Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization

Abstract

Understanding the fundamental alterations in brain functioning that lead to psychotic disorders remains a major challenge in clinical neuroscience. In particular, it is unknown whether any state-independent biomarkers can potentially predict the onset of psychosis and distinguish patients from healthy controls, regardless of paradigm. Here, using multi-paradigm fMRI data from the North American Prodrome Longitudinal Study consortium, we show that individuals at clinical high risk for psychosis display an intrinsic “trait-like” abnormality in brain architecture characterized as increased connectivity in the cerebello–thalamo–cortical circuitry, a pattern that is significantly more pronounced among converters compared with non-converters. This alteration is significantly correlated with disorganization symptoms and predictive of time to conversion to psychosis. Moreover, using an independent clinical sample, we demonstrate that this hyperconnectivity pattern is reliably detected and specifically present in patients with schizophrenia. These findings implicate cerebello–thalamo–cortical hyperconnectivity as a robust state-independent neural signature for psychosis prediction and characterization.

Effects of a patient-derived de novo coding alteration of CACNA1I in mice connect a schizophrenia risk gene with sleep spindle deficits

“…While these reports typically involve relatively small sample sizes, spindle deficits throughout the course of schizophrenia, in treatment-naïve patients 10 , and in firstdegree relatives 11 implicate abnormal function of thalamocortical circuitry. This abnormality before the onset of the disease is consistent with the finding of reduced thalamic volume and altered thalamocortical connection in ultra-high-risk adolescents for schizophrenia 12,13 . Further, reduced sleep spindle activity in schizophrenia has been correlated with impaired sleep-dependent cognitive functions [14][15][16][17][18] .…”

Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

“…This means that these profile maps can be interpreted as an answer to where in the brain connectivity may explain most of the variance in clinical improvement. The concept of using connectivity patterns to predict functional capacity and clinical symptoms has been a central dogma in contemporary studies (Beaty et al, 2018;Cao et al, 2018). We relied on this concept in order to draw conclusions about the optimal connectivity fingerprint that will ensure the best outcome.…”

Progression from being at-risk to psychosis: next steps

“…Longitudinal structural magnetic resonance imaging (MRI) findings suggest that an increased rate of grey matter loss, particularly in the frontal lobes, may be a predictor of transition to psychosis in CHR individuals 14,15 , which is supported by other longitudinal studies employing machine learning 16,17 . Several functional MRI (fMRI) studies have suggested that transition to psychosis might be associated with cerebello-thalamo-cortical hyperconnectivity 18,19 or other bidirectional changes in thalamic connectivity 20 . Although these findings are promising, much more work is required to characterize and understand these changes in brain structure and function.…”