Neuroscience. When is a Word Not a Word?

Science (New York, N.Y.). Jul, 2003  |  Pubmed ID: 12869747

Functional Connectivity of the Medial Temporal Lobe Relates to Learning and Awareness

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jul, 2003  |  Pubmed ID: 12878693

Learning with awareness is believed to require the involvement of the medial temporal lobe (MTL). In this study, the hypothesis tested was that this involvement is best appreciated by the pattern of MTL functional connectivity with other brain areas. In a sensory learning paradigm, human subjects were classified as AWARE or UNAWARE, on the basis of whether they noted that one of two tones predicted a visual event. Only AWARE subjects acquired and reversed a differential response to the tones. However, learned facilitation was evident in both groups. MTL activity, indexed by blood flow changes measured with positron emission tomography, was correlated with facilitation in both groups but in opposite directions (greater MTL activity was related to less facilitation in AWARE subjects but more facilitation in UNAWARE subjects). Discrimination and reversal in AWARE subjects involved anterior medial, inferior prefrontal, and lateral occipital cortices. Furthermore, unique regional patterns of MTL functional connectivity were observed: AWARE subjects engaged dorsolateral prefrontal and lateral occipital cortices, whereas UNAWARE subjects showed a more spatially restricted network involving contralateral MTL regions and the thalamus. In the AWARE group, the MTL functional connectivity pattern overlapped with regions associated with facilitation and discrimination, but in UNAWARE subjects, the MTL pattern was related only to facilitation. These results suggest that the MTL and functional connected regions, including dorsolateral and medial prefrontal cortex, acted to link facilitation and discrimination patterns in AWARE subjects. Thus, the contribution of the MTL to learning and awareness is shaped by the pattern of interregional interactions, the neural context.

Spatiotemporal Analysis of Event-related Potentials to Upright, Inverted, and Contrast-reversed Faces: Effects on Encoding and Recognition

Psychophysiology. Jul, 2004  |  Pubmed ID: 15189487

In an n-back face recognition task where subjects responded to repeated stimuli, ERPs were recorded to upright, inverted, and contrast-reversed faces. The effects of inversion and contrast reversal on face encoding and recognition were investigated using the multivariate spatiotemporal partial least squares (PLS) analysis. The configural manipulations affected early processing (100-200 ms) at posterior sites: Inversion effects were parietal and lateral, whereas contrast-reversal effects were more occipital and medial, suggesting different underlying generators. A later reactivation of face processing areas was unique to inverted faces, likely due to processing difficulties. PLS also indicated that the "old-new" repetition effect was maximal for upright faces and likely involved frontotemporal areas. Marked processing differences between inverted and contrast-reversed faces were seen, but these effects were similar at encoding and recognition.

Partial Least Squares Analysis of Neuroimaging Data: Applications and Advances

NeuroImage. 2004  |  Pubmed ID: 15501095

Partial least squares (PLS) analysis has been used to characterize distributed signals measured by neuroimaging methods like positron emission tomography (PET), functional magnetic resonance imaging (fMRI), event-related potentials (ERP) and magnetoencephalography (MEG). In the application to PET, it has been used to extract activity patterns differentiating cognitive tasks, patterns relating distributed activity to behavior, and to describe large-scale interregional interactions or functional connections. This paper reviews the more recent extension of PLS to the analysis of spatiotemporal patterns present in fMRI, ERP, and MEG data. We present a basic mathematical description of PLS and discuss the statistical assessment using permutation testing and bootstrap resampling. These two resampling methods provide complementary information of the statistical strength of the extracted activity patterns (permutation test) and the reliability of regional contributions to the patterns (bootstrap resampling). Simulated ERP data are used to guide the basic interpretation of spatiotemporal PLS results, and examples from empirical ERP and fMRI data sets are used for further illustration. We conclude with a discussion of some caveats in the use of PLS, including nonlinearities, nonorthogonality, and interpretation difficulties. We further discuss its role as an important tool in a pluralistic analytic approach to neuroimaging.

Hearing Two Things at Once: Neurophysiological Indices of Speech Segregation and Identification

Journal of Cognitive Neuroscience. May, 2005  |  Pubmed ID: 15904547

The discrimination of concurrent sounds is paramount to speech perception. During social gatherings, listeners must extract information from a composite acoustic wave, which sums multiple individual voices that are simultaneously active. The observers' ability to identify two simultaneously presented vowels improves with increasing separation between the fundamental frequencies (f0) of the two vowels. Event-related potentials to stimuli presented during attend and ignore conditions revealed activity between 130 and 170 msec after sound onset that reflected the f0 differences between the two vowels. Another, more posterior and right-lateralized, negative wave maximal at 250 msec, and a central-parietal slow negativity were observed only during vowel identification and may index stimulus categorization. This sequence of neural events supports a multistage model of auditory scene analysis in which the spectral pattern of each vowel constituent is automatically extracted and then matched against representations of those vowels in working memory.

