Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment. Using resting-state functional MRI, we examined the functional connectivity of the ventral tegmental area (VTA), the origin of the mesocorticolimbic dopamine projections, in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline (pre-treatment) and after 1 week of treatment with the antipsychotic drug risperidone (1-week posttreatment). Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups' participant-level functional connectivity maps. We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response. Compared with controls, patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions, including the dorsal anterior cingulate cortex (dACC) and thalamus. After 1 week of treatment, VTA/midbrain connectivity to bilateral regions of the thalamus was re-established. Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone, whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated. Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response.

Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22–33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemisphere damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage.

We investigated psychological stress response in the brain regions involved in emotion-motor-executive control in psychogenic non-epileptic seizures (PNES). 12 PNES patients and 12 healthy controls (HCs) underwent stress task and resting state functional MRI (fMRI), mood and quality of life (QOL) assessments, and measurements of salivary cortisol, alpha-amylase, and heart rate. Group differences were assessed, and we correlated beta values from a priori selected brain regions showing stress task fMRI group differences with other stress response measures. We also used the regions showing stress task fMRI group differences as seeds for resting state functional connectivity (rs-FC) analysis. Mood and QOL were worse in PNES versus HCs. Physiological and assessment measures were similar except ‘Planful Problem Solving’ coping that was greater for HCs (p = .043). Perceived stress associated negatively with heart rate change ( r s = −0.74, p = .0063). There was stress fMRI hyporeactivity in left/right amygdala and left hippocampus in PNES versus HCs (corrected p < .05). PNES exhibited a positive association between alpha-amylase change and right amygdala activation ( r s = 0.71, p = .010). PNES versus HCs exhibited greater right amygdala rs-FC to left precentral and inferior/middle frontal gyri (corrected p < .05). Our findings of fMRI hyporeactivity to psychological stress, along with greater emotion-motor-executive control network rs-FC in PNES when compared to HCs suggest a dysregulation in stress response circuitry in PNES.

Better understanding of the extent and scope of visual cortex plasticity following central vision loss is essential both for clarifying the mechanisms of brain plasticity and for future development of interventions to retain or restore visual function. This study investigated structural differences in primary visual cortex between normally-sighted controls and participants with central vision loss due to macular degeneration (MD). Ten participants with MD and ten age-, gender-, and education-matched controls with normal vision were included. The thickness of primary visual cortex was assessed using T1-weighted anatomical scans, and central and peripheral cortical regions were carefully compared between well-characterized participants with MD and controls. Results suggest that, compared to controls, participants with MD had significantly thinner cortex in typically centrally-responsive primary visual cortex – the region of cortex that normally receives visual input from the damaged area of the retina. Conversely, peripherally-responsive primary visual cortex demonstrated significantly increased cortical thickness relative to controls. These results suggest that central vision loss may give rise to cortical thinning, while in the same group of people, compensatory recruitment of spared peripheral vision may give rise to cortical thickening. This work furthers our understanding of neural plasticity in the context of adult vision loss.