Alok Madan

A Pilot Study of the Tolerability and Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Pain Perception

UNLABELLED Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. PERSPECTIVE This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain.

Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving.

This study examined whether a 20-min session of prefrontal transcranial direct current stimulation (tDCS) (anode over the right prefrontal cortex and cathode over the left prefrontal cortex) would reduce food cravings and increase the self-reported ability to resist foods in 19 healthy individuals who reported frequent food cravings. Participants viewed computerized images of food and used computerized visual analogue scales to rate food cravings and inability to resist foods before, during, and after receiving either real or sham tDCS. This study employed a randomized within-subject crossover design; participants received both real and sham tDCS and were blind to the condition. Food cravings ratings were reduced in both conditions, however, the percent change in cravings ratings from pre- to post-stimulation was significantly greater for real stimulation than for sham. The percent change in inability to resist food from pre- to post-stimulation also showed a greater decrease in the real condition than for sham. Post hoc analyses suggest that active prefrontal tDCS acutely and significantly decreased food cravings ratings for sweet foods and carbohydrates more so than sham tDCS. No significant differences were seen in the amount of food ingested between real and sham tDCS. These findings in healthy subjects indicate that tDCS is able to temporarily reduce food cravings and improve the self-reported ability to resist foods.

Development and evaluation of a portable sham transcranial magnetic stimulation system

BACKGROUND Transcranial magnetic stimulation (TMS) is a relatively noninvasive brain stimulation technology that can focally stimulate the human cortex. One significant limitation of much of the TMS research to date concerns the nature of the placebo or sham conditions used. When TMS pulses are delivered repetitively (especially prefrontal TMS), it is often experienced as painful. Most sham TMS techniques produce identical sounds to active TMS, but they do not cause much, if any, scalp or facial sensation or discomfort. This is a serious problem when investigators are attempting to evaluate the effects of TMS by using traditional sham techniques because of unintended systematic differences between real and sham TMS groups (ie, confounds). As long as traditional approaches to sham TMS are used, the validity of the inferences regarding the efficacy of TMS will be limited. Although some other sophisticated systems have been developed to address these concerns, they tend to be expensive and lack portability. Portability will likely become more and more important as TMS applications expand into different clinical areas (eg, TMS in the postanesthesia care unit after surgery). METHODS This study describes a portable electrical TMS sham system (eSham system) modeled after the James Long System that was designed to produce similar scalp sensations as real TMS. Preliminary results are presented on 9 healthy adults who received both real and eSham 10 Hz repetitive TMS (rTMS) (at 80%, 100%, and 120% of resting motor threshold) over the prefrontal cortex and rated the sensation quality (pain, tingling, sharpness, piercing, electric, tugging, pinching), tolerability, and location. RESULTS Real TMS and eSham TMS were rated similarly across all seven sensory dimensions examined. Real and eSham TMS were also rated similarly with respect to tolerability and perceived location of the TMS-induced sensations. CONCLUSIONS The eSham system may be a simple, affordable, and portable approach to providing convincing sham TMS for future clinical trials. This study provides preliminary evidence supporting the use of the eSham system. Future larger-scale studies are warranted.

Systematic Investigation of Initiatives to Reduce Seclusion and Restraint in a State Psychiatric Hospital

OBJECTIVES This study used an experimental design to examine the effect of systematic implementation of behavioral interventions on the rate of seclusion and restraint in an inpatient psychiatric hospital. METHODS With a variant of the multiple-baseline design, a model designed to reduce seclusion and restraint was implemented at a large state-funded hospital in the southeastern United States. The implementation schedule was established such that each of five inpatient units was randomly assigned to implement the intervention components in a different order, and each unit served as its own control. Participants were patients and staff, for a total of 89,783 patient-days over a 3.5-year period from January 2005 through June 2008. The components included trauma-informed care training, changes to unit rules and language, changes to the physical characteristics of the therapeutic environment, and involvement of patients in treatment planning. The rate of inpatient psychiatric seclusion and restraint (per patient day) was tracked continuously during the 3.5-year period. RESULTS A significant reduction of 82.3% (p=.008) in the rate of seclusion and restraint was observed between the baseline phase (January 2005 through February 2006) and the follow-up, postintervention phase (April 2008 through June 2008). After control for illness severity and nonspecific effects associated with an observation-only phase, changes to the physical environment were uniquely associated with a significant reduction in rate of seclusion and restraint during the intervention rollout period. CONCLUSIONS These data suggest that substantial reductions in use of seclusion and restraint are possible in inpatient psychiatric settings and that changes to the physical characteristics of the therapeutic environment may have a significant effect on use of seclusion and restraint.

