BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation RSS feed: Articles in Press. BRAIN STIMULATION aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) original articles (up to 5,000 words); b) brief reports (up to 2,000 words); c) invited and original reviews; d) technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) letters to the Editor. Special issues of the journal will be considered based on scientific merit. The scope of BRAIN STIMULATION extends across the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. This includes investigations that study the effects of brain stimulation on basic processes, such as gene expression and other aspects of molecular biology, neurochemical regulation, functional brain activity, sensorimotor function, and cognitive and affective processes at the systems level. The journal seeks the highest level of research on the biophysics and biopsychophysics of stimulation paradigms as well as the use of these techniques as a probe to outline patterns of neural connectivity. As an equal partner with this basic emphasis, the journal will have strong representation of research on the therapeutic potential and adverse effects of the stimulation technologies. The inclusion of research in therapeutics will represent not only clinical trials, but also conceptual pieces, discussions of ethics as they pertain to this field, services research, etc. http://www.brainstimjrnl.com//inpress?rss=yesElsevier Inc.en © 2010 Elsevier Inc. All rights reserved. BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation1935-861X2010-09-03 © 2010 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.brainstimjrnl.com/article/PIIS1935861X10001129/abstract?rss=yesOne of the more fascinating aspects of the vast new Brain Stimulation frontier involves the widely differing time course of therapeutic effects. These vary profoundly with the various brain stimulation methods and different diseases. For example, high frequency (>100 Hz) deep brain stimulation (DBS) of the subthalamic nucleus (STN) causes a near immediate cessation of the tremor of Parkinson’s disease (PD). The tremor continues to be treated for many years as long as the device is in the brain and turned on. However, if a lead breaks or the battery depletes, the tremor returns almost instantaneously. That is, in general, there is no durability of the therapeutic effect of DBS for PD tremor beyond the instant of stimulation. In contrast, the same technology, DBS, applied in much the same manner to treat dystonia, has a markedly slower onset of action over weeks to months, and the therapeutic effects do not always immediately return if the device malfunctions. Instead the dystonic symptoms can take weeks to months to reemerge. Why are there such differences in speed of onset and durability for different brain stimulation techniques and diseases? The Founding Editor of Brain Stimulation, Dr. Harold Sackeim, observed years ago that there might be an inverse relationship between the speed of onset of therapeutic action of a brain stimulation treatment and the durability of the effect. Sackeim’s rule, as I now choose to call it, suggests that treatments with quick effects will have short duration of effects after the treatment is stopped, and those with slower onsets of action will be more durable. Clinical improvements that occur rapidly, almost instantaneously, like DBS for PD tremor, also disappear quickly, whereas therapeutic effects that take longer to occur may be more durable. In the area of treating acute depression, some interventions, like depriving someone of sleep for a full night, work within a day. Unfortunately, most patients relapse overnight when they sleep again. In contrast, with vagus nerve stimulation (VNS) for treatment-resistant depression, the therapeutic effects take several months to appear, but appear quite durable over several years with continued treatment. Sackeim’s Rule is an interesting hypothesis, which researchers will continue to test and observe as they discover more therapeutic applications of the brain stimulation methods. If it is true, it obviously reflects the underlying translational mechanisms of the brain stimulations, and whether they are promoting and creating true plasticity and changes in the brain, or rather creating quick, and likely temporary modifications of brain function.From the Editor-in Chief’s Desk - Uncorrected ProofMark S. George10.1016/j.brs.2010.08.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-09-03BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-09-03EDITORIALhttp://www.brainstimjrnl.com/article/PIIS1935861X10001105/abstract?rss=yesBackground: Although transcranial magnetic stimulation (TMS) can be an effective acute antidepressant treatment, few studies systematically examine persistence of benefit.Objective: We assessed the durability of antidepressant effect after acute response to TMS in patients with major depressive disorder (MDD) using protocol-specified maintenance antidepressant monotherapy.Methods: Three hundred one patients were randomly assigned to active or sham TMS in a 6-week, controlled trial. Nonresponders could enroll in a second, 6-week, open-label study. Patients who met criteria for partial response (i.e., > 25% decrease from the baseline HAMD 17) to the either the sham-controlled or open-label study (n = 142) were tapered off TMS over 3 weeks, whereas