Intrinsic connectomes are a predictive biomarker of remission in major depressive disorder.

Although major depressive disorder (MDD) is associated with altered functional coupling between disparate neural networks, the degree to which such measures are ameliorated by antidepressant treatment is unclear. It is also unclear whether functional connectivity can be used as a predictive biomarker of treatment response. Here, we used whole-brain functional connectivity analysis to identify neural signatures of remission following antidepressant treatment, and to identify connectomic predictors of treatment response. 163 MDD and 62 healthy individuals underwent functional MRI during pre-treatment baseline and 8-week follow-up sessions. Patients were randomized to escitalopram, sertraline or venlafaxine-XR antidepressants and assessed at follow-up for remission. Baseline measures of intrinsic functional connectivity between each pair of 333 regions were analyzed to identify pre-treatment connectomic features that distinguish remitters from non-remitters. We then interrogated these connectomic differences to determine if they changed post-treatment, distinguished patients from controls, and were modulated by medication type. Irrespective of medication type, remitters were distinguished from non-remitters by greater connectivity within the default mode network (DMN); specifically, between the DMN, fronto-parietal and somatomotor networks, the DMN and visual, limbic, auditory and ventral attention networks, and between the fronto-parietal and somatomotor networks with cingulo-opercular and dorsal attention networks. This baseline hypo-connectivity for non-remitters also distinguished them from controls and increased following treatment. In contrast, connectivity for remitters was higher than controls at baseline and also following remission, suggesting a trait-like connectomic characteristic. Increased functional connectivity within and between large-scale intrinsic brain networks may characterize acute recovery with antidepressants in depression.

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 < .0001): the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 y: r = -.3, P = .005) and middle life (30 y: r = -.4, P = .004, 40 y: r = -.3, P = .04), but not beyond 50 years (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.

Assessment of system dysfunction in the brain through MRI-based connectomics.

Network-based analysis of structural and functional connections has provided a new technique to study the brains of healthy people and patients with neurological and psychiatric disorders. Graph theory provides a powerful method to quantitatively describe the topological organisation of brain connectivity. With such a framework, the brain can be depicted as a set of nodes connected by edges. Distinct modifications of network topological organisation in the brain have been identified during development and normal ageing, whereas disrupted functional and structural connectivities have been associated with several neurological and psychiatric disorders, including dementia, amyotrophic lateral sclerosis, multiple sclerosis, and schizophrenia. These assessments have improved understanding of the clinical manifestations noted in these patients, including disability and cognitive impairment. Future network-based research might enable indentification of different stages of disorders, subtypes for cognitive impairment, and connectivity profiles associated with different clinical outcomes.

Individual differences in anterior cingulate/paracingulate morphology are related to executive functions in healthy males.

The neuropsychological correlates of inter-individual variations in cortical folding are poorly understood. Anterior cingulate (AC) cortex is one region characterized by considerable variability, particularly with respect to the paracingulate sulcus (PCS), which is present in only 30-60% of individuals and more commonly found in the left cerebral hemisphere. To investigate whether inter-individual differences in this PCS asymmetry are related to cognitive performance, we classified 30 healthy right-handed males as displaying either a leftward, rightward or symmetric pattern of folding based on the incidence and extent of the PCS in each hemisphere, and compared their performance on tasks engaging executive cognitive processes associated with frontal lobe function. We found that the more common leftward PCS asymmetry was associated with better performance across verbal and non-verbal executive tasks, but that PCS variability had no effect on tasks less dependent on executive functions. These results suggest that the leftward pattern of folding is associated with a non-specific performance advantage on cognitively demanding executive function tasks, possibly due to differences in functional interactions between AC/paracingulate cortex and connected frontal regions. It therefore appears that normal variations in brain morphology are associated with individual differences in cognitive abilities.