An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness.

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia.

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

The intervention, the patient and the illness - Personalizing non-invasive brain stimulation in psychiatry.

Current hypotheses on the therapeutic action of non-invasive brain stimulation (NIBS) in psychiatric disorders build on the abundant data from neuroimaging studies. This makes NIBS a very promising tool for developing personalized interventions within a precision medicine framework. NIBS methods fundamentally vary in their neurophysiological properties. They comprise repetitive transcranial magnetic stimulation (rTMS) and its variants (e.g. theta burst stimulation - TBS) as well as different types of transcranial electrical stimulation (tES), with the largest body of evidence for transcranial direct current stimulation (tDCS). In the last two decades, significant conceptual progress has been made in terms of NIBS targets, i.e. from single brain regions to neural circuits and to functional connectivity as well as their states, recently leading to brain state modulating closed-loop approaches. Regarding structural and functional brain anatomy, NIBS meets an individually unique constellation, which varies across normal and pathophysiological states. Thus, individual constitutions and signatures of disorders may be indistinguishable at a given time point, but can theoretically be parsed along course- and treatment-related trajectories. We address precision interventions on three levels: 1) the NIBS intervention, 2) the constitutional factors of a single patient, and 3) the phenotypes and pathophysiology of illness. With examples from research on depressive disorders, we propose solutions and discuss future perspectives, e.g. individual MRI-based electrical field strength as a proxy for NIBS dosage, and also symptoms, their clusters, or biotypes instead of disorder focused NIBS. In conclusion, we propose interleaved research on these three levels along a general track of reverse and forward translation including both clinically directed research in preclinical model systems, and biomarker guided controlled clinical trials. Besides driving the development of safe and efficacious interventions, this framework could also deepen our understanding of psychiatric disorders at their neurophysiological underpinnings.

Effects of deep transcranial magnetic stimulation (dTMS) on cognition.

Deep transcranial magnetic stimulation (dTMS) is a modern non-invasive brain stimulation method demonstrated as effective in the treatment of major depression and obsessive-compulsive disorder (OCD). This review aims to survey present knowledge concerning the cognitive function changes identified in dTMS research. A systematic literature search in PubMed and Google Scholar was performed and 23 out of 64 studies on dTMS and cognitive functioning were included in the review. Ten studies were conducted with patients with affective disorders, six with healthy participants, two with schizophrenia patients, two with OCD patients, and one study each with patients suffering from central neuropathic pain, autistic disorder, and attention deficit hyperactivity disorder. The best outcomes were obtained after 20 sessions of high-frequency dTMS with OCD patients, where, in addition to clinical improvement, patients showed amelioration of cognitive functions, specifically in cognitive control domains. The studies on patients with depression appear to show inconsistent results, from cognitive improvement in open-label studies to no improvement versus sham dTMS in controlled trials. Experimental research in healthy volunteers suggests an influence of dTMS on memory and self-agency, and also contain contradictory results. Most studies did not demonstrate a significant improvement in cognitive functioning. However, randomized sham-controlled trials with larger groups of medication-free patients and inclusion of functional imaging or electrophysiological recording connected with dTMS application are necessary for more detailed and confident conclusions concerning the effect of dTMS on cognitive functions.

Repetitive Transcranial Magnetic Stimulation as a Therapeutic and Probe in Schizophrenia: Examining the Role of Neuroimaging and Future Directions.

Schizophrenia is a complex condition associated with perceptual disturbances, decreased motivation and affect, and disrupted cognition. Individuals living with schizophrenia may experience myriad poor outcomes, including impairment in independent living and function as well as decreased life expectancy. Though existing treatments may offer benefit, many individuals still experience treatment resistant and disabling symptoms. In light of the negative outcomes associated with schizophrenia and the limitations in currently available treatments, there is a significant need for novel therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate the activity of discrete cortical regions, allowing direct manipulation of local brain activation and indirect manipulation of the target's associated neural networks. rTMS has been studied in schizophrenia for the treatment of auditory hallucinations, negative symptoms, and cognitive deficits, with mixed results. The field's inability to arrive at a consensus on the use rTMS in schizophrenia has stemmed from a variety of issues, perhaps most notably the significant heterogeneity amongst existing trials. In addition, it is likely that factors specific to schizophrenia, rather than the rTMS itself, have presented barriers to the interpretation of existing results. However, advances in approaches to rTMS as a biologic probe and therapeutic, many of which include the integration of neuroimaging with rTMS, offer hope that this technology may still play a role in improving the understanding and treatment of schizophrenia.

