Search

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy. [ABSTRACT FROM AUTHOR]

• Subthalamic oscillations can be streamed for neurofeedback. • Parkinson patients can control subthalamic oscillations using neurofeedback and improve this control with training time. • DBS electrode-guided neurofeedback is effective even with concurrent stimulation and medication. Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application. In this study, seven patients with idiopathic Parkinson's disease and one with familial Parkinson's disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations. While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block). We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson's disease to rapidly control pathological subthalamic beta oscillations. Fully-implanted DBS electrode-guided neurofeedback is feasible and can now be explored over extended timespans. [ABSTRACT FROM AUTHOR]

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment. [ABSTRACT FROM AUTHOR]

• Thirty-nine studies explored the effect of age on responsiveness to non-invasive brain stimulation neuroplasticity paradigms. • Pooled findings revealed age-dependent reduction in corticospinal excitability following certain neuroplasticity paradigms. • Considerable heterogeneity within some paradigms was evident, limiting interpretations of pooled analyses. We aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex. Four databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered. 39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints. Whilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses. [ABSTRACT FROM AUTHOR]

• Non-invasive brain and spinal stimulation techniques have been investigated as a potential treatment in motoneuron disease. • Stimulation methods aim at counteracting glutamate-mediated excitotoxicity leading to motoneuron degeneration. • Targeted, individualized and home-deliverable treatments are critical challenges for future advancements. Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation. We also survey and discuss the trials that have been performed, and future perspectives. [ABSTRACT FROM AUTHOR]

• Cerebellar theta (θ)-tACS reduced movement regularity in a tapping task and prolonged the movement duration of a pointing task. • Cerebellar θ-tACS enhanced the effectiveness of CBI and the effect of θ-tACS on movement rhythm was correlated with changes in CBI. • tACS effects potentially involve the modulation of cerebellar neurons resonating with θ rhythm. To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects. Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp ('grasping') and (iii) arm reaching-to-point ('pointing') an object. Also, we evaluated possible changes in CBI during cerebellar-tACS. θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI. Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm. These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

• Home-based NIBS is a promising new treatment strategy for neuro-psychiatric pathologies ensuring frequent stimulation exposure. • There are currently no solutions to direct and monitor correct electrode placement for self-application. • We propose an easy-to-use, digital electrode placement tool that marks an important step to improve home-based set-ups. Home-based non-invasive brain stimulation (NIBS) has been suggested as an adjunct treatment strategy for neuro-psychiatric disorders. There are currently no available solutions to direct and monitor correct placement of the stimulation electrodes. To address this issue, we propose an easy-to-use digital tool to support patients for self-application. We recruited 36 healthy participants and compared their cap placement performance with the one of a NIBS-expert investigator. We tested participants' placement accuracy with instructions before (Pre) and after the investigator's placement (Post), as well as participants using the support tool (CURRENT). User experience (UX) and confidence were further evaluated. Permutation tests demonstrated a smaller deviation within the CURRENT compared with Pre cap placement (p = 0.02). Subjective evaluation of ease of use and usefulness of the tool were vastly positive (8.04 out of 10). CURRENT decreased the variability of performance, ensured placement within the suggested maximum of deviation (10 mm) and supported confidence of correct placement. This study supports the usability of this novel technology for correct electrode placement during self-application in home-based settings. CURRENT provides an exciting opportunity to promote home-based, self-applied NIBS as a safe, high-frequency treatment strategy that can be well integrated in patients' daily lives. [ABSTRACT FROM AUTHOR]

• Theta power and phase-stability may be candidate markers to optimize deep brain stimulation (DBS) dose (voltage) in obsessive–compulsive disorder. • Maximal DBS-induced cortical power increases were seen at the previously defined individual therapeutic dose (voltage). • Within most patients, spectral power density effects lasted beyond stimulation time (pre-vs post-DBS). Deep brain stimulation (DBS) is an effective treatment for refractory obsessive–compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. We explored how DBS doses between 3–5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs). We focused on theta power/ phase-stability, given their previously established role in DBS for OCD. Cortical theta power and theta phase-stability did not increase significantly with DBS voltage. DBS-induced theta power peaks were seen at the previously defined individualized therapeutic voltage. Although LFP power generally increased with DBS voltages, this occurred mostly in frequency peaks that overlapped with stimulation artifacts limiting its interpretability. Though highly idiosyncratic, three subjects showed significant acute DBS effects on electroencephalogram theta power and four subjects showed significant carry-over effects (pre-vs post DBS, unstimulated) on LFP and electroencephalogram theta power. Our findings challenge the presence of a consistent dose–response relationship between stimulation voltage and brain activity. Theta power may be investigated further as a neurophysiological marker to aid personalized DBS voltage optimization in OCD. [ABSTRACT FROM AUTHOR]