simultaneously starting maintenance antidepressant monotherapy. Patients were then followed for 24 weeks in a naturalistic follow-up study examining the long-term durability of TMS. During this durability study, TMS was readministered if patients met prespecified criteria for symptom worsening (i.e., a change of at least one point on the CGI-S scale for 2 consecutive weeks). Relapse was the primary outcome measure.Results: Ten of 99 (10%; Kaplan-Meier survival estimate = 12.9%) patients relapsed. Thirty-eight (38.4%) patients met criteria for symptom worsening and 32/38 (84.2%) reachieved symptomatic benefit with adjunctive TMS. Safety and tolerability were similar to acute TMS monotherapy.Conclusions: These initial data suggest that the therapeutic effects of TMS are durable and that TMS may be successfully used as an intermittent rescue strategy to preclude impending relapse.Durability of clinical benefit with transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant major depression: assessment of relapse during a 6-month, multisite, open-label study - Uncorrected ProofPhilip G. Janicak, Ziad Nahas, Sarah H. Lisanby, H. Brent Solvason, Shirlene M. Sampson, William M. McDonald, Lauren B. Marangell, Peter Rosenquist, W. Vaughn McCall, James Kimball, John P. O’Reardon, Colleen Loo, Mustafa H. Husain, Andrew Krystal, William Gilmer, Sheila M. Dowd, Mark A. Demitrack, Alan F. Schatzberg10.1016/j.brs.2010.07.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-08-12BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-08-12http://www.brainstimjrnl.com/article/PIIS1935861X10001099/abstract?rss=yesBackground: Noninvasive brain stimulation is a powerful way to modify excitability of the cerebral cortex in humans and is increasingly used to treat psychiatric disorders. The observed clinical effects are in the moderate range and it has been suggested that the efficiency of brain stimulation depends on the underlying cortical state.Objective: To isolate and manipulate brain rhythms associated with cortical excitability.Methods: In the first experiment electroencephalography (EEG) and transcranial magnetic stimulation (TMS) were interleaved to study associations between brain oscillations and the amplitude of the motor evoked potential (MEP) during isometric contraction. Results of the first experiment were used in a second experiment to selectively modulate cortical excitability levels by applying transcranial alternating current stimulation (tACS).Results: A linear regression showed that MEP amplitude could be modeled by θ (4-7 Hz) and β (13-30 Hz) oscillations recorded over the left and right M1. Significant increases in cortical excitability were found after θ (5 Hz)-β (20 Hz) tACS as compared with baseline and α (10 Hz) tACS.Conclusions: Scalp-recorded brain oscillations can serve as a proxy for the effective modulation of cortical excitability by mimicking natural brain rhythms using weak electric currents.Brain oscillations and frequency-dependent modulation of cortical excitability - Corrected ProofDennis J.L.G. Schutter, Ruud Hortensius10.1016/j.brs.2010.07.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-08-06BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-08-06http://www.brainstimjrnl.com/article/PIIS1935861X10000938/abstract?rss=yesBackground: It has recently been reported that unilateral fatiguing exercise affects not only the motor area innervating the exercising muscle but also the ipsilateral motor area innervating homologous nonexercised muscle.Objective: This study was designed to clarify the effects of fatiguing intermittent lower limb exercise on the excitability of the motor cortex representation of nonexercised muscles in the arm.Methods: Eight subjects performed an intermittent leg press exercise composed of three bouts of 5-minute leg press (T1, T2, and T3) at 50% of maximal voluntary contraction separated by a 2-minute rest. Motor-evoked potentials (MEP), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF), using paired-pulse transcranial magnetic stimulation, were assessed in two nonexercised arm muscles (first dorsal interosseous muscle: FDI, n = 8; biceps brachii muscle: BB, n = 6) and one exercised leg muscle (quadriceps femoris muscle: QF, n = 6) before and immediately after each bout of exercise and for 30 minutes during recovery after the end of the third exercise bout (Experiment 1). Experiment 2 was the same as Experiment 1, except that the test pulse intensity was adjusted to produce a given amplitude of MEPTEST at each time point.Results: MEPs and SICI in the exercised QF muscle were depressed at all time points during and after fatigue. In contrast, MEPs in nonexercised arm muscles were facilitated from T1-T3 (T3, only FDI), but were then depressed for up to 20 minutes in the recovery period. SICI was reduced in both muscles during T1-T3 and remained depressed until 20 minutes into recovery. ICF was unchanged in arm muscles but depressed in QF over T1-T3.Conclusions: The current study indicates that muscle fatigue induced by exercise of a large lower limb muscle group has powerful effects on the excitability of both SICI and the corticospinal projection to muscles of the nonexercised upper limb.Fatiguing intermittent lower limb exercise influences corticospinal and corticocortical excitability in the nonexercised upper limb - Corrected ProofKyohei Takahashi, Atsuo Maruyama, Kohji Hirakoba, Masato Maeda, Seiji Etoh, Kazumi Kawahira, John C. Rothwell10.1016/j.brs.2010.07.