Alterations in White Matter Evident Before the Onset of Psychosis

Background

Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.

Methods

Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.

Results

At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.

Conclusions

People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.     

Altered error-related activity in patients with schizophrenia

Deficits in working memory (WM) and executive cognitive control are core features of schizophrenia. However, findings regarding functional activation strengths are heterogeneous, partly due to differences in task demands and behavioral performance. Previous investigators proposed integrating these heterogeneous findings into a comprehensive model of cortical inefficiency assuming the inverted U-shaped relationship between performance and neuronal activation to be shifted in patients.The present study pursued a novel approach of precise performance balancing potentially resolving a number of discrepancies with regard to performance related cognitive activation patterns in schizophrenia. Error-related WM activity was examined in 55 patients and 55 controls by balancing the mean number of incorrect responses between the groups and analyzing remaining incorrect trials. A modified Sternberg Item Recognition task (SIRT) allowing for the segregation of encoding, executive maintenance and retrieval-related activation was applied.Relative to healthy controls, patients showed extended hypoactivations in inferior temporal, superior parietal, inferior, middle and superior frontal as well as cerebellar regions during encoding of incorrectly remembered items. During erroneous retrieval of information patients exhibited a significantly decreased activation in an executive control network comprising inferior and middle frontal areas, precuneus and cerebellum.Present data suggest that in patients with schizophrenia encoding of erroneously retrieved items as well as erroneous retrieval itself is associated with extended activation abnormalities in task-relevant regions even after balancing performance. Thus, present results clearly indicate that disorder-characteristic activation abnormalities become manifest during dysfunctional executive processing even when the moderating effect of performance is largely eliminated.     

Abnormal medial temporal activity for bound information during working memory maintenance in patients with schizophrenia

Alterations of binding in long‐term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between‐group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short‐term and long‐term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long‐term memory. © 2009 Wiley‐Liss, Inc.     

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

BACKGROUND: Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. METHODS: We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. RESULTS: Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. CONCLUSIONS: Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.     

Differences of cerebral activation between superior and inferior learners during motor sequence encoding and retrieval

Cerebral activation during memory encoding and retrieval might depend on subjects' learning capacity, either by corresponding to better performance in superior learners or by reflecting increased effort in inferior learners. To investigate these alternative hypotheses, the study compared cerebral activation during encoding and retrieval of a motor sequence in groups of subjects with superior and inferior learning performances. Ten healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a motor sequence encoding paradigm (i.e. finger tapping sequence) and a retrieval paradigm (i.e. reproduction of the learned sequence). Subjects were divided into superior and inferior learners according to the correctness of sequence reproduction during retrieval. During encoding, there was strong bilateral activation in the middle frontal gyrus, the supplementary motor area (SMA), the lateral parietal lobe and the cerebellum. During retrieval, again strong activation was found in identical areas of the prefrontal cortex, the parietal lobe and the cerebellum. During encoding, inferior learners showed more left-sided activations in the left middle frontal and inferior parietal gyri. Superior learners showed increased activation in the corresponding right-sided brain areas during encoding as well as during retrieval. Differences of cerebral activations in the prefrontal and parietal cortex during encoding and retrieval were found to be related to retrieval performance, i.e. success and effort. Further intervention studies are needed to assess whether these interindividual differences are the cause or the consequence of differences in memory performance.     

Abnormal cortical neural synchrony during working memory in schizophrenia

Objective

To better understand the origins of working memory (WM) impairment in schizophrenia we investigated cortical oscillatory activity in people with schizophrenia (PSZ) while they performed a WM task requiring encoding, maintenance, and retrieval/manipulation processes of spatial information.

Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal

Schizophrenia patients are often impaired in their memory for emotional events compared with healthy subjects. Investigations of the neural correlates of emotional memory in schizophrenia patients are scarce in the literature. The present study aimed to compare cerebral activations in schizophrenia patients and healthy controls during memory retrieval of emotional images that varied in both valence and arousal. In a study with functional magnetic resonance imaging, 37 schizophrenia patients were compared with 37 healthy participants while performing a yes/no recognition paradigm with positive, negative (differing in arousal intensity) and neutral images. Schizophrenia patients performed worse than healthy controls in all experimental conditions. They showed less cerebral activation in limbic and prefrontal regions than controls during retrieval of negatively valenced stimuli, but had a similar pattern of brain activation compared with controls during retrieval of positively valenced stimuli (particularly in the high arousal condition) in the cerebellum, temporal lobe and prefrontal cortex. Both groups demonstrated increased brain activations in the high relative to low arousing conditions. Our results suggest atypical brain function during retrieval of negative pictures, but intact functional circuitry of positive affect during episodic memory retrieval in schizophrenia patients. The arousal data revealed that schizophrenia patients closely resemble the control group at both the behavioral and neurofunctional level.     

Altered Prefrontal and Hippocampal Function During Verbal Encoding and Recognition in People With Prodromal Symptoms of Psychosis

Despite robust evidence of hippocampal abnormalities in schizophrenia, it is unclear whether hippocampal dysfunction predates the onset of psychosis. We used functional magnetic resonance imaging to investigate hippocampal function in subjects with an at-risk mental state (ARMS). Eighteen subjects meeting criteria for an ARMS and 22 healthy controls, matched for age, gender, and premorbid IQ, were scanned while performing a version of the Deese-Roediger-McDermott false memory task. During an encoding phase, subjects read lists of words aloud. Following a delay, they were presented with 24 target words, 24 semantically related lure words, and 24 novel words and required to indicate if each had been presented before. Behaviorally, the ARMS group made more false alarm responses for novel words than controls (P = .04) and had a lower discrimination accuracy for target words (P = .02). During encoding, ARMS subjects showed less activation than healthy controls in the left middle frontal gyrus, the bilateral medial frontal gyri, and the left parahippocampal gyrus. Correct recognition relative to false alarms was associated with differential engagement of the hippocampus bilaterally in healthy controls, but this difference was absent in the ARMS group. The ARMS was associated with altered function in the medial temporal cortex, as well as in the prefrontal regions, during both verbal encoding and recognition. These neurofunctional differences were associated with diminished recognition performance and may reflect the greatly increased risk of psychosis associated with the ARMS.     

Outcome in early-onset schizophrenia revisited: findings from the Early Psychosis Prevention and Intervention Centre long-term follow-up study

The present study combined a time-locked paradigm and high-time-resolution event-related potential (ERP) recordings to examine different phases of working memory, including early visual processing and late memory-related processes of encoding, maintenance, and retrieval, in 67 adults with schizophrenia and 46 healthy controls. Alterations in ERP components were correlated with task performance. Patients performed significantly worse in the working memory task than healthy subjects, although all subjects' accuracy exceeded 80%. During encoding, the N1 and P2 component amplitudes were lower while the P300 amplitude was higher in schizophrenic patients compared to healthy controls. There were no differences between groups with respect to the mean amplitudes of the negative slow waves in the early stage (the first 400 ms) of the maintenance phase. However, in the next 500-ms time window, the patients exhibited a more negative deflection in the middle fronto-central region than the control group. Likewise, a similar pattern was observed in the second 500-ms period in the middle fronto-central region, although the effect was marginally significant. There were no differences between groups in the remaining 1000 ms. During retrieval, the P1, N1 and P2 amplitudes were lower while the P300 amplitude and latency were higher in schizophrenic patients. The present results indicate early visual deficits in the working memory task in adults with schizophrenia. Impairments in the maintenance phase were confined to the late rehearsal stage. The increased P300 amplitude at the fronto-central electrode sites along with the poorer behavioral performance suggests that schizophrenic patients have an inefficient working memory system.     