• We examined the effect of anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) on heart rate variability (HRV) in patients with drug-resistant epilepsy. • ANT-DBS increased HRV in patients irrespective of responder-status, ANT-hit ratio-seemed to influence HRV-changes. • ANT-DBS might positively influence autonomic regulation, additional prospective studies are required to replicate this finding. Heart rate variability (HRV) changes were investigated by several studies after resective epilepsy surgery/vagus nerve stimulation. We examined anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) effects on HRV parameters. We retrospectively analyzed 30 drug-resistant epilepsy patients' medical record data and collected electrocardiographic epochs recorded during video- electroencephalography monitoring sessions while awake and during N1- or N2-stage sleep pre-DBS implantation surgery, post-surgery but pre-stimulation, and after stimulation began. The mean square root of the mean squared differences between successive RR intervals and RR interval standard deviation values differed significantly (p < 0.05) among time-points, showing increased HRV post-surgery. High (0.15–0.4 Hz) and very low frequency (<0.04 Hz) increased, while low frequency (0.04–0.15 Hz) and the LF/HF ratio while awake decreased, suggesting improved autonomic regulation post-surgery. Change of effect size was larger in patients where both activated contacts were located in the ANT than in those where only one or none of the contacts hit the ANT. In patients with drug-resistant epilepsy, ANT-DBS might positively influence autonomic regulation, as reflected by increased HRV. To gain a more comprehensive outcome estimation after DBS implantation, we suggest including HRV measures with seizure count in the post-surgery follow-up protocol. [ABSTRACT FROM AUTHOR]

• Central-positive complexes (CPCs) invariably arise during ECT generalized seizures. • CPCs localize to bilateral medial thalamus and cingulate cortical regions. • Gamma and delta band oscillations correlate with peak amplitude of CPCs in ketamine and etomidate seizures. Central-positive complexes (CPCs) are elicited during electroconvulsive therapy (ECT) as generalized high-amplitude waveforms with maximum positive voltage over the vertex. While these complexes have been qualitatively assessed in previous literature, quantitative analyses are lacking. This study aims to characterize CPCs across temporal, spatial, and spectral domains. High-density 64-electrode electroencephalogram (EEG) recordings during 50 seizures acquired from 11 patients undergoing right unilateral ECT allowed for evaluation of spatiotemporal characteristics of CPCs via source localization and spectral analysis. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Delta, beta, and gamma oscillations were correlated with the peak amplitude of CPCs during seizures induced during ketamine, whereas delta and gamma oscillations were associated with CPC peaks during etomidate anesthesia (excluding the dose-charge titration). Our findings demonstrate the consistency of CPC presence across participant, stimulus charge, time, and anesthetic agent, with peaks localized to bilateral medial thalamus and cingulate cortical regions and associated with delta, beta, and gamma band oscillations (depending on the anesthetic condition). The consistency and reproducibility of CPCs offers ECT as a new avenue for studying the dynamics of generalized seizure activity and thalamocortical networks. [ABSTRACT FROM AUTHOR]

• We studied effects of deep brain stimulation in subthalamic nucleus and globus pallidus on action control processes. • Stimulation in both targets induces fast impulsive action errors. • Stimulation in the subthalamic nucleus and globus pallidus also improves selective inhibitory control. Deep brain stimulation (DBS) is an effective treatment to improve motor symptoms in Parkinson's disease (PD). The Globus Pallidus (GPi) and the Subthalamic Nucleus (STN) are the most targeted brain regions for stimulation and produce similar improvements in PD motor symptoms. However, our understanding of stimulation effects across targets on inhibitory action control processes is limited. We compared the effects of STN (n = 20) and GPi (n = 13) DBS on inhibitory control in PD patients. We recruited PD patients undergoing DBS at the Vanderbilt Movement Disorders Clinic and measured their performance on an inhibitory action control task (Simon task) before surgery (optimally treated medication state) and after surgery in their optimally treated state (medication plus their DBS device turned on). DBS to both STN and GPi targets induced an increase in fast impulsive errors while simultaneously producing more proficient reactive suppression of interference from action impulses. Stimulation in GPi produced similar effects as STN DBS, indicating that stimulation to either target increases the initial susceptibility to act on strong action impulses while concomitantly improving the ability to suppress ongoing interference from activated impulses. Action impulse control processes are similarly impacted by stimulating dissociable nodes in frontal-basal ganglia circuitry. [ABSTRACT FROM AUTHOR]

• Non-invasive brain stimulation can effectively enhance cognition in Alzheimer's disease dementia. • The Neuro-ADTM and left DLPFC rTMS/tDCS have been the most effective protocols. • The beneficial cognitive effects of rTMS outlast for one month. Alzheimer's disease dementia (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain stimulation (NIBS) techniques have the potential to be effective tools for enhancing cognitive functioning. The main objective of our meta-analysis was to quantify and update the status of the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) when applied in AD and MCI. The systematic literature search was conducted in PubMed and Web of Science according to PRISMA statement. Pooled effect sizes (Hedges' g) from 32 studies were analyzed using random effect models. We found both, rTMS and tDCS to have significant immediate cognition-enhancing effect in AD with rTMS inducing also beneficial long-term effects. We found no evidence for synergistic effect of cognitive training with NIBS. In AD a clinical recommendation can be made for NEURO-ADTM system and for high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) as probably effective protocols (B-level of evidence) and for anodal tDCS over the left DLPFC as a possibly effective. According to scientific literature, NIBS may be an effective method for improving cognition in AD and possibly in MCI. [ABSTRACT FROM AUTHOR]

