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Repetitive transcranial magnetic stimulation (rTMS) is a rapidly developing therapeutic modality for the safe and effective treatment of neuropsychiatric disorders. However, clinical rTMS driving systems and head coils are large, heavy, and expensive, so miniaturized, affordable rTMS devices may facilitate treatment access for patients at home, in underserved areas, in field and mobile hospitals, on ships and submarines, and in space. The central component of a portable rTMS system is a miniaturized, lightweight coil. Such a coil, when mated to lightweight driving circuits, must be able to induce B and E fields of sufficient intensity for medical use. This paper newly identifies and validates salient theoretical considerations specific to the dimensional scaling and miniaturization of coil geometries, particularly figure-8 coils, and delineates novel, key design criteria. In this context, the essential requirement of matching coil inductance with the characteristic resistance of the driver switches is highlighted. Computer simulations predicted E- and B-fields which were validated via benchtop experiments. Using a miniaturized coil with dimensions of 76 mm × 38 mm and weighing only 12.6 g, the peak E-field was 87 V/m at a distance of 1.5 cm. Practical considerations limited the maximum voltage and current to 350 V and 3.1 kA, respectively; nonetheless, this peak E-field value was well within the intensity range, 60-120 V/m, generally held to be therapeutically relevant. The presented parameters and results delineate coil and circuit guidelines for a future miniaturized, power-scalable rTMS system able to generate pulsed E-fields of sufficient amplitude for potential clinical use.

We report a large study (n=120) investigating the effects of tDCS at Fp3 on the FIE. We used a double-blind design with subjects randomly assigned to one of the three tDCS groups and then engaged with a recognition task involving upright and inverted faces. Group 1 (control), subjects first received sham tDCS in the study phase (learning) followed by sham tDCS in the recognition phase; Group 2, subjects received anodal tDCS in the study phase followed by sham tDCS in the recognition phase; Group 3, subjects received anodal tDCS in the study phase followed by cathodal tDCS in the recognition phase. Group 2's results confirmed that anodal tDCS reduces the FIE vs. sham (Group 1) by disrupting performance for upright faces. Importantly, Group 3's results revealed that cathodal tDCS applied after anodal, increased the FIE vs. Group 2, bringing it back to control, by enhancing performance for upright faces. These results reveal that the negative effects of anodal tDCS on the FIE can be reversed by cathodal tDCS.

In a preregistered experiment, we tested whether interfering with primary motor cortex (M1) activation can change how people construe meaning from language. Participants were presented with sentences describing motor actions and asked to choose between a concrete and an abstract interpretation of their meaning. Prior to this task, participants' M1 was disrupted using repetitive transcranial magnetic stimulation (rTMS). The results suggested strong evidence against the idea that M1-rTMS affects meaning construction. Additional analyses and experiments suggest that the absence of effect cannot be accounted for by failure to inhibit M1, lack of task validity, or lack of power to detect a small effect. These results do not support a causal role for primary motor cortex in building meaning from action language.

Non-invasive vagus nerve stimulation has proven effective in modulating parasympathetic autonomic nervous system activity and various cognitive functions.This study investigated the effects of transauricular vagus nerve stimulation (taVNS) on body ownership and interoception in healthy subjects using a within-subjects experimental design (active taVNS/sham).The rubber hand illusion (RHI) and the Heartbeat Counting Task (HCT) were employed.Cardiac activity was recorded throughout the procedure to measure physiological indices of heart rate (HR) and heart rate variability (HRV).Ownership for the fake hand was observed in both active and sham stimulation, as indicated by drift and scores on illusion-relevant items (Q1-Q3).HR and HRV showed no variations between synchronous/asynchronous RHI or between stimulation conditions. Active taVNS resulted in decreased interoceptive meta-awareness.Individuals with lower interoceptive abilities exhibited heightened susceptibility to RHI during active taVNS, possibly due to perturbation of interoceptive signals and increased reliance on exteroceptive signals in constructing body representation.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique to enhance cognitive function in a non-invasive manner. Using electroencephalography and functional magnetic resonance imaging, it was investigated whether a tACS with different phase lags between central executive and default mode networks modulated cognitive performance in perception, working memory, and inhibitory control. It was found that phase-lag-dependent tACS mediated improvement in task performance, neurodynamically reflected in task-relevant cortical and subcortical activation as well as prefrontal-based top-down functional connectivity. Our observations provide neurophysiological correlates of network-wise tACS-phase-dependent neuromodulation and a feasible non-invasive approach to effectively modulate fundamental cognitive functions.