A Pilot Study Investigating the Effects of Fast Left Prefrontal rTMS on Chronic Neuropathic Pain

OBJECTIVE Stimulating the human cortex using transcranial magnetic stimulation (TMS) temporarily reduces clinical and experimental pain; however, it is unclear which cortical targets are the most effective. The motor cortex has been a popular target for managing neuropathic pain, while the prefrontal cortex has been investigated for an array of nociceptive pain conditions. It is unclear whether the motor cortex is the only effective cortical target for managing neuropathic pain, and no published studies to date have investigated the effects of prefrontal stimulation on neuropathic pain. DESIGN This preliminary pilot trial employed a sham-controlled, within-subject, crossover design to evaluate clinical pain as well as laboratory pain thresholds among four patients with chronic neuropathic pain. Each participant underwent three real and three sham 20-minute sessions of 10 Hz left prefrontal repetitive TMS. Daily pain diaries were collected for 3 weeks before and after each treatment phase along with a battery of self-report pain and mood questionnaires. RESULTS Time-series analysis at the individual patient level indicated that real TMS was associated with significant improvements in average daily pain in 3 of the 4 participants. These effects were independent of changes in mood in two of the participants. At the group level, a decrease of 19% in daily pain on average, pain at its worst, and pain at its least was observed while controlling for changes in mood, activity level and sleep. The effects of real TMS were significantly greater than sham. Real TMS was associated with increases in thermal and mechanical pain thresholds, whereas sham was not. No statistically significant effects were observed across the questionnaire data. CONCLUSIONS The prefrontal cortex may be an important TMS cortical target for managing certain types of pain, including certain neuropathic pain syndromes.

Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study

BACKGROUND Emerging evidence shows that transcranial direct current stimulation (tDCS), a minimally invasive brain stimulation technique, has analgesic effects in chronic pain patients and in healthy volunteers with experimental pain. No studies have examined the analgesic effects of tDCS immediately after surgical/endoscopic procedures. Endoscopy investigating abdominal pain, especially ERCP, can cause significant postprocedural pain. OBJECTIVE To test the feasibility, efficacy, and safety of tDCS on post-ERCP pain and analgesia use. DESIGN Randomized, sham-controlled, pilot study. SETTING Tertiary-care medical center. PATIENTS This study involved 21 patients who were hospitalized overnight for ERCP for unexplained right upper quadrant pain. INTERVENTION Twenty minutes of real 2.0 mA tDCS or sham (anode over left prefrontal cortex; cathode over gut-representation of right sensory cortex) immediately after ERCP. MAIN OUTCOME MEASUREMENTS Pain (visual analogue scale, McGill pain questionnaire, brief pain inventory), patient-controlled analgesia use, adverse events. RESULTS Real tDCS was associated with 22% less total hydromorphone use, versus sham. The slope of the cumulative patient-controlled analgesia usage curve was significantly steeper in the sham tDCS group (F [2,13] = 15.96; P = .0003). Real tDCS patients reported significantly less pain interference with sleep (t [17] = 3.70; P = .002) and less throbbing pain (t [16] = 2.37; P = .03). Visual analogue scale pain and mood scores (4 hours post-ERCP) suggested a nonsignificant advantage for real tDCS, despite less hydromorphone use. Side effects of tDCS were limited to mild, self-limited tingling, itching, and stinging under electrodes. LIMITATIONS Small sample size, variability in chronic pain, and chronic opioid use. CONCLUSION In this pilot study, tDCS appears to be safe, has minimal side effects, and may reduce postprocedural analgesia requirements and subjective pain ratings. Future studies appear warranted.