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-08-02BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-08-02http://www.brainstimjrnl.com/article/PIIS1935861X10000896/abstract?rss=yesTo the Editor: Despite the efficacy of electroconvulsive therapy (ECT) in the treatment of acute bipolar depression, manic, and mixed affective states, its long-term use as a maintenance treatment (mECT) described in unipolar depression remains controversial in bipolar disorder. Serious adverse events associated with ECT are uncommon and consist mostly of cardiovascular complications. The risk of complications is increased in elderly and physically ill patients. When complications with mECT arise, switching to maintenance repetitive transcranial magnetic stimulation (rTMS) could be an interesting strategy to continue the treatment and keep clinical improvement.Successful switch to maintenance rTMS after maintenance ECT in refractory bipolar disorder - Uncorrected ProofJerome Brunelin, Wissem Ben Maklouf, Alain Nicolas, Mohamed Saoud, Emmanuel Poulet10.1016/j.brs.2010.06.006BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-07-22BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-07-22LETTER TO THE EDITORhttp://www.brainstimjrnl.com/article/PIIS1935861X10000616/abstract?rss=yesBackground: Repetitive transcranial magnetic stimulation (rTMS) is increasingly used in research. However, cardiac safety is not routinely assessed.Objective: This study aims to investigate cardiac safety of rTMS in people with a bulimic eating disorder.Methods: Thirty-eight people with a bulimic disorder were enrolled in a randomized sham-controlled trial. High frequency rTMS was delivered to the left dorsolateral prefrontal cortex.Results: rTMS did not alter blood pressure or heart rate.Conclusions: Our findings indicated that this rTMS paradigm has no cardiac complications as assessed by blood pressure and heart rate. This adds to the emerging literature on the cardiac safety of rTMS.Cardiac safety of repetitive transcranial magnetic stimulation in bulimic eating disorders - Corrected ProofFrederique Van den Eynde, Angélica M. Claudino, Iain Campbell, Linda Horrell, Manoharan Andiappan, Daniel Stahl, Ulrike Schmidt10.1016/j.brs.2010.06.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-07-12BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-07-12http://www.brainstimjrnl.com/article/PIIS1935861X10000628/abstract?rss=yesBackground: Transcranial direct current stimulation (tDCS), applied to the left dorsolateral prefrontal cortex (DLPFC) has been found to improve working memory (WM) performance in both healthy and clinical participants. However, whether this effect can be enhanced by cognitive activity undertaken during tDCS has not yet been explored.Objective: This study aimed to explore whether tDCS applied to the left DLPFC during the persistent performance of one WM task would improve performance on a subsequent WM task, to a greater extent than either tDCS or cognitive activity alone.Methods: Ten healthy participants took part in three counterbalanced conditions. The conditions involved 10 minutes of either anodal tDCS while completing an n-back task, anodal tDCS while at rest, or sham tDCS while completing an n-back task. The n-back that was used in this study was a computer-based letter WM task that involved 5 minutes of two-back, followed by 5 minutes of three-back. Digit span forward and backward was administered immediately before and after each treatment, and performance change (pre- to posttreatment) calculated and compared across conditions. The digit span tasks involved a series of numbers being read to the participant, and the participant was required to repeat them back, either in the same order (Digits forward) or in the reverse order (Digits backward).Results: tDCS applied during completion of the n-back task was found to result in greater improvement in performance on digit span forward, compared with tDCS applied while at rest and sham tDCS during the n-back task. This finding was not evident with digit span backward.Conclusions: These results indicate that there may be potential for the use of adjunctive cognitive remediation techniques to enhance the effects of tDCS. However, further research needs to be undertaken in this area to replicate and extend this finding.Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex - Corrected ProofSophie C. Andrews, Kate E. Hoy, Peter G. Enticott, Zafiris J. Daskalakis, Paul B. Fitzgerald10.1016/j.brs.2010.06.004BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-07-12BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-07-12http://www.brainstimjrnl.com/article/PIIS1935861X10000604/abstract?rss=yesBackground: In Transcranial Magnetic Stimulation (TMS), the Motor Threshold (MT) is the minimum intensity required to evoke a liminal response in the target muscle. Because the MT reflects cortical excitability, the TMS intensity needs to be adjusted according to the subject's MT at the beginning of every TMS session.Objective: Shorten the MT estimation process compared to existing methods without compromising accuracy.Methods: We propose a Bayesian adaptive method for MT determination that incorporates prior MT knowledge and uses a stopping criterion based on estimation of MT precision. We compared the number of TMS pulses required with this new method with existing MT determination methods.Results: The proposed method achieved the accuracy of existing methods with as few as seven TMS pulses on average when using a common prior and three TMS pulses on average when using subject-specific priors.Conclusions: Our adaptive Bayesian method is effective in reducing the number of pulses to estimate the MT.Fast estimation of transcranial magnetic stimulation motor threshold - Corrected ProofFeng Qi, Allan D. Wu, Nicolas Schweighofer10.1016/j.brs.2010.06.