Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study

Abstract

Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the specialized H4 coil. Feasibility of dTMS was tested for disruption of tobacco self-administration, insula target engagement, and insula circuit modulation, all of which were a priori outcomes of interest. Twenty patients completed the study, consisting of weekday dTMS sessions (randomization to active dTMS or sham; double-blind; 10 patients per group), a laboratory tobacco self-administration paradigm (pre/post assessments), and multimodal imaging (three MRI total sessions). Results showed that participants assigned to active dTMS were slower to initiate smoking their first cigarette compared with sham, consistent with smoking disruption. The imaging analyses did not reveal significant Time × Group interactions, but effects were in the anticipated directions. In arterial spin labeling analyses testing for target engagement, an overall decrease in insula blood flow, measured during a post-treatment MRI versus baseline, was numerically more pronounced in the active dTMS group than sham. In fMRI analyses, resting-state connectivity between the insula and default mode network showed a numerically greater change from baseline in the active dTMS group than sham, consistent with a functional change to insula circuits. Exploratory analyses further suggested a therapeutic effect of dTMS on symptoms of psychosis. These initial observations pave the way for future confirmatory studies of dTMS in smoking patients with schizophrenia.

Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use

“…Another mechanistic, proof-of-concept study with the H4 coil revealed that participants assigned to active TMS were slower to initiate smoking their first cigarette than the sham group, an observation consistent with smoking disruption [39]. The neuroimaging data collected in this experiment showed an overall decrease in insula activity and changes in the resting-state connectivity between the insula and the default mode network (DMN) following active TMS.…”

“…This multisite clinical trial was the result of several decades of work in both preclinical research laboratories and small clinical trials using a variety of TMS coils [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In 2020, the United States Food and Drug Administration (FDA) cleared the H4 coil for use as an aid in short-term smoking cessation for adults (Deep TMS, BrainsWay, Jerusalem, Israel).…”

Abandon du tabagisme au moyen de la stimulation magnétique transcrânienne répétitive

“…Par ailleurs, ce traite ment n'a pas fait l'objet d'études chez toutes les populations, comme les personnes atteintes de schizophrénie, qui présentent des taux élevés de consommation chronique de tabac. Une étude de validation a montré son potentiel d'utilisation chez la patientèle schizophrène 16 , mais aucun essai de grande envergure visant à déterminer les issues liées à l'abandon du tabagisme n'a été mené pour l'instant. D'autres études devraient évaluer si les protocoles de traite ment combinant la SMTr et les pharmacothérapies antitaba giques peuvent mener à une hausse des taux ou de la longueur des périodes d'abstinence.…”

Behavioral and Functional Brain Activity Alterations Induced by TMS Coils with Different Spatial Distributions

“…Indeed, the LPFC, and especially the dorsolateral PFC (DLPFC) have been implicated in the pathogenesis of several psychiatric and neurologic disorders with affected reward-related behavior, including schizophrenia, anxiety, and posttraumatic stress disorder ( Hopper et al, 2008 ; Maresh et al, 2014 ; Subramaniam et al, 2015 ; Park et al, 2016 ; Pu et al, 2016 ; Zhang et al, 2016 ). Moreover, there is evidence for the efficacy of transcranial magnetic stimulation (TMS) over the PFC for the treatment of other conditions with impaired reward-related behavior such as depression, addictions, Alzheimer’s disease, schizophrenia, and eating disorders ( Fox et al, 2014 ; Moeller et al, 2022 ). These effects are attributed to the technique’s ability to redress imbalances in the excitability of brain networks and neurotransmitter concentrations that characterize these conditions ( Pell et al, 2011 ).…”