• Phase-locked transcranial alternating current stimulation over the cerebellum suppresses non-jerky tremor in dystonic tremor syndrome. • The cerebellum is causally involved in non-jerky tremor in dystonic tremor syndrome. • Pathophysiological heterogeneity mirrors clinical variability, which may guide optimal intervention targets. To establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked transcranial alternating current stimulation (TACS). We applied phase-locked TACS over the ipsilateral cerebellum (N = 14) and contralateral motor cortex (N = 17) in dystonic tremor syndrome patients, while patients assumed a tremor-evoking posture. We measured tremor power using accelerometery during 30 s stimulation periods at 10 different phase-lags (36-degrees increments) between tremor and TACS for each target. Post-hoc, TACS-effects were related to a key clinical feature: the jerkiness (regularity) of tremor. Cerebellar TACS modulated tremor amplitude in a phase-dependent manner, such that tremor amplitude was suppressed or enhanced at opposite sides of the phase-cycle. This effect was specific for patients with non-jerky (sinusoidal) tremor (n = 10), but absent in patients with jerky (irregular) tremor (n = 4). Phase-locked stimulation over the motor cortex did not modulate tremor amplitude. This study indicates that the cerebellum plays a causal role in the generation of (non-jerky) dystonic tremor syndrome. Our findings suggest pathophysiologic heterogeneity between patients with dystonic tremor syndrome, which mirrors clinical variability. We show tremor phenotype dependent involvement of the cerebellum in dystonic tremor syndrome. Tremor phenotype may thus guide optimal intervention targets. [ABSTRACT FROM AUTHOR]

• Combining multi-site rTMS and cognitive training is a proposed treatment for Alzheimer's disease. • This procedure was found to improve apathy in a series of 30 AD patients, even in the long term. • More general cognitive improvement was not found in the long-term, except for good initial responders. To assess the long-term effects of multi-site repetitive transcranial magnetic stimulation combined with cognitive training (NeuroAD procedure) on cognitive symptoms and apathy in patients with Alzheimer's disease (AD) as part of a 4-year chart review. The study included the 30 AD patients who underwent NeuroAD treatment between 2015 and 2019 at our center. The clinical evaluation was based on the Mini Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Apathy Inventory (AI). Assessment was performed before treatment (baseline), after an initial 6-week protocol of 30 sessions (M1.5), then 3 months (M3), 1 year (M12), and between 1.5 and 4 years (mean 28 months, M28) after treatment initiation. During the first year of follow-up, the AI score improved at all time points (M1.5, M3, M12, p < 0.0001), the ADAS-Cog score improved at the end of the initial procedure (M1.5, p = 0.003) then deteriorated (M12, p = 0.01), while the MMSE score did not change. At final assessment (M28), the AI score was still improved from baseline (p < 0.0001), while the MMSE and ADAS-Cog scores worsened (p < 0.0001). Regarding the ADAS-Cog score, the prolonged improvement at M12 or M28 was correlated with the initial improvement at M1.5. The NeuroAD procedure produced long-term improvement in apathy and more general cognitive improvement only in patients who responded well to the initial 6-week protocol. Our results suggest long-term beneficial effects of the NeuroAD procedure on apathy, which need to be confirmed in controlled studies. The criteria for predicting a good outcome before starting the procedure remain to be defined. [ABSTRACT FROM AUTHOR]

• Temporal properties of ictal high-frequency activity (HFA) from direct recordings of the human thalami (AN, CeM, and MD) are presented in a first-in-man study. • Ictal HFA is nucleus-specific and appears more robust during ictal onset in the AN and MD and during termination in the CeM. • Seizures with low amplitude fast activity onset patterns rapidly propagate to the thalamus. To characterize ictal high-frequency activity (HFA, 80–500 Hz) within the limbic thalami and correlate HFA with seizure onset patterns in patients with temporal lobe epilepsy (TLE). Patients with TLE undergoing stereoelectroencephalography (SEEG) for presurgical workup were prospectively recruited for electrode implantation in one of the anterior (AN), centromedian (CeM), or mediodorsal (MD) thalamic nuclei. HFA was computed by three complementary methods: (1.) power-spectral density (PSD), (2.) power-law based (i.e., 1/f) regression, and (3.) envelope-based (ENV) power analysis. Electrographic onset patterns in the seizure onset zone were classified in three distinct patterns, including low amplitude fast activity (LAFA). From 11 patients, 44 seizures were analyzed. Ictal HFA was observed in all three thalamic nuclei. HFA was greatest during ictal onset in the AN and MD and greatest during termination in the CeM (P < 0.001). LAFA-onset seizures were associated with earlier peak HFA compared to those with other onset patterns (P = 0.006). Dynamics of ictal HFA seem to vary by thalamic subnuclei. AN and MD may facilitate seizure propagation while CeM may play a role in termination. LAFA-onset seizures rapidly propagate to the thalamus. Characterizing nucleus-specific ictal dynamics of neural activities facilitates precise therapy for epilepsy treatment with closed-loop deep brain stimulation. [ABSTRACT FROM AUTHOR]

