Prefrontal Brain Network Connectivity Indicates Degree of Both Schizophrenia Risk and Cognitive Dysfunction

Objective:

Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study, we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia risk.

Methods:

A total of 235 adults representing 3 levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls [HCs]) completed resting-state functional magnetic resonance imaging and a battery of attention and working memory tasks (Brief Test of Attention, Hopkins Verbal Learning Test, and Brief Visuospatial Memory Test) on the same day. Functional networks were defined based on coupling with seeds in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and primary visual cortex. Networks were then dissected into regional clusters of connectivity that were used to generate individual interaction matrices representing functional connectivity within each network.

Results:

Both patients with schizophrenia and their first-degree relatives showed cognitive dysfunction compared with HCs. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC and MPFC networks. Multivariate analysis of variance revealed multivariate main effects of higher schizophrenia risk status on increased connectivity within the DLPFC and MPFC networks.

Conclusions:

These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working memory tasks to brain changes associated with schizophrenia.Key words: resting state, fMRI, default-mode network, attention, working memory     

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility,Cerebral Metabolism,and Functional Brain Connectivity

Objective:

In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil.

Methods:

We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia.

Results:

We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity.

Conclusions:

These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.     

Role of Visual Integration in Gaze Perception and Emotional Intelligence in Schizophrenia

Background:

Individuals with schizophrenia demonstrate a wide range of social cognitive deficits that significantly compromise functioning. Early visual processing is frequently disrupted in schizophrenia, and growing evidence suggests a role of perceptual dysfunctions in socioemotional functioning in the disorder. This study examined visual integration (the ability to effectively integrate individual, local visual features into a holistic representation), a target construct of basic perception identified by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative, and its relationship with eye- contact perception and emotional intelligence in schizophrenia.

Methods:

Twenty-nine participants with schizophrenia (SCZ) and 23 healthy controls (HC) completed tasks measuring visual integration (Coherent Motion Task, Contour Integration Task), an eye-contact perception task, and a measure of emotional intelligence.

Results:

SCZ participants showed compromised visual integration as suggested by poorer performance on the Contour Integration Task relative to HC. Visual integration was a significant predictor of eye-contact perception and emotional intelligence among SCZ. The amounts of variances in these 2 social cognitive areas accounted for by visual integration were comparable to and overlapped with those accounted for by the diagnosis of schizophrenia.

Conclusions:

Individuals with schizophrenia showed compromised visual integration, and this may play a significant role in the observed deficits in higher level processing of social information in the disorder.Key words: psychosis, visual perception, perceptual organization, social cognition, sensory processing     

Differential patterns of initial and sustained responses in amygdala and cortical regions to emotional stimuli in schizophrenia patients and healthy participants

Background

We sought to investigate the altered brain responses to emotional stimuli in patients with schizophrenia.

Methods

We analyzed data from 14 patients with schizophrenia and 14 healthy controls who performed an emotional face matching task. We evaluated brain activity and connectivity in the amygdala and cortical regions during the initial (first 21 seconds of each stimulation block) and sustained (last 21 seconds) stages of an emotional processing task, and we determined changes in amygdala activity across the emotional processing task.

Results

The patients with schizophrenia showed similar amygdala activation to the controls during the initial stage of processing, but their activation decreased during the sustained stage. The controls showed increasing amygdala activity across the emotional blocks, whereas activity progressively decreased in the schizophrenia group. The patients with schizophrenia showed increased cortical activity and interconnectivity in the medial frontal and inferior parietal cortex in the initial stage of emotional processing. There was increased activity in the superior temporal cortex and greater connectivity with the inferior parietal cortex in the sustained stage. Performance accuracy was lower in the schizophrenia group in the first part of the block, while their reaction time was longer in the latter part of the block.

Limitations

It was not possible to specify the moment at which the switch in amygdala response occurred.

Conclusion

Our findings suggest that patients with schizophrenia have an initial automatic emotional response but that they need to switch to a compensatory cognitive strategy to solve the task.     

