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  • Task-dependent effects of intracranial hippocampal stimulation on human memory and hippocampal theta power
    Brain Stimul. (IF 6.919) Pub Date : 2020-01-25
    Soyeon Jun; Sang Ah Lee; June Sic Kim; Woorim Jeong; Chun Kee Chung

    Background Despite its potential to revolutionize the treatment of memory dysfunction, the efficacy of direct electrical hippocampal stimulation for memory performance has not yet been well characterized. One of the main challenges to cross-study comparison in this area of research is the diversity of the cognitive tasks used to measure memory performance. Objective We hypothesized that the tasks that differentially engage the hippocampus may be differentially influenced by hippocampal stimulation and the behavioral effects would be related to the underlying hippocampal activity. Methods To investigate this issue, we recorded intracranial EEG from and directly applied stimulation to the hippocampus of 10 epilepsy patients while they performed two different verbal memory tasks – a word pair associative memory task and a single item memory task. Results Hippocampal stimulation modulated memory performance in a task-dependent manner, improving associative memory performance, while impairing item memory performance. In addition, subjects with poorer baseline cognitive function improved much more with stimulation. iEEG recordings from the hippocampus during non-stimulation encoding blocks revealed that the associative memory task elicited stronger theta oscillations than did item memory and that stronger theta power was related to memory performance. Conclusions We show here for the first time that stimulation-induced associative memory enhancement was linked to increased theta power during retrieval. These results suggest that hippocampal stimulation enhances associative memory but not item memory because it engages more hippocampal theta activity and that, in general, increasing hippocampal theta may provide a neural mechanism for successful memory enhancement.

    更新日期:2020-01-26
  • Treatment of Executive Function Deficits in Autism Spectrum Disorder with Repetitive Transcranial Magnetic Stimulation: A double-blind, sham-controlled, pilot trial
    Brain Stimul. (IF 6.919) Pub Date : 2020-01-15
    Stephanie H. Ameis; Daniel M. Blumberger; Paul E. Croarkin; Donald J. Mabbott; Meng-Chuan Lai; Pushpal Desarkar; Peter Szatmari; Zafiris J. Daskalakis

    Background In youth and young adults with autism spectrum disorder(ASD), executive function(EF) deficits may be a promising treatment target with potential impact on everyday functioning. Objective To conduct a pilot randomized, double-blind, parallel, controlled trial evaluating repetitive transcranial magnetic stimulation(rTMS) for EF deficits in ASD. Method In Toronto, Ontario (November 2014 to June 2017), a 20-session, 4-week course of 20Hz rTMS targeting dorsolateral prefrontal cortex (90%RMT) was compared to sham stimulation in 16-35 year-olds with ASD (28 male/12 female), without intellectual disability, who had impaired everyday EF performance(n=20 active/n=20 sham). Outcome measures evaluated protocol feasibility and clinical effects of active vs. sham rTMS on EF performance. The moderating effect of baseline functioning was explored. Results Of eligible participants, 95% were enrolled and 95% of randomized participants completed the protocol. Adverse events across treatment arms were mild-to-moderate. There was no significant difference between active vs. sham rTMS on EF performance. Baseline adaptive functioning moderated the effect of rTMS, such that participants with lower baseline functioning experienced significant EF improvement in the active vs. sham group. Conclusions Our pilot RCT demonstrated the feasibility and acceptability of using high frequency rTMS targeting DLPFC in youth and young adults with autism. No evidence for efficacy of active versus sham rTMS on EF performance was found. However, we found promising preliminary evidence of EF performance improvement following active versus sham rTMS in participants with ASD with more severe adaptive functioning deficits. Future work could focus on examining efficacy of rTMS in this higher-need population. Clinical Trial Registration Repetitive Transcranial Magnetic Stimulation (rTMS) for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure: A Pilot Study; https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751. The trial was funded by: an American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award, the Innovation Fund from the Alternate Funding Plan of the Academic Health Sciences Centres of Ontario, and an Ontario Mental Health Foundation (OMHF) Project A Grant and New Investigator Fellowship.

    更新日期:2020-01-15
  • Reliability of Targeting Methods in TMS for Depression: Beam F3 vs. 5.5 cm
    Brain Stimul. (IF 6.919) Pub Date : 2020-01-14
    Nicholas T. Trapp; Joel Bruss; Marcie King Johnson; Brandt D. Uitermarkt; Laren Garrett; Amanda Heinzerling; Chaorong Wu; Timothy R. Koscik; Patrick Ten Eyck; Aaron D. Boes

    Background No consensus exists in the clinical transcranial magnetic stimulation (TMS) field as to the best method for targeting the left dorsolateral prefrontal cortex (DLPFC) for depression treatment. Two common targeting methods are the Beam F3 method and the 5.5 cm rule. Objective Evaluate the anatomical reliability of technician-identified DLPFC targets and obtain consensus average brain and scalp MNI152 coordinates. Methods Three trained TMS technicians performed repeated targeting using both the Beam F3 method and 5.5 cm rule in ten healthy subjects (n=162). Average target locations were plotted on 7T structural MRIs to compare inter- and intra-rater reliability, respectively. Results (1) Beam F3 inter- and intra-rater reliability was superior to 5.5 cm targeting (p = 0.0005 and 0.0035). (2) The average Beam F3 location was 2.6 +/- 1.0 cm anterolateral to the 5.5 cm method. Conclusions Beam F3 targeting demonstrates greater precision and reliability than the 5.5 cm method and identifies a different anatomical target.

    更新日期:2020-01-15
  • Effect of Repetitive Transcranial Magnetic Stimulation on Altered Perception of One´s Own Face
    Brain Stimul. (IF 6.919) Pub Date : 2020-01-08
    Simple Futarmal Kothari; Lilja Kristin Dagsdottir; Mohit Kothari; Jakob Udby Blicher; Abhishek Kumar; Poul Erik Buchholtz; Mahmoud Ashkanian; Peter Svensson

    Background Chronic orofacial pain (COP) patients often perceive the painful face area as “swollen” without clinical signs; such self-reported illusions of the face are termed perceptual distortion (PD). The pathophysiological mechanisms underlying PD remain elusive. Objective To test the neuromodulatory effect of repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals, to gain insight into the cortical mechanisms underlying PD. Methods PD was induced experimentally by injections of local anesthetic (LA) around the infraorbital nerve and measured as perceived size changes of the affected area. Participants were randomly allocated to inhibitory rTMS (n=26) or sham rTMS (n=26) group. The participants rated PD at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. The rTMS (inhibitory and sham) was applied to face (lip) representation area of primary somatosensory cortex (SI) as an intervention at 10 min after the LA, when the magnitude of PD is large. As inhibitory rTMS, continuous theta-burst stimulation paradigm (50 Hz) for 40s was employed to inhibit cortical activity. Results We demonstrated a significant decrease in the magnitude of PD immediately and 20 min after the application of inhibitory rTMS compared with sham rTMS (P<0.006). In two control experiments, we also showed that peripheral muscle stimulation and stimulation of a cortical region other than the lip representation area had no effect on the magnitude of the PD. Conclusions Inhibitory rTMS applied to a somatotopical-relevant cortical region modulates PD of the face in healthy individuals and could potentially have therapeutic implications for COP patients.

    更新日期:2020-01-09
  • Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: A randomized, double-blind, parallel-group study
    Brain Stimul. (IF 6.919) Pub Date : 2020-01-03
    Jaber Alizadehgoradel; Vahid Nejati; Fariba Sadeghi Movahed; Saeed Imani; Mina Taherifard; Mohsen Mosayebi-Samani; Carmelo M. Vicario; Michael A. Nitsche; Mohammad Ali Salehinejad

    Background According to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction. Methods We assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to “active” and “sham” stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement. Results The group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well. Conclusions Improvement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.

    更新日期:2020-01-04
  • Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-31
    Anna Vázquez-Oliver; Cecilia Brambilla-Pisoni; Mikel Domingo-Gainza; Rafael Maldonado; Antoni Ivorra; Andrés Ozaita

    Background Vagus nerve stimulation (VNS) using non-invasive approaches have attracted great attention due to their anti-epileptic, anti-depressive and pro-cognitive effects. It has been proposed that auricular transcutaneous VNS (atVNS) could benefit intellectual disability disorders, but preclinical data supporting this idea is limited. Objective To develop an atVNS device for mice and to test its efficacy on memory performance in naïve mice and in a mouse model for intellectual disability. Methods Naïve outbreed CD-1 mice and a model for fragile X syndrome, the Fmr1 knockout (Fmr1KO), were used to assess the effect of atVNS in the novel object-recognition memory performance. Results We found that atVNS significantly improves memory persistence in naïve mice. Notably, atVNS was efficacious in normalizing the object-recognition memory deficit in the Fmr1KO model. Conclusion Our data show that atVNS improves memory persistence in naïve mice and in a model of intellectual disability and support further studies taking advantage of preclinical mouse models of cognitive disorders.

