Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Obsessive-compulsive disorder (OCD) is a mental illness characterized by the loss of control. Because the cingulate cortex is believed to be important in executive functions, such as inhibition, we used functional magnetic resonance imaging (fMRI) techniques to examine whether and how activity and functional connectivity (FC) of the cingulate cortex were altered in drug-naïve OCD patients.

Methods

Twenty-three medication-naïve OCD patients and 23 well-matched healthy controls received fMRI scans in a resting state. Functional connectivities of the anterior cingulate (ACC) and the posterior cingulate (PCC) to the whole brain were analyzed using correlation analyses based on regions of interest (ROI) identified by the fractional amplitude of low-frequency fluctuation (fALFF). Independent Component Analysis (ICA) was used to identify the resting-state sub-networks.

Results

fALFF analysis found that regional activity was increased in the ACC and decreased in the PCC in OCD patients when compared to controls. FC of the ACC and the PCC also showed different patterns. The ACC and the PCC were found to belong to different resting-state sub-networks in ICA analysis and showed abnormal FC, as well as contrasting correlations with the severity of OCD symptoms.

Conclusions

Activity of the ACC and the PCC were increased and decreased, respectively, in the medication-naïve OCD patients compared to controls. Different patterns in FC were also found between the ACC and the PCC with respect to these two groups. These findings implied that the cardinal feature of OCD, the loss of control, may be attributed to abnormal activities and FC of the ACC and the PCC.     

Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Previous studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms.

Methods

Participants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain.

Results

Compared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score.

Conclusion

This study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD.     

Specifically progressive deficits of brain functional marker in amnestic type mild cognitive impairment

Background

Deficits of the default mode network (DMN) have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI) who have a high risk of developing Alzheimer’s disease (AD). However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD.

Methodology/Principal Findings

Resting-state fMRI was acquired in aMCI subjects (n = 26) and controls (n = 18) at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu) hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group.

Conclusions/Significance

The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI.     

Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood

Background

Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males.

Methodology

The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG.

Conclusions

Females had a higher mean score than male tinnitus patients on the BDI–II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus.     

Functional and Anatomical Connectivity Abnormalities in Cognitive Division of Anterior Cingulate Cortex in Schizophrenia

Introduction

Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI).

Methods

Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively.

Results

Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients.

Conclusions

Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.     

Increased Prefrontal and Parahippocampal Activation with Reduced Dorsolateral Prefrontal and Insular Cortex Activation to Food Images in Obesity: A Meta-Analysis of fMRI Studies

Background and Objectives

Obesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli.

Data Source

We conducted a search using several journal databases and adhered to the ‘Preferred Reporting Items for Systematic Reviews and Meta-analyses’ (PRISMA) method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation) using the Activation Likelihood Estimation (ALE) technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images.

Results

In response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex.

Conclusions

Prefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.     

High Postoperative Serum Cortisol Level Is Associated with Increased Risk of Cognitive Dysfunction Early after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study

Context

Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction.

Objective

To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery.

Design

Prospective cohort study.

Setting

Two teaching hospitals.

Patients

One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009.

Intervention

None.

Main Outcome Measures

Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction.

Results

Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016).

Conclusions

High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.     

Abnormalities of Resting State Functional Connectivity Are Related to Sustained Attention Deficits in MS

Objectives

Resting state (RS) functional MRI recently identified default network abnormalities related to cognitive impairment in MS. fMRI can also be used to map functional connectivity (FC) while the brain is at rest and not adhered to a specific task. Given the importance of the anterior cingulate cortex (ACC) for higher executive functioning in MS, we here used the ACC as seed-point to test for differences and similarities in RS-FC related to sustained attention between MS patients and controls.

Design

Block-design rest phases of 3 Tesla fMRI data were analyzed to assess RS-FC in 31 patients (10 clinically isolated syndromes, 16 relapsing-remitting, 5 secondary progressive MS) and 31 age- and gender matched healthy controls (HC). Participants underwent extensive cognitive testing.