Accelerated and Amplified Neural Responses in Visual Discrimination: Two Features Are Processed Faster Than One

NeuroImage. Jul, 2005  |  Pubmed ID: 15961041

Psychological and neurophysiological models of visual processing have traditionally emphasized hierarchical models to explain how separate features of visual stimuli are combined. This concept has been challenged recently with the demonstration of simultaneous activation of multiple visual areas and rapid feedback to primary cortices. Here, we show human visual processing may involve similar mechanisms. Subjects discriminated targets from nontargets as a function of shape, color, or the conjunction of these features while event-related brain potentials (ERPs) were recorded. ERP components from 100 to 200 ms across posterior occipital-temporal cortices were fastest and largest for conjunction targets. These enhanced early responses were followed by task-specific sustained posterior activity (300-500 ms). Faster reaction times were correlated with enhanced and faster early processing in the visual ventral areas. These data demonstrate the human visual system conjoins features rapidly, accelerating and amplifying the processing of relevant stimulus dimensions.

Neuroanatomical Differences Between Mouse Strains As Shown by High-resolution 3D MRI

NeuroImage. Jan, 2006  |  Pubmed ID: 16084741

The search for new mouse models of human disease requires a sensitive metric to make three-dimensional (3D) anatomical comparisons in a rapid and quantifiable manner. This is especially true in the brain, where changes in complex shapes such as the hippocampus and ventricles are difficult to assess with 2D histology. Here, we report that the 3D neuroanatomy of three strains of mice (129S1/SvImJ, C57/Bl6, and CD1) is significantly different from one another. Using image co-registration, we 'morphed' together nine brains of each strain scanned by magnetic resonance imaging at (60 microm)3 resolution to synthesize an average image. We applied three methods of comparison. First, we used visual inspection and graphically examined the standard deviation of the variability in each strain. Second, we annotated 42 neural structures and compared their volumes across the strains. Third, we assessed significant local deviations in volume and displacement between the two inbred strains, independent of prior anatomical knowledge.

Children Recruit Distinct Neural Systems for Implicit Emotional Face Processing

Neuroreport. Feb, 2006  |  Pubmed ID: 16407774

The ability to properly distinguish facial emotions has a protracted development, not maturing until well into adolescence. Emotional faces activate emotion-specific neural networks in adults; whether these networks are operational in children is not known. Using an implicit face-processing task in 10-year-old children, we determined that the emotions of fear, disgust and sadness recruited distinct neural systems. These systems included a number of regions typically associated with processing emotions in adults, namely the amygdala and parahippocampal gyrus, insula and cingulate gyrus, as well as the fusiform and superior temporal gyri. Thus, in spite of immature behavioral responses to emotional faces in explicit tasks, neural networks for emotion-specific processing are present in young children.

Subcortical Hyperintensities in Alzheimer's Disease: No Clear Relationship with Executive Function and Frontal Perfusion on SPECT

Dementia and Geriatric Cognitive Disorders. 2007  |  Pubmed ID: 17934273

To investigate relationships between subcortical hyperintensities (SH), frontal perfusion and executive function (EF) in a sample of Alzheimer's disease (AD) patients with varying severities of SH.

Misclassified Tissue Volumes in Alzheimer Disease Patients with White Matter Hyperintensities: Importance of Lesion Segmentation Procedures for Volumetric Analysis

Stroke; a Journal of Cerebral Circulation. Apr, 2008  |  Pubmed ID: 18323507

MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18).

Quantitative Examination of a Novel Clustering Method Using Magnetic Resonance Diffusion Tensor Tractography

NeuroImage. Apr, 2009  |  Pubmed ID: 19159690

MR diffusion tensor imaging (DTI) can measure and visualize organization of white matter fibre tracts in vivo. DTI is a relatively new imaging technique, and new tools developed for quantifying fibre tracts require evaluation. The purpose of this study was to compare the reliability of a novel clustering approach with a multiple region of interest (MROI) approach in both healthy and disease (schizophrenia) populations. DTI images were acquired in 20 participants (n=10 patients with schizophrenia: 56+/-15 years; n=10 controls: 51+/-20 years) (1.5 T GE system) with diffusion gradients applied in 23 non-collinear directions, repeated three times. Whole brain seeding and creation of fibre tracts were then performed. Interrater reliability of the clustering approach, and the MROI approach, were each evaluated and the methods compared. There was high spatial (voxel-based) agreement within and between the clustering and MROI methods. Fractional anisotropy, trace, and radial and axial diffusivity values showed high intraclass correlation (p<0.001 for all tracts) for each approach. Differences in scalar indices of diffusion between the clustering and MROI approach were minimal. The excellent interrater reliability of the clustering method and high agreement with the MROI method, quantitatively and spatially, indicates that the clustering method can be used with confidence. The clustering method avoids biases of ROI drawing and placement, and, not limited by a priori predictions, may be a more robust and efficient way to identify and measure white matter tracts of interest.