    更新日期:2020-01-01
  • Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-30
    Zewdie E; Ciechanski P; Kuo H; Giuffre A; Kahl C; King R; Cole L; Godfrey H; Seeger T; Swansburg R; Damji O; Rajapakse T; Hodge J; Nelson S; Selby B; Gan L; Jadavji Z; Larson J; Kirton A

    Background Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. Objective To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. Methods A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. Results Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8–18.0). Populations included typical development (n=118), perinatal stroke/cerebral palsy (n=101), mild traumatic brain injury (n=121) neuropsychiatric disorders (n=37), and other (n=7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. Conclusions Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted.

    更新日期:2019-12-30
  • Comparison of fiber tract low frequency stimulation to focal and ANT stimulation in an acute rat model of focal cortical seizures
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-28
    Nicholas H. Couturier; Dominique M. Durand

    Background Current implementations of direct brain stimulation for epilepsy in patients involve high-frequency (HFS) electrical current and targeting of grey matter. Studies have shown that low-frequency (LFS) fiber-tract stimulation may also prove effective. To compare the efficacy of high-frequency grey matter stimulation to the low-frequency fiber tract stimulation technique a well-controlled set of experiments using a single animal model of epilepsy is needed. Objective The goal of this study was to determine the relative efficacy of different direct brain stimulation techniques for suppressing seizures using an acute rat model of focal cortical seizures. Methods 4-AP was injected into the S1 region of cortex in rodents over three hours. LFPs were recorded from the seizure focus and mirror focus to monitor seizure frequency during the experiments. CC-LFS, HFS-ANT, Focal-HFS, or a transection of the CC was applied. Results Stimulation of the CC yielded a 65%+/-14% (p = 0.0014) reduction of seizures in the focus and a 97% +/-15% (p = 0.0026) reduction in the mirror focus (n = 7). By comparison transection of the CC produced a 65%+/-18% reduction in the focus and a non-statistically significant reduction of 57% +/-18% (p = 0.1381) in the mirror focus (n = 5). All other methods of stimulation failed to have a statistically significant effect on seizure suppression. Conclusions LFS of the CC is the only method of stimulation to significantly reduce seizure frequency in this model of focal cortical seizures. These results support the hypothesis that LFS of fiber tracts has significant potential for seizure control.

    更新日期:2019-12-29
  • Model-driven neuromodulation of the right posterior region promotes encoding of long-term memories
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-19
    Ivan Alekseichuk; Zsolt Turi; Sibel Veit; Walter Paulus

    Background Long-term recognition memory depends both on initial encoding and on subsequent recognition processes. Objective In this study we aimed at improving long-term memory by modulating posterior parietal brain activity during the encoding process. If this area is causally involved in memory encoding, its facilitation should lead to behavioral improvement. Based on the dual-process memory framework, we also expected that the neuromodulation would dissociate subsequent familiarity-based and recollection-based recognition. Methods We investigated the role of the posterior parietal brain oscillations in facial memory formation in three separate experiments using electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and model-driven, multi-electrode transcranial alternating current stimulation (tACS). Results Using fMRI and EEG, we confirmed that the right posterior parietal cortex is an essential node that promotes the encoding of long-term memories. We found that single-trial low theta power in this region predicts subsequent long-term recognition. On this basis, we fine-tuned the spatial and frequency settings of tACS during memory encoding. Model-driven tACS over the right posterior brain area augmented subsequent long-term recognition memory and particularly the familiarity of the observed stimuli. The recollection process, and short-term task performance as control remained unchanged. Control stimulation over the left hemisphere had no behavioral effect. Conclusion We conclude that the right posterior brain area is crucial in long-term memory encoding.

    更新日期:2019-12-19
  • Interhemispheric facilitation of gesturing: A combined theta burst stimulation and diffusion tensor imaging study
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-18
    Tim Vanbellingen; Manuela Pastore-Wapp; Stefanie Kübel; Thomas Nyffeler; Anne-Catherine Schüpfer; Claus Kiefer; Leopold Zizlsperger; Kai Lutz; Andreas R. Luft; Sebastian Walther; Stephan Bohlhalter

    Background Imaging studies point to a posture (finger vs. hand) and domain-specific neural basis of gestures. Furthermore, modulation of gestures by theta burst stimulation (TBS) may depend on interhemispheric disinhibition. Objective /Hypothesis: In this randomized sham-controlled study, we hypothesized that dual site continuous TBS over left inferior frontal gyrus (IFG-L) and right inferior parietal gyrus (IPL-R) predominantly affects pantomime of finger postures. Furthermore, we predicted that dual cTBS improves imitation of hand gestures if the effect correlates with measures of callosal connectivity. Methods Forty-six healthy subjects participated in this study and were targeted with one train of TBS in different experimental sessions: baseline, sham, single site IFG-L, dual IFG-L/IPL-R, single site IPL-R. Gestures were evaluated by blinded raters using the Test for Upper Limb Apraxia (TULIA) and Postural Imitation Test (PIT). Callosal connectivity was analyzed by diffusion tensor imaging (DTI). Results Dual cTBS significantly improved TULIAtotal (F [3, 28] = 4.118, p = .009), but did not affect TULIApantomime. The beneficial effect was driven by the cTBS over IPL-R, which improved TULIAimitation (p = .038). Furthermore, TULIAimitation significantly correlated with the microstructure (fractional anisotropy) of the splenium (r = 0.420, p = .026), corrected for age and whole brain volume. Conclusions The study suggests that inhibition of IPL-R largely accounted for improved gesturing, possibly through transcallosal facilitation of IPL-L. Therefore, the findings may be relevant for the treatment of apraxic stroke patients. Gesture pantomime and postural gestures escaped the modulation by dual cTBS, suggesting a more widespread and/or variable neural representation.

    更新日期:2019-12-19
  • Non-invasive stimulation of vagal afferents reduces gastric frequency
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-18
    Vanessa Teckentrup; Sandra Neubert; João C.P. Santiago; Manfred Hallschmid; Martin Walter; Nils B. Kroemer
    更新日期:2019-12-19
  • Effects of the Anaesthetic-ECT Time Interval and Ventilation Rate on Seizure Quality in Electroconvulsive Therapy: A Prospective Randomised Trial
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-18
    Rohan Taylor; Harry Wark; John Leyden; Brett Simpson; Jenny McGoldrick; Dusan Hadzi-Pavlovic; Hank Ke Han; Stevan Nikolin; Donel Martin; Colleen Loo

    Background The anaesthetic approach adopted in ECT practice has the potential to influence patient outcomes. However, the impact of the time interval between anaesthetic induction and ECT stimulus administration has not been studied prospectively to date. This variable may represent an indirect measure of anaesthetic concentration at the time of stimulation, and therefore may influence the quality of seizures induced. Objective To examine the impact of the anaesthetic to ECT stimulus time interval, and ventilation rate pre-treatment, on ictal seizure quality. Methods In a prospective, crossover trial, 54 depressed participants were randomised to variations in anaesthetic technique at four sequential ECT treatment sessions, in a 2 x 2 design: randomisation to a short or long anaesthetic-ECT time interval, and randomisation to normal ventilation or hyperventilation during anaesthetic induction with thiopentone. Ictal EEG data were collected at each study session and assessed by a blinded rater for ictal quality (seizure amplitude, regularity, post-ictal suppression and general seizure quality), using a quantitative-qualitative structured rating scale. Linear mixed effects models were used to analyse the effect of the anaesthetic-ECT time interval, and that of ventilation rate, on seizure quality indices. Results The anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p<0.01), with longer time intervals producing higher quality seizures. Ventilation rate did not significantly influence quality measures. Conclusion The time between anaesthetic induction and ECT stimulus administration has a significant impact on ictal EEG seizure quality. Conversely, manipulations of ventilation rate did not significantly affect seizure quality. These results suggest the anaesthetic-ECT time interval should be routinely monitored clinically and potentially optimised for maximising seizure quality with ECT.

    更新日期:2019-12-19
  • Parietal conditioning enhances motor surround inhibition
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-18
    Nivethida Thirugnanasambandam; Giorgio Leodori; Traian Popa; Panagiotis Kassavetis; Alexandra Mandel; Alexander Shaft; Jaron Kee; Sarung Kashyap; Gregg Khodorov; Mark Hallett

    Background Motor surround inhibition (mSI) is a phenomenon supportive for executing selective finger movements, wherein synergist muscles are selectively facilitated while surround muscles are inhibited. Previous studies of conditioning inputs to several intracortical and cortico-cortical inhibitory networks did not show an influence on mSI. The inhibitory posterior parietal-motor network, which is crucial for executing fine movements, however, has not been studied. Objective/Hypothesis To investigate the role of inhibitory posterior parietal-motor network in mSI. We hypothesized that conditioning this inhibitory network would enhance mSI. Methods 11 healthy adults completed study. mSI was elicited by applying a TMS pulse over the motor cortex coupled with or without a conditioning input to an inhibitory spot in the posterior parietal cortex at 2 or 4ms interval. Results Conditioning input to the posterior parietal cortex increased mSI by ∼20%. Conclusion: The inhibitory posterior parietal-motor network appears to contribute to the genesis of mSI.

