Repetitive deep TMS in alcohol dependent patients halts progression of white matter changes in early abstinence.

AIM: Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter. METHODS: A total of 37 (14 females) AUD treatment-seeking patients were randomized to sham or active Deep TMS. Twenty (six females) age-matched healthy controls were included. White matter integrity was evaluated by fractional anisotropy (FA). Secondary measures included brain functional connectivity and self-reports of craving and drinking units in the 3 months of follow-up period. RESULTS: White matter integrity was compromised in patients with AUD relative to healthy controls, as reflected by the widespread reduction in FA. This alteration progressed during early abstinence (3 weeks) in the absence of Deep TMS. However, stimulation of midline frontocortical areas arrested the progression of FA changes in association with decreased craving and relapse scores. Reconstruction of axonal tracts from white-matter regions showing preserved FA values identified cortical regions in the posterior cingulate and dorsomedial prefrontal cortices where functional connectivity was persistently modulated. These effects were absent in the sham-stimulated group. CONCLUSIONS: By integrating brain structure and function to characterize the alcohol-dependent brain, this study provides mechanistic insights into the TMS effect, pointing to myelin plasticity as a possible mediator.

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study.

BACKGROUND/OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke. MATERIALS AND METHODS: Twelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20 Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded. RESULTS: No participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham. CONCLUSIONS: This exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.

Increased relapse to cocaine-seeking in a genetic model for depression.

The greatest difficulty in treating cocaine addiction is the enormous rates of relapse, which occur despite immense negative consequences. Relapse risks are even greater in addicts with comorbid depression, perhaps because they use drugs to alleviate depressive symptoms. Only a few preclinical studies have examined this comorbidity, mostly exploring depressive-like effects following drug exposure. We examined rats from two different depression-like models: (a) chronic-mild-stress (CMS), which respond to antidepressant medications and (b) depressed-rat-line (DRL), a genetic model of selective breeding, which is less responsive to antidepressant medications. We tested addictive behaviors in a cocaine self-administration procedure, including the "conflict model," where drug-seeking and relapse encounter adverse consequences: an electrified grid in front of the drug-delivering lever. Following behavioral testing, we explored a potential association between behavioral outcomes and protein expression of brain-derived neurotrophic factor (BDNF). We found that DRL rats self-administer more cocaine compared with both CMS and controls, while CMS and control groups did not differ significantly. Notably, DRL but not CMS rats, displayed higher rates of relapse than controls, and expressed higher levels of BDNF in the prelimbic cortex (PLC). Potential translation of these results suggest that medication-resistant depressed patients tend to consume more drugs and are more susceptible to relapse. The increase in PLC BDNF levels is consistent with previous rat models of depression, and concomitantly, with its suggested role in promoting cocaine-seeking.

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

UNLABELLED: The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders.

Bursts of high-frequency repetitive transcranial magnetic stimulation (rTMS), together with lorazepam, suppress seizures in a rat kainate status epilepticus model.

BACKGROUND: Status epilepticus (SE) is a condition of prolonged or recurrent and often drug-resistant seizures where nonsedating SE therapy remains an important unmet need. Repetitive transcranial magnetic stimulation (rTMS) is emerging as a means to suppress seizures but has not been extensively studied in models. OBJECTIVES: We aimed to test the antiepileptic potential of high-frequency rTMS in SE. As a step toward eventual coupling of rTMS with antiepileptic pharmacotherapy, we also tested whether high-frequency rTMS in combination with a low (ineffective but less likely to cause a side effect) lorazepam dose is as effective as a full lorazepam dose in suppressing seizures in a rat SE model. METHODS: EEG was recorded to measure epileptic spike frequency in the rat kainate SE model. Epileptic spikes were counted before, during, and after either high-frequency rTMS treatment alone or high-frequency rTMS treatment in combination with lorazepam, a firstline SE treatment. RESULTS: We found that rTMS alone decreases epileptic spike frequency only acutely. However, combinatory treatment with half-dose lorazepam together with rTMS was as effective as a full lorazepam dose. CONCLUSION: We report that high-frequency rTMS has modest antiepileptic potential alone but acts in complement with lorazepam to suppress seizures.

Chronic cocaine administration induces long-term impairment in the drive to obtain natural reinforcers in high- but not low-demanding tasks.