The influence of working-memory demand and subject performance on prefrontal cortical activity

Brain imaging and behavioral studies of working memory (WM) converge to suggest that the ventrolateral prefrontal cortex (PFC) mediates a capacity-limited storage buffer and that the dorsolateral PFC mediates memory organization processes that support supracapacity memory storage. Previous research from our laboratory has shown that the extent to which such memory organization processes are required depends on both task factors (i.e., memory load) and subject factors (i.e., response speed). Task factors exert their effects mainly during WM encoding while subject factors exert their effects mainly during WM retrieval. In this study, we sought to test the generalizability of these phenomena under more difficult memory-demand conditions than have been used previously. During scanning, subjects performed a WM task in which they were required to maintain between 1 and 8 letters over a brief delay. Neural activity was measured during encoding, maintenance, and retrieval task periods using event-related functional magnetic resonance imaging. With increasing memory load, there were reaction time increases and accuracy rate decreases, ventrolateral PFC activation decreases during encoding, and dorsolateral PFC activation increases during maintenance and retrieval. These results suggest that the ventrolateral PFC mediates WM storage and that the dorsolateral PFC mediates strategic memory organization processes that facilitate supracapacity WM storage. Additionally, high-performing subjects showed overall less activation than low-performing subjects, but activation increases with increasing memory load in the lateral PFC during maintenance and retrieval. Low-performing subjects showed overall more activation than high-performing subjects, but minimal activation increases in the dorsolateral PFC with increasing memory load. These results suggest that individual differences in both neural efficiency and cognitive strategy underlie individual differences in the quality of subjects' WM performance.     

Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities

Substantial evidence implicates working memory (WM) as a core deficit in schizophrenia (SCZ), purportedly due to primary deficits in dorsolateral prefrontal cortex functioning. Recent findings suggest that SCZ is also associated with abnormalities in suppression of certain regions during cognitive engagement—namely the default mode system—that may further contribute to WM pathology. However, no study has systematically examined activation and suppression abnormalities across both encoding and maintenance phases of WM in SCZ. Twenty-eight patients and 24 demographically matched healthy subjects underwent functional magnetic resonance imaging at 3T while performing a delayed match-to-sample WM task. Groups were accuracy matched to rule out performance effects. Encoding load was identical across subjects to facilitate comparisons across WM phases. We examined activation differences using an assumed model approach at the whole-brain level and within meta-analytically defined WM areas. Despite matched performance, we found regions showing less recruitment during encoding and maintenance for SCZ subjects. Furthermore, we identified 2 areas closely matching the default system, which SCZ subjects failed to deactivate across WM phases. Lastly, activation in prefrontal regions predicted the degree of deactivation for healthy but not SCZ subjects. Current results replicate and extend prefrontal recruitment abnormalities across WM phases in SCZ. Results also indicate deactivation abnormalities across WM phases, possibly due to inefficient prefrontal recruitment. Such regional deactivation may be critical for suppressing sources of interference during WM trace formation. Thus, deactivation deficits may constitute an additional source of impairments, which needs to be further characterized for a complete understanding of WM pathology in SCZ.     

Polygenic Risk for Schizophrenia Associated With Working Memory-related Prefrontal Brain Activation in Patients With Schizophrenia and Healthy Controls

Schizophrenia is a highly heritable and polygenic disease, and identified common genetic variants have shown weak individual effects. Many studies have reported altered working memory (WM)-related brain activation in schizophrenia, preferentially in the frontal lobe. Such differences in brain activations could reflect inherited alterations possibly involved in the disease etiology, or rather secondary disease-related mechanisms. The use of polygenic risk scores (PGRS) based on a large number of risk polymorphisms with small effects is a valuable approach to examine the effect of cumulative genetic risk on brain functioning. This study examined the impact of cumulative genetic risk for schizophrenia on WM-related brain activations, assessed with functional magnetic resonance imaging. For each participant (63 schizophrenia patients and 118 healthy controls), we calculated a PGRS for schizophrenia based on 18 862 single-nucleotide polymorphism in a large multicenter genome-wide association study including 9146 schizophrenia patients and 12 111 controls, performed by the Psychiatric Genomics Consortium. As expected, the PGRS was significantly higher in patients compared with healthy controls. Further, the PGRS was related to differences in frontal lobe brain activation between high and low WM demand. Specifically, even in absence of main effects of diagnosis, increased PGRS was associated with decreased activation difference in the right middle-superior prefrontal cortex (BA 10/11) and the right inferior frontal gyrus (BA 45). This effect was seen in both cases and controls, and was not influenced by sex, age, or task performance. The findings support the notion of dysregulation of frontal lobe functioning as an inherited vulnerability factor in schizophrenia.Key words: polygenic, schizophrenia, fMRI     

