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.     

Impaired interhemispheric connectivity in medication-naive patients with major depressive disorder

Background

Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in major depressive disorder (MDD). The purpose of this study was to investigate interhemispheric connectivity in medication-naive patients with MDD by measuring fractional anisotropy in the CC with diffusion tensor imaging (DTI) techniques.

Methods

We obtained DTI scans from medication-naive patients with MDD and from matched healthy controls. Fractional anisotropy values were compared using semiautomatic region of interest methods to localize the regional CC differences between these 2 groups.

Results

We enrolled 27 patients and 27 controls in our study. Fractional anisotropy values were significantly lower in the anterior genu of the CC in the MDD group than in the control group (p = 0.009, corrected); results were not significantly different in any other CC subregions.

Limitations

As patients with MDD were already experiencing acute episodes, future studies of individuals at risk for MDD are warranted to elucidate the interhemispheric connectivity abnormalities associated with the predisposition to MDD.

Conclusion

The findings demonstrate abnormalities in the structural integrity of the anterior genu of the CC in medication-naive individuals with MDD, which may contribute to impairment of interhemispheric connectivity in patients with this disorder.     

Resting-state functional connectivity abnormalities in patients with obsessive–compulsive disorder and their healthy first-degree relatives

Background

Obsessive–compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical–striatal–thalamic–cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives.

Methods

We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach.

Results

We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus.

Limitations

Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings.

Conclusion

Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.     

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.     

Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity

Background

Working memory processing and resting-state connectivity in the default mode network are altered in patients with post-traumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity.

Methods

We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls.

Results

During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahip-pocampal gyrus.

Limitations

Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses.

Conclusion

The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).     

The Effects of Taekwondo Training on Brain Connectivity and Body Intelligence

Objective

Many studies have reported that Taekwondo training could improve body perception, control and brain activity, as assessed with an electroencephalogram. This study aimed to assess body intelligence and brain connectivity in children with Taekwondo training as compared to children without Taekwondo training.

Methods

Fifteen children with Taekwondo training (TKD) and 13 age- and sex-matched children who had no previous experience of Taekwondo training (controls) were recruited. Body intelligence, clinical characteristics and brain connectivity in all children were assessed with the Body Intelligence Scale (BIS), self-report, and resting state functional magnetic resonance imaging.

Results

The mean BIS score in the TKD group was higher than that in the control group. The TKD group showed increased low-frequency fluctuations in the right frontal precentral gyrus and the right parietal precuneus, compared to the control group. The TKD group showed positive cerebellum vermis (lobe VII) seed to the right frontal, left frontal, and left parietal lobe. The control group showed positive cerebellum seed to the left frontal, parietal, and occipital cortex. Relative to the control group, the TKD group showed increased functional connectivity from cerebellum seed to the right inferior frontal gyrus.

Conclusion

To the best of our knowledge, this is the first study to assess the effect of Taekwondo training on brain connectivity in children. Taekwondo training improved body intelligence and brain connectivity from the cerebellum to the parietal and frontal cortex.     

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

Background

Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD.

Methods

Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups.

Results

Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions.

Limitations

All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population.

Conclusion

Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.     

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.     

Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness

Background

Magnetic resonance imaging (MRI) studies show reduced cortical thickness in patients with schizophrenia and bipolar disorder. These subtle brain abnormalities may provide insight into illness mechanisms. However, environmental and lifestyle-related factors, such as cigarette smoking, may contribute to brain structure changes. Cigarette smoking is highly prevalent in patients with severe mental illness. In nonpsychiatric samples, smoking has been associated with reduced thickness in the anterior (ACC) and posterior cingulate cortices, the insular cortex (INS), the dorsolateral prefrontal cortex and the orbitofrontal cortex.

Methods

We examined MRI scans from patients with schizophrenia, other psychotic disorders or bipolar disorder and healthy controls using FreeSurfer.

Results

We included 506 patients (49% smokers) and 237 controls (20% smokers) in our study. We found reduced cortical thickness in the left rostral ACC and the left INS in smoking patients compared with nonsmoking patients, but this difference was not found among healthy controls. No dose–response relationship was found between amount of smoking and cortical thickness in these regions. Among patients, maps of thickness along the whole cortical surface revealed reduced insular thickness but no effects in other regions. Among healthy controls, similar analyses revealed increased age-related cortical thinning in the left occipital lobe among smokers compared with nonsmokers.

Limitations

The causal direction could not be determined owing to the cross-sectional design and lack of detailed data on smoking addiction and smoking history.

Conclusion

The effect of cigarette smoking should be considered in MRI studies of patients with severe mental illness.     

Is the GABA System Related to the Social Competence Improvement Effect of Aripiprazole? An 18F-Fluoroflumazenil PET Study

Objective

Patients with schizophrenia who are treated with aripiprazole experience some benefits including an improvement of social competence, but the underlying mechanism of this improvement has not been investigated yet. This study aimed to provide preliminary evidence that the GABA system may be involved in the effect of aripiprazole on social competence.

Methods

Seventeen outpatients with schizophrenia (9 taking aripiprazole and 8 taking risperidone) and 18 healthy controls underwent ¹⁸F-fluoroflumazenil PET, and GABA_A receptor binding potential was compared between the three groups.

Results

Voxelwise one-way ANOVA showed that GABA_A receptor binding potentials in the right medial prefrontal cortex (p=0.04) and right dorsolateral prefrontal cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone group, and those in the left frontopolar cortex (p=0.03) and right premotor cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone and control groups.

Conclusion

Our results suggest that aripiprazole administration results in increased GABA transmission in the prefrontal regions, and that these increases may be a neural basis of aripiprazole''s clinical benefits on an improvement of social competence.     

Neural circuitry of emotional face processing in autism spectrum disorders

Background

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.