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-07-05BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-07-05http://www.brainstimjrnl.com/article/PIIS1935861X10000598/abstract?rss=yesBackground: One of the few novel treatments developed for major depression in recent years has been repetitive transcranial magnetic stimulation (rTMS). Despite mostly promising results, 50-60% of patients do not respond to rTMS. Therefore, it is important to investigate ways of enhancing the effectiveness of this treatment. To date, attempting to enhance the mood effects of rTMS via behavioral means has not been investigated. One such intervention involves concurrent exposure to affective stimuli that have been shown to result in activation of brain regions associated with emotion. This pilot study of ten participants investigates such an intervention.Objectives: The aim of this pilot study was to investigate whether exposing participants to affective stimuli while they were receiving 5 Hz rTMS resulted in greater mood change compared with rTMS or affective stimuli alone.Methods: Ten healthy male and female participants were exposed to affective stimuli while receiving rTMS. All participants took part in three counterbalanced conditions conducted a week apart in which they received rTMS (active or sham) delivered to the left dorsolateral prefrontal cortex (DLPFC) combined with affective stimuli (positive or neutral). To measure the impact of the dual intervention visual analogue mood scales and an affective go no go task were conducted pre- and post intervention for each session.Results: There was no effect of any rTMS condition on performances on the affective go no go task, or on any of the visual analogue scales.Conclusions: The current data do not provide support for the use of affective stimuli during rTMS. Methodological limitations that may have contributed to the lack of significant findings are discussed.Can a behavioral intervention enhance the effect of repetitive transcranial magnetic stimulation on mood? - Corrected ProofKate E. Hoy, Peter G. Enticott, Zafiris J. Daskalakis, Paul B. Fitzgerald10.1016/j.brs.2010.06.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-06-30BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-06-30http://www.brainstimjrnl.com/article/PIIS1935861X10000574/abstract?rss=yesTranscranial magnetic stimulation (TMS) devices suffer of poor targeting and penetration depth. A new approach to designing TMS coils is introduced in order to improve the focus of the stimulation region through the use of actively shielded probes. Iterative optimization techniques were used to design different active shielding coils for TMS probes. The new approach aims to increase the amount of energy deposited in a thin cylindrical region below the probe relative to the energy deposited elsewhere in the region (“sharpness”), whereas, simultaneously increase the induced electric field deep in the target region relative to the surface (“penetration”). After convergence, the resulting designs showed that there is a clear tradeoff between sharpness and penetration that can be controlled by the choice of a tuning parameter. The resulting designs were tested on a realistic human head conductivity model, taking the contribution from surface charges into account. The design of choice reduced penetration depths by 16.7%. The activated surface area was reduced by 24.1% and the volume of the activation was reduced from 42.6% by the shield. Restoring the lost penetration could be achieved by increasing the total power to the coil by 16.3%, but in that case, the stimulated volume reduction was only 13.1% and there was a slight increase in the stimulated surface area (2.9%).A numerically optimized active shield for improved transcranial magnetic stimulation targeting - Corrected ProofLuis Hernandez-Garcia, Timothy Hall, Luis Gomez, Eric Michielssen10.1016/j.brs.2010.05.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-06-21BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-06-21http://www.brainstimjrnl.com/article/PIIS1935861X10000586/abstract?rss=yesBackground: Transcranial direct current stimulation (tDCS) appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic mixture of local anesthetics (EMLA) on tDCS-related discomfort.Methods: Nine healthy adults received both anodal and cathodal 2.0 mA tDCS for 5 minutes over the prefrontal cortex with the skin pretreated for 20 minutes with either EMLA or placebo cream. Participants rated procedural discomfort six times across eight dimensions of sensation.Results: On average, the mean sensation ratings for EMLA-associated tDCS stimulation were significantly lower than placebo-associated stimulation for every cutaneous sensation evaluated. Cathodal stimulation was associated with higher ratings of “sharpness” and intolerability than anodal stimulation.Conclusions: Topical EMLA may reduce tDCS-related discomfort.Reducing procedural pain and discomfort associated with transcranial direct current stimulation - Corrected ProofJames L. McFadden, Jeff J. Borckardt, Mark S. George, William Beam10.1016/j.brs.2010.05.