Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n?=?20), elderly controls (n?=?32) and MCI patients (n?=?21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.
Ego disturbances in schizophrenia might be caused by a failure of the efference copy mechanism, which compares efferent with reafferent signals and attenuates the sensory consequences of self-produced movements. We carried out a functional magnetic resonance imaging study in which 16 patients with schizophrenia and 16 healthy matched controls were studied while performing both intentional and unintentional continuous hand movements in two consecutive experiments. We periodically varied the delay of visual feedback to create a sensory-motor discrepancy. Exclusively for intentional movements the activation pattern of the inferior frontal gyrus (IFG) in patients was opposite to that of controls: less attenuated during time-congruent feedback and less activated during time-incongruent feedback. Additionally, several functional connections within the mismatch detection network (IFG with insula, putamen, medial orbitofrontal cortex) were affected. Also, activity of the dysconnected orbitofrontal cortex was correlated with ego disturbance in patients. We discuss that in healthy individuals the IFG might enable a distinction between self and non-self using time-characteristics of feedback, whereas in patients this sensory mismatch detection appears to be altered. Moreover, due to the dysconnectivity of the IFG, the efferent and reafferent signal exchange between perceptual and motor areas seems to be affected. This might cause self-monitoring deficits in patients, phenomena that contribute to the emergence of ego disturbances.
Social cognition and the corresponding functionality of involved brain networks are essential for effortless social interaction. Patients with schizophrenia exhibit impaired social functioning. In this study, we focused on the neural networks involved in the automatic perception of cooperative behavior and their alterations in schizophrenia. We performed a functional magnetic resonance imaging study of 19 schizophrenia patients and 19 healthy matched controls. Participants watched a set of short videos with two actors manipulating objects, either with (C+) or without cooperation (C-). Additionally, we assessed delusional symptoms in patients using the Scales for the Assessment of Positive Symptoms and psychosis proneness in healthy controls using the brief schizotypal personality questionnaire. The observed group-by-condition interaction revealed a contrasting activation pattern for patients versus healthy controls in the medial and lateral prefrontal cortex, the middle cingulate cortex, and the left angular gyrus. Furthermore, increased activation of the middle prefrontal areas, left angular gyrus, and the posterior sulcus temporalis superior in response to the noncooperative condition (C-) was positively correlated with delusional symptoms in patients. Our findings suggest an overactivated "theory of mind" network in patients for the processing of noncooperative behavior. Thus, "overmentalizing" might be based on delusions and altered processing of cooperative behavior in patients with schizophrenia.
The aim of our study was to examine brain networks involved with sustaining memory encoding performance in healthy aging and in Alzheimers disease (AD). Since different brain regions are affected by degradation in these two conditions, it might be conceivable that different compensation mechanisms occur to keep up memory performance in aging and in AD. Using an event-related functional magnetic resonance imaging (FMRI) design and a correlation analysis, 8 patients suffering from AD and 29 elderly control subjects were scanned while they studied a list of words for a subsequent memory test. Individual performance was assessed on the basis of a subsequent recognition test, and brain regions were identified where functional activations during study correlated with memory performance. In both groups, successful memory encoding performance was significantly correlated with the activation of the right frontal cortex. Furthermore, in healthy controls, there was a significant correlation of memory performance and the activation of the left medial and lateral temporal lobe. In contrast, in AD patients, increasing memory performance goes along with increasing activation of the hippocampus and a bilateral brain network including the frontal and temporal cortices. Our data show that in healthy aging and in AD, common and distinct compensatory mechanisms are employed to keep up a certain level of memory performance. Both in healthy aging and in patients with AD, an increased level of monitoring and control processes mediated by the (right) frontal lobe seems to be necessary to maintain a certain level of memory performance. In addition, memory performance in healthy older subjects seems to rely on an increased effort in encoding item-specific semantic and contextual information in lateral areas of the (left) temporal lobe. In AD patients, on the other hand, the maintenance of memory performance is related to an increase of activation of the (left) hippocampus in conjunction with a bilateral network of cortical areas that might be involved with phonological and visual rehearsal of the incoming information.
Core psychopathological symptoms in patients with schizophrenia suggest that their sense of self may be disturbed. A disturbance in predictive motor mechanisms may be the cause of such symptoms. Ten patients with schizophrenia and ten healthy right-handed control subjects opened and closed their hand. This movement was filmed with an MRI compatible video camera and projected online onto a monitor. BOLD contrast was measured with fMRI. The temporal delay between movement and feedback was parametrically varied. Participants judged whether or not there was a delay. Patients were less sensitive to these delays than a matched control group. Comparing neural activation between the two groups showed a reduced attenuation of movement-sensitive perceptual areas in patients with increasing delay and a higher activation in the putamen in controls. The results provide further evidence that impaired efference copy mechanisms may contribute to the pathogenesis of schizophrenia and its first rank symptoms.