Observations

In both groups, signal changes in several brain areas demonstrated significant correlation with RS-activity in the ACC. These comprised the posterior cingulate cortex (PCC), insular cortices, the right caudate, right middle temporal gyrus, angular gyri, the right hippocampus, and the cerebellum. Compared to HC, patients showed increased FC between the ACC and the left angular gyrus, left PCC, and right postcentral gyrus. Better cognitive performance in the patients was associated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and the angular gyrus.

Conclusion

We provide evidence for adaptive changes in RS-FC in MS patients compared to HC in a sustained attention network. These results extend and partly mirror findings of task-related fMRI, suggesting FC may increase our understanding of cognitive dysfunction in MS.     

Subjective Cognitive Complaints and the Role of Executive Cognitive Functioning in the Working Population: A Case-Control Study

Background

Cognitive functioning is important for managing work and life in general. However, subjective cognitive complaints (SCC), involving perceived difficulties with concentration, memory, decision making, and clear thinking are common in the general and working population and can be coupled with both lowered well-being and work ability. However, the relation between SCC and cognitive functioning across the adult age-span, and in the work force, is not clear as few population-based studies have been conducted on non-elderly adults. Thus, the present study aimed to test the relation between SCC and executive cognitive functioning in a population-based sample of employees.

Methods

Participants were 233 employees with either high (cases) or low (controls) levels of SCC. Group differences in neuropsychological test performance on three common executive cognitive tests were analysed through a set of analyses of covariance tests, including relevant covariates.

Results & Conclusions

In line with the a priori hypotheses, a high level of SCC was associated with significantly poorer executive cognitive performance on all three executive cognitive tests used, compared to controls with little SCC. Additionally, symptoms of depression, chronic stress and sleeping problems were found to play a role in the relations between SCC and executive cognitive functioning. No significant associations remained after adjusting for all these factors. The current findings contribute to an increased understanding of what characterizes SCC in the work force and may be used at different levels of prevention of- and intervention for SCC and related problems with executive cognitive functioning.     

Aberrant Default-Mode Functional and Structural Connectivity in Heroin-Dependent Individuals

Background

Little is known about connectivity within the default mode network (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion-tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to investigate both structural and functional connectivity within the DMN in HDIs.

Methods

Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD derived from DTI tractography)and functional (temporal correlation coefficient derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT) performance in HDIs.

Results

HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs.

Conclusions

Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.     

Brain–Immune Interaction Accompanying Odor-Evoked Autobiographic Memory

The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.     

Higher Education Moderates the Effect of T2 Lesion Load and Third Ventricle Width on Cognition in Multiple Sclerosis

Background

Previous work suggested greater intellectual enrichment might moderate the negative impact of brain atrophy on cognition. This awaits confirmation in independent cohorts including investigation of the role of T2-lesion load (T2-LL), which is another important determinant of cognition in MS. We here thus aimed to test this cognitive reserve hypothesis by investigating whether educational attainment (EA) moderates the negative effects of both brain atrophy and T2-LL on cognitive function in a large sample of MS patients.

Methods

137 patients participated in the study. Cognition was assessed by the “Brief Repeatable Battery of Neuropsychological Tests.” T2-LL, normalized brain volume (global volume loss) and third ventricle width (regional volume loss) served as MRI markers.

Results

Both T2-LL and atrophy predicted worse cognition, with a stronger effect of T2-LL. Higher EA (as assessed by years of education) also predicted better cognition. Interactions showed that the negative effects of T2-LL and regional brain atrophy were moderated by EA.

Conclusions

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.     

Convergent evidence from multimodal imaging reveals amygdala abnormalities in schizophrenic patients and their first-degree relatives

Background

Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.

Methods

Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.

Results

Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.

Conclusions

Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.     

