Improved naming in patients with Broca's aphasia with tDCS.

BACKGROUND: Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type). METHODS: This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment. RESULTS: Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F(1)=4.23, p=0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit (R=0.35, p=0.03). CONCLUSIONS: These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies.

Is an uncomplicated postoperative recovery following total pelvic exenteration a more important prognostic factor than achieving R0 in the first 2 years?

AIM: Total pelvic exenteration (TPE) can achieve an R0 resection in locally advanced and recurrent rectal cancer (LARC and RRC) and remains the only curative option. The resultant high morbidity creates prolonged complex recoveries, rendering patients unfit for adjuvant chemotherapy. This study aims to evaluate the impact of this on overall survival (OS) and disease-free survival (DFS) as it has not been studied previously. METHOD: This is a retrospective single-centre study from 2017 to 2021 evaluating patients with LARC or RRC who underwent a curative TPE. Demographics, oncological history, perioperative data [using Clavien-Dindo (CD) scoring], disease recurrence and mortality were analysed using multivariate Cox regression to assess the impact of variables on DFS and OS. RESULTS: A total of 120 patients were included with a median follow-up of 3 years. 28% of patients received adjuvant chemotherapy, 27.5% had surgical follow-up and 44% missed systemic treatment. Missed treatment was predominantly due to prolonged recovery or poor performance status (59%). Patients who missed adjuvant chemotherapy experienced significantly higher CD scores (p = 0.0031), reintervention rates (p=0.0056) and further related surgeriesp (p = 0.0314). Missing adjuvant chemotherpy is a significant factor for poorer survival, with almost a three times higher mortality (p=0.0096, hazard ratio 2.7). R status was not a significant factor for OS following multivariate analysis (p = 0.336), indicating that another factor has an impact on survival within the first 2 years. CONCLUSIONS: In the initial 2 years after exenteration, an uncomplicated postoperative recovery allows for the delivery of adjuvant chemotherapy, prolonging survival. R0/R1 status was not the main prognostic factor. Longer follow-up and further multivariate analysis may influence decisions about aggressive R0 resection balanced against the patient being fit for chemotherapy postoperatively.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Time for Brain Medicine.

Unprecedented knowledge of the brain is inevitably contributing to the convergence of neurology and psychiatry. However, clinical training continues to follow a divergent approach established in the 19th century. An etiological approach will continue to shift more psychiatric patients to the care of neurologists who are untrained in psychiatric management. At the same time, this new era of diagnostic biomarkers and neuroscience-based precision treatments requires skills not readily available to those trained in psychiatry. The challenges in training the next generation of doctors include establishing competence involving aspects of the whole brain, fostering the subspecialized expertise needed to remain current, and developing programs that are feasible in duration and practical in implementation. A new 4-year residency training program proposed in this article could replace existing residency programs. The program includes 2 years of common and urgent training in various aspects of neurology and psychiatry followed by 2 years of elective subspecialty tracks. The concept is similar to internal medicine residencies and fellowships. No changes to existing departmental structures are necessary. In concert with the emerging biological approach to the brain, "brain medicine" is proposed as a new name to denote this practice in the simplest terms: a focus on all aspects of the brain.

Differences in quality of life of patients undergoing total pelvic exenteration compared with standard rectal cancer surgery: a scoping review.

AIM: Rectal cancer is often treated surgically with an anterior resection (AR) or abdominoperineal excision (APE). However, for patients with locally advanced disease or local recurrence total pelvic exenteration (TPE) surgery can be performed. The magnitude of surgery varies, and little research has been done to consider how quality of life (QoL) may vary according to the extent of surgery. METHOD: A search was conducted on MEDLINE and PubMed for papers published from 2010 to 2021. Inclusion criteria consisted of observational studies comparing adult populations with rectal cancer undergoing APE, AR or TPE, reporting QoL using validated tools. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Outcomes of interest were global QoL, gastrointestinal (GI) symptoms (nausea and vomiting, diarrhoea, and constipation) and pain. RESULTS: Seven studies including 1402 patients were analysed. QoL following TPE generally improves over time, back to baseline or better. AR and APE groups have similar patterns of improvement between baseline and 12 months after surgery, although scores declined in some studies at 12 months. TPE scores are lower overall, and the pattern of improvement differs, with patients tending to have worse nausea and vomiting symptoms. AR and APE patients tend to experience more lower GI symptoms. CONCLUSION: It is not possible to draw firm conclusions based on the studies analysed. However, QoL returns to baseline following TPE, APE and AR. Preoperative QoL appears to be an indication of postoperative outcomes. Further observational studies are required.