    更新日期:2019-12-18
  • Continuous Deep Brain Stimulation of the Subthalamic Nucleus may not Modulate Beta Bursts in Patients with Parkinson’s Disease
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-17
    Stephen L. Schmidt; Jennifer J. Peters; Dennis A. Turner; Warren M. Grill

    Background Neural oscillations represent synchronous neuronal activation and are ubiquitous throughout the brain. Oscillatory activity often includes brief high-amplitude bursts in addition to background oscillations, and burst activity may predict performance on working memory, motor, and comprehension tasks. Objective We evaluated beta burst activity as a possible biomarker for motor symptoms in Parkinson’s disease (PD). The relationship between beta amplitude dynamics and motor symptoms is critical for adaptive DBS for treatment of PD. Methods We applied threshold-based and support vector machine (SVM) analyses of burst parameters to a defined on/off oscillator and to intraoperative recordings of local field potentials from the subthalamic nucleus of 16 awake patients with PD. Results Filtering and time-frequency analysis techniques critically influenced the accuracy of identifying burst activity. Threshold-based analysis lead to biased results in the presence of changes in long-term beta amplitude and accurate quantification of bursts with thresholds required unknowable a priori knowledge of the time in bursts. We therefore implemented an SVM analysis, and we did not observe changes in burst fraction, rate, or duration with the application of cDBS in the participant data, even though SVM analysis was able to correctly identify bursts of the defined on/off oscillator. Conclusion Our results suggest that cDBS of the STN may not change beta burst activity. Additionally, threshold-based analysis can bias the fraction of time spent in bursts. Improved analysis strategies for continuous and adaptive DBS may achieve improved symptom control and reduce side-effects.

    更新日期:2019-12-18
  • Mechanical stimulation of cervical vertebrae modulates the discharge activity of ventral tegmental area neurons and dopamine release in the nucleus accumbens
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-04
    Kyle B. Bills, J.Daniel Obray, Travis Clarke, Mandy Parsons, James Brundage, Chae Ha Yang, Hee Young Kim, Jordan T. Yorgason, Jonathan D. Blotter, Scott C. Steffensen

    Background Growing evidence suggests that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) outside the canonical somatosensory circuits. Objective/Methods: We evaluate mechanical stimulation applied to the cervical spine at the C7-T1 level (termed “MStim”) on neurons and neurotransmitter release in the mesolimbic dopamine (DA) system, an area implicated in reward and motivation, utilizing electrophysiological, pharmacological, neurochemical and immunohistochemical techniques in Wistar rats. Results Low frequency (45-80 Hz), but not higher frequency (115 Hz), MStim inhibited the firing rate of ventral tegmental area (VTA) GABA neurons (52.8% baseline; 450 sec) while increasing the firing rate of VTA DA neurons (248% baseline; 500 sec). Inactivation of the nucleus accumbens (NAc), or systemic or in situ antagonism of delta opioid receptors (DORs), blocked MStim inhibition of VTA GABA neuron firing rate. MStim enhanced both basal (178.4 % peak increase at 60 min) and evoked DA release in NAc (135.0 % peak increase at 40 min), which was blocked by antagonism of DORs or acetylcholine release in the NAc. MStim enhanced c-FOS expression in the NAc, but inhibited total expression in the VTA, and induced translocation of DORs to neuronal membranes in the NAc. Conclusion These findings demonstrate that MStim modulates neuron firing and DA release in the mesolimbic DA system through endogenous opioids and acetylcholine in the NAc. These findings demonstrate the need to explore more broadly the extra-somatosensory effects of peripheral mechanoreceptor activation and the specific role for mechanoreceptor-based therapies in the treatment of substance abuse.

    更新日期:2019-12-04
  • High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-04
    Charles W. Lu, Karlo A. Malaga, Kelvin L. Chou, Cynthia A. Chestek, Parag G. Patil

    Background Subthalamic deep brain stimulation alleviates motor symptoms of Parkinson disease by activating precise volumes of neural tissue. While electrophysiological and anatomical correlates of clinically effective electrode sites have been described, therapeutic stimulation likely acts through multiple distinct neural populations, necessitating the need to characterize the full span of tissue activation. Microelectrode recordings have yet to be mapped to therapeutic tissue activation volumes and surveyed for predictive markers. Objective Combine high-density, broadband microelectrode recordings with detailed computational models of tissue activation to describe and to predict regions of therapeutic tissue activation. Methods Electrophysiological features were extracted from microelectrode recordings along 23 subthalamic deep brain stimulation implants in 16 Parkinson disease patients. These features were mapped in space against tissue activation volumes of therapeutic stimulation, modeled using clinically-determined stimulation programming parameters and fully individualized, atlas-independent anisotropic tissue properties derived from 3T diffusion tensor magnetic resonance images. Logistic LASSO was applied to a training set of 17 implants out of the 23 implants to identify predictors of therapeutic stimulation sites in the microelectrode recording. A support vector machine using these predictors was used to predict therapeutic activation. Performance was validated with a test set of six implants. Results Analysis revealed wide variations in the distribution of therapeutic tissue activation across the microelectrode recording-defined subthalamic nucleus. Logistic LASSO applied to the training set identified six oscillatory predictors of therapeutic tissue activation: theta, alpha, beta, high gamma, high frequency oscillations (HFO, 200-400 Hz), and high frequency band (HFB, 500-2000 Hz), in addition to interaction terms: theta x HFB, alpha x beta, beta x HFB, and high gamma x HFO. A support vector classifier using these features predicted therapeutic sites of activation with 64% sensitivity and 82% specificity in the test set, outperforming a beta-only classifier. A probabilistic predictor achieved 0.87 area under the receiver-operator curve with test data. Conclusions Together, these results demonstrate the importance of personalized targeting and validate a set of microelectrode recording signatures to predict therapeutic activation volumes. These features may be used to improve the efficiency of deep brain stimulation programming and highlight specific neural oscillations of physiological importance.

    更新日期:2019-12-04
  • Transcranial Direct Current Stimulation Facilitates Insight Learning
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-26
    Benjamin C. Gibson, Teagan S. Mullins, Melissa D. Heinrich, Katie Witkiewitz, Alfred B. Yu, Jeffrey T. Hansberger, Vincent P. Clark

    Background After two decades of transcranial direct current stimulation (tDCS) research, it is still unclear which applications benefit most from which tDCS protocols. One prospect is the acceleration of learning, where previous work has demonstrated that anodal tDCS applied to the right ventrolateral prefrontal cortex (rVLPFC) is capable of doubling the rate of learning in a visual camouflaged target detection and classification task. Goals Questions remain as to the specific cognitive mechanisms underlying this learning enhancement, and whether it generalizes to other tasks. The goal of the current project was to expand previous findings by employing a novel visual classification task. Methods Participants learned to classify pictures of European streets within a discovery learning paradigm. In a double-blind design, 54 participants were randomly assigned to 30 minutes of tDCS using either 2.0 mA anodal (n=18), cathodal (n=18), or 0.1 mA sham (n=18) tDCS over the rVLPFC. Results A linear mixed-model revealed a significant effect of tDCS condition on classification accuracy across training (p=0.001). Compared to a 4.2% increase in sham participants, anodal tDCS over F10 increased performance by 20.6% (d=1.71) and cathodal by 14.4% (d=1.16). Conclusions These results provide further evidence for the capacity of tDCS applied to rVLPFC to enhance learning, showing a greater than quadrupling of test performance after training (491% of sham) in a difficult image classification task requiring insight. Combined with our previous studies, these results suggest a generalized performance enhancement. Other tasks requiring sustained attention, insight or categorization learning may also benefit from this protocol.

    更新日期:2019-11-27
  • Clinical trials for deep brain stimulation: Current state of affairs
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-23
    Irene E. Harmsen, Gavin J.B. Elias, Michelle E. Beyn, Alexandre Boutet, Aditya Pancholi, Jürgen Germann, Alireza Mansouri, Christopher S. Lozano, Andres M. Lozano

    Background; Deep brain stimulation (DBS) is a surgical neuromodulation procedure with a historically wide range of possible therapeutic indications, including movement disorders, neuropsychiatric conditions, and cognitive disorders. Ongoing research in this field is critical to gain further insights into the mechanisms of DBS, to discover novel brain targets for new and existing indications, and to refine targeting and post-operative programming techniques for the optimization of therapeutic outcomes. Objective; To update on the state of DBS-related clinical human research by cataloging and summarizing clinical trials that have been completed or are currently ongoing in this field worldwide. Methods; A search was conducted for clinical trials pertaining to DBS, currently listed on the ClinicalTrials.gov database. Trials were analyzed to generate a detailed overview of ongoing DBS-related research. Specifically, trials were categorized by trial start date, study completion status, clinical phase, projected subject enrollment, disorder, brain target, country of origin, device manufacturer, funding source, and study topic. Results; In total, 384 relevant clinical trials were identified. The trials spanned 28 different disorders across 26 distinct brain targets, with almost 40% of trials being for conditions other than movement disorders. The majority of DBS trials have been US-based (41.9% of studies) but many countries are becoming increasingly active. The ratio of investigator-sponsored to industry-sponsored trials was 3:1. Emphasizing the need to better understand the mechanism of action of DBS, one-third of the studies predominantly focus on imaging or electrophysiological changes associated with DBS. Conclusions; This overview of current DBS-related clinical trials provides insight into the status of DBS research and what we can anticipate in the future concerning new brain targets, indications, techniques, and developing a better understanding of the mechanisms of action of DBS.