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-06-18BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-06-18http://www.brainstimjrnl.com/article/PIIS1935861X10000562/abstract?rss=yesBackground: In paired-pulse (conditioned-test) transcranial magnetic stimulation (TMS) protocols, the effect of the conditioning pulse on the test response can be substantial. Epidural recordings indicate that this is mediated through modulation of late indirect (I-) wave volleys. It is not well understood how strong effect sizes could arise from the later, and usually weaker, I-wave volleys.Objective: To formulate a model of I-wave summation at the spinal level to explore the contribution of late I-waves to the activation of the α-motoneuronal pool and to paired-pulse TMS measures of intracortical inhibition and facilitation.Methods: I-wave recruitment curves were modeled for the first three I-waves. A series of steps converted I-wave inputs to α-motoneuronal activation. The role of I3 in activating the α-motoneuronal pool was investigated by manipulating the amplitude of the I3 volley.Results: For all TMS intensities, I3 made a contribution to the firing of the α-motoneuronal pool that was disproportional to its contribution to the descending volley. At its most influential, I3 increased the descending volley by 23.5% but increased the proportion of motoneurons that fired by 567%. There was a U-like relationship to stimulus intensity with inhibition of I3, and an inverted-U relationship for facilitation of I3, in keeping with empirical observation. Changes in spinal excitability disproportionally influenced α-motoneuronal recruitment.Conclusions: Late I-waves have a pivotal role in determining the response to paired-pulse TMS. The spinal transfer function that converts I-wave input to α-motoneuron activation can amplify the role of late I-waves and potentially influence paired-pulse TMS measures of intracortical inhibition and facilitation.A model of the contribution of late I-waves to α-motoneuronal activation: implications for paired-pulse TMS - Corrected ProofGary W. Thickbroom10.1016/j.brs.2010.04.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-05-12BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-05-12http://www.brainstimjrnl.com/article/PIIS1935861X10000550/abstract?rss=yesBackground: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans.Objective: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model.Methods: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test.Results: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group.Conclusions: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety - Corrected ProofYoshihiro Tanaka, Jotaro Akiyoshi, Yoshinari Kawahara, Yoshinobu Ishitobi, Koji Hatano, Nobuhiko Hoaki, Ayumi Mori, Shinjiro Goto, Jusen Tsuru, Hirotaka Matsushita, Hiroaki Hanada, Kensuke Kodama, Koichi Isogawa, Hirokazu Kitamura, Yoshihisa Fujikura10.1016/j.brs.2010.04.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-05-10BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-05-10http://www.brainstimjrnl.com/article/PIIS1935861X10000495/abstract?rss=yesBackground: Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has shown beneficial effects in patients with chronic tinnitus. Recent preclinical data in healthy controls suggest that the effects of low-frequency rTMS can be enhanced by dopaminergic drugs.Objective: We investigated whether application of the dopamine reuptake inhibitor bupropion increases the clinical effects of low-frequency rTMS over the auditory cortex in tinnitus patients.Subjects and Methods: Eighteen subjects with chronic tinnitus received 10 sessions of 1 Hz rTMS (2000 pulses/day, 110% motor threshold) applied to the left temporal cortex. In addition, these subjects received one dosage of 150 mg bupropion (Wellbutrin XL/Elontril) 4 hours before each TMS session. Treatment outcome was assessed with a tinnitus questionnaire over a 3-month period. Treatment effects were compared with a control group of 100 tinnitus patients matched for age, tinnitus duration, and tinnitus questionnaire baseline scores, who received the same rTMS treatment without prior bupropion application.Results: For the whole sample, there was a significant effect of rTMS treatment over time. There were no significant differences between the bupropion and the control group.Conclusions: Our data suggest that 150 mg bupropion administration does not enhance the effect of rTMS in the treatment of tinnitus.Repetitive transcranial magnetic stimulation for tinnitus treatment: No enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion - Corrected ProofTobias Kleinjung, Thomas Steffens, Michael Landgrebe, Veronika Vielsmeier, Elmar Frank, Julia Burger, Juergen Strutz, Göran Hajak, Berthold Langguth10.1016/j.brs.2010.03.007BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-04-26BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-04-26http://www.brainstimjrnl.com/article/PIIS1935861X10000471/abstract?rss=yesDaily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has emerged as a potentially useful treatment