Understanding and modulating cognitive aspects of decision-making and reinforcement learning are crucial for addressing neuropsychiatric problems like substance use disorders (SUD). We developed a non-invasive stimulation method to modulate theta phase synchronization between the medial prefrontal cortex and right lateral prefrontal cortex. Our EEG-informed modulation led to bidirectional changes in learning-based decision-making, including error-related components and brain signatures. In fact, by combining HD-tACS with mathematical modeling, we revealed that in-phase/antiphase HD-tACS over the mPFC and rPFC significantly altered (synchronized/desynchronized) theta phase coupling between these regions, influencing decision accuracy (improved/impaired), and neurocomputational parameters of learning-based decision-making. Additionally, this modulation rescued/disrupted the causal link between brain error monitoring and cognitive control systems in healthy/SUD participants, and reshaped punishment-guided decision and learning components. We concluded theta rhythms in the mPFC and mPFC-rPFC coupling play a unifying causal role in regulating choice, learning, and behavioral adaptation in both healthy and patient populations.

Background and purpose Methods Results Conclusion Several surgical techniques have been used to treat cervical dystonia (CD), however, to date, the optimal surgical technique for CD remains controversial. We therefore conducted the first network meta‐analysis to compare different surgical strategies for CD to inform clinical practice.Electronic databases were searched for surgical strategies for treating CD. The primary outcome was improvement in total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score. Subgroup analysis was performed to compare short‐term (< 1 year) and long‐term (≥ 1 year) outcomes. Safety outcomes included surgery‐related adverse events (AEs).A total of 55 trials with 2032 patients employing five surgical strategies were identified, including globus pallidus internus (GPi)/subthalamic nucleus (STN)‐deep brain stimulation (DBS), selective peripheral denervation (SPD), microvascular decompression (MVD) and pallidotomy. All strategies led to significant improvement in total TWSTRS score (mean improvement range 18.65–28.22). GPi‐DBS showed significantly greater enhancement than SPD for the whole dataset (mean difference [MD] 7.03, 95% credible interval [Crl] 1.53–12.56), while both GPi‐DBS (MD 8.05, 95% Crl 2.35–13.80) and STN‐DBS (MD 10.71, 95% Crl 2.22–19.20) exhibited more long‐term improvement than SPD. Regarding safety outcomes, GPi/STN‐DBS and MVD were associated with fewer surgery‐related AEs than SPD (ln odds ratio range −1.68 to −1.41).We conclude that DBS should be the preferred surgical option for CD, and the STN is a promising alternative target choice due to its comparable efficacy with the GPi. However, more direct evidence is still required. [ABSTRACT FROM AUTHOR]