Neurosurgery for psychiatric disorders: reviewing the past and charting the future.

Surgical techniques targeting behavioral disorders date back thousands of years. In this review, the authors discuss the history of neurosurgery for psychiatric disorders, starting with trephination in the Stone Age, progressing through the fraught practice of prefrontal lobotomy, and ending with modern neurosurgical techniques for treating psychiatric conditions, including ablative procedures, conventional deep brain stimulation, and closed-loop neurostimulation. Despite a tumultuous past, psychiatric neurosurgery is on the cusp of becoming a transformative therapy for patients with psychiatric dysfunction, with an ever-increasing evidence base suggesting reproducible and ethical therapeutic benefit.

Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (taVNS) may be useful in treating disorders characterized by chronic parasympathetic disinhibition. Acute taVNS decreases resting heart rate in healthy individuals, but little is known regarding the effects of taVNS on the cardiac response to an acute stressor. To investigate effects on the acute stress response, we investigated how taVNS affected heart rate changes during a cold pressor test (CPT), a validated stress induction technique that reliably elicits a sympathetic stress response with marked increases in heart rate, anxiety, stress, and pain. MATERIALS AND METHODS: We recruited 24 healthy adults (ten women, mean age = 29 years) to participate in this randomized, crossover, exploratory trial. Each subject completed two taVNS treatments (one active, one sham) paired with CPTs in the same session. Order of active versus sham stimulation was randomized. Heart rate, along with ratings of anxiety, stress, and pain, was collected before, during, and after each round of taVNS/sham + CPT. RESULTS: In both stimulation conditions, heart rate was elevated from baseline in response to the CPT. Analyses also revealed a difference between active and sham taVNS during the first 40 seconds of the CPT (Δ heart rate [HR] = 12.75 ± 7.85 in the active condition; Δ HR = 16.09 ± 11.43 in the sham condition, p = 0.044). There were no significant differences in subjective ratings between active and sham taVNS. CONCLUSIONS: In this randomized, sham-controlled study, taVNS attenuated initial increases in HR in response to the CPT. Future studies are needed to investigate the effects of various taVNS doses and parameters on the CPT, in addition to other forms of stress induction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT00113453.

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury.

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.

The evidence is in: Repetitive transcranial magnetic stimulation is an effective, safe and well-tolerated treatment for patients with major depressive disorder.

Despite more than 25 years of research establishing the antidepressant efficacy of repetitive transcranial magnetic stimulation, there remains uncertainty about the depth and breadth of this evidence base, resulting in confusion as to where repetitive transcranial magnetic stimulation fits in the therapeutic armamentarium in the management of patients with mood disorders. The purpose of this article is to provide a concise description of the evidence base supporting the use of repetitive transcranial magnetic stimulation in the context of the stages of research that typically accompanies the development of evidence for a new therapy. The antidepressant efficacy for the use of repetitive transcranial magnetic stimulation in the treatment of depression has been established through a relatively traditional pathway beginning with small case series, progressing to single-site clinical trials and then to larger multisite randomised double-blind controlled trials. Antidepressant effects have been confirmed in numerous meta-analyses followed more recently by large network meta-analysis and umbrella reviews, with evidence that repetitive transcranial magnetic stimulation may have greater efficacy than alternatives for patients with treatment-resistant depression. Finally, repetitive transcranial magnetic stimulation has been shown to produce meaningful response and remission rates in real-world samples of greater than 5000 patients. The evidence for the antidepressant efficacy of repetitive transcranial magnetic stimulation therapy is overwhelming, and it should be considered a routine part of clinical care wherever available.

