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 Neuromodulation1935-861X2010-02-26 © 2010 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://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 - Uncorrected 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/PIIS1935861X10000136/abstract?rss=yesAbstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson's disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation.Patient-specific models of deep brain stimulation: Influence of field model complexity on neural activation predictions - Corrected ProofAshutosh Chaturvedi, Christopher R. Butson, Scott F. Lempka, Scott E. Cooper, Cameron C. McIntyre10.1016/j.brs.2010.01.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-04BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-04http://www.brainstimjrnl.com/article/PIIS1935861X10000021/abstract?rss=yesThe stability of hand-held coil positioning with neuronavigated versus conventional transcranial magnetic stimulation (TMS) is still underinvestigated. Eleven operators naïve for neuronavigation were asked to position and maintain a figure-of-eight-shaped coil over a dipole probe placed within of a polystyrene reproduction of the human head and scalp, in correspondence of the right primary motor cortex. Ten monophasic magnetic pulses were delivered at 46% maximal stimulator output (MSO) in two different experimental conditions: (1) assisted by an optically tracked neuronavigational system; and (2) without neuronavigation. With neuronavigated stimulation, both standard deviation and coefficient of variation of the voltages induced in the dipole probe were significantly lower than without neuronavigation. Results were confirmed in four operators performing a longer-lasting experiment using 50 magnetic pulses in each condition, at an intensity of at 40% MSO. Findings show that optically tracked neuronavigation improves the stability of focal coil positioning.Optically tracked neuronavigation increases the stability of hand-held focal coil positioning: Evidence from “transcranial” magnetic stimulation-induced electrical field measurements - Corrected ProofMassimo Cincotta, Fabio Giovannelli, Alessandra Borgheresi, Fabrizio Balestrieri, Lucia Toscani, Gaetano Zaccara, Filippo Carducci, Maria Pia Viggiano, Simone Rossi10.1016/j.brs.2010.01.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2010)2010-02-01BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2010-02-01http://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 Neuromodulation2009-12-31http://www.brainstimjrnl.com/article/PIIS1935861X09001090/abstract?rss=yesDuring the last two decades, transcranial magnetic stimulation (TMS) has rapidly become a valuable method to investigate noninvasively the human brain. In addition, repetitive TMS (rTMS) is able to induce changes in brain activity that last after stimulation. Therefore, rTMS has therapeutic potential in patients with neurologic and psychiatric disorders. It is, however, unclear by which mechanism rTMS induces these lasting effects on the brain. The effects of rTMS are often described as LTD- or LTP-like, because the duration of these alterations seems to implicate changes in synaptic plasticity. In this review we therefore discuss, based on rTMS experiments and knowledge about synaptic plasticity, whether the physiologic basis of rTMS-effects relates to changes in synaptic plasticity. We present seven lines of evidence that strongly suggest a link between the aftereffects induced by rTMS and the induction of synaptic plasticity. It is, nevertheless, important to realize that at present it is impossible to demonstrate a direct link between rTMS on the one hand and synaptic plasticity on the other. Therefore, we provide suggestions for future, innovating research, aiming to investigate both the local effects of rTMS on the synapse and the effects of rTMS on other, more global levels of brain organization. Only in that way can the aftereffects of rTMS on the brain be completely understood.Physiology of repetitive transcranial magnetic stimulation of the human brain - Corrected ProofJanna Marie Hoogendam, Geert M.J. Ramakers, Vincenzo Di Lazzaro10.1016/j.brs.2009.10.005BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-11-27BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-11-27http://www.brainstimjrnl.com/article/PIIS1935861X09001053/abstract?rss=yesObjective: The cerebellar influence on the motor cortex output is exerted mostly though the cerebellothalamocortical pathway (CTC). One way to explore this pathway is by the means of transcranial magnetic stimulation (TMS). A single-pulse conditioning magnetic stimulation delivered over the lateral cerebellum was shown to diminish the excitability of the contralateral motor cortex 5 milliseconds later (cerebellocortical inhibition [CBI]), most likely through transynaptic activation of cerebellar Purkinje cells, which in turn inhibit the tonic activity of the CTC. Repetitive TMS (rTMS) delivered over the lateral cerebellum was shown to induce a long-lasting change of the cortical excitability, as well, but the mechanism and time course of this effect are still debated.Methods: We tested the time course of the effects of rTMS on the CBI in five paradigms: (1) 1 Hz rTMS, (2) continuous theta burst stimulation (cTBS), and (3) intermittent TBS (iTBS) over the right cerebellum, (4) 1 Hz rTMS over the cervical nerve roots, and (5) 1 Hz rTMS over the left cerebellum. Surface