• Cathodal HD-tDCS targeting the seizure-onset zone is a valid non-invasive treatment option for patients with drug-resistant focal epilepsy. • Using a 2-week stimulation protocol, interictal epileptiform discharges and seizure frequency were reduced in the treatment group compared to the sham group. • Our cathodal stimulation protocol could improve the quality of life, although further study is warranted to confirm this finding. Epilepsy is a common neurological disease with recurrent seizures. Transcranial direct-current stimulation (tDCS) is a safe, non-invasive method used for neuromodulation. The aim of this study was to explore the efficacy of cathodal high-definition tDCS (HD-tDCS) as a noninvasive method for the treatment of patients with drug-resistant focal epilepsy (DRFE). This study was conducted as a randomized parallel and double-blind clinical trial. Twenty patients with DRFE were randomly selected through the convenience sampling method and then were divided into two groups. Ten patients received 2 mA cathodal HD-tDCS targeting the seizure-onset zone for 30 min for 2 weeks (5 consecutive days in each week and 10 days in total). Ten patients were randomized to the sham group. Seizure frequency and Interictal Epileptiform Discharges (IEDs) frequency were the primary outcome measures of this study. Quality of Life in Epilepsy Inventory (QoLIE-89) and Montreal Cognitive Assessment (MoCA) scores were used as secondary outcome measures. Seizure frequency decreased significantly among the patients in the treatment group 2 weeks (P-value ≤ 0.05), 1 month (P-value ≤ 0.05), and 2 months (P-value ≤ 0.05) after the stimulation in comparison to the sham group. Patients in the treatment group showed a decrease in the frequency of IED 2 weeks (P-value ≤ 0.05), 1 month (P-value ≤ 0.05), and 2 months (P-value ≤ 0.05) after stimulation. This cathodal stimulation protocol also improved the overall QoLIE-89 score after the stimulation compared to the sham group. The present study showed that cathodal HD-tDCS had a positive effect on seizure frequency and IED in patients with DRFE. More evidence is required to define the optimal stimulation parameters of HD-tDCS for the treatment of epilepsy. Cathodal HD-tDCS targeting the seizure-onset zone is a promising treatment modality for patients with drug-resistant focal epilepsy. [ABSTRACT FROM AUTHOR]

• When cognitive effort ends afterdischarges, there are widespread changes in coherence. • These coherence changes are similar throughout the cortex, regardless of the distance between recorded sites. • This similarity suggests a pan-cortical effect that may complement the activity of regional and multiregional networks. It is well known that activity in, or coordination among, brain regions, can underlie movement, sensation, language, and cognition but there are observations that tasks unrelated to specific brain regions can nonetheless alter activity in those regions. These tasks might invoke activity in multiregional networks, but it also is possible that they are associated with changes beyond these networks. We therefore evaluated the possibility that more widespread, or even whole-cortical, mechanisms might complement or alter focal or multifocal cortical activity. We assessed the extent of electroencephalographic changes occurring outside areas with epileptiform activity, but that were associated with termination of the epileptiform activity. To do this, we measured the distribution of wavelet cross-coherence changes based on electrocorticography from 15 patients who showed regional afterdischarges in response to electrical brain stimulation prior to epilepsy surgery and in whom cognitive tasks were used in attempts to end the afterdischarges. There were 1276 electrodes implanted in these patients, and we analyzed a total of 55,494 electrode combinations. We compared recordings when cognitive effort was versus when it was not successful in ending afterdischarges. We found that when afterdischarges were suppressed there were changes in electrocorticographic coherence that were similar throughout cortex, regardless of the distance between sites. The similarity implies coordination of the changes, and the similarity regardless of distance or location implies a pan-cortical effect. Our results provide physical support for hypotheses that pan-cortical processes complement the well-known regional and multiregional networks. These processes may participate in, be recruited by, modify, or underlie the conative experiences of waking life. [ABSTRACT FROM AUTHOR]

• This article traces the development of ECT from its origin until today. • The advent of rTMS in the neuropsychiatric field is described. • ECT and rTMS play a complementary role in treatment of neuropsychiatric disorders. Electroconvulsive therapy (ECT) was applied for the first time in humans in 1938: after 80 years, it remains conceptually similar today except for modifications of the original protocol aimed to reduce adverse effects (as persistent memory deficits) without losing clinical efficacy. We illustrate the stages of development as well as ups and downs of ECT use in the last eighty years, and the impact that it still maintains for treatment of certain psychiatric conditions. Targeted, individualized and safe noninvasive neuromodulatory interventions are now possible for many neuropsychiatric disorders thanks to repetitive transcranial magnetic stimulation (rTMS) that injects currents in the brain through electromagnetic induction, powerful enough to depolarize cortical neurons and related networks. Although ECT and rTMS differ in basic concepts, mechanisms, tolerability, side effects and acceptability, and beyond their conceptual remoteness (ECT) or proximity (rTMS) to "precision medicine" approaches, the two brain stimulation techniques may be considered as complementary rather than competing in the current treatment of certain neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

• This review is the second in the series of articles on the use of clinical neurophysiology for the study of movement disorders. • It focuses on the most useful non-invasive methods and techniques that can probe the neurophysiology of the central nervous system in humans. • Tools include reflex studies, transcranial brain stimulation, electroencephalography and reaction times. This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology. [ABSTRACT FROM AUTHOR]

• A minimum stimulation current of 2–4 mA is needed to elicit cortico-cortical evoked potentials (CCEPs) in responsive sites. • Several metrics quantifying CCEP amplitude, distribution, and morphology all show stimulation current-dependent relationships. • 6–7 mA is an asymptotic threshold for maximizing CCEP amplitude and spatial distribution and stabilizing waveform morphology. The aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks. We studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA). We found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology. We determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate. This titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans. [ABSTRACT FROM AUTHOR]

• This review presents the contribution of TMS to the management of dementia. • TMS can be used as a biomarker of the excitability and function of cerebral cortex in dementia. • Increasing evidence supports the beneficial effects of rTMS in Alzheimer's disease-related dementias at mild/early stage. Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such as excitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of the pathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment. [ABSTRACT FROM AUTHOR]