Synaptic Plasticity 101: The Story of the AMPA Receptor for the Brain Stimulation Practitioner.

The fields of Neurobiology and Neuromodulation have never been closer. Consequently, the phrase "synaptic plasticity" has become very familiar to non-basic scientists, without actually being very familiar. We present the "Story of the AMPA receptor," an easy-to-understand "10,000 ft" narrative overview of synaptic plasticity, oriented toward the brain stimulation clinician or scientist without basic science training. Neuromodulation is unparalleled in its capacity to both modulate and probe plasticity, yet many are not comfortable with their grasp of the topic. Here, we describe the seminal discoveries that defined the canonical mechanisms of long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity. We then provide a conceptual framework for how plasticity at the synapse is accomplished, describing the functional roles of N-methyl-d-aspartate (NMDA) receptors and calcium, their effect on calmodulin, phosphatases (ie, calcineurin), kinases (ie, calcium/calmodulin-dependent protein kinase [CaMKII]), and structural "scaffolding" proteins (ie, post-synaptic density protein [PSD-95]). Ultimately, we describe how these affect the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor. More specifically, AMPA receptor delivery to (LTP induction), removal from (LTD), or recycling within (LTP maintenance) the synapse is determined by the status of phosphorylation and protein binding at specific sites on the tails of AMPA receptor subunits: GluA1 and GluA2. Finally, we relate these to transcranial magnetic stimulation (TMS) treatment, highlighting evidences for LTP as the basis of high-frequency TMS therapy, and briefly touch on the role of plasticity for other brain stimulation modalities. In summary, we present Synaptic Plasticity 101 as a singular introductory reference for those less familiar with the mechanisms of synaptic plasticity.

Electric Field Strength From Prefrontal Transcranial Direct Current Stimulation Determines Degree of Working Memory Response: A Potential Application of Reverse-Calculation Modeling?

BACKGROUND: Transcranial direct current stimulation (tDCS) for working memory is an enticing treatment, but there is mixed evidence to date. OBJECTIVES: We tested the effects of electric field strength from uniform 2 mA dosing on working memory change from prestimulation to poststimulation. Second, we statistically evaluated a reverse-calculation method of individualizing tDCS dose and its effect on normalizing electric field at the cortex. MATERIALS AND METHODS: We performed electric field modeling on a data set of 28 healthy older adults (15 women, mean age = 73.7, SD = 7.3) who received ten sessions of active 2 mA tDCS (N = 14) or sham tDCS (N = 14) applied over bilateral dorsolateral prefrontal cortices (DLPFC) in a triple-blind design. We evaluated the relationship between electric field strength and working memory change on an N-back task in conditions of above-median, high electric field from active 2 mA (N = 7), below-median, low electric field from active 2 mA (N = 7), and sham (N = 14) at regions of interest (ROI) at the left and right DLPFC. We then determined the individualized reverse-calculation dose to produce the group average electric field and measured the electric field variance between uniform 2 mA doses vs individualized reverse-calculation doses at the same ROIs. RESULTS: Working memory improvements from pre- to post-tDCS were significant for the above-median electric field from active 2 mA condition at the left DLPFC (mixed ANOVA, p = 0.013). Furthermore, reverse-calculation modeling significantly reduced electric field variance at both ROIs (Levene's test; p < 0.001). CONCLUSIONS: Higher electric fields at the left DLPFC from uniform 2 mA doses appear to drive working memory improvements from tDCS. Individualized doses from reverse-calculation modeling significantly reduce electric field variance at the cortex. Taken together, using reverse-calculation modeling to produce the same, high electric fields at the cortex across participants may produce more effective future tDCS treatments for working memory.

Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression.

