Neuroimaging auditory verbal hallucinations in schizophrenia patient and healthy populations

BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers. METHODS: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls. RESULTS: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes. CONCLUSIONS: We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects

Linking cortical and connectional pathology in schizophrenia

Schizophrenia is associated with cortical thickness (CT) deficits and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relationship between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map CT and fractional anisotropy in regionally adjacent infracortical white matter at various cortical depths. We found a robust and reproducible relationship between thickness and anisotropy deficits, which were inversely correlated across cortical regions (r = -.5, P .05). Frontal pathology contributed most to this pattern, with cortical thinning in patients compared to controls at all ages (P < .05); in contrast to initially elevated frontal white matter anisotropy in patients at 30 years, followed by rapid white matter decline with age (rate of annual decline; patients: 0.0012, controls 0.0006, P < .001). Our findings point to pathological dependencies between gray and white matter in a large sample of schizophrenia patients. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration

Structural connectivity and weight loss in children with obesity: A study of the “connectobese”

Background Previous studies suggest that obesity (OB) is associated with disrupted brain network organization; however, it remains unclear whether these differences already exist during childhood. Moreover, it should be investigated whether deviant network organization may be susceptible to treatment. Methods Here, we compared the structural connectomes of children with OB with age-matched healthy weight (HW) controls (aged 7–11 years). In addition, we examined the effect of a multidisciplinary treatment program, consisting of diet restriction, cognitive behavioral therapy, and physical activity for children with OB on brain network organization. After stringent quality assessment criteria, 40 (18 OB, 22 HW) data sets of the total sample of 51 participants (25 OB, 26 HW) were included in further analyses. For all participants, anthropometric measurements were administered twice, with a 5-month interval between pre- and post tests. Pre- and post T1- and diffusion-weighted imaging scans were also acquired and analyzed using a graph-theoretical approach and network-based statistics. Results Global network analyses revealed a significantly increased normalized clustering coefficient and small-worldness in children with OB compared with HW controls. In addition, regional analyses revealed increased betweenness centrality, reduced clustering coefficient, and increased structural network strength in children with OB, mainly in the motor cortex and reward network. Importantly, children with OB lost a considerable amount of their body mass after the treatment; however, no changes were observed in the organization of their brain networks. Conclusion This is the first study showing disrupted structural connectomes of children with OB, especially in the motor and reward network. These results provide new insights into the pathophysiology underlying childhood obesity. The treatment did result in a significant weight loss, which was however not associated with alterations in the brain networks. These findings call for larger samples to examine the impact of short-term and long-term weight loss (treatment) on children’s brain network organization

Abnormal white matter integrity in synthetic cannabinoid users

Synthetic cannabinoids have become increasingly popular in the last few years especially among adolescents and young adults. However, no previous studies have assessed the effects of synthetic cannabinoids on the structure of the human brain. Understanding the harms of synthetic cannabinoid use on brain structure is therefore crucial given its increasing use. Diffusion tensor imaging (DTI) was performed in 22 patients who used synthetic cannabinoids more than five times a week for at least 1 year and 18 healthy controls. Fractional anisotropy (FA) was significantly reduced in the cannabinoid group compared to controls in a cluster of white matter voxels spanning the left temporal lobe, subcortical structures and brainstem. This cluster was predominantly traversed by the inferior frontooccipital fasciculus, inferior longitudinal fasciculus, fornix, cingulum-hippocampus and corticospinal tracts. Long-term use of synthetic cannabinoids is associated with white matter abnormalities in adolescents and young adults. Disturbed brain connectivity in synthetic cannabinoid users may underlie cognitive impairment and vulnerability to psychosis. (C) 2016 Elsevier B.V. and ECNP. All rights reserved

Risk and resilience brain networks in treatment-resistant schizophrenia

Background Genes, molecules and neural circuits that are associated with, or confer risk to developing schizophrenia have been studied and mapped. It is hypothesized that certain neural systems may counterbalance familial risk of schizophrenia, and thus confer resilience to developing the disorder. This study sought to identify resting-state functional brain connectivity (rs-FC) representing putative risk or resilience endophenotypes in schizophrenia. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 42 individuals with treatment resistant schizophrenia (TRS), 16 unaffected first-degree family members (UFM) and 42 healthy controls. Whole-brain rs-FC networks were mapped for each individual and analysed graph theoretically to identify network markers associated with schizophrenia risk or resilience. Results The ~ 900 functional connections showing between-group differences were operationalized as conferring: i) resilience, ii) risk, or iii) precipitating risk and/or illness effects. Approximately 95% of connections belonged to the latter two categories, with substantially fewer connections associated with resilience. Schizophrenia risk primarily involved reduced frontal and occipital rs-FC, with patients showing additional reduced frontal and temporal rs-FC. Functional brain networks were characterized by greater local efficiency in UFM, compared to TRS and controls. Conclusions TRS and UFM share frontal and occipital rs-FC deficits, representing a ‘risk’ endophenotype. Additional reductions in frontal and temporal rs-FC appear to be associated with risk that precipitates psychosis in vulnerable individuals, or may be due to other illness-related effects, such as medication. Functional brain networks are more topologically resilient in UFM compared to TRS, which may protect UFM from psychosis onset despite familial liability