electromyography was recorded from the right first dorsal interosseous (FDI) and adductor digiti minimi. A double-cone coil was used for single-pulse cerebellar stimulation, whereas a figure-of-eight coil was used for the rTMS. The stimulus intensity was set at 90% of the M1 resting motor threshold for 1 Hz rTMS, and at 80% of the M1 active motor threshold for TBS. Both types of cerebellar stimulation were performed under magnetic resonance image (MRI)-guided neuronavigation centered over the right VIII B lobule, and stimulation intensities were adjusted for cerebellar cortex depth. A figure-of-eight coil was used for left motor cortex stimulation.Results: There was significant CBI suppression to the left motor cortex up to 30 minutes after the 900 stimuli of 1 Hz rTMS over either cerebellar hemisphere, and after 600 stimuli of cTBS over the right cerebellum, but not after 600 stimuli of iTBS over the right cerebellum, or after 900 of 1 Hz rTMS stimuli delivered over the cervical nerve roots. The 1 Hz rTMS over the left cerebellum significantly reduced the CBI in the right FDI 10 minutes after the end of the intervention. The amplitudes of the unconditioned cortical motor-evoked potentials were not significantly changed.Conclusions: Our findings suggest that repetitive cerebellar stimulation operate at a cerebellar level, rather then at a cortical level.Long-lasting inhibition of cerebellar output - Corrected ProofT. Popa, M. Russo, S. Meunier10.1016/j.brs.2009.10.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-11-02BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-11-02http://www.brainstimjrnl.com/article/PIIS1935861X09001065/abstract?rss=yesThere is evidence that the right dorsolateral prefrontal cortex (DLPFC) may play a certain role in decision making related to reward value and time perception and, in particular, in the inhibitory control of impulsive decision making. Using the theta burst stimulation (TBS) and a delay discounting (DD) task, we investigated the potential role of right DLPFC in impulsive decision making defined by the rate of discounting delayed reward. Healthy right-handed volunteers underwent three stimulation sessions, intermittent TBS (iTBS), continuous TBS (cTBS), and sham. The steepness of the discount function (k-value), reaction time for choice and consistency were measured for each subjects. cTBS of the DLPFC reduced by 36.88 % the k-value of the DD task compared to sham condition. In contrast, iTBS did not affect impulsivity level. There were no changes neither in reaction time for choice nor consistency after either the iTBS or cTBS compared with the sham stimulation. These results demonstrate that cTBS-induced modulation of cortical excitability of the right DLPFC may affect and reduce impulsive decision making. These observations may provide some insights into the role of the right DLPFC in modulating impulsivity level and calculating reward value at different time scales under less ambiguous circumstances.Continuous theta burst stimulation of right dorsolateral prefrontal cortex induces changes in impulsivity level - Corrected ProofSang Soo Cho, Ji Hyun Ko, Giovanna Pellecchia, Thilo Van Eimeren, Roberto Cilia, Antonio P. Strafella10.1016/j.brs.2009.10.002BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-11-02BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-11-02http://www.brainstimjrnl.com/article/PIIS1935861X09001077/abstract?rss=yesBackground: One major attribute of transcranial magnetic stimulation (TMS) is the variability of motor-evoked potential (MEP) amplitudes, to which variations of coil positioning may contribute. Navigated TMS allows the investigator to retrieve a stimulation site with an accuracy of 2.5 mm and to retain coil position with low spatial divergence during stimulation.Objective: The purpose of this study was to investigate whether increased spatial constancy of the coil using a navigational system decreases the variability of MEP amplitudes and increases their reproducibility between different points in time of investigation.Methods: We investigated eight healthy subjects (mean age 23.8 ± 1.2 years, range 22-25, four women, four men) at three different points in time with and without an optically tracked frameless navigational device, respectively. Input-output curves, motor threshold, and MEP amplitudes were recorded. We calculated the coefficient of variation as statistical parameter of variability. Reproducibility between different sessions was assessed via the MEP amplitude.Results: The coefficient of variance of MEP amplitudes did not show a distinct difference between navigated and non-navigated TMS in input-output curves. MEP amplitudes, indicating reproducibility, did not significantly differ between sessions with and without navigated TMS, either.Conclusions: Our results do not support the hypothesis that increased spatial constancy using a navigational system improves variability and reproducibility of MEP amplitudes. Variability of MEPs might mainly be due to not influenceable neurophysiologic factors such as undulant cortical excitability and spinal desynchronization.Navigated transcranial magnetic stimulation does not decrease the variability of motor-evoked potentials - Corrected ProofNikolai H. Jung, Igor Delvendahl, Nicola G. Kuhnke, Dieter Hauschke, Sabine Stolle, Volker Mall10.1016/j.brs.2009.10.