Time course of cortical response complexity during extended wakefulness and its differential association with vigilance in young and older individuals.

Characterization of the complexity of electroencephalogram (EEG) responses has provided important insights in cognitive function as well as in the brain bases of consciousness and vigilance. Whether brain response complexity changes during prolonged wakefulness and sleep deprivation -when vigilance level considerably varies- is not fully elucidated yet. In the present study, we repeatedly assessed EEG responses to transcranial magnetic stimulation (TMS) over 34 h of sleep deprivation under constant routine conditions in healthy younger (N = 13; 5 women; 18-30 y) and older (N = 12; 6 women; 50-70 y) individuals, while they were performing a vigilance task. Response complexity was computed both at the global (all scalp sensors) and local (sensors surrounding TMS hotspot) levels using the Lempel-Ziv algorithm. Response complexity was significantly higher in the older compared to the young volunteers over the entire protocol. Global complexity response significantly changed with time spent awake, with an increasing trend from the beginning to the middle of the biological night, followed by a decreasing trend from the middle of the biological night to the following afternoon. An unexpected different link between vigilance performance and brain response complexity was detected across age groups: higher response complexity was associated with lower performance in the older group, particularly in the morning sessions. These findings show that cortical activity complexity changes with vigilance variation, as experienced during sleep deprivation and circadian misalignment, in two age groups, with no evident time course difference across age-groups. Aside from classical linear EEG analyses, computation of Lempel-Ziv complexity provides additional insights on the neurophysiology of the processes associated with vigilance and their modifications throughout ageing.

Clinical Benefit of Rehabilitation Training in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury. SUMMARY OF BACKGROUND DATA: Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial. METHODS: Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software. RESULTS: Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls. CONCLUSION: Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.Level of Evidence: 1.

Feasibility of TMS in patients with new generation cochlear implants.

OBJECTIVE: The presence of a cochlear implant is being considered an absolute contraindication for experiments and/or treatments. We aimed to verify TMS (Transcranial Magnetic Stimulation) compatibility of a new generation of cochlear implants. METHODS: In a series of experiments, we test if MED-EL cochlear implants -compatible with stable fields of magnetic resonance imaging scanning- are fully resistant even to rapidly varying magnetic fields as those generated by single pulses and low and high-frequency trains of repetitive TMS (rTMS) applied with a figure of eight coil and different magnetic stimulators. RESULTS: With a TMS intensity equal or below 2.2 Tesla (T) the cochlear implant and all its electronic components remain fully functional, even when the combination of frequency, intensity and number of pulses exceeds the currently available safety guidelines. Induced forces on the implant are negligible. With higher magnetic fields (i.e., 3.2 T), one device was corrupted. CONCLUSIONS: Results exclude the risk of electronic damaging, demagnetizing or displacements of the studied cochlear implants when exposed to magnetic fields of up to 2.2 T delivered through a focal coil. SIGNIFICANCE: They open the way to use focal rTMS protocols with the aim of promoting neural plasticity in auditory networks, possibly helping the post-implant recovery of speech perception performance.

Repetitive transcranial magnetic stimulation for major depression: A naturalistic observational study in an Australian private hospital.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depression, which is now as a mainstream treatment in clinical practice. However, there is limited data concerning its use in Australian private psychiatric hospital settings. This retrospective study examined routinely collected data of 153 inpatients, who received 20 rTMS treatments over four weeks. Primary outcomes measures were the 17-item Hamilton Depression Rating Scale (HAMD-17) and the 21-item Depression, Anxiety and Stress Scale (DASS-21). At post-treatment, response and remission rates were 54% and 28%, respectively, for the HAMD-17; and 53% response and 16% remission rates, for the DASS-21 Depression subscale, respectively. Although no gender differences were observed, younger patients demonstrated more improvements during acute rTMS but the effect was not significant after accounting for pre-treatment symptom severity. The findings of this naturalistic study suggest that an acute course of rTMS provided in private clinical settings resulted in similar response and remission rates to longer rTMS courses. Shorter rTMS courses appear to have satisfactory efficacy in treating major depression, in clinically diverse and real-world practice.

[Non-invasive brain stimulation for the treatment of depression]. / Niet-invasieve hersenstimulatie als behandeling voor depressie.