    更新日期:2019-11-26
  • TMS for staging and predicting functional decline in Frontotemporal Dementia
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-22
    Alberto Benussi, Valentina Dell’Era, Valentina Cantoni, Maria Sofia Cotelli, Maura Cosseddu, Marco Spallazzi, Anna Micheli, Rosanna Turrone, Antonella Alberici, Barbara Borroni

    Objective To evaluate if transcranial magnetic stimulation (TMS) measures correlate with disease severity and predict functional decline in frontotemporal dementia (FTD) phenotypes. Methods Paired-pulse TMS was used to investigate the activity of different intracortical circuits in 171 FTD patients (122 bvFTD, 31 avPPA, 18 svPPA) and 74 healthy controls. Pearson’s correlations were used to analyze the association between TMS measures and disease severity, while multiple regression analysis was used to identify the best clinical or neurophysiological measure to predict functional decline at 12 months. Results We observed significant strong correlations between TMS measures [short interval intracortical inhibition-facilitation (SICI-ICF) and long interval intracortical inhibition (LICI)], and disease severity (evaluated with the FTLD-CDR) (all r>0.5, p<0.005). SICI-ICF, short interval intracortical facilitation (SICF) and LICI were also significant predictors of functional decline, evaluated as the change in FTLD-CDR scores at 12 months (all p<0.005), while at the stepwise multiple regression analysis, SICI was the best predictor of disease progression, accounting for 72.5% of the variation in FTLD-CDR scores at 12 months (adjusted R2=0.72, p<0.001). Conclusions The present study has shown that the dysfunction of inhibitory and facilitatory intracortical circuits, evaluated with TMS, correlates with disease severity and progression, accurately predicting functional decline at 12 months, better than any other investigated marker.

    更新日期:2019-11-22
  • Transcranial electrical stimulation nomenclature
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-17
    Marom Bikson, Zeinab Esmaeilpour, Devin Adair, Greg Kronberg, William J. Tyler, Andrea Antal, Abhishek Datta, Bernhard A. Sabel, Michael A. Nitsche, Colleen Loo, Dylan Edwards, Hamed Ekhtiari, Helena Knotkova, Adam J. Woods, Benjamin M. Hampstead, Bashar W. Badran, Angel V. Peterchev

    Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.

    更新日期:2019-11-18
  • Effects of beta-tACS on corticospinal excitability: A meta-analysis
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-28
    Miles Wischnewski, Dennis J.L.G. Schutter, Michael A. Nitsche

    Over the past decade several studies have shown that transcranial alternating current stimulation (tACS) delivered at the beta (15–25 Hz) frequency range can increase corticospinal excitability of the primary motor cortex (M1). The aim of this study was to systematically quantify the effect size of beta-tACS on corticospinal excitability in healthy volunteers, as well as to identify significant outcome predictors. A meta-analysis was performed on the results of 47 experiments reported in 21 studies. Random effects modelling of the effect sizes showed that beta-tACS significantly increases M1 excitability (Ē = 0.287, 95% CI = 0.133–0.440). Further analysis showed that tACS intensities above 1 mA peak-to-peak yield a robust increase in M1 excitability, whereas intensities of 1 mA peak-to-peak and below do not induce a reliable change. Additionally, results showed an impact of tACS montages on these effects. No difference in effect size for online compared to offline application of tACS was found. In conclusion, these findings indicate that beta-tACS can increase cortical excitability if stimulation intensity is above 1 mA, yet more research is needed to titrate the stimulation parameters that yield optimal results.

    更新日期:2019-11-18
  • Electrical stimulation of the ventral hippocampal commissure delays experimental epilepsy and is associated with altered microRNA expression
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-07
    Lara S. Costard, Valentin Neubert, Morten T. Venø, Junyi Su, Jørgen Kjems, Niamh M.C. Connolly, Jochen H.M. Prehn, Gerhard Schratt, David C. Henshall, Felix Rosenow, Sebastian Bauer

    Background Up to 80% of mesial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS) are resistant to pharmacological treatment, often necessitating surgical resection. Deep brain stimulation (DBS) has emerged as an alternative treatment for patients who do not qualify for resective brain surgery. Brain stimulation may also exert disease-modifying effects, and noncoding microRNAs have recently been proposed to shape the gene expression landscape in epilepsy. Objective We compared the effect of DBS of 4 different hippocampal target regions on epileptogenesis and manifest epilepsy in a rat model of mTLE-HS. To explore mechanisms, we profiled the effect of the most effective DBS paradigm on hippocampal microRNA levels. Methods MTLE-HS was induced by electrical stimulation of the perforant pathway (PP) in rats. This paradigm leads to spontaneous seizures within 4 weeks. We investigated DBS of 4 targets: PP, fimbria fornix (FF) formation, dentate gyrus (DG) and ventral hippocampal commissure (VHC). We applied both high- (130 Hz) and low-frequency (5 Hz or 1 Hz) stimulation. Functional microRNAs were identified in the hippocampus immediately after VHC-DBS and after a 97-day recording period by sequencing small RNAs bound to Argonaute-2, a component of the miRNA silencing complex. Results Low frequency DBS of the VHC significantly delayed the occurrence of the first spontaneous recurrent seizure in the PPS model by ∼300%, from 19 to 56 days. No other stimulation regime altered the latency phase. Upregulation of 5 microRNAs during epileptogenesis was suppressed by VHC-stimulation. Conclusion We conclude that DBS of the VHC delays epilepsy in the PPS model in rats and is associated with differential regulation of several miRNAs. Additional studies are required to determine whether VHC-regulated miRNAs serve causal roles in the anti-epileptogenic effects of this DBS model.

    更新日期:2019-11-18
  • Theoretical principles of deep brain stimulation induced synaptic suppression
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-10
    AmirAli Farokhniaee, Cameron C. McIntyre

    Background Deep brain stimulation (DBS) is a successful clinical therapy for a wide range of neurological disorders; however, the physiological mechanisms of DBS remain unresolved. While many different hypotheses currently exist, our analyses suggest that high frequency (∼100 Hz) stimulation-induced synaptic suppression represents the most basic concept that can be directly reconciled with experimental recordings of spiking activity in neurons that are being driven by DBS inputs. Objective The goal of this project was to develop a simple model system to characterize the excitatory post-synaptic currents (EPSCs) and action potential signaling generated in a neuron that is strongly connected to pre-synaptic glutamatergic inputs that are being directly activated by DBS. Methods We used the Tsodyks-Markram (TM) phenomenological synapse model to represent depressing, facilitating, and pseudo-linear synapses driven by DBS over a wide range of stimulation frequencies. The EPSCs were then used as inputs to a leaky integrate-and-fire neuron model and we measured the DBS-triggered post-synaptic spiking activity. Results Synaptic suppression was a robust feature of high frequency stimulation, independent of the synapse type. As such, the TM equations were used to define alternative DBS pulsing strategies that maximized synaptic suppression with the minimum number of stimuli. Conclusions Synaptic suppression provides a biophysical explanation to the intermittent, but still time-locked, post-synaptic firing characteristics commonly seen in DBS experimental recordings. Therefore, network models attempting to analyze or predict the effects of DBS on neural activity patterns should integrate synaptic suppression into their simulations.