• Acute effects of brain responsive stimulation were studied in a large ambulatory intracranial EEG (iEEG) dataset captured with the NeuroPace® RNS® System. • 20.7% relative reduction in spectral power was observed in a 2-second window following active stimulation compared to sham in iEEG records. • Modest to strong associations between acute effects of stimulation and clinical outcomes were observed on individual detection channels. Understanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings. In patients implanted with the NeuroPace® RNS® System, acute changes in iEEG spectral power following active and sham stimulation periods were quantified and compared within individual iEEG channels. Additionally, acute stimulation-induced acute iEEG changes were compared within iEEG channels before and after patients experienced substantial reductions in clinical seizure frequency. Responsive stimulation resulted in a 20.7% relative decrease in spectral power in the 2–4 second window following active stimulation, compared to sham stimulation. On several detection channels, the AERS features changed when clinical outcomes improved but were relatively stable otherwise. AERS change direction associated with clinical improvement was generally consistent within detection channels. In this retrospective analysis, patients with drug-resistant partial epilepsy treated with direct brain-responsive neurostimulation showed an acute stimulation related reduction in iEEG spectral power that was associated with reductions in clinical seizure frequency. Identifying favorable stimulation related changes in iEEG activity could help physicians to more rapidly optimize stimulation settings for each patient. [ABSTRACT FROM AUTHOR]

• In caffeine naïve participants, LTP-like aftereffects induced by paired associative stimulation (PAS 25) were prolonged and enhanced by caffeine. • In caffeine-adapted participants, cortical excitability was suppressed after a short duration of light deprivation. • Cortical excitability and plasticity vary depending on caffeine consumption behaviour. We examined the effects of caffeine, time of day, and alertness fluctuation on plasticity effects after transcranial alternating current stimulation (tACS) or 25 ms paired associative stimulation (PAS25) in caffeine-naïve and caffeine-adapted subjects. In two randomised, double-blinded, cross-over or placebo-controlled (caffeine) studies, we measured sixty subjects in eight sessions (n = 30, Male: Female = 1:1 in each study). We found caffeine increased motor cortex excitability in caffeine naïve subjects. The aftereffects in caffeine naïve subjects were enhanced and prolonged when combined with PAS 25. Caffeine also increased alertness and the motor evoked potentials (MEPs) were reduced under light deprivation in caffeine consumers both with and without caffeine. In caffeine consumers, the time of day had no effect on tACS-induced plasticity. We conclude that caffeine should be avoided or controlled as confounding factor for brain stimulation protocols. It is also important to keep the brightness constant in all sessions and study groups should not be mixed with caffeine-naïve and caffeine consuming participants. Caffeine is one of the confounding factors in the plasticity induction studies and it induces different excitability effects in caffeine-naïve and caffeine-adapted subjects. This study was registered in the ClinicalTrials.gov with these registration IDs: 1) NCT03720665 https://clinicaltrials.gov/ct2/results?cond=NCT03720665&term=&cntry=&state=&city=&dist= 2) NCT04011670 https://clinicaltrials.gov/ct2/results?cond=&term=NCT04011670&cntry=&state=&city=&dist= [ABSTRACT FROM AUTHOR]

• This study examined the effects of combined left prefrontal intermittent theta-burst stimulation (iTBS) and bifrontal transcranial direct current stimulation (tDCS) on stress. • Combining iTBS with tDCS did not attenuate the psychophysiological stress response. • Concurrent tDCS and iTBS of the prefrontal cortex resulted in more pain and feelings of discomfort. Research suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress. Sixty-eight healthy individuals were submitted to a bifrontal tDCS + iTBS and sham tDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures. The stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the bifrontal tDCS + iTBS protocol. In this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects. There is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers. [ABSTRACT FROM AUTHOR]

• Anodal transcranial direct current stimulation (tDCS) alone and transcranial near-infrared stimulation (tNIRS) alone both enhance corticospinal excitability. • Simultanous tNIRS and tDCS enhance corticospinal excitability stronger than either one of the single interventions. • Simultanous tNIRS and tDCS is a promising new brain stimulation method for clinical neuroplasticity research. Non-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability. Sixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition. tDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity. Simultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect. The simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection. [ABSTRACT FROM AUTHOR]

• Transcranial random noise stimulation (tRNS) improved clinical symptoms in unmedicated children with ADHD. • The improvement using tRNS was greater than transcranial direct current stimulation (tDCS) with a montage that was highlighted as promising in previous meta-analyses. • The effect of intervention yielded further improvement after completion of treatment, suggesting a neuroplasticity-related effect. Improving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactivity-disorder (ADHD), the most common neurodevelopmental disorder in childhood. We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while completing executive functions training. For our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in working memory. We found that our intervention can have a lasting effect, rather than a merely immediate effect as was shown for in previous medical interventions in ADHD. Our results provide a promising direction toward a novel intervention in ADHD. [ABSTRACT FROM AUTHOR]

• The field of NIBS is expanding and adequate training for all NIBS practitioners is needed. • Training should be matched to the responsibilities of Technicians, Clinicians, and Scientists. • We define competencies and propose curricula for TMS and tES organized in Core knowledge, Safety/ethics, Basic Skills, and Advanced Skills. As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines. [ABSTRACT FROM AUTHOR]

