Thalamic contributions to psychosis susceptibility: Evidence from co-activation patterns accounting for intra-seed spatial variability (μCAPs)

Abstract

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (μCAPs) by employing this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain μCAPs with specific activity patterns within the thalamus. Unlike conventional methods, μCAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the μCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a μCAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was significantly less frequent in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, the activity within the auditory-visual cortex and their respective geniculate nuclei were expressed in two different μCAPs. One of these auditory-visual μCAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN+visuo-auditory-thalamus micro CAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity as specific hyper-occurrence of these circuits with the task negative brain networks.

Psychiatric manifestations in moyamoya disease: more than a puff of smoke? a systematic review and a case-reports meta-analysis

“…Similarly, Liu and colleagues (62) highlighted structural and functional alterations of the left thalamus in schizophrenic patients, and these impairments correlated with symptoms. Thalamus involvement in psychosis is, indeed, well-established and supported by fMRI studies (63). Finally, a systematic review on neural underpinnings of delusional symptoms in schizophrenia and Alzheimer's disease patients reported lateralized findings of gray matter reductions in the left claustrum (64), reinforcing the notion of left hemisphere involvement in the genesis of psychotic symptoms.…”