Effective connectivity of working memory performance: a DCM study of MEG data.

Visual working memory (WM) engages several nodes of a large-scale network that includes frontal, parietal, and visual regions; however, little is understood about how these regions interact to support WM behavior. In particular, it is unclear whether network dynamics during WM maintenance primarily represent feedforward or feedback connections. This question has important implications for current debates about the relative roles of frontoparietal and visual regions in WM maintenance. In the current study, we investigated the network activity supporting WM using MEG data acquired while healthy subjects performed a multi-item delayed estimation WM task. We used computational modeling of behavior to discriminate correct responses (high accuracy trials) from two different types of incorrect responses (low accuracy and swap trials), and dynamic causal modeling of MEG data to measure effective connectivity. We observed behaviorally dependent changes in effective connectivity in a brain network comprising frontoparietal and early visual areas. In comparison with high accuracy trials, frontoparietal and frontooccipital networks showed disrupted signals depending on type of behavioral error. Low accuracy trials showed disrupted feedback signals during early portions of WM maintenance and disrupted feedforward signals during later portions of maintenance delay, while swap errors showed disrupted feedback signals during the whole delay period. These results support a distributed model of WM that emphasizes the role of visual regions in WM storage and where changes in large scale network configurations can have important consequences for memory-guided behavior.

Alpha phase-coding supports feature binding during working memory maintenance.

The ability to successfully retain and manipulate information in working memory (WM) requires that objects' individual features are bound into cohesive representations; yet, the mechanisms supporting feature binding remain unclear. Binding (or swap) errors, where memorized features are erroneously associated with the wrong object, can provide a window into the intrinsic limits in capacity of WM that represent a key bottleneck in our cognitive ability. We tested the hypothesis that binding in WM is accomplished via neural phase synchrony and that swap errors result from perturbations in this synchrony. Using magnetoencephalography data collected from human subjects in a task designed to induce swap errors, we showed that swaps are characterized by reduced phase-locked oscillatory activity during memory retention, as predicted by an attractor model of spiking neural networks. Further, we found that this reduction arises from increased phase-coding variability in the alpha-band over a distributed network of sensorimotor areas. Our findings demonstrate that feature binding in WM is accomplished through phase-coding dynamics that emerge from the competition between different memories.

Auditory hallucinations activate language and verbal short-term memory, but not auditory, brain regions.

Auditory verbal hallucinations (AVH, 'hearing voices') are an important symptom of schizophrenia but their biological basis is not well understood. One longstanding approach proposes that they are perceptual in nature, specifically that they reflect spontaneous abnormal neuronal activity in the auditory cortex, perhaps with additional 'top down' cognitive influences. Functional imaging studies employing the symptom capture technique-where activity when patients experience AVH is compared to times when they do not-have had mixed findings as to whether the auditory cortex is activated. Here, using a novel variant of the symptom capture technique, we show that the experience of AVH does not induce auditory cortex activation, even while real speech does, something that effectively rules out all theories that propose a perceptual component to AVH. Instead, we find that the experience of AVH activates language regions and/or regions that are engaged during verbal short-term memory.

Interindividual variability of functional connectome in schizophrenia.

Schizophrenia is a complex psychiatric disorder that displays an outstanding interindividual variability in clinical manifestation and neurobiological substrates. A better characterization and quantification of this heterogeneity could guide the search for both common abnormalities (linked to lower intersubject variability) and the presence of biological subtypes (leading to a greater heterogeneity across subjects). In the current study, we address interindividual variability in functional connectome by means of resting-state fMRI in a large sample of patients with schizophrenia and healthy controls. Among the different metrics of distance/dissimilarity used to assess variability, geodesic distance showed robust results to head motion. The main findings of the current study point to (i) a higher between subject heterogeneity in the functional connectome of patients, (ii) variable levels of heterogeneity throughout the cortex, with greater variability in frontoparietal and default mode networks, and lower variability in the salience network, and (iii) an association of whole-brain variability with levels of clinical symptom severity and with topological properties of brain networks, suggesting that the average functional connectome overrepresents those patients with lower functional integration and with more severe clinical symptoms. Moreover, after performing a graph theoretical analysis of brain networks, we found that patients with more severe clinical symptoms had decreased connectivity at both whole-brain level and within the salience network, and that patients with higher negative symptoms had large-scale functional integration deficits.

Brain imaging of executive function with the computerised multiple elements test.

