Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes

Abstract

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain’s functional organization. The E-field, which is determined by electrode placement (right unilateral or bitemporal) and pulse amplitude (600, 700, or 800 milliamperes), is associated with the ECT response. However, the neural mechanisms underlying the relationship between E-field, functional brain changes, and clinical outcomes of ECT are not well understood. Here, we investigated the relationships between whole-brain E-field (Ebrain, the 90th percentile of E-field magnitude in the brain), cerebro-cerebellar functional network connectivity (FNC), and clinical outcomes (cognitive performance and depression severity). A fully automated independent component analysis framework determined the FNC between the cerebro-cerebellar networks. We found a linear relationship between Ebrain and cognitive outcomes. The mediation analysis showed that the cerebellum to middle occipital gyrus (MOG)/posterior cingulate cortex (PCC) FNC mediated the effects of Ebrain on cognitive performance. In addition, there is a mediation effect through the cerebellum to parietal lobule FNC between Ebrain and antidepressant outcomes. The pair-wise t-tests further demonstrated that a larger Ebrain was associated with increased FNC between cerebellum and MOG and decreased FNC between cerebellum and PCC, which were linked with decreased cognitive performance. This study implies that an optimal E-field balancing the antidepressant and cognitive outcomes should be considered in relation to cerebro-cerebellar functional neuroplasticity.

Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy

“…The previous studies found that extensive cerebellar‐cortex interactions underlie the cerebellum's regulation of movement, thought, and emotion 40,41 . Numerous studies have demonstrated that disruption of cerebellar‐cortex FC is one of the neurobiological changes in depression 42,43 and this abnormal cerebellar‐cortex FC can be ameliorated by ECT 44,45 . These findings collectively demonstrate that altered cerebellar‐brain resting‐state FC is strongly associated with ECT‐induced antidepressant effects, which is consistent with our findings that we found that increased FC between PCL and TP in MDD patients after ECT.…”

“…40,41 Numerous studies have demonstrated that disruption of cerebellar-cortex FC is one of the neurobiological changes in depression 42,43 and this abnormal cerebellar-cortex FC can be ameliorated by ECT. 44,45 These findings collectively demonstrate that altered cerebellar-brain resting-state FC is strongly associated with ECT-induced antidepressant effects, which is consistent with our findings that we found that increased FC between PCL and TP in MDD patients after ECT. The TP plays an important role in emotional processing, and TP lesions lead to emotional deficits.…”

Neuromodulation (Brain Stimulation) Technologies for Treatment of Substance Use Disorders

“…Electroconvulsive Therapy (ECT) is a psychiatric treatment involving the delivery of electric currents (around 800-900 mA) through scalp electrodes. These currents pass through the skull and cerebrospinal fluid, generating a strong electric field throughout the brain, which induces seizures and reorganizes brain function [42,43]. ECT can lead to cognitive side effects, including attention, memory, and executive function impairments [44][45][46].…”