Brain dysfunctions during facial discrimination in schizophrenia: Selective association to affect decoding

Schizophrenia patients exhibit impaired facial affect perception, yet the exact nature of this impairment remains unclear. We investigated neural activity related to processing facial emotional and non-emotional information and complex images in 12 schizophrenia patients and 15 healthy controls using functional magnetic resonance imaging. All subjects performed a facial information processing task with three conditions: matching facial emotion, matching facial identity, and matching complex visual patterns. Patients and controls showed comparable behavioral performance in all task conditions. The neural activation patterns in schizophrenia patients and healthy controls were distinctly different while processing affect-related facial information but not other non-emotional facial features. During emotion matching, orbital frontal cortex and left amydala activations were found in controls but not in patients. When comparing emotion versus identity matching, controls activated the fusiform and middle temporal gyri, left superior temporal gyrus, and right inferior and middle frontal gyrus, whereas schizophrenia patients only activated the middle and inferior frontal gyri, the frontal operculi and the right insular cortex. Our findings suggest that schizophrenia patients and healthy controls may utilize different neural networks when processing facial emotional information.     

An event-related fMRI study of the neural networks underlying the encoding, maintenance, and retrieval phase in a delayed-match-to-sample task

Memory loads exceeding the limited capacity of working memory (WM) have been shown to expand the prefrontal areas that participate in WM and have revealed substantial individual differences in performance. We used a delayed-match-to-sample (DMS) task in an event-related fMRI study to map the full extent of the expanded regional activations associated with supracapacity loads. A 6-letter study array was compared to arrays of 1 and 3 letters. The task comprised separate encoding, retention, and retrieval fMRI epochs. A brain-wide spatial covariance analysis was applied to the data of all task epochs to identify patterns of correlated regional activations whose expression increased monotonically across 3 memory-load levels on a subject-by-subject basis. Such load-related activation patterns were in all task phases. Of greatest interest is the activation pattern that was obtained during the maintenance phase: increasing activation with memory load was found not only in the lateral PFC (BA 9,44) but also in the parietal lobe (BA 7,40), anterior cingulate (BA 32), and cerebellum. Decreasing activation was found in the occipito-temporal lobe (BA 19,39) as well as the medial prefrontal cortex (BA 9,10). Subject increases in pattern expression from 1 to 6 items were positively correlated with the corresponding reaction time increases (p<0.05) and negatively correlated with NARTIQ (p<0.05), indicating that people who were faster in their responses and had higher NARTIQ had to increase their subject expression of the memory-load-related activation pattern less and were more efficient at the cognitive task. Our method thus not only reproduced findings of other WM studies but also addressed the issue of interactions between lateral PFC and other parts of the brain during the task, for the retention of the to-be-remembered information. The load-related activation patterns from encoding and retrieval phase and their relationship to behavior are also discussed.     

No hypofrontality,but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia

Hypofrontality and decreased lateralization have been two major, albeit controversial, results from functional neuroimaging studies of schizophrenia. We used fMRI to study cortical activation during a verbal and spatial working memory (WM) task (2-back) in 15 inpatients acutely ill with schizophrenia and 15 matched control subjects. We hypothesized (i) hypofrontality in patients in both tasks and (ii) decreased lateralization of prefrontal activation in patients under the assumption that, in controls, left prefrontal cortex (PFC) is engaged preferentially in the verbal task (verbal domain dominance) and the right prefrontal cortex is engaged preferentially in the spatial task (spatial domain dominance). Our results showed no significant differences in frontal activation between controls and patients, i.e. no hypofrontality in patients, even at a very liberal threshold (p<0.01). This may be explained by the fact that nearly all patients studied received atypical neuroleptics. Nonetheless, we found evidence for more subtle, domain-related prefrontal dysfunction. Whereas controls showed verbal WM domain dominance in left inferior frontal cortex and spatial WM domain dominance in right prefrontal cortex, these domain dominance effects were absent in the patient group, i.e. there were no lateralization effects. Finally, only patients showed an inverse correlation between performance and right prefrontal activation in verbal WM. We conclude that the finding of hypofrontality may depend on the medication of the patients and that there is prefrontal dysfunction even in the absence of hypofrontality.     