    更新日期:2019-11-18
  • MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-06
    Ting-Chun Lin, Yu-Chun Lo, Hui-Ching Lin, Ssu-Ju Li, Sheng-Huang Lin, Han-Fang Wu, Ming-Chia Chu, Chi-Wei Lee, I-Cheng Lin, Ching-Wen Chang, Yin-Chieh Liu, Ting-Chieh Chen, Yu-Ju Lin, Yen-Yu Ian Shih, You-Yin Chen

    Background Social deficit is a core symptom in autism spectrum disorder (ASD). Although deep brain stimulation (DBS) has been proposed as a potential treatment for ASD, an ideal target nucleus is yet to be identified. DBS at the central thalamic nucleus (CTN) is known to alter corticostriatal and limbic circuits, and subsequently increase the exploratory motor behaviors, cognitive performance, and skill learning in neuropsychiatric and neurodegenerative disorders. Objective We first investigated the ability of CTN-DBS to selectively engage distinct brain circuits and compared the spatial distribution of evoked network activity and modulation. Second, we investigated whether CTN-DBS intervention improves social interaction in a valproic acid–exposed ASD rat offspring model. Methods Brain regions activated through CTN-DBS by using a magnetic resonance (MR)-compatible neural probe, which is capable of inducing site-selective microstimulations during functional MRI (fMRI), were investigated. We then performed functional connectivity MRI, the three-chamber social interaction test, and Western blotting analyses to evaluate the therapeutic efficacy of CTN-DBS in an ASD rat offspring model. Results The DBS-evoked fMRI results indicated that the activated brain regions were mainly located in cortical areas, limbic-related areas, and the dorsal striatum. We observed restoration of brain functional connectivity (FC) in corticostriatal and corticolimbic circuits after CTN-DBS, accompanied with increased social interaction and decreased social avoidance in the three-chamber social interaction test. The dopamine D2 receptor decreased significantly after CTN-DBS treatment, suggesting changes in synaptic plasticity and alterations in the brain circuits. Conclusions Applying CTN-DBS to ASD rat offspring increased FC and altered the synaptic plasticity in the corticolimbic and the corticostriatal circuits. This suggests that CTN-DBS could be an effective treatment for improving the social behaviors of individuals with ASD.

    更新日期:2019-11-18
  • Long-term enhancement of visual responses by repeated transcranial electrical stimulation of the mouse visual cortex
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-18
    Despoina Tsapa, Mehran Ahmadlou, J. Alexander Heimel

    Background Transcranial electrical stimulation (tES) is a popular method to modulate brain activity by sending a weak electric current through the head. Despite its popularity, long-term effects are poorly understood. Objective We wanted to test if anodal tES immediately changes cerebral responses to visual stimuli, and if repeated sessions of tES produce plasticity in these responses. Methods We applied repeated anodal tES, like transcranial direct current stimulation (tDCS), but pulsed (8 s on, 10 s off), to the visual cortex of mice while visually presenting gratings. We measured the responses to these visual stimuli in the visual cortex using the genetically encoded calcium indicator GCaMP3. Results We found an increase in the visual response when concurrently applying tES on the bone without skin (epicranially). This increase was only transient when tES was applied through the skin (transcutaneous). There was no immediate after-effect of tES. However, repeated transcutaneous tES for four sessions at two-day intervals increased the visual response in the visual cortex. This increase was not specific to the grating stimulus coupled to tES and also occurred for an orthogonal grating presented in the same sessions but without concurrent tES. No increase was found in mice that received no tES. Conclusion Our study provides evidence that tES induces long-term changes in the mouse brain. Results in mice do not directly translate to humans, because of differences in stimulation protocols and the way current translates to electric field strength in vastly different heads.

    更新日期:2019-11-18
  • Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-25
    Fernando Santos-Valencia, Salvador Almazán-Alvarado, Alejandro Rubio-Luviano, Alejandro Valdés-Cruz, Victor Manuel Magdaleno-Madrigal, David Martínez-Vargas

    Background Variation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. Objective The purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. Methods Temporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. Results Temporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. Conclusion These results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy.

    更新日期:2019-11-18
  • Reversible neuroinhibition by focused ultrasound is mediated by a thermal mechanism
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-23
    David P. Darrow, Parker O'Brien, Thomas J. Richner, Theoden I. Netoff, Emad S. Ebbini

    Background Transcranial focused ultrasound (tFUS) at low intensities has been reported to directly evoke responses and reversibly inhibit function in the central nervous system. While some doubt has been cast on the ability of ultrasound to directly evoke neuronal responses, spatially-restricted transcranial ultrasound has demonstrated consistent, inhibitory effects, but the underlying mechanism of reversible suppression in the central nervous system is not well understood. Objective/hypothesis In this study, we sought to characterize the effect of transcranial, low-intensity, focused ultrasound on the thalamus during somatosensory evoked potentials (SSEP) and investigate the mechanism by modulating the parameters of ultrasound. Methods TFUS was applied to the ventral posterolateral nucleus of the thalamus of a rodent while electrically stimulating the tibial nerve to induce an SSEP. Thermal changes were also induced through an optical fiber that was image-guided to the same target. Results Focused ultrasound reversibly suppressed SSEPs in a spatially and intensity-dependent manner while remaining independent of duty cycle, peak pressure, or modulation frequency. Suppression was highly correlated and temporally consistent with in vivo temperature changes while producing no pathological changes on histology. Furthermore, stereotactically-guided delivery of thermal energy through an optical fiber produced similar thermal effects and suppression. Conclusion We confirm that tFUS predominantly causes neuroinhibition and conclude that the most primary biophysical mechanism is the thermal effect of focused ultrasound.

    更新日期:2019-11-18
  • Vagus nerve stimulation during extinction learning reduces conditioned place preference and context-induced reinstatement of cocaine seeking
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-03
    Jessica E. Childs, Suhyeong Kim, Christopher M. Driskill, Emily Hsiu, Sven Kroener

    Background Drug use causes the formation of strong cue/reward associations which persist long after cessation of drug-taking and contribute to the long-term risk of relapse. Extinguishing these associations may reduce cue-induced craving and relapse. Previously, we found that pairing vagus nerve stimulation (VNS) with extinction of cocaine self-administration reduces cue-induced reinstatement; however, it remains unclear whether this was primarily caused by extinguishing the context, the instrumental response, or both. Objective Hypothesis: We hypothesized that VNS can facilitate the extinction of both contextual cues and instrumental responding. Methods Extinction of context was first tested using Pavlovian conditioned place preference (CPP). Next, the impact of VNS on the extinction of instrumental responding was assessed under ABA and AAA context conditions. In each extinction context separate groups of rats were either provided the opportunity to perform the instrumental response, or the levers were retracted for the duration of extinction training. Reinstatement was induced by reintroduction of the conditioned stimuli and/or the drug-paired context. Data were analyzed using one-way or two-way repeated measures ANOVAs. Results VNS during extinction reduced reinstatement of CPP. VNS also reduced cue- and context-induced reinstatement of the instrumental response under both AAA and ABA conditions. The subjects’ ability to engage with the lever during extinction was crucial for this effect. P values < 0.05 were considered significant. Conclusions Craving occurs in response to a range of conditioned stimuli and contexts; VNS may improve outcomes of behavioral therapy by facilitating extinction of both an instrumental response and/or contextual cues.

    更新日期:2019-11-18
  • tDCS to the left DLPFC modulates cognitive and physiological correlates of executive function in a state-dependent manner
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-06
    Laura Dubreuil-Vall, Peggy Chau, Giulio Ruffini, Alik S. Widge, Joan A. Camprodon

    Background The use of transcranial Direct Current Stimulation (tDCS) to study anatomical and physiological dynamics and circuits supporting cognition and executive functions in particular has dramatically increased in recent years. However, its mechanisms of action remain only partially understood. Objective In this study we assess the cognitive and physiological effects of anodal tDCS to the DLPFC on executive function in order to understand (1) the role of DLPFC laterality, (2) the physiological dynamics sustaining the modulation of executive function by tDCS, and (3) the impact of state-dependent dynamics. Methods In a randomized, placebo-controlled, cross-over study, we applied anodal tDCS targeting the left vs. right DLPFC vs. sham in 20 healthy individuals (10 males, 10 females). Immediately before and after tDCS, subjects performed the Flanker Task while we measured behavioral (reaction time and accuracy) and neurophysiological (ERP) responses. Specifically, the amplitude of N200, P300, ERN and Pe is compared before and after stimulation. Results Anodal tDCS to the left DLPFC lead to a significant improvement in reaction time, an increase in P300 amplitude and a decrease in N200 amplitude in a state-dependent manner: baseline ERP amplitudes conditioned the effects of tDCS. Conclusion Given the role of these ERPs in conflict-related tasks, we speculate that tDCS is modulating the subconstructs of selective attention, conflict monitoring and response inhibition. These findings contribute to a further understanding of the role of left DLPFC in the modulation of executive function, and shed light into the mechanisms of action and the state dependent nature of tDCS.

    更新日期:2019-11-18
  • After-effects of 10 Hz tACS over the prefrontal cortex on phonological word decisions
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-20
    Vera Moliadze, Leon Sierau, Ekaterina Lyzhko, Tristan Stenner, Michael Werchowski, Michael Siniatchkin, Gesa Hartwigsen

    Introduction Previous work in the language domain has shown that 10 Hz rTMS of the left or right posterior inferior frontal gyrus (pIFG) in the prefrontal cortex impaired phonological decision-making, arguing for a causal contribution of the bilateral pIFG to phonological processing. However, the neurophysiological correlates of these effects are unclear. The present study addressed the question whether neural activity in the prefrontal cortex could be modulated by 10 Hz tACS and how this would affect phonological decisions. Methods In three sessions, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the bilateral prefrontal cortex before task processing. Resting state EEG was recorded before and after tACS. We also recorded EEG during task processing. Results Relative to sham stimulation, 10 Hz tACS significantly facilitated phonological response speed. This effect was task-specific as tACS did not affect a simple control task. Moreover, 10 Hz tACS significantly increased theta power during phonological decisions. The individual increase in theta power was positively correlated with the behavioral facilitation after 10 Hz tACS. Conclusion Our results show a facilitation of phonological decisions after 10 Hz tACS over the bilateral prefrontal cortex. This might indicate that 10 Hz tACS increased task-related activity in the stimulated area to a level that was optimal for phonological performance. The significant correlation with the individual increase in theta power suggests that the behavioral facilitation might be related to increased theta power during language processing.