for acute major depression and is now United Stated Food and Drug Administration approved. TMS was initially developed as a treatment based on the theory that in depression the prefrontal cortex was deficient in many tasks, including governing limbic activity. Repeated subconvulsive stimulation of the prefrontal cortex was theorized to reset the normal corticolimbic regulatory circuit. Recent animal work supports this notion. Maier and colleagues have studied the neurobiological basis of learned helplessness and resilience to repeated stressors. In this model of depression or posttraumatic stress disorder (PTSD), the animal with control over a stressor does not develop learned helplessness while being shocked, whereas the animal without control does. Both animals receive the same stress. Thus, the “concept” of being in control prevents the animal from developing learned helplessness. In a series of recent studies, Maier and colleagues have recently shown that the “concept of control” is actually a signal from the prefrontal cortex to the dorsal raphe nucleus (DRN). Lesioning this circuit makes an animal who actually has behavioral control over a stressor still develop learned helplessness. Stimulating this circuit even while not providing a control lever protects from learned helplessness. They thus conclude that the concept of control is a regulatory circuit from the prefrontal cortex to the DRN.Feasibility of simultaneous cognitive behavioral therapy and left prefrontal rTMS for treatment resistant depression - Corrected ProofAndrei Vedeniapin, Laura Cheng, Mark S. George10.1016/j.brs.2010.03.005BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-04-20BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-04-20http://www.brainstimjrnl.com/article/PIIS1935861X10000483/abstract?rss=yesObjective: Though a cortical visual prosthesis is a promising method for treating severe visual disturbances, long-term blindness is known to depress visual cortex activity. We examined the use of repetitive transcranial magnetic stimulation (rTMS) with a navigation system as a direct functional assessment tool for the visual cortex.Methods: We performed rTMS of the occipital cortex at three different stimulus frequencies (1 Hz, 5 Hz, and 20 Hz), on five stimulus targets around the calcarine fissure in 10 healthy subjects and 3 patients with visual impairment.Results: In the subjects with normal vision, phosphenes were mostly induced in the visual hemifield contralateral to the stimulation site, and stimulation on the targets inferior to the calcarine fissure predominantly induced phosphenes in the upper visual hemifield. High-frequency stimulation induced larger and complicated-shaped phosphenes at higher rates. The phosphenes induced rate and spatial distribution were altered in the blind patients.Conclusions: The rTMS has the ability to directly assess the regional visual function of the occipital cortex both in normal-sighted subjects and blind patients. Precise targeting with a navigation system appropriately stimulated the lingual gyri, which contributed to consistently inducing the phosphenes in the upper visual fields. Atypical representation of the phosphenes in patients with visual impairment suggests the alteration of regional cortical excitations and spatial representation due to the cortical reorganization after the loss of visual inputs.Quantitative analysis of phosphenes induced by navigation-guided repetitive transcranial magnetic stimulation - Corrected ProofNaoki Tani, Masayuki Hirata, Yu Motoki, Youichi Saitoh, Takufumi Yanagisawa, Tetsu Goto, Koichi Hosomi, Ayako Kozu, Haruhiko Kishima, Shiro Yorifuji, Toshiki Yoshimine10.1016/j.brs.2010.03.006BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-04-20BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-04-20http://www.brainstimjrnl.com/article/PIIS1935861X10000197/abstract?rss=yesThis case report describes a 52-year-old woman who received a diagnosis of bipolar I disorder of the mixed type, resistant to bilateral electroconvulsive shock therapy (ECT) and successfully treated with intensive left-sided high frequency repetitive transcranial magnetic stimulation (HF-rTMS).Intensive high-frequency repetitive transcranial magnetic stimulation treatment in an electroconvulsive shock theray-resistant bipolar I patient with mixed episode - Corrected ProofDieter Zeeuws, Kim De Rycker, Rudi De Raedt, Matthieu De Beyne, Chris Baeken, Nathalie Vanderbruggen10.1016/j.brs.2010.03.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-03-22BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-03-22http://www.brainstimjrnl.com/article/PIIS1935861X10000203/abstract?rss=yesBackground: Deep brain stimulation (DBS) has been used for neuropsychiatric disorders in clinical and research settings for almost 50 years now. Recent evidence demonstrates some efficacy in treating obsessive-compulsive disorder and major depression in patients refractory to other treatment modalities beyond single case reports. This has led to a considerable surge of clinical and commercial interest in DBS for psychiatric indications. Because of the high vulnerability of psychiatric patients, the lack of extensive short- and long-term data about effectiveness and the rapid spread of questionable indications this new field in psychiatry requires ethical criteria that can be applied to both research and clinical decision-making.Objective and Methods: We here present an evidence-based systematic ethical analysis of psychiatric DBS using the criteria of beneficence, nonmaleficence, and autonomy.Results and Conclusions: The proposed criteria are helpful in analyzing empirical evidence, informing research investigations and guiding clinical decision-making. This will prepare the ground for ethically justified, empirically comprehensive DBS in this highly vulnerable population and allow stringent future societal discussions about its legitimation.Electrodes in the brain—Ethical criteria for research and treatment with deep brain stimulation for neuropsychiatric disorders - Corrected ProofMatthis Synofzik, Thomas E. Schlaepfer10.1016/j.brs.2010.03.