The Computerised Multiple Elements Test (CMET) is a novel executive task to assess goal management and maintenance suitable for use within the fMRI environment. Unlike classical executive paradigms, it resembles neuropsychological multi-elements tests that capture goal management in a more ecological way, by requiring the participant to switch between four simple games within a specified time period. The present study aims to evaluate an fMRI version of the CMET and examine its brain correlates. Thirty-one healthy participants performed the task during fMRI scanning. During each block, they were required to play four simple games, with the transition between games being made either voluntarily (executive condition) or automatically (control condition). The executive condition was associated with increased activity in fronto-parietal and cingulo-opercular regions, with anterior insula activity linked to better task performance. In an additional analysis, the activated regions showed to form functional networks during resting-state and to overlap the executive fronto-parietal and cingulo-opercular networks identified in resting-state with independently defined seeds. These results show the ability of the CMET to elicit activity in well-known executive networks, becoming a potential tool for the study of executive impairment in neurological and neuropsychiatric populations in a more ecological way than classical paradigms.

Autobiographical memory and default mode network function in schizophrenia: an fMRI study.

BACKGROUND: The brain functional correlates of autobiographical recall are well established, but have been little studied in schizophrenia. Additionally, autobiographical memory is one of a small number of cognitive tasks that activates rather than de-activates the default mode network, which has been found to be dysfunctional in this disorder. METHODS: Twenty-seven schizophrenic patients and 30 healthy controls underwent functional magnetic resonance imaging while viewing cue words that evoked autobiographical memories. Control conditions included both non-memory-evoking cues and a low level baseline (cross fixation). RESULTS: Compared to both non-memory evoking cues and low level baseline, autobiographical recall was associated with activation in default mode network regions in the controls including the medial frontal cortex, the posterior cingulate cortex and the hippocampus, as well as other areas. Clusters of de-activation were seen outside the default mode network. There were no activation differences between the schizophrenic patients and the controls, but the patients showed clusters of failure of de-activation in non-default mode network regions. CONCLUSIONS: According to this study, patients with schizophrenia show intact activation of the default mode network and other regions associated with recall of autobiographical memories. The finding of failure of de-activation outside the network suggests that schizophrenia may be associated with a general difficulty in de-activation rather than dysfunction of the default mode network per se.

Brain imaging correlates of self- and other-reflection in schizophrenia.

BACKGROUND: An alteration in self/other differentiation has been proposed as a basis for several symptoms in schizophrenia, including delusions of reference and social functioning deficits. Dysfunction of the right temporo-parietal junction (TPJ), a region linked with social cognition, has been proposed as the basis of this alteration. However, imaging studies of self- and other-processing in schizophrenia have shown, so far, inconsistent results. METHODS: Patients with schizophrenia and healthy controls underwent fMRI scanning while performing a task with three conditions: self-reflection, other-reflection and semantic processing. RESULTS: Both groups activated similar brain regions for self- and other-reflection compared to semantic processing, including the medial prefrontal cortex, the precuneus and the TPJ. Compared to healthy subjects, patients hyperactivated the left lateral frontal cortex during self- and other-reflection. In other-reflection, compared to self-reflection, patients failed to increase right TPJ activity. CONCLUSIONS: Altered activity in the right TPJ supports a disturbance in self/other differentiation in schizophrenia, which could be linked with psychotic symptoms and affect social functioning in patients. Hyperactivity of the lateral frontal cortex for self- and other-reflection suggests the presence of greater cognitive demand to perform the task in the patient group.

Shared and differential default-mode related patterns of activity in an autobiographical, a self-referential and an attentional task.

The default-mode network (DMN) comprises a set of brain regions that show deactivations during performance of attentionally demanding tasks, but also activation during certain processes including recall of autobiographical memories and processing information about oneself, among others. However, the DMN is not activated in a homogeneous manner during performance of such tasks, so it is not clear to what extent its activation patterns correspond to deactivation patterns seen during attention-demanding tasks. In this fMRI study we compared patterns of activation in response to an autobiographical memory task to those observed in a self/other-reflection task, and compared both to deactivations observed during the n-back working memory task. Autobiographical recall and self-reflection activated several common DMN areas, which were also deactivated below baseline levels by the n-back task. Activation in the medial temporal lobe was seen during autobiographical recall but not the self/other task, and right angular gyrus activity was specifically linked to other-reflection. ROI analysis showed that most, but not all DMN regions were activated above baseline levels during the autobiographical memory and self-reflection tasks. Our results provide evidence for the usefulness of the autobiographical memory task to study DMN activity and support the notion of interacting subsystems within this network.