Summary: Researchers report that reduced connectivity between the thalamus and prefrontal cortex may be a common feature in people with schizophrenia.
Source: Vanderbilt University
Executive cognitive functions — including working memory, mental control, and self-regulation — are consistently impaired in schizophrenia. Current drug and behavioral treatments offer only modest improvements in these cognitive abilities.
In a study comparing individuals with schizophrenia to healthy volunteers, Neil Woodward, PhD, and colleagues evaluated executive functions and used diffusion-weighted MRI to map anatomical connections between brain regions that support those functions.
The team reports that anatomical connectivity between the prefrontal cortex (PFC) and the thalamus is reduced in people with schizophrenia. This reduction was specifically associated with impaired working memory, while other executive domains such as cognitive flexibility and inhibitory control were not correlated with the same connectivity change. In contrast, thalamic connections to somatosensory and occipital cortical regions were increased in the patient group.
Using probabilistic tractography to quantify thalamocortical pathways, the researchers examined connections between the thalamus and six cortical regions, including lateral prefrontal cortex. Voxelwise analysis pinpointed reductions in connectivity within portions of the mediodorsal thalamus that are specifically linked to lateral PFC. The pattern suggests a targeted breakdown in the anatomical pathways that support working memory processes.
Importantly, the observed decrease in PFC–thalamic connectivity correlated with poorer working memory performance in patients, supporting the idea that disrupted communication between these structures contributes to cognitive deficits in schizophrenia. At the same time, increased thalamic connectivity with sensory regions (somatosensory and occipital cortices) may indicate a reorganization of thalamic projections or compensatory changes, though the functional implications of these increases require further study.
Funding: This research was supported by the National Institutes of Health (grants MH102266, RR024975).
Source: Leigh MacMillan, Vanderbilt University
Publisher: Organized by NeuroscienceNews.com
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract in Biological Psychiatry.
doi: 10.1016/j.biopsych.2017.09.022
Vanderbilt University. Brain Connections in Schizophrenia. NeuroscienceNews. March 8, 2018.
Abstract
Prefrontal–Thalamic Anatomical Connectivity and Executive Cognitive Function in Schizophrenia
Background
Executive cognitive functions — such as working memory, cognitive flexibility, and inhibition — are commonly impaired in schizophrenia. These functions depend on coordinated processing between the prefrontal cortex and thalamus, particularly the mediodorsal nucleus. This study tested whether anatomical connectivity between the prefrontal cortex and mediodorsal thalamus is reduced in schizophrenia and whether such reductions relate to executive function deficits.
Methods
The study included 62 patients with a schizophrenia spectrum disorder and 45 healthy comparison subjects. Participants completed a battery of executive function tests and underwent diffusion-weighted MRI. Researchers applied probabilistic tractography to estimate anatomical connectivity between the thalamus and six cortical regions, including the prefrontal cortex. Group comparisons used both region-of-interest and voxelwise approaches, and the relationship between PFC–thalamic connectivity and executive function severity was assessed in patients.
Results
Connectivity between the thalamus and prefrontal cortex was reduced in the schizophrenia group, with voxelwise mapping localizing reductions to mediodorsal thalamic regions connected to lateral PFC. In patients, lower PFC–thalamic connectivity correlated with worse working memory performance but did not correlate with measures of cognitive flexibility or inhibition. Conversely, thalamic connectivity with somatosensory and occipital cortices was increased in patients.
Conclusions
These results support models that implicate disrupted PFC–thalamic connectivity in the pathophysiology of schizophrenia and in mechanisms underlying cognitive impairment. Anatomical connectivity between the prefrontal cortex and thalamus may represent a promising target for interventions aimed at improving cognition. Additional research is necessary to clarify the meaning and consequences of increased thalamic connectivity with sensory cortical areas.