Dysconnectivity of multiple resting-state networks in patients with schizophrenia who have persistent auditory verbal hallucinations

Background

Functional neuroimaging studies on schizophrenia have suggested abnormal task-related functional connectivity in patients with schizophrenia who have auditory verbal hallucinations (AVHs). However, little is known about intrinsic functional connectivity in these patients.

Methods

Between January 2009 and February 2010, we studied patients with schizophrenia who had persistent and treatment-refractory AVHs in comparison with healthy controls. Using functional magnetic resonance imaging, we studied the functional connectivity of multiple resting state networks (RSNs) and their relation to symptom severity. We analyzed the data using a spatial group independent component analysis, and we used random-effects t tests to compare spatial components between groups.

Results

There were 10 patients and 14 controls enrolled in this study. In total, 16 RSNs were identified, from which we selected 4 networks of interest for further analyses. Within a speech-related network, patients showed increased connectivity in bilateral temporal regions and decreased connectivity in the cingulate cortex. Within 2 additional RSNs associated with attention and executive control, respectively, patients exhibited abnormal connectivity in the precuneus and right lateral prefrontal areas. We found correlations between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and right lateral prefrontal cortex.

Limitations

The relatively small sample size, the patients’ use of antipsychotic medication and the lack of a clinical control group have to be considered as potential limitations.

Conclusion

Our findings indicate that disrupted intrinsic connectivity of a speech-related network could underlie persistent AVHs in patients with schizophrenia. In addition, the occurrence of hallucinatory symptoms seems to modulate RSNs associated with attention and executive control.     

Left-Dominant Temporal-Frontal Hypercoupling in Schizophrenia Patients With Hallucinations During Speech Perception

Background:

Task-based functional neuroimaging studies of schizophrenia have not yet replicated the increased coordinated hyperactivity in speech-related brain regions that is reported with symptom-capture and resting-state studies of hallucinations. This may be due to suboptimal selection of cognitive tasks.

Methods:

In the current study, we used a task that allowed experimental manipulation of control over verbal material and compared brain activity between 23 schizophrenia patients (10 hallucinators, 13 nonhallucinators), 22 psychiatric (bipolar), and 27 healthy controls. Two conditions were presented, one involving inner verbal thought (in which control over verbal material was required) and another involving speech perception (SP; in which control verbal material was not required).

Results:

A functional connectivity analysis resulted in a left-dominant temporal-frontal network that included speech-related auditory and motor regions and showed hypercoupling in past-week hallucinating schizophrenia patients (relative to nonhallucinating patients) during SP only.

Conclusions:

These findings replicate our previous work showing generalized speech-related functional network hypercoupling in schizophrenia during inner verbal thought and SP, but extend them by suggesting that hypercoupling is related to past-week hallucination severity scores during SP only, when control over verbal material is not required. This result opens the possibility that practicing control over inner verbal thought processes may decrease the likelihood or severity of hallucinations.Key words: schizophrenia, inner speech, speech perception, functional magnetic resonance imaging, functional connectivity     

Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder

Background

Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics.

Methods

Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls.

Results

We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders.

Limitations

Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants.

Conclusion

We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.     

Static and Dynamic Characteristics of Cerebral Blood Flow During the Resting State in Schizophrenia

Background:

The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts.

Methods:

A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test.

Results:

Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = −16/−64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01).

Conclusions:

In schizophrenia patients, the posterior hub—which is considered the strongest part of the DMN—showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances.Key words: psychosis, default mode network, arterial spin labeling, functional connectivity, precuneus     

Schizophrenic Patients and Their Unaffected Siblings Share Increased Resting-State Connectivity in the Task-Negative Network but Not Its Anticorrelated Task-Positive Network

Background:

Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls.

Methods:

Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups.

Results:

Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls.

Conclusion:

Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.     

Abnormal interhemispheric connectivity in male psychopathic offenders

Background

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking.

Methods

We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity.

Results

We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere.

Limitations

The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders.

Conclusion

To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.     