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-11-02BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-11-02http://www.brainstimjrnl.com/article/PIIS1935861X09001089/abstract?rss=yesTo the Editor: The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) have been recently demonstrated in a large randomized placebo-controlled multicenter trial and supported by critical reviews and meta-analyses. However, the clinical relevance of its efficacy is still critically discussed.Intermittent theta burst stimulation (iTBS) ameliorates therapy-resistant depression: A case series - Corrected ProofMaria Holzer, Frank Padberg10.1016/j.brs.2009.10.004BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-11-02BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-11-02LETTER TO THE EDITORhttp://www.brainstimjrnl.com/article/PIIS1935861X09001004/abstract?rss=yesBackground: The amplitude of compound muscle action potentials (CMAPs) evoked in response to magnetic cervical motor root stimulation (MRS) has rarely been used as a diagnostic parameter because of the difficulty in obtaining supramaximal CMAPs.Objective: To clarify whether supramaximal CMAPs could be elicited by MRS, and if so, whether their amplitude and area could be used to evaluate the conduction of proximal motor roots.Method: With the use of a custom-made high-power magnetic stimulator, the CMAPs evoked in response to MRS of the first dorsal interosseous, abductor digiti minimi, and abductor pollicis brevis (APB) muscles were compared with those evoked by electrical stimulation at the wrist, brachial plexus, and cervical motor roots. The collision technique was also used to exclude volume conduction. The correlation between MRS-induced CMAP latency and body height was evaluated.Results: In 32 of 36 normal subjects, supramaximal CMAPs were obtained in response to MRS. The size of CMAPs occurring in response to MRS was the same as the size of those occurring in response to high-voltage electrical cervical motor root stimulation. The collision technique revealed that the APB muscle was highly contaminated by volume conduction from adjacent muscles. CMAP latency correlated significantly with body height.Conclusions: Supramaximal CMAPs can be obtained in most normal subjects. In subjects exhibiting confirmed supramaximal CMAPs in response to MRS, not only the latency of these CMAPs but also their amplitude and area can be clinically useful, excluding CMAPs in the APB muscle.Supramaximal responses can be elicited in hand muscles by magnetic stimulation of the cervical motor roots - Corrected ProofLumine Matsumoto, Ritsuko Hanajima, Hideyuki Matsumoto, Shinya Ohminami, Yasuo Terao, Shoji Tsuji, Yoshikazu Ugawa10.1016/j.brs.2009.09.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-10-22BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-10-22http://www.brainstimjrnl.com/article/PIIS1935861X09000850/abstract?rss=yesBackground: Repetitive transcranial magnetic stimulation (rTMS) treatment of depression utilizes numerous predetermined patterns of stimulation. As an alternative to using invariant stimulus timing parameters, the interactive technique delivers individual stimuli based on the background electroencephalogram (EEG) activity.Objective: This study examines the use of an EEG-dependent technique as a means to enhance the efficacy of rTMS in the treatment of depression.Methods: Forty-four patients with treatment-refractory major depression were treated, in a randomized, doubleblind, 4-week trial, with two different rTMS stimulus timing techniques (left dorsolateral prefrontal cortex). Standard rTMS utilized 10-Hz stimuli, whereas interactive rTMS applied individual stimuli in response to a selected pattern of background EEG activity analyzed in real time. Hamilton Depression Rating Scale (HDRS) and the Beck's Depression Inventory-II (BDI) scores were recorded at baseline, 2 weeks and after the final treatment.Results: The interactive group showed a trend toward greater efficacy than the standard group in both absolute (t=−1.68; P=.100) and percentage (t=−1.74; P=.090) change in scores on HDRS (and similarly BDI). The response rate (>50% reduction) for the interactive technique of 43% (9/21) was also different to that of the standard technique (22%; 5/23; odds ratio: 2.70).Conclusions: The use of EEG-based TMS stimuli has been shown to be feasible in an rTMS clinical trial in treatment-resistant depression. The EEG-based interactive technique was associated with an indication of a trend toward a greater clinical effect than the standard rTMS technique. The interactive technique thus has the potential to refine the rTMS methodology and to enhance efficacy in the treatment of depression.The use of background EEG activity to determine stimulus timing as a means of improving rTMS efficacy in the treatment of depression: A controlled comparison with standard techniques - Corrected ProofGregory W. Price, Joseph W.Y. Lee, Carrie-Anne L. Garvey, Nathan Gibson10.1016/j.brs.2009.08.004BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-09-22BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-09-22http://www.brainstimjrnl.com/article/PIIS1935861X09000849/abstract?rss=yesBackground: Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship.Methods: An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US−). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS−/US+).Results: Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm.Conclusions: We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.Conditioning of transcranial magnetic stimulation: Evidence of sensory-induced responding and prepulse inhibition - Corrected ProofKevin A. Johnson, Gordon C. Baylis, Donald A. Powell, F. Andrew Kozel, Scott W. Miller, Mark S. George10.1016/j.brs.2009.08.003BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-09-18BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-09-18http://www.brainstimjrnl.com/article/PIIS1935861X09000837/abstract?rss=yesBackground: Bupropion is associated with a dose-related increased seizure risk. This effect could correlate with a change in motor cortex excitability. Transcranial magnetic stimulation (TMS) can assess changes in motor cortical excitability by measuring resting motor threshold (RMT).Methods: RMT was determined before and during 2 weeks concomitant administration of bupropion at two different doses (150 mg/d and 300 mg/d) in a 41-year-old woman enrolled in a study of repetitive TMS (rTMS) for the treatment of depression.Results: RMT was significantly lower when the patient took 300 mg/d of bupropion compared with no bupropion and 150 mg/d of bupropion. When bupropion was reduced to 150 mg, RMT returned to the premedication level.Conclusions: Bupropion 300 mg/d increased cortical excitability as demonstrated by decreased RMT. This finding emphasizes the importance of assessing RMT regularly during rTMS treatment, especially in the context of new or changed doses of medications.Bupropion decreases resting motor threshold: A case report - Corrected ProofMustafa A. Mufti, Paul E. Holtzheimer, Charles M. Epstein, Sinéad C. Quinn, Nancie Vito, William M. McDonald10.1016/j.brs.2009.08.001BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-09-14BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-09-14http://www.brainstimjrnl.com/article/PIIS1935861X09000801/abstract?rss=yesBackground: Cortisol may fulfill all criteria for a neuromodulator. However, it is not known whether it may rapidly influence motor system activity in humans.Objective: Circulating cortisol levels were manipulated by administration of a single intravenous dose of hydrocortisone or saline solution, on separate days, to study changes in corticospinal and motor cortical excitability.Methods: Motor-evoked potentials (MEPs) to single- and paired-pulse transcranial magnetic stimulation from the resting first dorsal interosseous muscle, and cortisol plasma levels were assessed before and after either a bolus of 20 mg of hydrocortisone or saline solution in seven healthy subjects.Results: Mean cortisol plasma level rapidly rose, peaked between 5 and 10 minutes after hydrocortisone injection, to slowly decay afterward. Mean MEP amplitude significantly increased from preinjection levels, and mean standard deviation of MEPs significantly increased between 8-12 minutes postinjection. Short-intracortical inhibition, tested during the same period, was significantly decreased. No significant changes in the above measures were observed after saline solution administration.Conclusions: Our results suggest that high circulating levels of cortisol rapidly increase corticospinal excitability and reduce gamma aminobutyric acid activity, as measured by short-intracortical inhibition, in humans. These effects, lasting about 10 minutes, were observed within 15 minutes from the pharmacological intervention. They are therefore compatible with a nongenomic mechanism. These findings are important in view of the notion that a decrease in intracortical gamma aminobutyric acid activity appears to be a prerequisite for motor learning and plastic processes in the human motor cortex.Cortisol-induced effects on human cortical excitability - Corrected ProofPaolo Milani, Pietro Piu, Traian Popa, Raimondo della Volpe, Marco Bonifazi, Alessandro Rossi, Riccardo Mazzocchio10.1016/j.brs.2009.07.004BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-08-21BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-08-21http://www.brainstimjrnl.com/article/PIIS1935861X09000813/abstract?rss=yesThe majority of high-frequency repetitive transcranial magnetic stimulation (rTMS) studies in depressed patients use 10 Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). However, several placebo-controlled trials have used different stimulation frequencies such as 5, 10, 15, 17, 20, and 25 Hz and all found antidepressant effects. The choice of high-stimulation frequencies to date has remained fairly random and has rarely been based on individual physiological characteristics of a patient. To the authors' knowledge, only two studies, neither in depressed patients, have used an electroencephalogram (EEG)-based approach to establish the rTMS frequency that was linked to the individual patients' alpha peak frequency (iAPF). Klimesch et al. and Jin et al. both demonstrated that subjects with a personalized iAPF, it was detemined that rTMS had a greater effect (better improvement at a mental rotation task and a higher improvement in negative symptoms in a group of patients with schizophrenia) in comparison to two groups that received treatment with 3 Hz and 20 Hz stimulation frequencies. Both these studies demonstrated frequency-specific effects titrated to the individual subject.Potential differential effects of 9 Hz rTMS and 10 Hz rTMS in the treatment of depression - Corrected ProofMartijn Arns, Desirée Spronk, Paul B. Fitzgerald10.1016/j.brs.2009.07.005BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation (2009)2009-08-20BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation2009-08-20