Executive control circuitry differentiates degree of success in weight loss following gastric‐bypass surgery

While overall success rates of bariatric surgery are high, approximately 20% of patients either regain or never lose the expected amount of weight. The purpose of this study was to determine whether, after gastric‐bypass surgery, the degree of weight loss can be differentiated based on the neural response to food cues.

Food cravings and the effects of left prefrontal repetitive transcranial magnetic stimulation using an improved sham condition.

This study examined whether a single session of repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex (PFC) would inhibit food cravings in healthy women who endorsed frequent food cravings. Ten participants viewed images of food and completed ratings for food cravings before and after receiving either real or sham rTMS over the left PFC (10 Hz, 100% resting motor threshold, 10 s-on, 20 s-off for 15 min; 3000 pulses). Sham-TMS was matched with real TMS with respect to perceived painfulness of the stimulation. Each participant received both real and sham rTMS in random order and were blind to the condition in a within-subject cross-over design. With an improved sham control condition, prefrontal rTMS inhibited food cravings no better than sham rTMS. The mild pain from the real and sham rTMS may distract or inhibit food craving, and the decreased craving may not be caused by the effect of rTMS itself. Further studies are needed to elucidate whether rTMS has any true effects on food craving and whether painful stimuli inhibit food or other cravings. A sham condition which matches the painfulness is important to understand the true effects of TMS on behaviors and diseases.

Fast Left Prefrontal rTMS Acutely Suppresses Analgesic Effects of Perceived Controllability on the Emotional Component of Pain Experience

&NA; The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain, stress, and learned helplessness. Although the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as modulating pain, little is known about whether TMS over this area may affect perceived controllability. The present study explored the immediate effects of fast TMS over the left dorsolateral prefrontal cortex on the analgesic effects of perceived pain controllability. Twenty‐four healthy volunteers underwent a laboratory pain task designed to manipulate perception of pain controllability. Real TMS, compared with sham, suppressed the analgesic benefits of perceived control on the emotional dimension of pain, but not the sensory/discriminatory dimension. Findings suggest that, at least acutely, fast TMS over the left dorsolateral prefrontal cortex may interrupt the perceived‐controllability effect on the emotional dimension of pain experience. Although it is not clear whether this cortical area is directly involved with modulating perceived controllability or whether downstream effects are responsible for the present findings, it appears possible that left dorsolateral prefrontal TMS may produce analgesic effects by acting through a cortical perceived‐control circuit regulating limbic and brainstem areas of the pain circuit. Despite evidence that prefrontal TMS can have analgesic effects, fast left prefrontal TMS appears to acutely suppress analgesia associated with perceived‐control. This effect may be limited to the emotional dimension of pain experience.

Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).

Background:Although pain is often a symptom that precedes total knee arthroplasty (TKA), the procedure itself is associated with considerable postoperative pain lasting days to weeks. Postoperative pain control is an important factor in determining recovery time, hospital length of stay, and rehabilitation success. Several brain stimulation technologies including transcranial direct current stimulation (tDCS) have demonstrated promise as treatments for a variety of pain conditions. The present study examined the effects of 4 sessions of tDCS on post-TKA pain and opioid consumption. Materials and Methods:Forty patients undergoing unilateral TKA were randomly assigned to receive a total of 80 minutes of real (n=20) or sham tDCS (n=20) with the anode over the knee representation of the motor strip (C1h or C2h corresponding to the target knee) and cathode over the right dorsolateral prefrontal cortex (F3; located by the EEG 10-20 System). Patient-controlled analgesia ( hydromorphone) use was tracked during the ∼48 hours postsurgery. Results:Patients in the real tDCS group used an average of 6.6 mg (SD=5.3) of patient-controlled analgesia hydromorphone, whereas those in the sham group used 12.3 mg (SD=6.6; t37=2.93, P=0.006). Despite using less opioid medication, participants in the real tDCS group reported no pain exacerbation or worse mood with respect to those in the sham tDCS group. Conclusions:Results from this pilot feasibility study suggest that tDCS may be able to reduce post-TKA opioid requirements. Although these results are preliminary, the data support further research in the area of adjunctive cortical stimulation in the management of postsurgical pain.