• Ambulatory surface electromyography (EMG) with accelerometry (ACC) gives dynamic information about motor fluctuations in Parkinson's disease. • EMG and ACC parameters correlate with patient's condition as quantified by the clinical scores and follow home diaries. • Home-based monitoring reveals improvement of neuromuscular activity after reprogramming of directional deep brain stimulation. To evaluate motor fluctuations in patients with advanced Parkinson's disease (PD) using a small-sized wearable device for surface electromyography (EMG) with accelerometry (ACC) for 24 hours. Seven PD patients with medication were measured once, and nine patients with directional deep brain stimulation (dDBS) twice: before and after the dDBS reprogramming. EMG and ACC parameters were compared with clinical rating scores and patients' home diaries. The combination of EMG and ACC parameters (first principal component PC 1) correlated significantly with patient's condition as quantified by the motor score of Unified Parkinson's Disease Rating Scale and it changed significantly with dDBS reprogramming in line with decreased PD symptoms. Monitoring data detected in comparison with the home diaries: 91 % concordance with tremor, 76 % with rigidity, and 74 % with dyskinesia. In the DBS group, the wake-up time with abnormal neuromuscular function was reduced with reprogramming in all except one patient based on measurements. A wearable device measuring simultaneously both muscle activity and motion can provide continuous and dynamic information about patient's condition and motor fluctuations at home. The present method may help to modify pharmacologic management and DBS treatment in advanced PD. [ABSTRACT FROM AUTHOR]

• Exploration of structural volumetric brain changes due to subsensory SCS. • Gray and white matter volumetric changes were observed in failed back surgery syndrome. • This study confirmed supraspinal effects of SCS in this population. Despite the clinical effectiveness of Spinal Cord Stimulation (SCS), potential structural brain modifications have not been explored. Our aim was to identify structural volumetric changes during subsensory SCS, in patients with Failed Back Surgery Syndrome (FBSS). In this cohort study, twenty-two FBSS patients underwent a magnetic resonance imaging protocol before SCS and 3 months after SCS. Clinical parameters were correlated with volumetric changes, calculated with voxel-based morphometry. After 3 months, a significant volume decrease was found in the inferior frontal gyrus, precuneus, cerebellar posterior lobe and middle temporal gyrus. Significant increases were found in the inferior temporal gyrus, precentral gyrus and the middle frontal gyrus after SCS. Additionally, significant increases in volume of superior frontal and parietal white matter and a significant decrease in volume of white matter underlying the premotor/middle frontal gyrus were revealed after SCS. A significant correlation was highlighted between white matter volume underlying premotor/middle frontal gyrus and leg pain relief. This study revealed for the first time that SCS is able to induce volumetric changes in gray and white matter, suggesting the reversibility of brain alterations after chronic pain treatment. Volumetric brain alterations are observable after 3 months of subsensory SCS in FBSS patients. [ABSTRACT FROM AUTHOR]

• Multisession paired-associative stimulation (PAS) and motor learning was performed in older adults. • Skill acquisition and consolidation during visuomotor training was unaffected by priming PAS. • Long-term skill retention assessed 7 days after the final training session was improved by PAS that induced long-term depression (PAS LTD). Priming non-invasive brain stimulation (NIBS) can improve motor learning in the elderly, but it remains unclear how benefits observed in a single training session translate to multiple training sessions. The current study therefore examined the influence of priming NIBS on acquisition and retention of a novel motor skill over sequential training days in older adults. In 30 older adults (68.2 ± 5.3 years, 14 females), paired-associative stimulation (PAS) was applied prior to visuomotor training on 3 consecutive days. The interstimulus interval used for PAS was either 10 ms (PAS LTD) or 100 ms (PAS Control) and long-term retention was assessed by quantifying motor performance 7 days after the final training session. During training, skill progressively increased across sessions (P < 0.0001), but this was not different between PAS LTD and PAS Control (P > 0.1). In contrast, the magnitude of skill retained 7 days after training was significantly greater in the PAS LTD group (P = 0.02), suggesting significantly greater long-term retention of the trained skill. PAS LTD over multiple sessions may represent an effective tool to help maintain newly learned motor skills in older adults. While multisession priming with PAS can influence long-term skill retention, improving skill acquisition requires investigation of alternative protocols. [ABSTRACT FROM AUTHOR]

• Motor adverse deep brain stimulation (DBS) activates cortex at shorter latencies than therapeutic DBS. • This latency shift is maintained under general anesthesia. • DBS-evoked cortical activation can accurately predict DBS motor side effects. Here, we investigate whether cortical activation predicts motor side effects of deep brain stimulation (DBS) and whether these potential biomarkers have utility under general anesthesia. We recorded scalp potentials elicited by DBS during surgery (n = 11), both awake and under general anesthesia, and in an independent ambulatory cohort (n = 8). Across a range of stimulus configurations, we measured the amplitude and timing of short- and long-latency response components and linked them to motor side effects. Regardless of anesthesia state, in both cohorts, DBS settings with capsular side effects elicited early responses with peak latencies clustering at <1 ms. This early response was preserved under anesthesia in all participants (11/11). In contrast, the long-latency components were suppressed completely in 6/11 participants. Finally, the latency of the earliest response could predict the presence of postoperative motor side effects both awake and under general anesthesia (84.8% and 75.8% accuracy, awake and under anesthesia, respectively). DBS elicits short-latency cortical activation, both awake and under general anesthesia, which appears to reveal interactions between the stimulus and the corticospinal tract. Short-latency evoked cortical activity can potentially be used to aid both DBS lead placement and post-operative programming. [ABSTRACT FROM AUTHOR]