Repeated drug exposure induces short- and long-term neuroadaptations in brain reward circuitries that are normally involved in the regulation of motivation. Hence, repeated drug exposure has been suggested to also affect the drive to acquire natural reinforcers. Here, we tested how chronic exposure of rats to cocaine, as well as a subsequent withdrawal period, affects acquisition of natural reinforcers in high- and low-demanding tasks (HD and LD tasks, respectively). We chronically administered cocaine (i.p., 15 mg/kg once daily, or saline in control) for 30 days, followed by a 30-day withdrawal period. We tested the effect of this treatment on the acquisition of two natural appetitive reinforcers, namely self-administering a 10% sucrose solution and mounting a receptive female, under LD and HD conditions. During the cocaine exposure period, behavioral testing took place 18 hours after cocaine injection, namely after the acute pharmacologic effect of the drug dissipated. We show that chronic i.p. cocaine exposure decreased procurement of both reinforcers in HD but not in LD tasks. The effect was observed throughout the administration period with partial recovery after withdrawal. Taken together, we present empirical evidence that chronic exposure to a constant dose of cocaine is sufficient to reduce natural reinforcement, and that this decrease can outlast drug exposure. Importantly, such effects are observed only when high demands are opposing the consumption of the natural reinforcer.

Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study.

While Major Depressive Disorder (MDD) is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS), a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC) can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS) were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART) at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n = 21) and after 4 weeks (n = 13) of high-frequency (20 Hz) repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n = 26) were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer-term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment.

Neural correlates of clinical improvement after deep transcranial magnetic stimulation (DTMS) for treatment-resistant depression: a case report using functional magnetic resonance imaging.

We report the effects of a 4-week trial of deep transcranial magnetic stimulation (DTMS) on depressive and anxious symptoms and brain activity in a patient (Mrs A) with treatment-resistant depression (TRD). The protocol involved a pre- and a post-functional magnetic resonance imaging (fMRI) scan during which Mrs A had to perform a working memory task (i.e., n-back). Her baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D21) was 24, indicating severe depressive symptoms. Immediately after 4 weeks of daily DTMS treatment applied over the left dorsolateral prefrontal cortex (DLPFC), her HAM-D21 score decreased to 13 (a 46% reduction), and 1 month later, it was 12 (a 50% reduction). Moreover, Mrs A's accuracy scores on the n-back task (i.e., 2-back condition) improved from 79% (baseline) to 96% (after DTMS treatment). At the neural level, Mrs A showed significantly increased brain activity in the working memory network (e.g., DLPFC, parietal cortex) during the execution of the 2-back condition after DTMS treatment compared to baseline.

Deep TMS on alcoholics: effects on cortisolemia and dopamine pathway modulation. A pilot study.

The hypothalamic pituitary adrenal axis and dopamine have a key role in transition from alcohol social use to addiction. The medial prefrontal cortex was shown to modulate dopaminergic activity and cortisol releasing factor (CRF) release in hypothalamic and extra-hypothalamic systems. The recent advancements in non-invasive neurostimulation technologies has enabled stimulation of deeper brain regions using H-coil transcranial magnetic stimulation (TMS) in humans. This randomized double-blind placebo-controlled pilot study aims to evaluate H-coil efficacy in stimulating the medial prefrontal cortex. Cortisolemia and prolactinemia were evaluated as effectiveness markers. Alcohol intake and craving were considered as secondary outcomes. Eighteen alcoholics were recruited and randomized into 2 homogeneous groups: 9 in the real stimulation group and 9 in the sham stimulation group. Repetitive TMS (rTMS) was administered through a magnetic stimulator over 10 sessions at 20 Hz, directed to the medial prefrontal cortex. rTMS significantly reduced blood cortisol levels and decreased prolactinemia, thus suggesting dopamine increase. Craving visual analogic scale (VAS) in treated patients decreased, as well as mean number of alcoholic drinks/day and drinks on days of maximum alcohol intake (DMAI). In the sham group there was no significant effect observed on cortisolemia, prolactinemia, mean number of alcoholic drinks/day, or drinks/DMAI. Thus, deep rTMS could be considered a potential new treatment for alcoholism.

Induction of depressive-like effects by subchronic exposure to cocaine or heroin in laboratory rats.