Imaging of an Inflammatory Injury in the Newborn Rat Brain with Photoacoustic Tomography

Background

The precise assessment of cerebral saturation changes during an inflammatory injury in the developing brain, such as seen in periventricular leukomalacia, is not well defined. This study investigated the impact of inflammation on locoregional cerebral oxygen saturation in a newborn rodent model using photoacoustic imaging.

Methods

1 mg/kg of lipopolysaccharide(LPS) diluted in saline or saline alone was injected under ultrasound guidance directly in the corpus callosum of P3 rat pups. Coronal photoacoustic images were carried out 24 h after LPS exposure. Locoregional oxygen saturation (SO₂) and resting state connectivity were assessed in the cortex and the corpus callosum. Microvasculature was then evaluated on cryosection slices by lectin histochemistry.

Results

Significant reduction of SO₂ was found in the corpus callosum; reduced SO₂ was also found in the cortex ipsilateral to the injection site. Seed-based functional connectivity analysis showed that bilateral connectivity was not affected by LPS exposure. Changes in locoregional oxygen saturation were accompanied by a significant reduction in the average length of microvessels in the left cortex but no differences were observed in the corpus callosum.

Conclusion

Inflammation in the developing brain induces marked reduction of locoregional oxygen saturation, predominantly in the white matter not explained by microvascular degeneration. The ability to examine regional saturation offers a new way to monitor injury and understand physiological disturbance non-invasively.     

Cognitive Styles and Psychotic Experiences in a Community Sample

Introduction

In clinical populations paranoid delusions are associated with making global, stable and external attributions for negative events. Paranoia is common in community samples but it is not known whether it is associated with a similar cognitive style. This study investigates the association between cognitive style and paranoia in a large community sample of young adults.

Methods

2694 young adults (mean age 17.8, SD 4.6) from the ALSPAC cohort provided data on psychotic experiences and cognitive style. Psychotic experiences were assessed using a semi-structured interview and cognitive style was assessed using the Cognitive Styles Questionnaire-Short Form (CSQ-SF) on the same occasion. Logistic regression was used to investigate associations between paranoia and CSQ-SF scores, both total and domain-related (global, stable, self, external). The role of concurrent self-reported depressive symptoms in the association was explored.

Results

Paranoia was associated with Total CSQ-SF scores (adjusted OR 1.69 95% CI 1.29, 2.22), as well as global (OR 1.56 95% CI 1.17, 2.08), stable (OR 1.56 95% CI 1.17, 2.08) and self (OR 1.37 95% CI 1.05, 1.79) domains, only Total score and global domain associations remained after additional adjustment for self-reported depression. There was no association between paranoia and external cognitive style (OR 1.10 95% CI 0.83, 1.47).

Conclusion

Paranoid ideation in a community sample is associated with a global rather than an external cognitive style. An external cognitive style may be a characteristic of more severe paranoid beliefs. Further work is required to determine the role of depression in the association between cognitive style and paranoia.     

Absence of Auditory M100 Source Asymmetry in Schizophrenia and Bipolar Disorder: A MEG Study

Background

Whether schizophrenia and bipolar disorder are the clinical outcomes of discrete or shared causative processes is much debated in psychiatry. Several studies have demonstrated anomalous structural and functional superior temporal gyrus (STG) symmetries in schizophrenia. We examined bipolar patients to determine if they also have altered STG asymmetry.

Methods

Whole-head magnetoencephalography (MEG) recordings of auditory evoked fields were obtained for 20 subjects with schizophrenia, 20 with bipolar disorder, and 20 control subjects. Neural generators of the M100 auditory response were modeled using a single equivalent current dipole for each hemisphere. The source location of the M100 response was used as a measure of functional STG asymmetry.

Results

Control subjects showed the typical M100 asymmetrical pattern with more anterior sources in the right STG. In contrast, both schizophrenia and bipolar disorder patients displayed a symmetrical M100 source pattern. There was no significant difference in the M100 latency and strength in bilateral hemispheres within three groups.