Background: Temporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex. Methods: 40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel's intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC. Results: For CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P < 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P < 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P < 0.001). For mean dFC, a significant main effect of time was found (P < 0.001). TI–T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P < 0.001). Results were consistent across different window sizes. Conclusion: 20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex's natural resonance. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically assess the clinical efficacy of non-invasive brain stimulation (NIBS) for treating post-stroke sleep disorders (PSSD). Methods: We conducted thorough literature search across multiple databases, including PubMed, Web of Science, EmBase, Cochrane Library, Scopus, China Biology Medicine (CBM); China National Knowledge Infrastructure (CNKI); Technology Periodical Database (VIP), and Wanfang Database, focusing on RCTs examining NIBS for PSSD. Meta-analyses were performed using RevMan 5.4 and Stata 14. Results: Eighteen articles were reviewed, including 16 on repetitive Transcranial Magnetic Stimulation (rTMS), one on Theta Burst Stimulation (TBS), and two on transcranial Direct Current Stimulation (tDCS). Meta-analysis results indicated that rTMS within NIBS significantly improved the Pittsburgh Sleep Quality Index (PSQI) score (MD = −1.85, 95% CI [−2.99, −0.71], p < 0.05), the 17-item Hamilton Depression Rating Scale (HAMD-17) score [MD = −2.85, 95% CI (−3.40, −2.30), p < 0.05], and serum brain-derived neurotrophic factor (BDNF) levels [MD = 4.19, 95% CI (2.70, 5.69), p < 0.05], while reducing the incidence of adverse reactions [RR = 0.36, 95% CI (0.23, 0.55), p < 0.05]. TBS significantly improved the PSQI score in patients with PSSD (p < 0.05). Conversely, tDCS significantly improved the HAMD-17 score in PSSD patients [MD = −1.52, 95% CI (−3.41, −0.64), p < 0.05]. Additionally, rTMS improved sleep parameters, including Stage 2 sleep (S2%) and combined Stage 3 and 4 sleep (S3 + S4%) (p < 0.05), while tDCS improved total sleep time (TST) and sleep efficiency (SE) (p < 0.05).Subgroup analysis results indicated: (1) Both LF-rTMS and HF-rTMS improved PSQI scores (p < 0.05). (2) Both rTMS combined with medication and rTMS alone improved PSQI scores (p < 0.05). Compared to the sham/blank group, the rTMS group showed improvements in SE, sleep latency (SL), S1%, S3 + S4%, and REM sleep (REM%). The rTMS combined with medication group showed improved SL compared to the medication-only group (p < 0.05). Conclusion: NIBS effectively improves sleep quality, structure, depression levels, and BDNF levels in PSSD patients, while also being safe. Further investigations into the potential of NIBS in PSSD treatment may provide valuable insights for clinical applications. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42023485317. [ABSTRACT FROM AUTHOR]

Background: Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, is recognized for its ability to modulate cortical neuronal activity. However, its effects over time and the dynamics following stimulation are less well understood. Understanding the temporal dynamics of iTBS effects is essential for optimizing the timing and frequency of stimulation in therapeutic applications. Objective: This study investigated the temporal changes in protein expression induced by iTBS in Neuro-2a cells. Methods: We analyzed protein expression in retinoic acid-differentiated Neuro-2a cells at multiple time points — 0.5, 3, 6, 12, and 24 hours post-iTBS — using Western blot and immunocytochemistry techniques. Results: Our findings reveal a significant early increase in neurotransmitter receptor subunits, neurotrophic factors, and cytoskeletal proteins within the first 0.5 hour following iTBS. Notably, proteins such as mGLuR1, NMDAR1, GABBR2, and β-tubulin III showed substantial increase in expression. However, the effects of iTBS on protein expression was not sustained at later timepoints. Conclusion: Our results suggest that iTBS can transiently alter the expression of specific proteins in Neuro-2a cells. Future research should investigate the potential benefits of repeated stimulations within the early time window to refine iTBS interventions, potentially expanding their research and clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both. Method: Data presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography. Results: Slow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090). Conclusions: Findings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period. Clinical trial registration: This study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&country=United%20States&state=Arizona&cond=insomnia&intr=tms%20&rank=1 [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Selective serotonin reuptake inhibitors are thought to exert a clinical effect through various mechanisms, including through alteration in synaptic plasticity. Repetitive transcranial magnetic stimulation can induce temporary changes in synaptic excitability in cerebral cortex that resemble long‐term potentiation and long‐term depression that serve as a measure of synaptic plasticity in vivo. A version of repetitive transcranial magnetic stimulation called continuous theta burst stimulation can induce inhibition of cortical excitability that can be measured through a motor evoked potential. Previous work has suggested that this response can be modulated by administration of selective serotonin reuptake inhibitors.Thirty‐one healthy volunteers received both fluoxetine 20 mg and placebo in randomly ordered sessions, followed by spaced continuous theta burst stimulation to motor cortex. Changes in Motor Evoked Potentials were then recorded over 60 min.The response to spaced continuous theta burst stimulation did not differ significantly between fluoxetine and placebo sessions. Spaced continuous theta burst stimulation produced a paradoxical excitatory response in an unexpected number of participants.A single dose of fluoxetine 20 mg does not influence the response to continuous theta burst stimulation. Previous results suggesting an effect of selective serotonin reuptake inhibitors on inhibitory non‐invasive brain stimulation protocols may be due to insufficiently large sample sizes. [ABSTRACT FROM AUTHOR]

