Elin Thörnblom: On the physiology of psychiatric brain stimulation

Abstract

This thesis examines physiological aspects of two psychiatric brain stimulation treatments: electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).

ECT’s therapeutic effect depends on epileptic seizures that activate subcortical regions, and involves increased gamma-aminobutyric acid (GABA) inhibition. Clinical ECT seizure evaluation parameters show varying correlation to clinical outcome and uncertain correlation to subcortical activation. Serum prolactin and cortisol increase postictally, and postictal prolactin reflects subcortical seizure activation. The GABA-agonistic hormone allopregnanolone affects psychiatric illness and increases postictally in epilepsy, but is unexplored after ECT seizures.

RTMS’s therapeutic effect depends on altering cortical excitability which affects synapse plasticity, subsequently modulating functional neural network activity. Motor cortex excitability measured with TMS paired with electromyography (TMS-EMG), which includes GABA modulated indices, may be altered in psychiatric illness. Prefrontal rTMS affects motor cortex excitability, and TMS-EMG may predict rTMS treatment outcome, but the rTMS protocol intermittent theta burst stimulation (iTBS) is less explored. 

Study I analysed correlations between clinical ECT seizure evaluation parameters and prolactin and cortisol serum levels. Ictal tachycardia correlated with postictal prolactin, but not cortisol, suggesting that ictal tachycardia reflects subcortical seizure engagement. 

Study II investigated progesterone and allopregnanolone serum levels after an ECT seizure, finding no postictal increase or correlation to seizure evaluation parameters. Postictal progesterone increased in men in a subgroup analysis.

Study III examined GABAA receptor availability measured with positron emission tomography and TMS-EMG indices in participants with depression before and after iTBS. Baseline comparisons showed no difference from healthy. After iTBS, changes in GABAA receptor availability and TMS-EMG motor threshold correlated negatively, indicating GABAA mediated regulation of motor cortex signalling. 

Study IV investigated whether iTBS affects TMS-EMG and whether baseline TMS-EMG predicts iTBS outcome on negative symptoms in schizophrenia and depression, with negative results. Compared to participants with depression and healthy, participants with schizophrenia had more GABAB receptor dependent inhibition, which also correlated with antipsychotic medication dose.

These results contribute to the understanding of ECT and rTMS physiology, facilitating future developments for improved efficacy and reduced side effects.