    更新日期:2019-11-18
  • Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-19
    Simone N. Vigod, Kellie E. Murphy, Cindy-Lee Dennis, Tim F. Oberlander, Joel G. Ray, Zafiris J. Daskalakis, Daniel M. Blumberger

    Background Depression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy. Objective To conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression. Methods In this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum. Results Of 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04). Conclusions Results support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).

    更新日期:2019-11-18
  • Efficiently searching through large tACS parameter spaces using closed-loop Bayesian optimization
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-04
    Romy Lorenz, Laura E. Simmons, Ricardo P. Monti, Joy L. Arthur, Severin Limal, Ilkka Laakso, Robert Leech, Ines R. Violante

    Background Selecting optimal stimulation parameters from numerous possibilities is a major obstacle for assessing the efficacy of non-invasive brain stimulation. Objective We demonstrate that Bayesian optimization can rapidly search through large parameter spaces and identify subject-level stimulation parameters in real-time. Methods To validate the method, Bayesian optimization was employed using participants’ binary judgements about the intensity of phosphenes elicited through tACS. Results We demonstrate the efficiency of Bayesian optimization in identifying parameters that maximize phosphene intensity in a short timeframe (5 min for >190 possibilities). Our results replicate frequency-dependent effects across three montages and show phase-dependent effects of phosphene perception. Computational modelling explains that these phase effects result from constructive/destructive interference of the current reaching the retinas. Simulation analyses demonstrate the method's versatility for complex response functions, even when accounting for noisy observations. Conclusion Alongside subjective ratings, this method can be used to optimize tACS parameters based on behavioral and neural measures and has the potential to be used for tailoring stimulation protocols to individuals.

    更新日期:2019-11-18
  • LTD-like plasticity of the human primary motor cortex can be reversed by γ-tACS
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-03
    Andrea Guerra, Antonio Suppa, Francesco Asci, Giovanna De Marco, Valentina D'Onofrio, Matteo Bologna, Vincenzo Di Lazzaro, Alfredo Berardelli

    Background Cortical oscillatory activities play a role in regulating several brain functions in humans. However, whether motor resonant oscillations (i.e. β and γ) modulate long-term depression (LTD)-like plasticity of the primary motor cortex (M1) is still unclear. Objective To address this issue, we combined transcranial alternating current stimulation (tACS), a technique able to entrain cortical oscillations, with continuous theta burst stimulation (cTBS), a transcranial magnetic stimulation (TMS) protocol commonly used to induce LTD-like plasticity in M1. Methods Motor evoked potentials (MEPs) elicited by single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated before and 5, 15 and 30 min after cTBS alone or cTBS delivered during β-tACS (cTBS-β) or γ-tACS (cTBS-γ). Moreover, we tested the effects of β-tACS (alone) on short-latency afferent inhibition (SAI) and γ-tACS on SICI in order to verify whether tACS-related interneuronal modulation contributes to the effects of tACS-cTBS co-stimulation. Results cTBS-γ turned the expected after-effects of cTBS from inhibition to facilitation. By contrast, responses to cTBS-β were similar to those induced by cTBS alone. β- and γ-tACS did not change MEPs evoked by single-pulse TMS. β-tACS reduced SAI and γ-tACS reduced SICI. However, the degree of γ-tACS-induced modulation of SICI did not correlate with the effects of cTBS-γ. Conclusion γ-tACS reverses cTBS-induced plasticity of the human M1. γ-oscillations may therefore regulate LTD-like plasticity mechanisms.

    更新日期:2019-11-18
  • Real-time estimation of electric fields induced by transcranial magnetic stimulation with deep neural networks
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-17
    Tatsuya Yokota, Toyohiro Maki, Tatsuya Nagata, Takenobu Murakami, Yoshikazu Ugawa, Ilkka Laakso, Akimasa Hirata, Hidekata Hontani

    Background Transcranial magnetic stimulation (TMS) plays an important role in treatment of mental and neurological illnesses, and neurosurgery. However, it is difficult to target specific brain regions accurately because the complex anatomy of the brain substantially affects the shape and strength of the electric fields induced by the TMS coil. A volume conductor model can be used for determining the accurate electric fields; however, the construction of subject-specific anatomical head structures is time-consuming. Objective The aim of this study is to propose a method to estimate electric fields induced by TMS from only T1 magnetic resonance (MR) images, without constructing a subject-specific anatomical model. Methods Very large sets of electric fields in the brain of subject-specific anatomical models, which are constructed from T1 and T2 MR images, are computed by a volume conductor model. The relation between electric field distribution and T1 MR images is used for machine learning. Deep neural network (DNN) models are applied for the first time to electric field estimation. Results By determining the relationships between the T1 MR images and electric fields by DNN models, the process of electric field estimation is markedly accelerated (to 0.03 s) due to the absence of a requirement for anatomical head structure reconstruction and volume conductor computation. Validation shows promising estimation accuracy, and rapid computations of the DNN model are apt for practical applications. Conclusion The study showed that the DNN model can estimate the electric fields from only T1 MR images and requires low computation time, suggesting the possibility of using machine learning for real-time electric field estimation in navigated TMS.

    更新日期:2019-11-18
  • Prestimulus cortical EEG oscillations can predict the excitability of the primary motor cortex
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-12
    Katsuya Ogata, Hisato Nakazono, Taira Uehara, Shozo Tobimatsu

    Background The motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) vary considerably at rest, but the mechanism underlying this amplitude variation is largely unknown. We hypothesized that prestimulus EEG oscillations modulate the subsequent MEPs in a state-dependent manner. Objective We studied the relationship between prestimulus alpha/beta oscillations and MEPs during eyes open (EO)/closed (EC) conditions, and then modulated TMS intensity in the EO condition. Furthermore, we developed an EEG-triggered TMS system (“informed open-loop”) to verify our hypothesis. Methods TMS was applied to the left motor cortex. We first compared EEG power differences between high- and low-amplitude MEP epochs in the EO and EC conditions when using a high TMS intensity. Next, we evaluated the effects of varying TMS intensities (high vs. low) on the EEG–MEP relationship. Finally, we used EEG-triggered TMS to determine whether prestimulus EEG oscillations predicted MEP amplitudes. Results Prestimulus higher-power alpha/low-beta bands produced larger MEPs only in the high-intensity EO condition. A positive relationship between EEG power and MEP amplitude was observed at C3 and left frontal electrodes. This relationship was obscured when using the lower TMS intensity but was observed in the high-intensity condition at the C3 electrode. EEG-triggered TMS demonstrated that higher alpha power predicted higher MEP amplitudes, but beta power at around 20 Hz did not. Conclusions A causal relationship between alpha/low-beta oscillations and MEP amplitudes at rest requires high TMS intensity delivered when eyes are open. This association may allow us to develop a new informed open-loop TMS protocol.

    更新日期:2019-11-18
  • Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease
    Brain Stimul. (IF 6.919) Pub Date : 2019-06-11
    Andrea Guerra, Antonio Suppa, Valentina D'Onofrio, Flavio Di Stasio, Francesco Asci, Giovanni Fabbrini, Alfredo Berardelli

    Background Animal models of Parkinson's Disease (PD) demonstrated increased facilitatory cortico-striatal activity, reflecting overactive glutamatergic neurotransmission and contributing to the pathophysiology of l-dopa induced dyskinesias (LIDs). Objective To assess different facilitatory intracortical circuits in the primary motor cortex (M1) in patients with PD and LIDs by means of a combination of transcranial magnetic stimulation (TMS) protocols. Methods We tested the Input/Output (I/O) curve, intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) at baseline (T0), ‘OFF’ and ‘ON’ state, in 20 PD patients with LIDs. The same parameters were examined after 2 weeks of chronic intake of 50 mg (T1) and 100 mg/day (T2) of safinamide. Finally, we tested SICF in a further group of patients without LIDs. Results At T0, patients with LIDs showed increased I/O curve steepness, which was partly ameliorated by l-dopa. These patients also had normal ICF, and abnormally increased SICF, which did not change with l-dopa. Safinamide improved the I/O curve both at T1 and T2, it reduced SICF at T1 and normalized this measure at T2. In patients with PD and LIDs, SICF correlated with the severity of dyskinesia. In patients without LIDs, SICF was less prominently abnormal and responsive to l-dopa. Conclusions Patients with PD and LIDs have abnormal cortical facilitation, possibly suggesting overactive glutamatergic neurotransmission in specific circuits within M1. Although not responsive to l-dopa, this dysfunction is restored by the anti-glutamatergic properties of safinamide 100 mg. The results suggest that the abnormal cortical facilitation in M1 contributes to the pathophysiology of LIDs.