Methods

Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.

Results

In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.

Limitations

The small sample size may have affected our ability to detect additional group differences.

Conclusion

When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.     

Altered white matter tract property related to impaired focused attention,sustained attention,cognitive impulsivity and vigilance in attention-deficit/hyperactivity disorder

Background

The neural substrate for clinical symptoms and neuropsychological performance in individuals with attention-deficit/hyperactivity disorder (ADHD) has rarely been studied and has yielded inconsistent results. We sought to compare the microstructural property of fibre tracts associated with the prefrontal cortex and its association with ADHD symptoms and a wide range of attention performance in youth with ADHD and healthy controls.

Methods

We assessed youths with ADHD and age-, sex-, handedness-, coil- and intelligence-matched controls using the Conners’ Continuous Performance Test (CCPT) for attention performance and MRI. The 10 target tracts, including the bilateral frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging tractography. We computed generalized fractional anisotropy (GFA) values to indicate tract-specific microstructural property.

Results

We included 50 youths with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in the left frontostriatal tracts, bilateral SLF and right cingulum bundle and performed worse in the CCPT than controls. Furthermore, alteration of the right SLF GFA was most significantly associated with the clinical symptom of inattention in youths with ADHD. Finally, youths with ADHD had differential association patterns of the 10 fibre tract GFA values with attention performance compared with controls.

Limitations

Ten of the youths with ADHD were treated with methylphenidate, which may have long-term effects on microstructural property.

Conclusion

Our study highlights the importance of the SLF, cingulum bundle and frontostriatal tracts for clinical symptoms and attention performance in youths with ADHD and demonstrates the involvement of different fibre tracts in attention performance in these individuals.     

Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high Risk for Psychosis: A Preliminary Study

Objective

Recent neuroimaging studies have suggested that brain changes occur in subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal symptoms, among which depression may increase the risk of developing a psychotic disorder. The goal of this study is to examine brain metabolite levels in the anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left thalamus in subjects at UHR for psychosis and to compare brain metabolite levels between the UHR subjects with comorbid major depressive disorder and healthy controls.

Methods

Proton magnetic resonance spectroscopy was used to examine brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence quotient (IQ)-matched healthy controls were included in this study.

Results

Overall, no significant differences were observed in any metabolite between the UHR and healthy control group. However, UHR subjects with major depressive disorder showed significantly higher myo-inositol (Ins) levels in the left thalamus, compared to the healthy control.

Conclusion

Our results demonstrate that increased thalamic Ins level is associated with prodromal depressive symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are required to investigate the function of Ins concentrations as a biomarker of vulnerability to psychosis.     

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     

Reduced interhemispheric coherence in dyslexic adults

Introduction

Developmental dyslexia has been associated with reduced interhemispheric neural connectivity in children. The present study investigated functional interhemispheric connectivity in male dyslexic adults.

Methods

A group of 19 dyslexic men were compared to a group of 15 controls on interhemispheric coherence of the dominant frequency in the power spectrum during a visuo-spatial attention task. The coherence between a left hemisphere central-parietal electrode and the respective right hemisphere electrode and surrounding sites was analysed.

Results

Compared to controls, the dyslexic group demonstrated reduced, and more diffuse, interhemispheric coherence of alpha activity in the central-parietal cortex. No group differences in interhemispheric coherence were found on frontal, temporal or central sites.

Conclusions

The deviant pattern of functional connectivity in dyslexics is suggestive of an altered development of neural circuitry that may lead to deficits in magnocellular processing.     

Neural correlates of set-shifting: decomposing executive functions in schizophrenia

Background

Although there is considerable evidence that patients with schizophrenia have impaired executive functions, the neural mechanisms underlying these deficits are unclear. Generation and selection is one of the basic mechanisms of executive functioning. We investigated the neural correlates of this mechanism by means of functional magnetic resonance imaging (fMRI) in patients with schizophrenia and healthy controls.

Methods

We used the Wisconsin Card Sorting Test (WCST) in an event-related fMRI study to analyze neural activation patterns during the distinct components of the WCST in 36 patients with schizophrenia and 28 controls. We focused our analyses on the process of set-shifting. After participants received negative feedback, they had to generate and decide on a new sorting rule.

Results

A widespread activation pattern encompassing the inferior and middle frontal gyrus, parietal, temporal and occipital cortices, anterior cingulate cortex (ACC), supplementary motor area, insula, caudate, thalamus and brainstem was observed in patients with schizophrenia after negative versus positive feedback, whereas in healthy controls, significant activation clusters were more confined to the cortical areas. Significantly increased activation in the rostral ACC after negative feedback and in the dorsal ACC during matching after negative feedback were observed in schizophrenia patients compared with controls. Controls showed activation in the bilateral dorsolateral prefrontal cortex (Brodmann area 46), whereas schizophrenia patients showed activation in the right dorsolateral pre-frontal cortex only.

Limitations

All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism.

Conclusion

Our data suggest that, in patients with schizophrenia, set-shifting is associated with increased activation in the rostral and dorsal ACC, reflecting higher emotional and cognitive demands, respectively.     

Brain functional connectivity during induced sadness in patients with obsessive-compulsive disorder

Background

Obsessive–compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.

Methods

Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.

Results

We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.

Limitations

Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.

Conclusion

The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized “OCD circuit,” which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.     

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Background

Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.

Methods

Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.

Results

Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.

Limitations

Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.

Conclusion

These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.     

Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa

Background

Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives.

Methods

This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC).

Results

We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding.

Limitations

The results we obtained using monetary stimuli might not generalize to other forms of reward.

Conclusion

Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral–frontal brain circuitry in recovered patients suggests an elevated degree of self-regulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom–up and top–down processes may be a trait marker of the disorder.     

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.