Depression is one of the most common psychiatric disorders and is a heavy burden, not only for the patient and his or her environment but also in economic and social terms. 35% of depressed patients do not recover after standard treatment with medication or psychotherapy. There is a need for more effective treatment options for depression. In recent decades, new forms of brain stimulation have been developed for the treatment of depression, the most important of which is transcranial magnetic stimulation (TMS). TMS uses magnetic pulses to influence brain activity. Meta-analyses show approximately 30-40% of patients respond to treatment with repetitive TMS. The depression goes into remission in about 20-30% of cases. Research has led to new treatment protocols and variations on the conventional TMS method. More research into the effectiveness of these developments is needed. We recommend using TMS as an add-on treatment more often when the patient has completed two steps of the treatment guideline.

LTP-like cortical plasticity predicts conversion to dementia in patients with memory impairment.

BACKGROUND: New diagnostic criteria consider Alzheimer's disease (AD) as a clinico-biological entity identifiable in vivo on the presence of specific patterns of CSF biomarkers. OBJECTIVE: Here we used transcranial magnetic stimulation to investigate the mechanisms of cortical plasticity and sensory-motor integration in patients with hippocampal-type memory impairment admitted for the first time in the memory clinic stratified according to CSF biomarkers profile. METHODS: Seventy-three patients were recruited and divided in three groups according to the new diagnostic criteria: 1) Mild Cognitive Impaired (MCI) patients (n = 21); Prodromal AD (PROAD) patients (n = 24); AD with manifest dementia (ADD) patients (n = 28). At time of recruitment all patients underwent CSF sampling for diagnostic purposes. Repetitive and paired-pulse transcranial magnetic stimulation protocols were performed to investigate LTP-like and LTD-like cortical plasticity, short intracortical inhibition (SICI) and short afferent inhibition (SAI). Patients were the followed up during three years to monitor the clinical progression or the conversion to dementia. RESULTS: MCI patients showed a moderate but significant impairment of LTP-like cortical plasticity, while ADD and PROAD groups showed a more severe loss of LTP-like cortical plasticity. No differences were observed for LTD-like cortical plasticity, SICI and SAI protocols. Kaplan-Meyer analyses showed that PROAD and MCI patients converting to dementia had weaker LTP-like plasticity at time of first evaluation. CONCLUSION: LTP-like cortical plasticity could be a novel biomarker to predict the clinical progression to dementia in patients with memory impairment at prodromal stages of AD identifiable with the new diagnostic criteria based on CSF biomarkers.

Repetitive transcranial magnetic stimulation in traumatic brain injury: Evidence from animal and human studies.

We provide here the first systematic review on the studies dealing with repetitive transcranial magnetic stimulation (rTMS) for traumatic brain injury (TBI) in animals and humans. Several experimental studies in animal models have explored with promising results the use of rTMS to enhance neuroprotection and recovery after TBI. However, there are surprisingly few studies that have obtained substantial evidence regarding effects of rTMS in humans with TBI, many of them are case reports investigating the heterogeneous conditions linked to TBI. The most studies have investigated the effects of rTMS in subjects with post-traumatic depression and variable effects have been observed. rTMS has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC), but in subjects with TBI therapeutic effects on DOC have also been variously documented. Beneficial effects have been reported in subjects with cognitive/emotional disturbances and auditory dysfunction (tinnitus and hallucinations), although the results are somewhat conflicting. rTMS applied over the left prefrontal cortex may relieve, at least transiently, post-traumatic headache. Isolated rTMS studies have been performed in TBI patients with motor impairment, chronic dizziness or pain. Especially whether provided in combination, rTMS and neurorehabilitation may be synergistic in the potential to translate experimental findings in the clinical practice. In order to reach definitive conclusions, well-designed randomized controlled studies with larger patient samples, improved design and optimized rTMS setup, are warranted to verify and corroborate the initial promising findings.

Non-invasive Brain Stimulation for Alcohol Use Disorders: State of the Art and Future Directions.

Alcohol use disorders remain one of the leading causes of mortality and morbidity across the world, yet despite this impact, there are few treatment options for patients suffering from these disorders. To this end, non-invasive brain stimulation, most commonly utilizing technologies including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has recently emerged as promising potential treatments for alcohol use disorders. Enthusiasm for these interventions is fueled by their non-invasive nature, generally favorable safety profile, and ability to target and modulate brain regions implicated in substance use disorders. In this paper, we describe the underlying principles behind these commonly used stimulation technologies, summarize existing experiments and randomized controlled trials, and provide an integrative summary with suggestions for future areas of research. Currently available data generally supports the use of non-invasive brain stimulation as a near-term treatment for alcohol use disorder, with important caveats regarding the use of stimulation in this patient population.