• Normal/abnormal vision can be modulated by non-invasive stimulation beyond the stimulation period. • Clinical impact on plasticity and restoration in patients with low vision is critically evaluated. • Challenges are discussed in the field of transcranial/extracranial stimulation of the eye and brain. The visual system has one of the most complex structures of all sensory systems and is perhaps the most important sense for everyday life. Its functional organization was extensively studied for decades in animal and humans, for example by correlating circumscribed anatomical lesions in patients with the resulting visual dysfunction. During the past two decades, significant achievements were accomplished in characterizing and modulating visual information processing using non-invasive stimulation techniques of the normal and damaged human eye and brain. Techniques include transcranial magnetic stimulation (TMS) and low intensity electric stimulation using either direct or alternating currents applied transcranially (tDCS or tACS) near or above the visual cortex, or alternating currents applied transorbitally (trACS). In the case of transorbital stimulation of the visual system the electrodes are attached near the eye, to the eyelids (transpalpebral electrical stimulation – TPES) or the cornea (tanscorneal electrical stimulation TcES). Here, we summarize the state-of-the-art of visual system magnetic and electric stimulation as a method to modulate normal vision, induce brain plasticity, and to restore visual functions in patients. We review this field's history, models of current flow paths in the eye and brain, neurophysiological principles (e.g. entrainment and after-effects), the effects on vision in normal subjects and the clinical impact on plasticity and vision restoration in patients with low vision, with a particular focus on "off-line" or "after-effects". With regard to the therapeutic possibilities, ACS was demonstrated to be effective in patients affected by glaucoma and optic neuropathy, while tDCS and random noise stimulation (tRNS) are most promising for the treatment of amblyopia, hemianopia and myopia. In addition, rTMS applied above the occipital area is a promising approach to treat migraine, neglect and hemianopia. Although the response to these treatment options is better than to sham stimulation in double blinded clinical studies, the clinical efficacy is still rather variable and a proportion of patients do not respond. It is therefore imperative to better understand the mechanisms of action to be able to optimize treatment protocols possibly through personalization of brain stimulation protocols. By identifying the current opportunities and challenges in the field, we hope to provide insights to help improve neuromodulation protocols to restore visual function in patients with visual system damage. [ABSTRACT FROM AUTHOR]

• Local and distant connections are differently modulated by sleep. • Clear interhemispheric difference in epileptogenic areas' connectivity during sleep. • Different patterns of information flow during sleep in physiologic versus pathologic structures. Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition. [ABSTRACT FROM AUTHOR]

• Pre-articulatory neural activity can predict correct naming responses in individuals with aphasia. • Electrode/time-range/energy combinations with the highest accuracies varied between individuals. • Future individualized pre-articulatory models could be used to predict and treat aphasic utterances. To investigate whether pre-articulatory neural activity could be used to predict correct vs. incorrect naming responses in individuals with post-stroke aphasia. We collected 64-channel high density electroencephalography (hdEEG) data from 5 individuals with chronic post-stroke aphasia (2 female/3 male, median age: 54 years) during naming of 80 concrete images. We applied machine learning on continuous wavelet transformed hdEEG data separately for alpha and beta energy bands (200 ms pre-stimulus to 1500 ms post-stimulus, but before articulation), and determined whether electrode/time-range/energy (ETE) combinations were predictive of correct vs incorrect responses for each participant. The five participants correctly named between 30% and 70% of the 80 stimuli correctly. We observed that pre-articulatory scalp EEG ETE combinations could predict correct vs incorrect responses with accuracies ranging from 63% to 80%. For all but one participant, the prediction accuracies were statistically better than chance. Our findings indicate that pre-articulatory neural activity may be used to predict correct vs incorrect naming responses for some individuals with aphasia. The individualized pre-articulatory neural pattern associated with correct naming responses could be used to both predict naming problems in aphasia and lead to the development of brain stimulation strategies for treatment. [ABSTRACT FROM AUTHOR]

• There are a variety of technologies valuable for exploring human brain connectivity. • The main aspects of anatomical, functional and effective connectivity are described. • A multimodality approach can be useful to evaluate the human brain connectome. The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural–functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity. [ABSTRACT FROM AUTHOR]

• Chronic ambulatory baseline ECoGs captured over 7 years from mesial temporal lobe (MTL) epilepsy patients were analyzed. • Interictal spike rate strongly differentiates MTL patients with best clinical outcomes. • Baseline ECoGs captured during months with no clinical seizures had the least interictal spike rate. Find interictal electrocorticographic (ECoG) biomarkers of clinical outcomes in mesiotemporal lobe (MTL) epilepsy patients. In the NeuroPace® RNS® System clinical trials with 256 patients, 20 MTL patients with the most reduction in clinical seizures at Year 7 compared to baseline (upper response quartile; −96.5% median change) and 20 with the least reduction in clinical seizures (lower response quartile; −17.4% median change) were evaluated. Clinical and interictal ECoG features from the two response quartiles were compared. Demographic and clinical features were similar in the upper and lower response quartiles. Interictal spike rate (ISR) was substantially lower (p < 0.0001) in the upper quartile patients, while normalized theta (4–8 Hz) and normalized gamma (>25 Hz) were also different (p < 0.05) between the two response quartiles. ISR was positively correlated (p < 0.05) with clinical seizure rates in 71% of the channels analyzed. ECoG records captured during months with no clinical seizures had the lowest ISR. ISR is a strong differentiator of clinical response in MTL patients. Normalized theta and gamma also differentiates clinical response. In MTL patients, the interictal spike rate along with spectral power computed from chronic ambulatory baseline ECoGs may serve as biomarkers of clinical outcomes and maybe used as treatment endpoints. [ABSTRACT FROM AUTHOR]