    更新日期:2019-11-18
  • Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-03
    Bhedita J. Seewoo, Kirk W. Feindel, Sarah J. Etherington, Jennifer Rodger

    Background Evidence suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, alters resting brain activity. Despite anecdotal evidence that rTMS effects wear off, there are no reports of longitudinal studies, even in humans, mapping the therapeutic duration of rTMS effects. Objective Here, we investigated the longitudinal effects of repeated low-intensity rTMS (LI-rTMS) on healthy rodent resting-state networks (RSNs) using resting-state functional MRI (rs-fMRI) and on sensorimotor cortical neurometabolite levels using proton magnetic resonance spectroscopy (MRS). Methods Sprague-Dawley rats received 10 min LI-rTMS daily for 15 days (10 Hz or 1 Hz stimulation, n = 9 per group). MRI data were acquired at baseline, after seven days and after 14 days of daily stimulation and at two more timepoints up to three weeks post-cessation of daily stimulation. Results 10 Hz stimulation increased RSN connectivity and GABA, glutamine, and glutamate levels. 1 Hz stimulation had opposite but subtler effects, resulting in decreased RSN connectivity and glutamine levels. The induced changes decreased to baseline levels within seven days following stimulation cessation in the 10 Hz group but were sustained for at least 14 days in the 1 Hz group. Conclusion Overall, our study provides evidence of long-term frequency-specific effects of LI-rTMS. Additionally, the transient connectivity changes following 10 Hz stimulation suggest that current treatment protocols involving this frequency may require ongoing “top-up” stimulation sessions to maintain therapeutic effects.

    更新日期:2019-11-18
  • Characterizing and minimizing the contribution of sensory inputs to TMS-evoked potentials
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-17
    Mana Biabani, Alex Fornito, Tuomas P. Mutanen, James Morrow, Nigel C. Rogasch

    Background Transcranial magnetic stimulation (TMS) evokes voltage deflections in electroencephalographic (EEG) recordings, known as TMS-evoked potentials (TEPs), which are increasingly used to study brain dynamics. However, the extent to which TEPs reflect activity directly evoked by magnetic rather than sensory stimulation is unclear. Objective To characterize and minimize the contribution of sensory inputs to TEPs. Methods Twenty-four healthy participants received TMS over the motor cortex using two different intensities (below and above cortical motor threshold) and waveforms (monophasic, biphasic). TMS was also applied over the shoulder as a multisensory control condition. Common sensory attenuation measures, including coil padding and noise masking, were adopted. We examined spatiotemporal relationships between the EEG responses to the scalp and shoulder stimulations at sensor and source levels. Furthermore, we compared three different filters (independent component analysis, signal-space projection with source informed reconstruction (SSP-SIR) and linear regression) designed to attenuate the impact of sensory inputs on TEPs. Results The responses to the scalp and shoulder stimulations were correlated in both temporal and spatial domains, especially after ∼60 ms, regardless of the intensity and stimuli waveform. Among the three filters, SSP-SIR showed the best trade-off between removing sensoryrelated signals while preserving data not related to the control condition. Conclusions The findings demonstrate that TEPs elicited by motor cortex TMS reflect a combination of transcranially and peripherally evoked brain responses despite adopting sensory attenuation methods during experiments, thereby highlighting the importance of adopting sensory control conditions in TMS-EEG studies. Offline filters may help to isolate the transcranial component of the TEP from its peripheral component, but only if these components express different spatiotemporal patterns. More realistic control conditions may help to improve the characterization and attenuation of sensory inputs to TEPs, especially in early responses.

    更新日期:2019-11-18
  • Impact of prior treatment on remission with intermittent theta burst versus high-frequency repetitive transcranial magnetic stimulation in treatment resistant depression
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-17
    Jonathan H. Hsu, Jonathan Downar, Fidel Vila-Rodriguez, Zafiris J. Daskalakis, Daniel M. Blumberger

    Background Multiple prior treatment failures are associated with reduced rates of remission to subsequent antidepressant treatment, including rTMS. The degree of treatment resistance that is especially predictive of inferior outcome is uncertain. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS where less is known regarding clinical predictors of remission. The THREE-D study demonstrated that iTBS is non-inferior to 10 Hz rTMS for the treatment of depression. Objective Determine if the number and type of prior pharmacotherapy trials affect the rate of remission with two types of rTMS. Method Compare remission rates based on prior pharmacotherapy using data from the THREE-D trial (NCT01887782). Results No differences in remission rates were noted between the three levels of treatment resistance, however, participants with 3 compared to <3 treatment failures had lower rates of remission: 17.3% versus 29.4% (χ2 4.87; df = 1; p = 0.03). Conclusions Three or more treatment failures may be associated with lower remission rates with rTMS.

    更新日期:2019-11-18
  • Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-25
    G. Harika-Germaneau, F. Rachid, A. Chatard, C. Lafay-Chebassier, M. Solinas, B. Thirioux, B. Millet, N. Langbour, N. Jaafari

    Background Obsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60 % of patients resistant to treatment. Theta burst transcranial magnetic stimulation (TBS) is a promising new technique that has been shown to induce potent and long lasting effects on cortical excitability. The present study evaluated for the first time therapeutic efficacy and tolerability of continuous TBS (cTBS) over the supplementary motor area (SMA) in treatment resistant OCD patients using a double blind, sham-controlled design. Methods Thirty treatment resistant OCD outpatients were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 600 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, at the end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale-Brown Obsessive Compulsive Scale. Results There was no significant difference between active and sham cTBS groups in treatment efficacy. Responder rates were not different between the two groups at week 6 (cTBS 28% versus sham 36%; p = 0.686) and week 12 (cTBS 28% versus sham 36%; p = 0.686). Depressive and anxious symptoms improvements were similar in the two groups. Conclusion This study is the first controlled trial using cTBS in treatment resistant OCD patients. The use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to identify the optimal parameters to be used in OCD patients.

    更新日期:2019-11-18
  • The effects of repetitive transcranial magnetic stimulation on body weight and food consumption in obese adults: A randomized controlled study
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-25
    Se-Hong Kim, Ju-hye Chung, Tae-Hong Kim, Seong Hoon Lim, Youngkook Kim, Young-Mi Eun, Yun-Ah Lee

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

    更新日期:2019-11-18
  • The relationship between individual alpha peak frequency and clinical outcome with repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD)
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-25
    Juliana Corlier, Linda L. Carpenter, Andrew C. Wilson, Eric Tirrell, A. Polly Gobin, Brian Kavanaugh, Andrew F. Leuchter

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

    更新日期:2019-11-18
  • Cerebellar rTMS for motor control in progressive supranuclear palsy
    Brain Stimul. (IF 6.919) Pub Date : 2019-07-25
    M.L. Dale, W.H. DeVries, M. Mancini, M.S. George

    Background Stimulatory cerebellar TMS is a promising tool to improve motor control in neurodegenerative disorders. Objective/hypothesis: Our goal was to use 10Hz cerebellar rTMS to augment cerebellar-brain inhibition (CBI) for improved postural stability and speech in patients with progressive supranuclear palsy (PSP). Methods We performed CBI assessments with neuronavigation before and after high frequency cerebellar rTMS or sham TMS in two patients with PSP, using a double cone coil for the conditioning pulse and a figure-of-eight coil for the test pulse and treatments. We collected posturography data and speech samples before and after treatment. Results After treatment, CBI increased by 50% in subject 1 and by 32% in subject 2, and postural stability and speech improved. The protocol was well tolerated, but the sham was not consistently believable. Conclusion Cerebellar rTMS may improve postural stability and speech in PSP, but cooled coils with vibrotactile sham capability are needed for larger future studies.

    更新日期:2019-11-18
  • Electrodes in the brain—Ethical criteria for research and treatment with deep brain stimulation for neuropsychiatric disorders
    Brain Stimul. (IF 6.919) Pub Date : 2010-02-13
    Matthis Synofzik, Thomas E. Schlaepfer

    Background 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.

    更新日期:2019-11-18
  • Intensive HF-rTMS treatment in an ECT resistant bipolar I patient with mixed episode
    Brain Stimul. (IF 6.919) Pub Date : 2010-02-10
    Dieter Zeeuws, Kim De Rycker, Rudi De Raedt, Matthieu De Beyne, Chris Baeken, Nathalie Vanderbruggen

    Although 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.