The Value of Preoperative Planning Based on Navigated Transcranical Magnetic Stimulation for Surgical Treatment of Brain Metastases Located in the Perisylvian Area.

BACKGROUND: Brain metastases are the most common neoplasms in adults. When brain metastases are located in eloquent areas, their treatment still seems controversial and not clearly defined. It is therefore essential to provide correct preoperative planning to better define extension and characterization of brain metastasis. METHODS: We retrospectively looked for the tumor database of our institution, patients with single brain metastasis, located in the sylvian area, who underwent resection with the support of intraoperative neurophysiologic monitoring between 2008 and 2018. RESULTS: We retrieved data for 30 adults, each with a single brain metastasis that was located in the sylvian area, including the insula and the lower portion of the motor cortex. Neuronavigation and the intraoperative visualization of the navigated transcranial magnetic stimulation-based reconstruction of functional networks were used to delineate the ideal trajectory toward the lesion. The Karnofsky Performance Status significantly improved in the postoperative period. CONCLUSIONS: The correct planning of brain metastasis allows more secure removal of the neoplastic lesion, avoiding and/or reducing the appearance of neurologic deficits. Navigated transcranial magnetic stimulation represents a new method that can promote a more complete and safer resection of the metastatic lesion in eloquent areas. An optimal surgical result, in the absence of postoperative neurologic deficits, allows the patient to undertake adjuvant therapy able to prolong survival.

Efficacy and tolerability of deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the efficacy of deep transcranial magnetic stimulation (dTMS) for treatment-resistant depression (TRD). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Medline, PsycINFO, Embase, and Cochrane Library were systematically searched from the time of their inception until July 17, 2019. Data were pooled using a random-effects model. Primary outcomes were mean change of depression and anxiety severity. Secondary outcomes were response and remission rate of depression. RESULTS: Fifteen studies including three randomized controlled trials (RCTs) (n = 417, mean age: 50.6 years) and twelve uncontrolled clinical trials (n = 284, mean age: 46.4 years) were included. dTMS significantly improved the depressive (Hedges' g = -1.323, 95% CI = -1.651 to -0.995, p < .001) and anxiety symptoms (Hedges' g = -1.282, 95% CI = -1.514 to -1.051, p < .001) in patients with TRD. Subgroup analysis showed that non-RCTs had a larger effect size than RCTs (-1.461 vs -0.756) on depression severity. Although the response and remission rates of the dTMS group were high, only studies using both dTMS and antidepressant medications achieved significance. The anxiolytic effect of dTMS was more heterogeneous, and the results were obtained mainly from non-RCTs. Importantly, the dTMS group showed favorable tolerability without major adverse events. CONCLUSIONS: dTMS is a safe and effective intervention in patients with TRD. Studies combining dTMS and antidepressant medications seemed to show greater therapeutic effects. Future studies are needed to address the interaction effect of dTMS with different classes of antidepressant medications.

Effects of concomitant neuromuscular electrical stimulation during repetitive transcranial magnetic stimulation before repetitive facilitation exercise on the hemiparetic hand.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and Repetitive facilitative exercise (RFE) improves motor impairment after stroke. OBJECTIVE: To investigate whether neuromuscular electrical stimulation (NMES) can facilitate the effects of rTMS and RFE on the function of the hemiparetic hand in stroke patients. METHODS: This randomized double-blinded crossover study divided 20 patients with hemiparesis into two groups and provided treatment for 4 weeks at 5 days/week. NMES-before-sham group and NMES-following-sham group performed NMES sessions and sham NMES sessions for each 2 weeks. Patients received NMES or sham NMES for the affected extensor muscle concurrently with 1 Hz rTMS for the unaffected motor cortex for 10 min and performed RFE for 60 min. The Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), Box and Block Test (BBT) and Modified Ashworth Scale (MAS) were used for evaluation. RESULTS: FMA and ARAT improved significantly during both sessions. The gains in the BBT during an NMES session were significantly greater than those during a sham NMES session. MAS for the wrist and finger significantly decreased only during an NMES session. CONCLUSIONS: NMES combined with rTMS might facilitate, at least in part, the beneficial effects of RFE on motor function and spasticity of the affected upper limb.

Anhedonia across borders: Transdiagnostic relevance of reward dysfunction for noninvasive brain stimulation endophenotypes.