Diffusion Tensor Tractography Findings in Schizophrenia Across the Adult Lifespan

Brain : a Journal of Neurology. May, 2010  |  Pubmed ID: 20237131

In healthy adult individuals, late life is a dynamic time of change with respect to the microstructural integrity of white matter tracts. Yet, elderly individuals are generally excluded from diffusion tensor imaging studies in schizophrenia. Therefore, we examined microstructural integrity of frontotemporal and interhemispheric white matter tracts in schizophrenia across the adult lifespan. Diffusion tensor imaging data from 25 younger schizophrenic patients (< or = 55 years), 25 younger controls, 25 older schizophrenic patients (> or = 56 years) and 25 older controls were analysed. Patients with schizophrenia in each group were individually matched to controls. Whole-brain tractography and clustering segmentation were employed to isolate white matter tracts. Groups were compared using repeated measures analysis of variance with 12 within-group measures of fractional anisotropy: (left and right) uncinate fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, inferior occipito-frontal fasciculus, cingulum bundle, and genu and splenium of the corpus callosum. For each white matter tract, fractional anisotropy was then regressed against age in patients and controls, and correlation coefficients compared. The main effect of group (F(3,92) = 12.2, P < 0.001), and group by tract interactions (F(26,832) = 1.68, P = 0.018) were evident for fractional anisotropy values. Younger patients had significantly lower fractional anisotropy than younger controls (Bonferroni-corrected alpha = 0.0042) in the left uncinate fasciculus (t(48) = 3.7, P = 0.001) and right cingulum bundle (t(48) = 3.6, P = 0.001), with considerable effect size, but the older groups did not differ. Schizophrenic patients did not demonstrate accelerated age-related decline compared with healthy controls in any white matter tract. To our knowledge, this is the first study to examine the microstructural integrity of frontotemporal white matter tracts across the adult lifespan in schizophrenia. The left uncinate fasciculus and right cingulum bundle are disrupted in younger chronic patients with schizophrenia compared with matched controls, suggesting that these white matter tracts are related to frontotemporal disconnectivity. The absence of accelerated age-related decline, or differences between older community-dwelling patients and controls, suggests that these patients may possess resilience to white matter disruption.

Automatic Segmentation of White Matter Hyperintensities in the Elderly Using FLAIR Images at 3T

Journal of Magnetic Resonance Imaging : JMRI. Jun, 2010  |  Pubmed ID: 20512882

To determine the precision and accuracy of an automated method for segmenting white matter hyperintensities (WMH) on fast fluid-attenuated inversion-recovery (FLAIR) images in elderly brains at 3T.

The Role of the Corpus Callosum in Transcranial Magnetic Stimulation Induced Interhemispheric Signal Propagation

Biological Psychiatry. Nov, 2010  |  Pubmed ID: 20708172

The corpus callosum, the main interhemispheric connection in the brain, may serve to preserve functional asymmetry between homologous cortical regions.

Diffusion Tensor Imaging Abnormalities in Cognitively Impaired Multiple Sclerosis Patients

The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. Sep, 2010  |  Pubmed ID: 21059506

Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients.

The Brain-derived Neurotrophic Factor Val66Met Polymorphism and Prediction of Neural Risk for Alzheimer Disease

Archives of General Psychiatry. Feb, 2011  |  Pubmed ID: 21300947

The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism may predict the risk of Alzheimer disease (AD). However, genetic association studies of the BDNF gene with AD have produced equivocal results. Imaging-genetics strategies may clarify the manner in which BDNF gene variation predicts the risk of AD via characterization of its effects on at-risk structures or neural networks susceptible in this disorder.