    更新日期:2019-11-18
  • Matching stimulation paradigms resolve apparent differences between optogenetic and electrical VTA stimulation
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-09
    Theresa CS. Weidner, Daniel Vincenz, Marta Brocka, Jennifer Tegtmeier, Anja M. Oelschlegel, Frank W. Ohl, Jürgen Goldschmidt, Michael T. Lippert

    Background Optogenetic stimulation has grown into a popular brain stimulation method in basic neuroscience while electrical stimulation predominates in clinical applications. In order to explain the effects of electrical stimulation on a cellular level and evaluate potential advantages of optogenetic therapies, comparisons between the two stimulation modalities are necessary. This comparison is hindered, however, by the difficulty of effectively matching the two fundamentally different modalities. Objective Comparison of brain-wide activation patterns in response to intensity-matched electrical and optogenetic VTA stimulation. Methods We mapped optogenetic and electrical self-stimulation rates in the same mice over stimulation intensity and determined iso-behavioral intensities. Using functional 99mTc-HMPAO SPECT imaging of cerebral blood flow in awake animals, we obtained brain-wide activation patterns for both modalities at these iso-behavioral intensities. We performed these experiments in two mouse lines commonly used for optogenetic VTA stimulation, DAT::Cre and TH::Cre mice. Results We find iso-behavioral intensity matching of stimulation gives rise to similar brain activation patterns. Differences between mouse lines were more pronounced than differences between modalities. Conclusions Previously found large differences of electrical and optogenetic stimulation might be due to unmatched stimulation intensity, particularly relative electrical overstimulation. These findings imply that therapeutic electrical VTA stimulation might be relatively specific if employed with optimized parameters.

    更新日期:2019-11-11
  • A Novel tDCS Sham Approach Based on Model-Driven Controlled Shunting
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-09
    Francesco Neri, Lucia Mencarelli, Arianna Menardi, Fabio Giovannelli, Simone Rossi, Giulia Sprugnoli, Alessandro Rossi, Alvaro Pascual-Leone, Ricardo Salvador, Giulio Ruffini, Emiliano Santarnecchi

    Background Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects. Objective /hypothesis: To ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation, while preventing currents from reaching the cortex and cause changes in brain excitability. Methods A novel model-based multielectrode technique —optimizing the location and currents of a set of small electrodes placed on the scalp— was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and -Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG). Results Subjects perceived Multifocal-tDCS and ActiSham similarly in terms of both scalp sensations and their localization on the scalp, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F(1,13)= 6.67, p=.023), with higher MEPs amplitudes after the application of Bifocal-Sham. Conclusions Compared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.

    更新日期:2019-11-11
  • Brain Stimulation’s Expanding Impact – Now Immediately Free to Download by Anyone, Anywhere and at Anytime
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-08
    Mark S. George

    The brain stimulation revolution continues to grow and even accelerate. Business models around academic publishing are also changing. Beginning Jan 1, 2020, Brain Stimulation content will become fully open access. The author argues that this change will likely expand the overall impact of the journal, without compromising editorial quality. However there are some concerns to consider with this transition to full open access. This editorial looks back on the history of brain stimulation academic publishing and summarizes the reasons for this optimistic view of the open access future.

    更新日期:2019-11-08
  • SICI during changing brain states: differences in methodology can lead to different conclusions
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-04
    Jaime Ibáñez, Danny A. Spampinato, Varshini Paraneetharan, John C. Rothwell

    Background Short-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states. Objective Here, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used. Methods We measured SICI using a range of CS intensities at rest and during a warned simple reaction time task. Conclusions Our results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes.

    更新日期:2019-11-04
  • Transcranial alternating current stimulation of α but not β frequency sharpens multiple visual functions
    Brain Stimul. (IF 6.919) Pub Date : 2019-11-03
    Hisato Nakazono, Katsuya Ogata, Akinori Takeda, Emi Yamada, Takahiro Kimura, Shozo Tobimatsu

    Background Transcranial alternating current stimulation (tACS) can entrain and enhance cortical oscillatory activity in a frequency-dependent manner. In our previous study (Nakazono et al.2016), 20 Hz (β) tACS significantly increased excitability of primary motor cortex compared with 10 Hz (α) tACS. α oscillations are a prominent feature of the primary visual cortex (V1) in a resting electroencephalogram. Hence, we investigated whether α and β tACS can differentially influence multiple visual functions. Methods Firstly, we evaluated the after-effects of α and β tACS on pattern-reversal (PR) and focal-flash (FF) visual evoked potentials (VEPs). Secondly, we determined the relationship between resting α oscillations and PR-VEPs modulated by tACS. Thirdly, the behavioral effects of tACS were assessed by contrast sensitivity. Results α tACS modulated the amplitudes of PR-VEPs, compared with β tACS, but did not modulate the FF-VEPs. Time-frequency analysis revealed that α tACS facilitated event-related α phase synchronizations without increasing power, which consequently increased the PR-VEP amplitudes. There was a significant positive correlation between PR-VEP amplitudes and resting α oscillations. These findings suggested that α tACS modulated α oscillations, and affected visual functions of contrast and spatial frequency. Indeed, α tACS also improved subjects’ contrast sensitivity at the behavioral level. Conversely, β tACS increased posterior α activity, but did not change VEP amplitudes. Conclusions α tACS can influence different neuronal populations from those influenced by β tACS. Thus, our results provide evidence that α tACS sharpens multiple visual functions by modulating α oscillations in V1.

    更新日期:2019-11-04
  • Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm, blinded, randomized controlled trial
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-31
    Katharine Dunlop, Jack Sheen, Laura Schulze, Peter Fettes, Farrokh Mansouri, Kfir Feffer, Daniel M. Blumberger, Zafiris J. Daskalakis, Sidney H. Kennedy, Peter Giacobbe, Blake Woodside, Jonathan Downar

    Background Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. Objective The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. Methods 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. Results Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians’ treatment arm guesses were significantly above chance. Conclusion DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.

    更新日期:2019-11-01
  • Transcranial Direct Current Stimulation ASsociated With Physical-therapy In Acute Stroke Patients - the tDCS ASAP - a Randomized, Triple Blind, Sham-controlled Study
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-31
    Stephen Bornheim, Jean-Louis Croisier, Pierre Maquet, Jean-François Kaux

    Background Transcranial Direct Current Stimulation has been increasing in popularity in the last few years. Despite vast amounts of articles on the use of tDCS on stroke patients, very little has been done during the acute phase. Objectives Measure the effects of tDCS on functional and sensory outcomes throughout the first year post onset of stroke. Methods 50 acute stroke patients were randomized and placed into either the treatment or sham group. Anodal tDCS was applied (2 mA, 20 min) 5 times a week during the first month post stroke. Patients were evaluated with the Wolf Motor Function Test, the Semmes Weinstein Monofilament Test, the Upper Extremity section (UEFM), the Lower Extremity section (LEFM) and the Somatosensory section of the Fugl Meyer Test, the Tardieu Spasticity Scale, the Stroke Impact Scale (SIS), the Hospital Anxiety and Depression Scale (HADS) and the Barthel Index. Evaluations were held at 48h post stroke, week 1, 2, 3, 4, 3 months, 6 months and 1 year. Results There were statistically and clinically significant improvements after tDCS in all functional motor outcomes, and somatosensory functions. Differences between both groups for the main outcome (WMFT time) were 51% (p = 0.04) at one month, and 57% (p = 0.02) at one year. Conclusion: tDCS seems to be an effective adjuvant to conventional rehabilitation techniques. If applied in the acute stages of stroke, functional recovery is not only accelerated, but improved, and results are maintained up to one-year post stroke.

    更新日期:2019-11-01
  • Barriers and opportunities of cortical stimulation via cerebral venous approach.
    Brain Stimul. (IF 6.919) Pub Date : 2019-12-02
    Ali Alawieh,L Fernando Gonzalez,Wuwei Feng

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Color perception matches selectivity in human early visual cortex.
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-23
    Qian Wang,Lu Luo,Jing Wang,Guoming Luan

    更新日期:2019-11-01
  • Deep transcranial magnetic stimulation in patients with intracranial aneurysm clips: A case report and guidelines for clinicians.
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-23
    Mason Stillman,Nicole Chandonnet,Lindsey Davis,Randall Buzan,Theodore Wirecki

    更新日期:2019-11-01
  • Automated speech analysis to improve TMS-based language mapping: Algorithm and proof of concept.
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-22
    Laura Seynaeve,Deepak Baby,Hugo Van Hamme,Steven De Vleeschouwer,Patrick Dupont,Wim Van Paesschen

    更新日期:2019-11-01
  • Effects of bilateral anodal transcranial direct current stimulation over the tongue primary motor cortex on cortical excitability of the tongue and tongue motor functions.
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-20
    Hitoshi Maezawa,Carmelo Mario Vicario,Min-Fang Kuo,Masayuki Hirata,Tatsuya Mima,Michael A Nitsche

    更新日期:2019-11-01
  • A case series exploring the effect of twenty sessions of repetitive transcranial magnetic stimulation (rTMS) on cannabis use and craving.
    Brain Stimul. (IF 6.919) Pub Date : 2019-10-18
    Gregory L Sahlem,Margaret A Caruso,E Baron Short,James B Fox,Brian J Sherman,Andrew J Manett,Robert J Malcolm,Mark S George,Aimee L McRae-Clark

    更新日期:2019-11-01
  • 更新日期:2019-11-01
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