Highlights • EEG studies in PD were reviewed, with the focus on oscillatory activities and DBS. • Knowledge of EEG patterns in PD enables progress particularly in DBS therapy. • Progress was reported recently using advanced analytical methods. Abstract Clinical symptoms of Parkinson's disease (PD) are accompanied by pathological phenomena detected locally in the basal ganglia (BG) as changes in local field potentials (LFPs) and also in cortical regions by electroencephalography (EEG). The literature published mainly between 2000 and 2017 was reviewed with an emphasis on approaches emerging after 2000, in particular on oscillatory dynamics, connectivity studies, and deep brain stimulation. Eighty-five articles were reviewed. The main observations were a general slowing of background activity, excessive synchronization of beta activity, and disturbed movement-related gamma oscillations in the BG and in the cortico-subcortical and cortico-cortical motor loops, suppressible by dopaminergic medication as well as by high-frequency deep brain stimulation (DBS). Non-motor symptoms are related mainly to changes in the alpha frequency range. EEG parameters can be useful in defining the risk of dementia in PD. Further progress was reported recently using advanced analytical technologies and high-performance computing (graph theory). Detailed knowledge of LFPs in PD enabled progress particularly in DBS therapy, which requires optimizing the clinical effect and minimizing adverse side effects. The neurocognitive networks and their dysfunction in PD and DBS therapy are promising targets for future research. [ABSTRACT FROM AUTHOR]

Highlights • Automatic STN detection improves the efficiency and accuracy of target location. • Both spike independent and dependent features are useful for detection of STN. • Further research required for STN sub territories. Abstract Objective This study seeks to systematically review the selection of features and algorithms for machine learning and automation in deep brain stimulation surgery (DBS) for Parkinson's disease. This will assist in consolidating current knowledge and accuracy levels to allow greater understanding and research to be performed in automating this process, which could lead to improved clinical outcomes. Methods A systematic literature review search was conducted for all studies that utilized machine learning and DBS in Parkinson's disease. Results Ten studies were identified from 2006 utilizing machine learning in DBS surgery for Parkinson's disease. Different combinations of both spike independent and spike dependent features have been utilized with different machine learning algorithms to attempt to delineate the subthalamic nucleus (STN) and its surrounding structures. Conclusion The state-of-the-art algorithms achieve good accuracy and error rates with relatively short computing time, however, the currently achievable accuracy is not sufficiently robust enough for clinical practice. Moreover, further research is required for identifying subterritories of the STN. Significance This is a comprehensive summary of current machine learning algorithms that discriminate the STN and its adjacent structures for DBS surgery in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Highlights • Cerebral hemodynamics of non-invasive brain stimulation using TCD is less explored. • Cerebral blood flow velocity changes in response to rTMS and tDCS. • Need for a more standardized approach with future studies. Abstract Objective Non-invasive brain stimulation (NIBS), such as repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS), are promising neuromodulatory priming techniques to promote task-specific functional recovery after stroke. Despite promising results, clinical application of NIBS has been limited by high inter-individual variability. We propose that there is a possible influence of neuromodulation on cerebral blood flow (CBF), as neurons are spatially and temporally related to blood vessels. Transcranial Doppler (TCD), a clinically available non-invasive diagnostic tool, allows for evaluation of CBF velocity (CBFv). However, little is known about the role of neuromodulation on CBFv. Methods A systematic review of literature to understand the effects of NIBS on CBFv using TCD in stroke was conducted. Results Twelve studies fit our inclusion criteria and are included in this review. Our review suggested that CBFv and/or vasomotor reactivity maybe influenced by rTMS dosage (intensity and frequency) and the type of tDCS electrode montage. Conclusion There is limited evidence regarding the effects of NIBS on cerebral hemodynamics using TCD and the usefulness of TCD to capture changes in CBFv after NIBS is not evident from this review. We highlight the variability in the experimental protocols, differences in the applied neurostimulation protocols and discuss open questions that remain regarding CBF and neuromodulation. Significance TCD, a clinically accessible tool, may potentially be useful to understand the interaction between cortical neuromodulation and CBFv. [ABSTRACT FROM AUTHOR]

Highlights • Broadband gamma mapping identified receptive language areas in 22 of 23 subjects. • Comparison with stimulation mapping resulted in 95% sensitivity and 59% specificity. • 82% of contacts identified using broadband gamma were within 1.5 cm of an ECS+ site. Abstract Objective To validate the use of passive functional mapping using electrocorticographic (ECoG) broadband gamma signals for identifying receptive language cortex. Methods We mapped language function in 23 patients using ECoG and using electrical cortical stimulation (ECS) in a subset of 15 subjects. Results The qualitative comparison between cortical sites identified by ECoG and ECS show a high concordance. A quantitative comparison indicates a high level of sensitivity (95%) and a lower level of specificity (59%). Detailed analysis reveals that 82% of all cortical sites identified by ECoG were within one contact of a site identified by ECS. Conclusions These results show that passive functional mapping reliably localizes receptive language areas, and that there is a substantial concordance between the ECoG- and ECS-based methods. They also point to a more refined understanding of the differences between ECoG- and ECS-based mappings. This refined understanding helps to clarify the instances in which the two methods disagree and can explain why neurosurgical practice has established the concept of a "safety margin." Significance Passive functional mapping using ECoG signals provides a fast, robust, and reliable method for identifying receptive language areas without many of the risks and limitations associated with ECS. [ABSTRACT FROM AUTHOR]