The influence of working memory load on phase specific patterns of cortical activity

This study investigated patterns of cortical activity associated with the temporally separated encoding, maintenance and retrieval phases of a working memory (WM) task. Eighteen healthy subjects completed a variable load version of the Sternberg Item Recognition Task. Brain regions showing activity on average across load were determined for each task phase. In addition, brain regions showing activity that increased linearly with load were determined for encoding and retrieval. Although previous fMRI studies have used event-related designs to isolate phase specific activity, this study differed in that design and analysis methods were optimized to ensure low multicollinearity between the conditions of interest: the duration of the intermediate phase (maintenance) was varied and load was selectively modeled for the encoding and retrieval phases. The brain areas showing activity on average across load for each phase combine to encompass regions identified in previous studies that have not attempted to separate phase specific activity. Encoding is associated with extensive load dependent activity, with the most robust activity in bilateral occipital and posterior parietal regions. Retrieval is associated with more selective load dependent activity, primarily in the anterior supplementary motor region and the right posterior cerebellum. The analysis strategies employed in this study could be used to further delineate the phases of WM that are most severely compromised in clinical populations with WM disturbances.     

Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis.     

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.     

Neural activity during working memory encoding,maintenance, and retrieval: A network‐based model and meta‐analysis

It remains unclear whether and to what extent working memory (WM) temporal subprocesses (i.e., encoding, maintenance, and retrieval) involve shared or distinct intrinsic networks. To address this issue, I constructed a model of intrinsic network contributions to different WM phases and then evaluated the validity of the model by performing a quantitative meta‐analysis of relevant functional neuroimaging data. The model suggests that the transition from the encoding to maintenance and to retrieval stages involves progressively decreasing involvement of the dorsal attention network (DAN), but progressively increasing involvement of the frontoparietal control network (FPCN). Separate meta‐analysis of each phase effect and direct comparisons between them yielded results that were largely consistent with the model. This evidence included between‐phase double dissociations that were consistent with the model, such as encoding > maintenance contrast showing some DAN, but no FPCN, regions, and maintenance > encoding contrast showing the reverse, that is, some FPCN, but no DAN, regions. Two closely juxtaposed regions that are members of the DAN and FPCN, such as inferior frontal junction versus caudal prefrontal cortex and superior versus inferior intraparietal sulcus, showed a high degree of functional differentiation. Although all regions identified in the present study were already identified in previous WM studies, this study uniquely enhances our understating of their roles by clarifying their network membership and specific associations with different WM phases.     

Aberrant visual circuitry associated with normal spatial match-to-sample accuracy in schizophrenia

A goal of this study was to evaluate the function of the anterior cingulate cortex (ACC) and of the dorsolateral prefrontal cortex (DLPFC) in medicated patients with schizophrenia (SZ), a small group of first-degree relatives, and healthy controls using a visual delayed match-to-sample task in conjunction with functional magnetic resonance imaging (fMRI). To mitigate performance differences between SZ and healthy controls, we used a novel task that allows for individualized adjustment of task difficulty to match ability level. We also trained participants on the task prior to scanning. Using an event-related design, we modeled three components of the match-to-sample trial: visual encoding, delay, and discrimination. We did not find significant differences in ACC/medial frontal cortex activation between the groups. However, compared to healthy controls, SZ showed decreased activation in visual processing areas during the encoding and discrimination phases of the task and in the ventrolateral prefrontal cortex during the delay. These findings emphasize the tendency of schizophrenia subjects to solve perceptual memory problems by engaging diverse regions.