BACKGROUND: Although repetitive transcranial magnetic stimulation ('TMS') is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran's Health Administration. METHODS: Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at 'baseline' pre-TMS commencement, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. DISCUSSION: To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663481 , December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

The Effects of Focal Electrically Administered Seizure Therapy Compared With Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy on Suicidal Ideation: A 2-Site Clinical Trial.

BACKGROUND: Preliminary data suggest that focal electrically administered seizure therapy (FEAST) has antidepressant effects and less adverse cognitive effects than traditional forms of electroconvulsive therapy (ECT). This study compared the impact of FEAST and ultrabrief pulse, right unilateral (UB-RUL) ECT on suicidal ideation. METHODS: At 2 sites, patients in a major depressive episode were treated openly with FEAST or UB-RUL ECT, depending on their preference. The primary outcome measure was scores on the Beck Scale for Suicide Ideation (SSI). Scores on the suicide item of the Hamilton Rating Scale for Depression (HRSD-SI) provided a secondary outcome measure. RESULTS: Thirty-nine patients were included in the intent-to-treat sample (FEAST, n = 20; UB-RUL ECT, n = 19). Scores on both the SSI and HRSD-SI were equivalently reduced with both interventions. Both responders and nonresponders to the interventions showed substantial reductions in SSI and HRSD-SI scores, although the magnitude of improvement was greater among treatment responders. CONCLUSIONS: Although limited by the open-label, nonrandomized design, FEAST showed comparable effects on suicidal ideation when compared with routine use of UB-RUL ECT. These results are encouraging and support the need for further research and a noninferiority trial.

Contributions of posttraumatic stress disorder (PTSD) and mild TBI (mTBI) history to suicidality in the INTRuST consortium.

OBJECTIVE: Mild TBI (mTBI) and posttraumatic stress disorder (PTSD) are independent risk factors for suicidal behaviour (SB). Further, co-occurring mTBI and PTSD increase one's risk for negative health and psychiatric outcomes. However, little research has examined the role of comorbid mTBI and PTSD on suicide risk. METHODS: The present study utilized data from the Injury and TRaUmatic STress (INTRuST) Consortium to examine the prevalence of suicidal ideation (SI) and behaviours among four groups: 1) comorbid mTBI+PTSD, 2) PTSD only, 3) mTBI only, and 4) healthy controls. RESULTS: Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI+PTSD was 40%, 25%, and 19%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with PTSD only was 29%, 11%, and 11%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI only was 14%, 1%, and 2%, respectively. Group comparisons showed that individuals with mTBI alone experienced elevated rates of lifetime SI compared to healthy controls. History of mTBI did not add significantly to risk for suicidal ideation and behaviour beyond what is accounted for by PTSD. CONCLUSION: Findings suggest that PTSD seems to be driving risk for suicidal behaviour.

Use of imperceptible wrist vibration to modulate sensorimotor cortical activity.

Peripheral sensory stimulation has been used as a method to stimulate the sensorimotor cortex, with applications in neurorehabilitation. To improve delivery modality and usability, a new stimulation method has been developed in which imperceptible random-frequency vibration is applied to the wrist concurrently during hand activity. The objective of this study was to investigate effects of this new sensory stimulation on the sensorimotor cortex. Healthy adults were studied. In a transcranial magnetic stimulation (TMS) study, resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation for the abductor pollicis brevis muscle were compared between vibration on vs. off, while subjects were at rest. In an electroencephalogram (EEG) study, alpha and beta power during rest and event-related desynchronization (ERD) for hand grip were compared between vibration on vs. off. Results showed that vibration decreased EEG power and decreased TMS short-interval intracortical inhibition (i.e., disinhibition) compared with no vibration at rest. Grip-related ERD was also greater during vibration, compared to no vibration. In conclusion, subthreshold random-frequency wrist vibration affected the release of intracortical inhibition and both resting and grip-related sensorimotor cortical activity. Such effects may have implications in rehabilitation.