The editorial titled "How does brain stimulation work? Neuroversion and other putative mechanisms of action" explores the evolving field of brain stimulation techniques in psychiatry and neurology. It discusses various methods such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS) that trigger neurochemical and electrophysiological changes in the brain to produce therapeutic effects. The research topic includes 10 articles authored by 76 individuals covering a range of brain stimulation techniques and their applications in neuropsychiatric disorders, aiming to enhance understanding and influence further research and clinical practice. The findings presented in the editorial highlight the diverse applications of brain stimulation techniques and their potential benefits, contributing to the advancement of clinical practice and stimulating further investigation into the mechanisms underlying these therapies. [Extracted from the article]

Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits. Previous studies have demonstrated the safety, feasibility, and efficacy of one single tACS session in different clinical populations. However, the effects of tACS appear limited and need to be sustained to be considered an effective cognitive neurorehabilitation tool. Recent studies have used home-based, repeated tACS sessions in individuals with neurodegenerative diseases. To our knowledge, the safety and feasibility of such an intensive protocol remains to be tested in a younger population with neurodevelopmental disorders. Using a randomized double-blind sham-controlled design, we administered home-based, repeated tACS sessions to seven individuals aged 14–25 with 22q11.2 deletion syndrome (22q11.2DS), which confers an increased risk for neurodevelopmental disorders. We aimed to assess the safety, tolerability, and feasibility of tACS. Findings from this ongoing clinical trial revealed a favorable safety profile, with frequent yet transient and mainly mild adverse effects. The intervention proved to be feasible, shown by very high adherence rates and positive user experiences. Future studies should therefore investigate whether prolonged exposure to tACS can lead to long-lasting cognitive outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT05664412. [ABSTRACT FROM AUTHOR]

Neuromodulation stands as a cornerstone in the therapeutic landscape for neurological disorders, yet the quest for selective stimulation of specific brain regions with minimal invasiveness and high spatiotemporal precision remains a formidable challenge. In this study, a multifunctional nano‐optical electrode (NOE) to mitigate depressive symptoms in animal models of depression is introduced. The NOEs' core–shell architecture integrates mesoporous carbon shells for optimal absorption of near‐infrared (NIR) light, alongside superparamagnetic ferric oxide nanocluster cores for magnetic resonance imaging (MRI) visibility. This configuration enables the precise excitation of untransfected neurons using NIR irradiation. The MRI‐guided NIR neuromodulation via NOEs can significantly alleviate depressive symptoms in mice. This is evidenced by the observed enhancement in pleasure‐seeking behaviors, improved motor functions, and a decrease in behaviors indicative of despair. The alleviation of depressive symptoms is ascribed to the NOEs' role as an efficient NIR light transducer, which boosts neuronal activity in the medial prefrontal cortex (mPFC). The MRI compatibility of the NOEs augments the spatial resolution, further refining the precision of neuromodulation. The multimodal, precise, transcranial, and non‐genetic approach of the NOEs‐based neuromodulation strategy heralds a new era in the optical‐theranostics of neurological disorders. [ABSTRACT FROM AUTHOR]

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naive), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naive or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain. [ABSTRACT FROM AUTHOR]