The effect of psychoactive drugs on depression has usually been studied in cases of prolonged drug addiction and/or withdrawal, without much emphasis on the effects of subchronic or recreational drug use. To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long-term effects on (i) depressive-like behaviors, (ii) brain-derived neurotrophic factor (BDNF) levels in reward-related brain regions, and (iii) depressive-like behavior following an additional chronic mild stress procedure. The long-term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in BDNF levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive-like behavior which is accompanied by modifications in BDNF expression and increases the vulnerability to develop depressive-like behavior following chronic stress. Implications for recreational and small-scale drug users are discussed. In the present study, we examined the long-term effects of limited subchronic drug exposure on depressive-like symptoms. Our results demonstrate that short-term, subchronic administration of either cocaine or heroin promotes some depressive-like behaviors, while inducing alterations in BDNF protein levels similar to alterations observed in several animal models of depression. In addition, subchronic cocaine or heroin enhanced the anhedonic effect of chronic stress.

Inherited behaviors, BDNF expression and response to treatment in a novel multifactorial rat model for depression.

Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role. Here we used, for the first time, a multifactorial selective breeding procedure to generate a distinct 'depressed' rat line (DRL); our selection was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined. We show that decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited and not necessarily triggered by salient chronic stress. We therefore provide a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease.

Effects of deep repetitive transcranial magnetic stimulation on brain-derived neurotrophic factor serum concentration in healthy volunteers.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, safe and efficacious technique for treating various neuropsychiatric disorders, but its underlying mechanisms are poorly understood. A newly developed H-coil allows the stimulation of deeper brain regions. This study is the first to investigate the effects of deep high-frequency rTMS on brain-derived neurotrophic factor (BDNF) serum concentrations in healthy volunteers. We aimed to evaluate the short-term effect of deep rTMS on BDNF serum concentrations. METHODS: This was a double-blind, randomized deep high-frequency rTMS study using an H-coil on a cohort of 13 healthy volunteers (NCT01106365). The following stimulation protocols were applied: 18-Hz stimulation of the left dorsolateral prefrontal cortex (PFC), 5-Hz stimulation of the primary motor cortex (MC) and sham stimulation in random order. Blood samples were obtained before, 30 min after and 60 min after each treatment. RESULTS: The BDNF serum concentration decreased significantly after MC and PFC stimulation, but not after sham stimulation. Furthermore, BDNF serum level changes were associated with changes in individual alertness. CONCLUSION: Although BDNF serum concentrations do not necessarily correlate with BDNF levels in the cerebrospinal fluid or the brain, these results indicate an acute biological effect of deep rTMS on BDNF release, and demonstrate that this change correlates with alertness.

Deep repetitive transcranial magnetic stimulation with H-coil on lower limb motor function in chronic stroke: a pilot study.

OBJECTIVES: To assess the efficacy of high-frequency (20 Hz) brain stimulation on lower limb motor function in subjects with chronic (> 6 mo) subcortical stroke. DESIGN: Double-blind, placebo-controlled crossover study. SETTING: University hospital. PARTICIPANTS: Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. INTERVENTIONS: Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. MAIN OUTCOME MEASURES: Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. RESULTS: Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. CONCLUSIONS: These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.

Modulation of Alcohol Use Disorder by Brain Stimulation.

Currently available therapeutic modalities for alcohol use disorder (AUD) produce limited effect sizes or long-term compliance. Recent methods that were developed to modulate brain activity represent potential novel treatment options. Various methods of brain stimulation, when applied repeatedly, can induce long-term neurobiological, behavioral, and cognitive modifications. Recent studies in alcoholic subjects indicate the potential of brain stimulation methods to reduce alcohol craving, consumption, and relapse. Specifically, deep brain stimulation (DBS) of the nucleus accumbens or non-surgical stimulation of the dorsolateral prefrontal cortex (PFC) or medial PFC and anterior cingulate cortex using transcranial magnetic stimulation (TMS) has shown clinical benefit. However, further preclinical and clinical research is needed to establish understanding of mechanisms and the treatment protocols of brain stimulation for AUD. While efforts to design comparable apparatus in rodents continue, preclinical studies can be used to examine targets for DBS protocols, or to administer temporal patterns of pulsus similar to those used for TMS, to more superficial targets through implanted electrodes. The clinical field will benefit from studies with larger sample sizes, higher numbers of stimulation sessions, maintenance sessions, and long follow-up periods. The effect of symptoms provocation before and during stimulation should be further studied. Larger studies may have the power to explore predictive factors for the clinical outcome and thereby to optimize patient selection and eventually even develop personalization of the stimulation parameters.

