Functional and structural effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations in schizophrenia: A systematic review.

BACKGROUND: Auditory verbal hallucinations (AVH) are a disabling symptom for people with schizophrenia (SCZ), and do not always respond to antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for medication-refractory AVH, though the underlying neural mechanisms by which rTMS produces these effects remain unclear. This systematic review evaluated the structural and functional impact of rTMS for AVH in SCZ, and its association with clinical outcomes. METHODS: A systematic search was conducted in Medline, PsychINFO, and PubMed using terms for four key concepts: AVH, SCZ, rTMS, neuroimaging. Using PRISMA guidelines, 18 studies were identified that collected neuroimaging data of an rTMS intervention for AVH in SCZ. Risk of bias assessments was conducted. RESULTS: Low frequency (<5 Hz) rTMS targeting left hemispheric language processing regions may normalize brain abnormalities in AVH patients at structural, functional, electrophysiological, and topological levels, with concurrent symptom improvement. Amelioration of aberrant neural activity in frontotemporal networks associated with speech and auditory processing was commonly observed, as well as in cerebellar and emotion regulation regions. Neuroimaging analyses identified neural substrates with direct correlations to post-rTMS AVH severity, propounding their use as therapeutic targets. DISCUSSION: Combined rTMS-neuroimaging highlights the multidimensional alterations of rTMS on brain activity and structure in treatment-resistant AVH, which may be used to develop more efficacious therapies. Larger randomized, sham-controlled studies are needed. Future studies should explore alternate stimulation targets, investigate the neural effects of high-frequency rTMS and evaluate long-term neuroimaging outcomes.

A systematic review and meta-analysis of neuromodulation therapies for substance use disorders.

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

A Systematic Review of Noninvasive Brain Stimulation for Opioid Use Disorder.

BACKGROUND: There is a great public health need to identify novel treatment strategies for opioid use disorder (OUD) in order to reduce relapse and overdose. Noninvasive brain stimulation (NIBS) has demonstrated preliminary effectiveness for substance use, but little is known about its use in OUD. Neuromodulation may represent a potential adjunctive treatment modality for OUD, so we conducted a systematic review to understand the state of the current research in this field. METHODS: We conducted a systematic review of studies using noninvasive brain stimulation to affect clinical outcomes related to substance use for adults with opioid use disorder. We searched the following online databases: PubMed, The Cochrane Library, PsycINFO (EBSCOhost, 1872-present), and Science Citation Index Expanded (ISI Web of Science, 1945-present). All studies that measured clinical outcomes related to substance use, including cue-induced craving, were included. We assessed risk of bias using the Cochrane Handbook. RESULTS: The initial search yielded 5590 studies after duplicates were removed. After screening titles and abstracts, 14 full-text studies were assessed for eligibility. Five studies were determined to meet inclusion criteria with a combined total subjects of N = 150. Given the paucity of studies and small number of total subjects, no quantitative analysis was performed. These studies used TMS (n = 3), tDCS (n = 1), and the BRIDGE device (n = 1), a noninvasive percutaneous electrical nerve field stimulator, to reduce cue-induced craving (n = 3), reduce clinical withdrawal symptoms (n = 1), or measure substance-use-related cortical plasticity (n = 1). CONCLUSIONS: There is a dearth of research in the area of noninvasive brain stimulation for OUD. NIBS represents a novel treatment modality that should be further investigated for OUD.

Tobacco use and psychosis risk in persons at clinical high risk.

AIM: To evaluate the role of tobacco use in the development of psychosis in individuals at clinical high risk. METHOD: The North American Prodrome Longitudinal Study is a 2-year multi-site prospective case control study of persons at clinical high risk that aims to better understand predictors and mechanisms for the development of psychosis. The cohort consisted of 764 clinical high risk and 279 healthy comparison subjects. Clinical assessments included tobacco and substance use and several risk factors associated with smoking in general population studies. RESULTS: Clinical high risk subjects were more likely to smoke cigarettes than unaffected subjects (light smoking odds ratio [OR] = 3.0, 95% confidence interval [CI] = 1.9-5; heavy smoking OR = 4.8, 95% CI = 1.7-13.7). In both groups, smoking was associated with mood, substance use, stress and perceived discrimination and in clinical high risk subjects with childhood emotional neglect and adaption to school. Clinical high risk subjects reported higher rates of several factors previously associated with smoking, including substance use, anxiety, trauma and perceived discrimination. After controlling for these potential factors, the relationship between clinical high risk state and smoking was no longer significant (light smoking OR = 0.9, 95% CI = 0.4-2.2; heavy smoking OR = 0.3, 95% CI = 0.05-2.3). Moreover, baseline smoking status (hazard ratio [HR] = 1.16, 95% CI = 0.82-1.65) and categorization as ever smoked (HR = 1.3, 95% CI = 0.8-2.1) did not predict time to conversion. CONCLUSION: Persons at high risk for psychosis are more likely to smoke and have more factors associated with smoking than controls. Smoking status in clinical high risk subjects does not predict conversion. These findings do not support a causal relationship between smoking and psychosis.