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-03-22BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-03-22http://www.brainstimjrnl.com/article/PIIS1935861X10000185/abstract?rss=yesThe best way to select the charge to be given during electroconvulsive therapy (ECT) treatment is still controversial. Although the method of limits titration procedure developed by Sackeim et al. is generally accepted as the best one, being encouraged by the American Psychiatric Association, many practitioners have concerns regarding the cardiac safety of this method. Subthreshold stimuli used during titration induce parasympathetic autonomic release that is not compensated by the sympathetic response because of seizure induction and leads to bradycardia, sometimes with asystole .Cardiovascular safety of the method of limits titration procedure for electroconvulsive therapy dosing: a retrospective study - Corrected ProofCelso Ricardo Bueno, Marina O. Rosa, Demetrio O. Rumi, Rafael B. Ribeiro, Moacyr A. Rosa10.1016/j.brs.2010.02.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-26BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-26http://www.brainstimjrnl.com/article/PIIS1935861X10000161/abstract?rss=yesElectroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions.Neuropsychologic effects of neuromodulation techniques for treatment-resistant depression: A review - Corrected ProofJared L. Moreines, Shawn M. McClintock, Paul E. Holtzheimer10.1016/j.brs.2010.01.005BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-15BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-15http://www.brainstimjrnl.com/article/PIIS1935861X10000173/abstract?rss=yesBackground: Deep brain stimulation (DBS) has been used for neuropsychiatric disorders in clinical and research settings for almost 50 years now. Recent evidence demonstrates some efficacy in treating obsessive-compulsive disorder and major depression in patients refractory to other treatment modalities beyond single case reports. This has led to a considerable surge of clinical and commercial interest in DBS for psychiatric indications. Because of the high vulnerability of psychiatric patients, the lack of extensive short- and long-term data about effectiveness and adverse effects and the haunting history of psychosurgery, this new field in psychiatry raises important and specific ethical issues that have only rarely been systematically addressed so far.Objective and Methods: We here review an evidence-based systematic ethical analysis of psychiatric DBS using the criteria of beneficence, nonmaleficence, and autonomy.Conclusions: These criteria can easily be applied to research and future clinical application of DBS in neuropsychiatric disorders. This will prepare the ground for ethically justified, empirically comprehensive DBS in this highly vulnerable population and allow stringent future societal discussions about its legitimation.Electrodes in the brain—Ethical criteria for research and treatment with deep brain stimulation for neuropsychiatric disorders - Uncorrected ProofMatthis Synofzik, Thomas E. Schlaepfer10.1016/j.brs.2010.01.006BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-15BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-15http://www.brainstimjrnl.com/article/PIIS1935861X1000015X/abstract?rss=yesAlthough electroconvulsive shock therapy (ECT) remains a successful treatment strategy in medication-resistant bipolar disorder, not all patients respond well. Here, we report on a successful high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) therapy in a highly treatment-resistant bipolar I patient during a mixed episode. This case illustrates that “combative” HF-rTMS therapy could be a safe and valid treatment alternative for refractory bipolar I patients with mixed episodes.Intensive HF-rTMS treatment in an ECT resistant bipolar I patient with mixed episode - Uncorrected ProofDieter Zeeuws, Kim De Rycker, Rudi De Raedt, Matthieu De Beyne, Chris Baeken, Nathalie Vanderbruggen10.1016/j.brs.2010.01.004BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-11BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-11http://www.brainstimjrnl.com/article/PIIS1935861X09001120/abstract?rss=yesBackground: The brain-derived neurotrophic factor (BDNF) gene is involved in mechanisms of synaptic plasticity in the adult brain. It has been demonstrated that BDNF also plays a significant role in shaping externally induced human brain plasticity. Plasticity induced in the human motor cortex by intermittent theta-burst stimulation (iTBS) was impaired in individuals expressing the Val66Met polymorphism.Methods: To explore whether this polymorphism