Cerebellar dysfunction may be at the root of negative symptoms and cognitive dysfunction; possible treatment identified

in at least two large, independent data sets involving a total of more than 3,700 individuals, cerebellar volume has been found to be significantly reduced in patients with schizophrenia and significantly correlated with psychotic symptoms (6, 7). Moreover, a study of clinical high-risk subjects demonstrated cerebellar-thalamo-cortical dysconnectivity as a state-independent neural trait for prediction of psychosis.

In this issue of the Journal, Brady and colleagues (9) present a two-step study to approach this question by combining resting-state functional MRI, state-of-the-art brain network analysis, and brain stimulation. Considering the fact that negative symptoms are strongly associated with cognitive impairments and are a major rate-limiting feature of long-term functional outcomes in schizophrenia, these investigators started with a completely data-driven approach to exhaustively search for connectome-wide associations.

they discovered that the connectivity between dorsolateral prefrontal cortex (DLPFC) and midline posterior cerebellum showed the strongest correlation with negative symptoms across the whole brain during resting state. Specifically, patients with higher negative symptoms had significantly lower cerebellar-prefrontal connectivity, suggesting that disrupted synchronization in the cerebellar-prefrontal circuitry underlies negative symptoms and possibly also cognitive dysfunction.

In the second part of the study, Brady and colleagues investigated whether the altered connectivity between the cerebellum and DLPFC could be a causal mechanism for negative symptoms or rather an epiphenomenon. They performed a repetitive transcranial magnetic stimulation (rTMS) trial targeting the posterior cerebellum in an independent group of patients (N=11) to examine whether rTMS could boost the functional connectivity of the cerebellar-prefrontal circuitry and in turn ameliorate clinical symptoms.

Intriguingly, after a 5-day (4 hours per day) rTMS administration, most patients in the sample showed an increase in cerebellar-prefrontal connectivity, the degree of which was significantly correlated with improvement in negative symptom severity. Notably, more than 60% of total variance in symptom change could be attributed to the change in cerebellar-prefrontal connectivity, corroborating a possible causal relationship from disrupted connectivity in cerebellar-prefrontal circuitry to negative symptoms in schizophrenia.

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Thanks @twinklestars , thanks for posting.

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Very interesting!

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Awesome news !!

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