Altered Hub Functioning and Compensatory Activations in the Connectome: A Meta-Analysis of Functional Neuroimaging Studies in Schizophrenia

Background:

Functional neuroimaging studies of schizophrenia have identified abnormal activations in many brain regions. In an effort to interpret these findings from a network perspective, we carried out a meta-analysis of this literature, mapping anatomical locations of under- and over-activation to the topology of a normative human functional connectome.

Methods:

We included 314 task-based functional neuroimaging studies including more than 5000 patients with schizophrenia and over 5000 controls. Coordinates of significant under- or over-activations in patients relative to controls were mapped to nodes of a normative connectome defined by a prior meta-analysis of 1641 functional neuroimaging studies of task-related activation in healthy volunteers.

Results:

Under-activations and over-activations were reported in a wide diversity of brain regions. Both under- and over-activations were significantly more likely to be located in hub nodes that constitute the “rich club” or core of the normative connectome. In a subset of 121 studies that reported both under- and over-activations in the same patients, we found that, in network terms, these abnormalities were located in close topological proximity to each other. Under-activation in a peripheral node was more frequently associated specifically with over-activation of core nodes than with over-activation of another peripheral node.

Conclusions:

Although schizophrenia is associated with altered brain functional activation in a wide variety of regions, abnormal responses are concentrated in hubs of the normative connectome. Task-specific under-activation in schizophrenia is accompanied by over-activation of topologically central, less functionally specialized network nodes, which may represent a compensatory response.Key words: schizophrenia, connectome, fMRI, graph analysis, hubs     

Visual sensory processing deficits in patients with bipolar disorder revealed through high-density electrical mapping

Background

Etiological commonalities are apparent between bipolar disorder and schizophrenia. For example, it is becoming clear that both populations show similar electrophysiological deficits in the auditory domain. Recent studies have also shown robust visual sensory processing deficits in patients with schizophrenia using the event-related potential technique, but this has not been formally tested in those with bipolar disorder. Our goal here was to assess whether early visual sensory processing in patients with bipolar disorder, as indexed by decreased amplitude of the P1 component of the visual evoked potential (VEP), would show a similar deficit to that seen in those with schizophrenia. Since the P1 deficit has already been established as an endophenotype in schizophrenia, a finding of commonality between disorders would raise the possibility that it represents a measure of common genetic liability.

Methods

We visually presented isolated-check stimuli to euthymic patients with a diagnosis of bipolar disorder and age-matched healthy controls within a simple go/no-go task and recorded VEPs using high-density (72-channel) electroencephalography.

Results

The P1 VEP amplitude was substantially reduced in patients with bipolar disorder, with an effect size of f = 0.56 (large according to Cohen’s criteria).

Limitations

Our sample size was relatively small and as such, did not allow for an examination of potential relations between the physiologic measures and clinical measures.

Conclusion

This reduction in P1 amplitude among patients with bipolar disorder represents a dysfunction in early visual processing that is highly similar to that found repeatedly in patients with schizophrenia and their healthy first-degree relatives. Since the P1 deficit has been related to susceptibility genes for schizophrenia, our results raise the possibility that the deficit may in fact be more broadly related to the development of psychosis and that it merits further investigation as a candidate endophenotype for bipolar disorder.     

Neuroplasticity-Based Auditory Training Via Laptop Computer Improves Cognition in Young Individuals With Recent Onset Schizophrenia

Objective:

Cognitive deficits that characterize schizophrenia are present in the prodrome, worsen with illness onset, and predict functional outcome. Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia.

Method:

This 2-site double-blind randomized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks. We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and functioning. We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement.

Results:

Auditory training subjects demonstrated significant improvements in global cognition, verbal memory, and problem solving compared with those of computer games control subjects. Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures. Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours.

Conclusion:

Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia. An individual’s baseline motivational system functioning (reward anticipation), and ability to engage in auditory processing speed improvement, may represent important predictors of treatment outcome. Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions.Key words: cognitive remediation, cognitive training, motivation, first-episode schizophrenia, early psychosis     

Methamphetamine Enhances the Development of Schizophrenia in First-Degree Relatives of Patients With Schizophrenia

Objective:

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare.