is also important for other neuroplasticity-inducing tools in humans with modes of action differing from that of iTBS, namely, transcranial direct current (tDCS) and random noise stimulation (tRNS), we retrospectively analyzed the data of 64 subjects studied in our laboratory with regard to BDNF genotype.Results: Fifteen subjects with the Val66Met allele, 46 subjects with the Val66Val allele, and 3 Met66Met carriers were identified. The response of the Val66Met allele carriers to stimulation differed in two protocols compared with the response of Val66Val individuals. For iTBS (15 subjects, 5 heterozygotes), plasticity could be only induced in the Val66Val allele carriers. However, for facilitatory tDCS (24 subjects, 10 heterozygotes), as well as for inhibitory tDCS, (19 subjects, 8 heterozygotes), carriers of the Val66Met allele displayed enhanced plasticity, whereas for transcranial random noise stimulation (29 subjects, 8 heterozygotes), the difference between groups was not so pronounced.Conclusions: BDNF polymorphism has a definite impact on plasticity in humans, which might differ according to the mechanism of plasticity induction. This impact of BDNF on plasticity should be taken into account for future studies, as well as having wider ranging implications for the treatment of neuropsychiatric disorders with transcranial stimulation tools, as it may predetermine their efficacy for the treatment of disease and rehabilitation.Brain-derived neurotrophic factor (BDNF) gene polymorphisms shape cortical plasticity in humans - Corrected ProofAndrea Antal, Leila Chaieb, Vera Moliadze, Katia Monte-Silva, Csaba Poreisz, Nivethida Thirugnanasambandam, Michael A. Nitsche, Moneef Shoukier, Harald Ludwig, Walter Paulus,10.1016/j.brs.2009.12.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-01-15BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-01-15http://www.brainstimjrnl.com/article/PIIS1935861X09001107/abstract?rss=yesBackground: The efficacy of transcranial magnetic stimulation (TMS) in the treatment of major depression has already been shown. Novel TMS coils allowing stimulation of deeper brain regions have recently been developed and studied.Objective: Our study is aimed at exploring the possible efficacy of deep TMS in patients with resistant depression, who previously underwent electroconvalsive therapy (ECT).Methods: Using Brainsway's deep TMS H1 coil, six patients who previously underwent ECT, were treated with 120% power of the motor threshold at a frequency of 20 Hz. Patients underwent five sessions per week, up to 4 weeks. Before the study, patients were evaluated using the Hamilton depression rating scale (HDRS, 24 items), the Hamilton anxiety scale, and the Beck depression inventory and were again evaluated after 5, 10, 15, and 20 daily treatments. Response to treatment was considered a reduction in the HDRS of at least 50%, and remission was considered a reduction of the HDRS-24 below 10 points.Results: Two of six patients responded to the treatment with deep TMS, including one who achieved full remission.Conclusions: Our results suggest the possibility of a subpopulation of depressed patients who may benefit from deep TMS treatment, including patients who did not respond to ECT previously. However, the power of the study is small and similar larger samples are needed.Response to deep TMS in depressive patients with previous electroconvulsive treatment - Corrected ProofOded Rosenberg, Abraham Zangen, Rafael Stryjer, Moshe Kotler, Pinhas N. Dannon10.1016/j.brs.2009.12.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-12-31BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-12-31http://www.brainstimjrnl.com/article/PIIS1935861X09001119/abstract?rss=yesNumerous brain structures are involved in the control of saccadic eye movements forming an extensive network. Situated within this network are the ventral-anterior thalamus and the mediodorsal thalamus as part of a corticobasal gangliathalamic “oculomotor” loop. More lateral thalamic regions such as the ventrolateral (VL) thalamus of the motor thalamus appear additionally involved. For instance, neuroanatomic labeling studies in the monkey found neurons in the dentate nucleus that project via nucleus X of the VL thalamus to the saccade region of the frontal eye field. In addition, immediately posterior to nucleus X is the monkey ventral posterior lateral nucleus pars oralis where microelectrode recording experiments revealed neurons activated by visually guided saccades. These two nuclei of the VL thalamus in the monkey correspond to the ventrooralis posterior and ventrointermedius (VIM) nucleus in humans, where thalamic stroke decreased the amplitude of the primary saccades of visually guided saccades directed away from the side of the lesion. These thalamic lesions included several thalamic segments, making the evidence for the involvement of thalamic subnuclei in the control of visually guided saccades in humans less clear.Involvement of the human ventrolateral thalamus in the control of visually guided saccades - Corrected ProofMartin Kronenbuerger, Esther G. González, Liu D. Liu, Elena Moro, Martin J. Steinbach, Andres M. Lozano, Moji Hodaie, Jonathan O. Dostrovsky, James A. Sharpe, William D. Hutchison10.1016/j.brs.2009.12.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-12-31BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-12-31