An Exploration of Smoking-to-Vaping Transition Attempts Using a "Smart" Electronic Nicotine Delivery System.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) are used to aid smoking cessation attempts; however, many smokers continue to smoke while using an ENDS (dual use). Although uncertainty remains regarding whether specific ENDS patterns hinder or support successful smoking cessation, recent advances in "smart" technology allow passive and active recording of behaviors in real time, enabling more detailed insights into how smoking and vaping patterns may coevolve. We describe patterns of ENDS initiation, and subsequent use, including any changes in cigarette consumption, among daily smokers using a "smart" ENDS (S-ENDS) to quit smoking. METHOD: An 8-week long mixed-methods feasibility study used Bluetooth-enabled S-ENDS that passively recorded real-time device use by participants (n = 11). Daily surveys administered via smartphones collected data on self-reported cigarette consumption. RESULTS: All 11 participants were dual users, at least initially, during their quit attempt. We observed three provisional vaping and smoking patterns: immediate and intensive ENDS initiation coupled with immediate, dramatic, and sustained smoking reduction, leading to smoking abstinence; gradual ENDS uptake with gradual smoking reductions, leading to daily dual use throughout the study period; and ENDS experimentation with return to exclusive smoking. For six participants, the patterns observed in week 1 were similar to the vaping and smoking patterns observed throughout the rest of the study period. CONCLUSION: Technological advances now allow fine-grained description of ENDS use and smoking patterns. Larger and longer studies describing smoking-to-vaping patterns, and estimating associations with smoking outcomes, could inform ENDS-specific cessation advice promoting full transition from smoking to exclusive ENDS use. IMPLICATIONS: The use of an S-ENDS that recorded real-time device use among daily smokers engaged in a quit attempt provides insight into patterns and trajectories of dual use (continuing to smoke while using ENDS), and the possible associations between ENDS initiation, subsequent use, and smoking cessation outcomes. Such work could support more targeted cessation counseling and technical advice for smokers using ENDS to quit smoking, reduce the risk of users developing long-term dual use patterns, and enhance the contributions ENDS may make to reducing smoking prevalence.

Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder.

OBJECTIVES: This is a small preliminary but novel study assessing the feasibility of repetitive transcranial magnetic stimulation (rTMS) delivery to veterans with posttraumatic stress disorder (PTSD) while they simultaneously receive prolonged exposure (PE) therapy. METHODS: A prospective, randomized, double-blinded, active sham-controlled design combined weekly sessions of rTMS and standard PE at the Veterans Administration Hospital. Eight adult patients received a full course of protocol-driven PE therapy and were randomly assigned to receive either rTMS or sham rTMS. Repetitive transcranial magnetic stimulation was delivered to the right or left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hz, 5-second train duration, and 10-second intertrain interval for 30 minutes (6000 pulses) weekly for 5 weeks (30,000 stimuli). RESULTS: Of the 12 veterans consented, 8 completed the study treatment protocol. The dropout rate was 34%, roughly equivalent to the pooled average dropout rates observed in traditional PE therapy with Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, suggesting that veterans had no difficulty tolerating the addition of rTMS to PE therapy and that this is a feasible study design for larger trials in the future. Clinician-Administered PTSD Symptom scores reflected a general nonsignificant trend toward improvement, and subjects with comorbid major depression appeared to experience significant antidepressant benefit with treatment despite the fact that the doses used in this protocol were much smaller than those used to treat patients with major depressive disorder. CONCLUSIONS: This pilot study demonstrates the safety and feasibility of rTMS delivery to PTSD patients while they simultaneously receive PE. This unique approach to the treatment of PTSD highlights the need for further studies with larger sample sizes to assess treatment outcomes.

Transcranial Magnetic Stimulation (TMS) in the Elderly.

