safety and discusses potential applications in basic and translational neurosciences.

Reduced Anterior Temporal and Hippocampal Functional Connectivity During Face Processing Discriminates Individuals with Social Anxiety Disorder from Healthy Controls and Panic Disorder, and Increases Following Treatment

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Jan, 2014  |  Pubmed ID: 24084831

Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety disorders are associated with anomalous brain activation and functional connectivity (FC). However, brain-based features sensitive enough to discriminate individual subjects with a specific anxiety disorder and that track symptom severity longitudinally, desirable qualities for putative disorder-specific biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI during emotional face perceptual tasks and a new, large-scale and condition-dependent FC and machine learning approach were used to identify features (pair-wise correlations) that discriminated patients with social anxiety disorder (SAD, N=16) from controls (N=19). We assessed whether these features discriminated SAD from panic disorder (PD, N=16), and SAD from controls in an independent replication sample that performed a similar task at baseline (N: SAD=15, controls=17) and following 8-weeks paroxetine treatment (N: SAD=12, untreated controls=7). High SAD vs HCs discrimination (area under the ROC curve, AUC, arithmetic mean of sensitivity and specificity) was achieved with two FC features during unattended neutral face perception (AUC=0.88, P<0.05 corrected). These features also discriminated SAD vs PD (AUC=0.82, P=0.0001) and SAD vs HCs in the independent replication sample (FC during unattended angry face perception, AUC=0.71, P=0.01). The most informative FC was left hippocampus-left temporal pole, which was reduced in both SAD samples (replication sample P=0.027), and this FC increased following the treatment (post>pre, t(11)=2.9, P=0.007). In conclusion, SAD is associated with reduced FC between left temporal pole and left hippocampus during face perception, and results suggest promise for emerging FC-based biomarkers for SAD diagnosis and treatment effects.

Amodal Brain Activation and Functional Connectivity in Response to High-energy-density Food Cues in Obesity

Obesity (Silver Spring, Md.). Nov, 2014  |  Pubmed ID: 25098957

The obesogenic environment is pervasive, yet only some people become obese. The aim was to investigate whether obese individuals show differential neural responses to visual and auditory food cues, independent of cue modality.

Tissue Specific Arterial Spin Labeling FMRI: a Superior Method for Imaging Cerebral Blood Flow in Aging and Disease

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference. 2014  |  Pubmed ID: 25571530

Cerebral blood flow (CBF) is a physiological correlate of brain function and metabolism and as such an essential parameter for investigating how aging and disease affect the brain. Arterial spin labeling (ASL) is an fMRI method that provides absolute measurement of CBF non-invasively and with higher spatial resolution than non-MRI methods. However, application of ASL in older populations is hampered by partial volume effects (PVE) and tissue dependent changes in CBF. We have developed a tissue-specific ASL method (ts-ASL) that provides `flow density' measures by quantifying CBF for each tissue separately and independently of tissue content. Using simulated functional and structural images, we investigated the effects of brain atrophy and random noise on the SNR of GM CBF measured with conventional and ts-ASL. Results showed that: (1) For all noise levels, the SNR of ts-ASL was higher. For example, for a random Gaussian noise with standard deviation σ = 4, the SNR of GM CBF obtained with ts-ASL was ~3 times higher than the SNR of the conventional method. (2) In contrast to conventional ASL, which was substantially affected by brain atrophy, ts-ASL was virtually independent of it. (3) The sensitivity of ts-ASL for detecting focal changes in CBF (ΔCBF) in the presence of atrophy and noise was also higher compared to the conventional method. In hippocampus, for 15% atrophy and Gaussian noise with σ = 4, conventional and ts-ASL retrieved 73% and 90% of the modeled ΔCBF, respectively. Taken together, these results indicate that ts-ASL may be better suited for measuring CBF in the presence of atrophy and random noise, both of which are expected to increase with aging and disease.

Negative Blood Oxygen Level Dependent Signals During Speech Comprehension

Brain Connectivity. May, 2015  |  Pubmed ID: 25412406

Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.

Brief Report: Anomalous Neural Deactivations and Functional Connectivity During Receptive Language in Autism Spectrum Disorder: a Functional MRI Study

Journal of Autism and Developmental Disorders. Jun, 2015  |  Pubmed ID: 25526952

Neural mechanisms that underlie language disability in autism spectrum disorder (ASD) have been associated with reduced excitatory processes observed as positive blood oxygen level dependent (BOLD) responses. However, negative BOLD responses (NBR) associated with language and inhibitory processes have been less studied in ASD. In this study, functional magnetic resonance imaging showed that the NBR in ASD participants was reduced during passive listening to spoken narratives compared to control participants. Further, functional connectivity between the superior temporal gyrus and regions that exhibited a NBR during receptive language in control participants was increased in ASD participants. These findings extend models for receptive language disability in ASD to include anomalous neural deactivations and connectivity consistent with reduced or poorly modulated inhibitory processes.

A Pilot Study of Gray Matter Volume Changes Associated with Paroxetine Treatment and Response in Social Anxiety Disorder

Psychiatry Research. Mar, 2015  |  Pubmed ID: 25659476

Social anxiety disorder (SAD) has received relatively little attention in neurobiological studies. We sought to identify neuro-anatomical changes associated with successful treatment for the disorder. Fourteen patients (31 years; 57% female) with DSM-IV generalized SAD were imaged before and after 8-weeks of paroxetine treatment on a 1.5 T GE Signa MRI scanner. Symptoms were assessed by a clinician using the Liebowitz Social Anxiety Scale (LSAS). Longitudinal changes in voxel based morphometry (VBM) were determined using the VBM8 Toolbox for SPM8. Symptom severity decreased by 46% following treatment (p<0.001). At week 8, significant gray matter reductions were detected in bilateral caudate and putamen, and right thalamus, and increases in the cerebellum. Gray matter decreases in left thalamus were correlated with clinical response. This is the first study to our knowledge to identify treatment related correlates of symptom improvement for SAD. Replication in larger samples with control groups is needed to confirm these findings, as well as to test their specificity and temporal stability.

Brain Activity Classifies Adolescents with and Without a Familial History of Substance Use Disorders

Frontiers in Human Neuroscience. 2015  |  Pubmed ID: 25954186

We aimed to uncover differences in brain circuits of adolescents with parental positive or negative histories of substance use disorders (SUD), when performing a task that elicits emotional conflict, testing whether the brain circuits could serve as endophenotype markers to distinguish these adolescents. We acquired functional magnetic resonance imaging data from 11 adolescents with a positive familial history of SUD (FH+ group) and seven adolescents with a negative familial history of SUD (FH- group) when performing an emotional stroop task. We extracted brain features from the conflict-related contrast images in group level analyses and granger causality indices (GCIs) that measure the causal interactions among regions. Support vector machine (SVM) was applied to classify the FH+ and FH- adolescents. Adolescents with FH+ showed greater activity and weaker connectivity related to emotional conflict, decision making and reward system including anterior cingulate cortex (ACC), prefrontal cortex (PFC), and ventral tegmental area (VTA). High classification accuracies were achieved with leave-one-out cross validation (89.75% for the maximum conflict, 96.71% when combining maximum conflict and general conflict contrast, 97.28% when combining activity of the two contrasts and GCIs). Individual contributions of the brain features to the classification were further investigated, indicating that activation in PFC, ACC, VTA and effective connectivity from PFC to ACC play the most important roles. We concluded that fundamental differences of neural substrates underlying cognitive behaviors of adolescents with parental positive or negative histories of SUD provide new insight into potential neurobiological mechanisms contributing to the elevated risk of FH+ individuals for developing SUD.

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