INTRODUCTION: Anhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its neural correlates and to explore its potential relevance as a predictor of treatment response, in this article we systematically reviewed studies involving anhedonia and neuromodulation interventions, across different disorders. METHODS: We included seven studies fulfilling inclusion/exclusion criteria and involving different measures of anticipatory and consummatory anhedonia, as well as different noninvasive brain stimulation interventions (transcranial magnetic stimulation and transcranial direct current stimulation). Studies not exploring hedonic measures or not involving neuromodulation intervention were excluded. RESULTS: All the included studies entailed the use of rTMS protocols in one of the diverse prefrontal targets. The limited amount of studies and the heterogeneity of stimulation protocols did not allow to draw any conclusion with regard to the efficacy of rTMS in the treatment of transnosographic anhedonia. A potential for anhedonia in dissecting possible endophenotypes of different psychopathological conditions preliminarily emerged. CONCLUSIONS: Anhedonia is an underexplored condition in neuromodulation trials. It may represent a valuable transdiagnostic dimension that requires further examination in order to discover new clinical predictors for treatment response.

The effects of repetitive transcranial magnetic stimulation on body weight and food consumption in obese adults: A randomized controlled study.

BACKGROUND: Although some studies have reported significant reductions in food cravings following the single-session of repetitive transcranial magnetic stimulation (rTMS), there is little research on the effects of multi-session of rTMS on food consumption and body weight in obese subjects. OBJECTIVE: We conducted 4-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of rTMS on body weight in obese adults. METHODS: Forty-three obese patients (body mass index [BMI] ≥25 kg/m2) aged between 18 and 70 years were randomized to the sham or real treatment group (21 in the TMS group and 22 in the sham treatment group). A total of 8 sessions of rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) was provided over a period of 4 weeks. The primary outcome measure was weight change in kilograms from baseline to 4 weeks. Secondary endpoints included changes in anthropometric measures, cardiovascular risk factors, food intake, and appetite. RESULTS: Participants in the rTMS group showed significantly greater weight loss from baseline following the 8 session of rTMS (-2.75 ±â€¯2.37 kg vs. 0.38 ±â€¯1.0 kg, p < 0.01). Consistent with weight loss, there was a significant reduction in fat mass and visceral adipose tissue at week 4 in the rTMS group compared with the control group (p < 0.01). After the 8 sessions of rTMS, the TMS group consumed fewer total kilocalories and carbohydrates per day than the control group (p < 0.05). CONCLUSIONS: 8 sessions of HF rTMS delivered to the left DLPFC were effective in inducing weight loss and decreasing food intake in obese patients. TRIAL REGISTRATION: Clinical trial registered with the Clinical Trials Registry at http://cris.cdc.go.kr (KCT0002548).

The relationship between individual alpha peak frequency and clinical outcome with repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD).

BACKGROUND: The individual α frequency (IAF) has been associated with the outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD), but the association has been inconsistent. HYPOTHESIS: Proximity of IAF to the stimulation frequency, rather than the value of IAF per se, is associated with outcome for patients receiving 10 Hz rTMS. METHODS: We examined the relationships between IAF, rTMS stimulation frequency, and treatment outcome in 147 patients. All patients initially received 10 Hz rTMS unilateral treatment delivered to left dorsolateral prefrontal cortex (DLPFC) (10UL), with subsets of patients changed to unilateral 5 Hz to left DLPFC (5UL) or sequential bilateral (SB) stimulation (10 Hz/1Hz) to left and right DLPFC based upon worsening symptoms with or intolerance of 10UL. Outcome was percent change in total score on the Inventory of Depressive Symptomatology - Self Report (IDS-SR) scale from pre-treatment baseline to the 30th treatment. IAF values and absolute difference between IAF and 10 Hz (|IAF-10Hz|) were examined in relation to outcome for the overall sample and for each stimulation group separately. RESULTS: There was no correlation between IAF value, or |IAF-10Hz| and outcome in the overall sample. ANCOVA showed a significant interaction between IAF measures and treatment type. Post-hoc analyses revealed that IAF and |IAF-10Hz| were both significantly associated with degree of improvement (IDS-SR % change) for patients who received 10UL (P < 0.01) but not 5UL or SB stimulation. There was a trend-level difference in IAF between responders and non-responders only within the 10 Hz group, but not within the other treatment groups (n.s.). For the 10UL group, membership in the highest IAF quartile was associated with significantly greater clinical improvement than membership in the lowest IAF quartile (p = 0.0034). CONCLUSIONS: IAF measures were associated with clinical outcome of patients treated with 10UL but not 5UL or SB rTMS treatment. This suggests that interactions between endogenous frequencies and treatment outcome may be related to the selected stimulation parameters and/or physiologic and clinical characteristics of patients who benefit from those parameters.