PURPOSE OF REVIEW: This article aims to review select applications of Transcranial Magnetic Stimulation (TMS) that have significant relevance in geriatric psychiatry. RECENT FINDINGS: Small study sizes and parameter variability limit the generalizability of many TMS studies in geriatric patients. Additionally, geriatric patients have unique characteristics that can moderate the efficacy of TMS. Nonetheless, several promising experimental applications in addition to the FDA-approved indication for major depression have emerged. Cognitive impairment, neuropathic pain, and smoking cessation are experimental applications with special significance to the elderly. Cognitive impairment has been researched the most in this population and evidence thus far suggests that TMS has potential therapeutic benefit. There is also evidence to suggest benefit from TMS for neuropathic pain and smoking cessation in working age adults. TMS is consistently reported as a safe and well-tolerated treatment modality with no adverse cognitive side effects. TMS is a safe treatment modality that can be effective for certain applications in the elderly. Additional research that specifically includes older subjects is needed to replicate findings and to optimize treatment protocols for this population.

Effects of Combining a Brief Cognitive Intervention with Transcranial Direct Current Stimulation on Pain Tolerance: A Randomized Controlled Pilot Study.

Objective: Cognitive behavioral therapy has been shown to be effective for treating chronic pain, and a growing literature shows the potential analgesic effects of minimally invasive brain stimulation. However, few studies have systematically investigated the potential benefits associated with combining approaches. The goal of this pilot laboratory study was to investigate the combination of a brief cognitive restructuring intervention and transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex in affecting pain tolerance. Design: Randomized, double-blind, placebo-controlled laboratory pilot. Setting: Medical University of South Carolina. Subjects: A total of 79 healthy adult volunteers. Methods: Subjects were randomized into one of six groups: 1) anodal tDCS plus a brief cognitive intervention (BCI); 2) anodal tDCS plus pain education; 3) cathodal tDCS plus BCI; 4) cathodal tDCS plus pain education; 5) sham tDCS plus BCI; and 6) sham tDCS plus pain education. Participants underwent thermal pain tolerance testing pre- and postintervention using the Method of Limits. Results: A significant main effect for time (pre-post intervention) was found, as well as for baseline thermal pain tolerance (covariate) in the model. A significant time × group interaction effect was found on thermal pain tolerance. Each of the five groups that received at least one active intervention outperformed the group receiving sham tDCS and pain education only (i.e., control group), with the exception of the anodal tDCS + education-only group. Cathodal tDCS combined with the BCI produced the largest analgesic effect. Conclusions: Combining cathodal tDCS with BCI yielded the largest analgesic effect of all the conditions tested. Future research might find stronger interactive effects of combined tDCS and a cognitive intervention with larger doses of each intervention. Because this controlled laboratory pilot employed an acute pain analogue and the cognitive intervention did not authentically represent cognitive behavioral therapy per se, the implications of the findings on chronic pain management remain unclear.

Repetitive transcranial magnetic stimulation (rTMS) administration to heavy cannabis users.

BACKGROUND: Cannabis use disorder (CUD) is a common condition with few treatments. Several studies in other substance use disorders have found that applying repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) decreases cue-elicited craving and possibly decreases use. To date, there have been no studies attempting to use rTMS in CUD. OBJECTIVES: This study was conducted to determine if rTMS could be feasibly delivered to a group of non-treatment seeking CUD participants. Secondarily, the study aimed to estimate the effect of rTMS on craving. METHODS: In a double-blind, sham-controlled, crossover design, a single session of active or sham rTMS (Left DLPFC, 10 Hz, 110% rMT, 4000 pulses) was delivered during a validated cannabis cue paradigm. Participants crossed over to complete the other condition one week later. The feasibility and tolerability were measured by the rate of retention, and the percentage of participants able to tolerate full dose rTMS, respectively. Craving was measured using the Marijuana Craving Questionnaire (MCQ). RESULTS: Eighteen non-treatment seeking CUD participants were recruited from the community; 16 (three women) completed the trial (89% retained for the three study visits). All of the treatment completers tolerated rTMS at full dose without adverse effects. There was not a significant reduction in the total MCQ when participants received active rTMS as compared to sham rTMS. CONCLUSION: rTMS can be safely and feasibly delivered to CUD participants, and treatment is well tolerated. A single session of rTMS applied to the DLPFC may not reduce cue-elicited craving in heavy cannabis users.