Methods:

In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated.

Results:

Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers.

Conclusion:

Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.     

Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: a placebo-controlled pilot study

Objective

To investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia.

Methods

A 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test.

Results

Memantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant.

Conclusion

Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia.     

Aberrant connectivity of resting-state networks in borderline personality disorder

Background

Several functional neuroimaging studies have reported regionally abnormal activation of the frontal cortex in individuals with borderline personality disorder (BPD) during cognitive and affective task performance. However, little is known about neural function in individuals with BPD during the resting state. Using functional magnetic resonance imaging (fMRI), this study investigated the functional connectivity of prefrontal and limbic networks in patients with BPD.

Methods

Between January 2009 and March 2010, we investigated patients with BPD according to DSM-IV criteria and healthy controls by means of resting-state fMRI. The data were analyzed using a spatial group independent component analysis, and random effects t tests were used to compare spatial components between groups (p < 0.005, uncorrected).

Results

There were 17 women with BPD and 17 female healthy controls enrolled in this study. Within a network comprising cortical midline regions (“default mode network”), patients with BPD showed an increase in functional connectivity in the left frontopolar cortex (FPC) and the left insula, whereas decreased connectivity was found in the left cuneus. Within a network comprising predominantly right lateral prefrontal and bilateral parietal regions, patients with BPD showed decreased connectivity of the left inferior parietal lobule and the right middle temporal cortex compared with healthy controls. Two networks comprising lateral prefrontal and cingulate regions did not exhibit significant between-group differences. We found correlations between functional connectivity of the FPC and measures of impulsivity as well as between connectivity of the insula/cuneus and dissociation tension.

Limitations

Co-occurrent axis I disorders and medication use in this sample of patients with BPD have to be considered as potential limitations.

Conclusion

These data suggest that abnormal functional connectivity of temporally coherent resting-state networks may underlie certain symptom clusters in patients with BPD.     

Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study

Background

Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in connectivity at an early period of cortical maturation can result in widespread defects in gyrification. Investigating the anatomic distribution of gyrification defects can provide important information about neurodevelopment in patients with schizophrenia.

Methods

We undertook an automated surface-based morphometric assessment of gyrification on 3-dimensionally reconstructed cortical surfaces across multiple vertices that cover the entire cortex. We used a sample from our previous research of 57 patients (50 men) with schizophrenia and 41 controls (39 men) in whom we had tested a specific hypothesis regarding presence of both hypo-and hypergyria in the prefrontal cortex using a frontal region-of-interest approach.

Results

Regions with significant reductions in gyrification (hypogyria) were seen predominantly in the left hemisphere, involving the insula and several regions of the multimodal association cortex. Although the prefrontal hypergyria documented earlier did not survive the statistical correction required for a whole brain search (cluster inclusion at p = 0.0001), significant hypergyric frontal clusters emerged when the threshold was lowered (cluster inclusion at p = 0.05). In the insula, a reduction in gyrification was related to reduced cortical thickness in patients with schizophrenia.

Limitations

We studied a sample of patients taking antipsychotic medications, which could have confounded the results. Our sample was predominantly male, limiting the generalizability of our findings.

Conclusion

Our observations suggest that the disturbances in cortical gyrification seen in patients with schizophrenia might be related to a disrupted interaction between the paralimbic and the multimodal association cortex and thus might contribute to the pathogenesis of the illness.     

Prefrontal-Thalamic Anatomical Connectivity and Executive Cognitive Function in Schizophrenia

Background

Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses.

Abnormal functional connectivity of high-frequency rhythms in drug-naïve schizophrenia

Objective

The “dysconnection hypothesis” has been proposed as a core neural basis for schizophrenia. Although growing neuroimaging-based evidence suggests atypical functional connectivity in patients with schizophrenia, the results are inconsistent and the effects of antipsychotic treatment remain elusive.

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa

Background

Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess negatively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa.

Methods

All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging.

Results

We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing.

Limitations

Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels.

Conclusion

Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.