The experience of being the initiator of ones own actions seems to be infallible at first glance. Misattributions of agency of ones actions in certain neurological or psychiatric patients reveal, however, that the central mechanisms underlying this experience can go astray. In particular, delusions of influence in schizophrenia might result from deficits in an inferential mechanism that allows distinguishing whether or not a sensory event has been self-produced. This distinction is made by comparing the actual sensory information with the consequences of ones action as predicted on the basis of internal action-related signals such as efference copies. If this internal prediction matches the actual sensory event, an action is registered as self-caused; in case of a mismatch, the difference is interpreted as externally produced. We tested the hypothesis that delusions of influence are based on deficits in this comparator mechanism. In particular, we tested whether patients impairments in action attribution tasks are caused by imprecise predictions about the sensory consequences of self-action. Schizophrenia patients and matched controls performed pointing movements in a virtual-reality setup in which the visual consequences of movements could be rotated with respect to the actual movement. Experiment 1 revealed higher thresholds for detecting experimental feedback rotations in the patient group. The size of these thresholds correlated positively with patients delusions of influence. Experiment 2 required subjects to estimate their direction of pointing visually in the presence of constantly rotated visual feedback. When compared to controls, patients estimates were significantly better adapted to the feedback rotation and exhibited an increased variability. In interleaved trials without visual feedback, i.e. when pointing estimates relied solely on internal action-related signals, this variability was likewise increased and correlated with both delusions of influence and the size of patients detection thresholds as assessed in the first experiment. These findings support the notion that delusions of influence are based on imprecise internal predictions about the sensory consequences of ones actions. Moreover, we suggest that such imprecise predictions prompt patients to rely more strongly on (and thus adapt to) external agency cues, in this case vision. Such context-dependent weighted integration of imprecise internal predictions and alternative agency cues might thus reflect the common basis for the various misattributions of agency in schizophrenia patients.
Gestures are an important part of human communication. However, little is known about the neural correlates of gestures accompanying speech comprehension. The goal of this study is to investigate the neural basis of speech-gesture interaction as reflected in activation increase and decrease during observation of natural communication. Fourteen German participants watched video clips of 5 s duration depicting an actor who performed metaphoric gestures to illustrate the abstract content of spoken sentences. Furthermore, video clips of isolated gestures (without speech), isolated spoken sentences (without gestures) and gestures in the context of an unknown language (Russian) were additionally presented while functional magnetic resonance imaging (fMRI) data were acquired. Bimodal speech and gesture processing led to left hemispheric activation increases of the posterior middle temporal gyrus, the premotor cortex, the inferior frontal gyrus, and the right superior temporal sulcus. Activation reductions during the bimodal condition were located in the left superior temporal gyrus and the left posterior insula. Gesture related activation increases and decreases were dependent on language semantics and were not found in the unknown-language condition. Our results suggest that semantic integration processes for bimodal speech plus gesture comprehension are reflected in activation increases in the classical left hemispheric language areas. Speech related gestures seem to enhance language comprehension during the face-to-face communication.
The crucial role of lateral parietal regions in episodic memory has been confirmed in previous studies. While aging has an influence on retrieval of episodic memory, it remains to be examined how the involvement of lateral parietal regions in episodic memory changes with age. We investigated episodic memory retrieval in two age groups, using faces as stimuli and retrieval success as a measure of episodic memory. Young and elderly participants showed activation within a similar network, including lateral and medial parietal as well as prefrontal regions, but elderly showed a higher level of brain activation regardless of condition. Furthermore, we examined functional connectivity in the two age groups and found a more extensive network in the young group, including correlations of parietal and prefrontal regions. In the elderly, the overall stronger activation related to memory performance may indicate a compensatory process for a less extensive functional network.
It has been shown that social deficits contribute to psychopathology in schizophrenia, such as the bleulerian autism. A possible dysfunction in the mirror neuron system may be the reason for these deficits in the disorder. We wanted to better characterize the neural networks involved in the perception of social behavior. Fifteen healthy participants were presented with video clips of 8 seconds duration depicting either (1) one actor manipulating an object, (2) two actors with only one manipulating an object or (3) two actors cooperating in manipulating an object and 2 other control conditions. Functional magnetic resonance imaging data were acquired during watching these videos. We found the perception of social cooperation is supported by a neural network comprising the precuneus, the temporoparietal junction (supramarginal gyrus, angular gyrus, BA 39/40), the middle temporal gyrus (including superior temporal sulcus) and frontal regions (medial frontal gyrus, inferior frontal gyrus). These areas form a complex network also being activated during theory of mind and cooperative behavior tasks. Its nodes overlap with those of the mirror neuron system. Consequently, both theory of mind abilities and mirror mechanisms are relevant in the perception and understanding of social cooperative behavior. We outline the consequences of these results for a further understanding of schizophrenic psychopathology with respect to social deficits and ego disturbances.
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