Conclusions

Our results indicate that disturbed asymmetry of temporal lobe function may reflect a common deviance present in schizophrenia and bipolar disorder, suggesting the two disorders might share etiological and pathophysiological factors.     

Reduced Regional Homogeneity in Bilateral Frontostriatal System Relates to Higher Impulsivity Behavior in Codeine-Containing Cough Syrups Dependent Individuals

Background

In the past twenty years, codeine-containing cough syrups (CCS) was recognized as a new type of addictive drugs. However, the exact neurobiologic mechanisms underlying CCS-dependence are still ill-defined. The aims of this study are to identify CCS-related modulations of neural activity during the resting-state in CCS-dependent individuals and to investigate whether these changes of neural activity can be related to duration of CCS use, the first age of CCS use and impulse control deficits in CCS-dependent individuals. We also want to observe the impact of gray matter deficits on these functional results.

Methodology/Principal Findings

Thirty CCS-dependent individuals and 30 control subjects participated. Resting-state functional MRI was performed by using gradient-echo echo-planar imaging sequence. Regional homogeneity (ReHo) was calculated by using REST software. Voxel-based analysis of the ReHo maps between controls and CCS-dependent groups was performed using two-sample t tests (p<0.05, corrected for multiple comparisons). The Barratt Impulsiveness Scale 11 (BIS.11) was surveyed to assess participants'' impulsivity trait soon after MR examination. Abnormal clusters revealed by group comparison were extracted and correlated with impulsivity, duration of CCS use, and age of first CCS use. ReHo was diminished in the bilateral medial orbitofrontal cortex (mOFC) and left dorsal striatum in CCS-dependent individuals. There were negative correlations between mean ReHo in the bilateral medial OFC, left dorsal striatum and duration of CCS use, BIS.11 total scores, and the subscale of attentional impulsivity in CCS-dependent individuals. There was a significantly positive correlation between mean ReHo in the left dorsal striatum and age of first CCS use in CCS-dependent individuals. Importantly, these results still remain significant after statistically controlling for the regional gray matter deficits.

Conclusion

Resting-state abnormalities in CCS-dependent individuals revealed in the present study may further improve our understanding about the neural substrates of impulse control dysfunction in CCS-dependent individuals.     

Altered connectivity pattern of hubs in default-mode network with Alzheimer's disease: an Granger causality modeling approach

Background

Evidences from normal subjects suggest that the default-mode network (DMN) has posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC) and inferior parietal cortex (IPC) as its hubs; meanwhile, these DMN nodes are often found to be abnormally recruited in Alzheimer''s disease (AD) patients. The issues on how these hubs interact to each other, with the rest nodes of the DMN and the altered pattern of hubs with respect to AD, are still on going discussion for eventual final clarification.

Principal Findings

To address these issues, we investigated the causal influences between any pair of nodes within the DMN using Granger causality analysis and graph-theoretic methods on resting-state fMRI data of 12 young subjects, 16 old normal controls and 15 AD patients respectively. We found that: (1) PCC/MPFC/IPC, especially the PCC, showed the widest and distinctive causal effects on the DMN dynamics in young group; (2) the pattern of DMN hubs was abnormal in AD patients compared to old control: MPFC and IPC had obvious causal interaction disruption with other nodes; the PCC showed outstanding performance for it was the only region having causal relation with all other nodes significantly; (3) the altered relation between hubs and other DMN nodes held potential as a noninvasive biomarker of AD.

Conclusions

Our study, to the best of our knowledge, is the first to support the hub configuration of the DMN from the perspective of causal relationship, and reveal abnormal pattern of the DMN hubs in AD. Findings from young subjects provide additional evidence for the role of PCC/MPFC/IPC acting as hubs in the DMN. Compared to old control, MPFC and IPC lost their roles as hubs owing to the obvious causal interaction disruption, and PCC was preserved as the only hub showing significant causal relations with all other nodes.