Relapse after electric barrier-induced voluntary abstinence: A review.

Relapse to drug use during abstinence is a defining feature of addiction. To date, however, results from studies using rat relapse/reinstatement models have yet to result in FDA-approved medications for relapse prevention. To address this translational gap, we and others have developed rat models of relapse after voluntary abstinence from drug self-administration. One of these models is the electric barrier conflict model. Here, we introduce the model, and then review studies on behavioral and neuropharmacological mechanisms of cue-induced relapse and incubation of drug seeking (time-dependent increase in drug seeking during abstinence) after electric barrier-induced abstinence. We also briefly discuss future directions and potential clinical implications. One major conclusion of our review is that the brain mechanisms controlling drug relapse after electrical barrier-induced voluntary abstinence are likely distinct from those controlling relapse after homecage forced abstinence.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Abnormal functional asymmetry and its behavioural correlates in adults with ADHD: A TMS-EEG study.

OBJECTIVES: Abnormal functional brain asymmetry and deficient response inhibition are two core symptoms of attention deficit hyperactivity disorder (ADHD). We investigated whether these symptoms are inter-related and whether they are underlined by altered frontal excitability and by compromised interhemispheric connectivity. METHODS: We studied these issues in 52 ADHD and 43 non-clinical adults by comparing: (1) stop-signal reaction time (SSRT); (2) frontal asymmetry of the N200 event-related potential component, which is evoked during response inhibition and is lateralised to the right hemisphere; (3) TMS-evoked potential (TEP) in the right frontal hemisphere, which is indicative of local cortical excitability; and (4) frontal right-to-left interhemispheric TMS signal propagation (ISP), which is reversely indicative of interhemispheric connectivity. RESULTS: Compared to controls, the ADHD group demonstrated elongated SSRT, reduced N200 right-frontal-asymmetry, weaker TEP, and stronger ISP. Moreover, in the ADHD group, N200 right-frontal-asymmetry correlated with SSRT, with TEP, and with symptoms severity. Conversely, no relationship was observed between ISP and N200 right-frontal-asymmetry, and both TEP and ISP were found to be unrelated to SSRT. CONCLUSIONS: Our results indicate that abnormal frontal asymmetry is related to a key cognitive symptom in ADHD and suggest that it is underlined by reduced right-frontal excitability.

Brain stimulation therapeutics.

This chapter covers how repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) presently affects smoking cessation. 14 human studies have examined the efficacy of rTMS on cue craving, cigarette consumption, or smoking cessation using a variety of different coils, locations, and treatment parameters. These studies included 7 randomized-controlled trials (RCT) and 7 experimental studies. Most studies (12/14) reported that rTMS reduced cue-induced craving, 5 showed that it decreased cigarette consumption, and 3/4 reported that multiple sessions of rTMS increased the quit rate. In contrast to rTMS, tDCS has 6 RCT studies, of which only 2 studies reported that tDCS reduced craving, and only 1 reported that it reduced cigarette consumption. Three studies failed to find an effect of tDCS on cravings. No tDCS studies reported changing quitting rates in people who smoke. Despite the early positive results of tDCS on nicotine dependence symptoms, 2 larger RCTs recently failed to find a therapeutic effect of tDCS for smoking cessation. In conclusion, rTMS studies demonstrate that multiple sessions help quit smoking, and it has gained FDA approval for that purpose. However, more studies are needed to examine the effect of tDCS with different treatment parameters.

Revisiting the Rotational Field TMS Method for Neurostimulation.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that has shown high efficacy in the treatment of major depressive disorder (MDD) and is increasingly utilized for various neuropsychiatric disorders. However, conventional TMS is limited to activating only a small fraction of neurons that have components parallel to the induced electric field. This likely contributes to the significant variability observed in clinical outcomes. A novel method termed rotational field TMS (rfTMS or TMS 360°) enables the activation of a greater number of neurons by reducing the sensitivity to orientation. Recruitment of a larger number of neurons offers the potential to enhance efficacy and reduce variability in the treatment of clinical indications for which neuronal recruitment and organization may play a significant role, such as MDD and stroke. The potential of the method remains to be validated in clinical trials. Here, we revisit and describe in detail the rfTMS method, its principles, mode of operation, effects on the brain, and potential benefits for clinical TMS.