Visual Attention Deficits in Alzheimer's Disease: Relationship to HMPAO SPECT Cortical Hypoperfusion

Neuropsychologia. Jun, 2011  |  Pubmed ID: 21377483

Patients with Alzheimer's disease (AD) display a multiplicity of cognitive deficits in domains such as memory, language, and attention, all of which can be clearly linked to the underlying neuropathological alterations. The typical degenerative changes occur early on in the disease in the temporal-parietal lobes, with other brain regions, such as the frontal cortex, becoming more affected as the disease progresses. In light of the importance of the parietal cortex in mediating visuospatial attentional processing, in the present study, we investigated a deficit in covert orienting of visual attention and its relationship to cortical hypoperfusion in AD. We characterized the visual attentional profile of 21 AD patients, relative to that of 26 matched normal individuals, and then assessed the correspondence between behavior and hypoperfusion, as measured by regional cerebral blood flow using SPECT. Relative to controls, the AD group demonstrated a unilateral attentional deficit, with disproportionate slowing in reorienting attention to targets in the left compared to the right hemispace, especially following an invalid peripheral cue. Furthermore, even in the presence of bilateral pathology typical of AD, there was a positive correlation between this unilateral attentional disorder and the magnitude of the right superior parietal lobe hypoperfusion. The association of the altered attentional processing profile (i.e., greater difficulty disengaging attention from right-sided stimuli) with right-hemisphere-predominant hypoperfusion not only confirms the critical role of the right parietal lobe in covert attentional orienting but, more importantly, identifies a potential locus of the behavioral alterations in visuospatial processing in AD.

The ZNF804A Gene: Characterization of a Novel Neural Risk Mechanism for the Major Psychoses

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Aug, 2011  |  Pubmed ID: 21525856

Schizophrenia and bipolar disorder share genetic risk, brain vulnerability, and clinical symptoms. The ZNF804A risk variant, rs1344706, confers susceptibility for both disorders. This study aimed to identify neural mechanisms common to both schizophrenia and bipolar disorder through this variant's potential effects on cortical thickness, white matter tract integrity, and cognitive function. Imaging, genetics, and cognitive measures were ascertained in 62 healthy adults aged between 18 and 59 years. High-resolution multimodal MRI/DTI imaging was used to measure cortical thickness and major frontotemporal and interhemispheric white matter tracts. The general linear model was used to examine the influence of the ZNF804A rs1344706 risk variant on cortical thickness, white matter tract integrity, and cognitive measures. Individuals homozygous for the risk variant ('A' allele) demonstrated reduced cortical gray matter thickness in the superior temporal gyrus, and in the anterior and posterior cingulate cortices compared with C-allele carriers. No effect of the risk variant on microstructural integrity of white matter tracts was found. Reduced attention control was found in risk allele homozygotes, aligning with findings in the anterior cingulate cortex. Our data provide a novel, genetically based neural risk mechanism for the major psychoses by effects of the ZNF804A risk variant on neural structures and cognitive function susceptible in both disorders. Our findings link genetic, imaging, and cognitive susceptibility relevant to both schizophrenia and bipolar disorder.

Imaging Genetics in Multiple Sclerosis: a Volumetric and Diffusion Tensor MRI Study of APOE ε4

NeuroImage. Oct, 2011  |  Pubmed ID: 21723395

Evidence linking the ε4 allele of APOE to more severe brain MRI abnormalities in multiple sclerosis (MS) has been conflicting and limited to studies of lesion load and whole brain atrophy. The purpose of the present study was to determine whether the ε4 allele of APOE is associated with more extensive brain pathology in MS using structural and diffusion tensor MRI. Using a case-control design, 43 MS patients with the ε4 allele and 47 ε4 negative MS patients underwent structural and diffusion tensor imaging (DTI) at 3T. Hypo- and hyperintense lesion volumes, whole brain and medial temporal volumes, and DTI parameters (fractional anisotropy (FA) and mean diffusivity (MD)) in normal-appearing brain tissue and lesions were compared between the groups. ε4+ and ε4- MS patients were well-matched on demographic characteristics, disease variables, and proportions receiving disease-modifying therapy. ε4+ and ε4- patients did not differ on any MRI or DTI measure. This study refutes a role for the ε4 allele in MRI abnormalities in MS, particularly those linking ε4 to greater T1 hypointense lesion volume and brain atrophy. Previous work on this putative gene-MRI relationship is extended by comparing DTI measures within lesions and normal-appearing brain tissue. A lack of differences in medial temporal regions, areas that have been linked to ε4-associated changes in health and disease, further supports the conclusion that that ε4 is not associated with more subtle MRI markers of brain pathology in MS.

Whole-brain White Matter Disruption in Semantic and Nonfluent Variants of Primary Progressive Aphasia

Human Brain Mapping. Nov, 2011  |  Pubmed ID: 22109837

Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.

Impaired Structural Connectivity of Socio-emotional Circuits in Autism Spectrum Disorders: a Diffusion Tensor Imaging Study

PloS One. 2011  |  Pubmed ID: 22132206

Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD.

Age-related Decline in White Matter Tract Integrity and Cognitive Performance: a DTI Tractography and Structural Equation Modeling Study

Neurobiology of Aging. Jan, 2012  |  Pubmed ID: 20363050

Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.