Background: Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network. Objectives: This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial direct current stimulation (tDCS). Methods: In a prospective, randomized, double‐blinded, crossover trial, 21 PD patients (mean age 59.7 years, mean Hoehn & Yahr [H&Y] 2.4) received multifocal tDCS targeting the a‐priori network. Twenty‐minute sessions of tDCS and sham were administered on 2 days in randomized order. Movement Disorder Society‐Unified Parkinson's Disease Rating Scale—Part III (MDS‐UPDRS‐III) scores were assessed. Results: Before intervention, MDS‐UPDRS‐III scores were comparable in both conditions (stimulation days: 37.38 (standard deviation [SD] = 12.50, confidence interval [CI] = 32.04, 42.73) vs. sham days: 36.95 (SD = 13.94, CI = 30.99, 42.91), P = 0.63). Active stimulation resulted in a reduction by 3.6 points (9.7%) to 33.76 (SD = 11.19, CI = 28.98, 38.55) points, whereas no relevant change was observed after sham stimulation (36.43 [SD = 14.15, CI = 30.38, 42.48], average improvement: 0.5 [1.4%]). Repeated‐measures analysis of variance (ANOVA) confirmed significance (main effect of time: F(1,20)=4.35, P < 0.05). Tukey's post hoc tests indicated MDS‐UPDRS‐III improvement after active stimulation (t [20] = 2.9, P = 0.03) but not after sham (t [20] = 0.42, P > 0.05). In a subset of patients that underwent DBS surgery later, their DBS response correlated with tDCS effects (R = 0.55, P(1) = 0.04). Conclusion: Noninvasive, multifocal tDCS targeting a DBS‐derived network significantly improved PD motor symptoms. Despite a small effect size, this study provides proof of principle for the successful noninvasive neuromodulation of an invasively identified network. Future studies should investigate repeated tDCS sessions and their utility for screening before DBS surgery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson's disease. These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework, subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits versus costs, reward delay aversion and learning from outcomes. Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with neurological disorders. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta‐analysis aimed to assess the effectiveness of non‐invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). Objective: We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. Methods: The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta‐analysis was performed. Results: Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = −2.49, [95% confidence interval: −3.34, −1.64]) and ICARS (−5.27 [−7.06, −3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. Conclusion: Non‐invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high‐quality RCTs are required. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) continues to lack definitive curative therapies, necessitating an urgent exploration of innovative approaches. This review provides a comprehensive analysis of recent clinical trials focusing on invasive and non-invasive brain stimulation techniques as potential interventions for AD. Deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are evaluated for their therapeutic efficacy, safety, and applicability. DBS, though invasive, has shown promising results in mitigating cognitive decline, but concerns over surgical risks and long-term effects persist. On the other hand, non-invasive methods like rTMS, tDCS, and tACS have demonstrated potential in enhancing cognitive performance and delaying disease progression, with minimal side effects, but with varied consistency. The evidence hints towards an individualized, patient-centric approach to brain stimulation, considering factors such as disease stage, genetic traits, and stimulation parameters. The review also highlights emerging technologies and potential future directions, emphasizing the need for larger, multi-center trials to confirm preliminary findings and establish robust clinical guidelines. In conclusion, while brain stimulation techniques present a promising avenue in AD therapy, further research is imperative for more comprehensive understanding and successful clinical implementation. Through this review, we aim to catalyze the scientific discourse and stimulate further investigation into these novel interventions for AD. [ABSTRACT FROM AUTHOR]

With the progress of modern science and technology, magnetic therapy technology develops rapidly, and many types of magnetic therapy methods continue to emerge, making magnetic therapy one of the main techniques of physiotherapy. With the continuous development of magnetic field research and clinical applications, magnetic therapy, as a non-invasive brain stimulation therapy technology, has attracted much attention due to its potential in the treatment of motor dysfunction, cognitive impairment and speech disorders in patients with neurodegenerative diseases. However, the role of magnetic fields in the prognosis and treatment of neurodegenerative diseases and their mechanisms remain largely unexplored. In this paper, the therapeutic effect and neuroprotective mechanism of the magnetic field on neurodegenerative diseases are reviewed, and the new magnetic therapy techniques are also summarized. Although the neuroprotective mechanism of magnetic field cannot be fully elaborated, it is helpful to promote the application of magnetic field in neurodegenerative diseases and provide a new theoretical basis for the related magnetic field research in the later period. • Summarize the therapeutic effect of magnetic field on neurodegenerative diseases and new magnetic therapy technology. • A variety of potential mechanisms play a neuroprotective role of magnetic field. • Magnetic therapy technology have great potential in the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Non‐invasive brain stimulation techniques offer therapeutic potential for neurological and psychiatric disorders. However, current methods are often limited in their stimulation depth. The novel transcranial temporal interference stimulation (tTIS) aims to overcome this limitation by non‐invasively targeting deeper brain regions. In this study, we aimed to evaluate the efficacy of tTIS in modulating alpha activity during a mental rotation task. The effects of tTIS were compared with transcranial alternating current stimulation (tACS) and a sham control. Participants were randomly assigned to a tTIS, tACS, or sham group. They performed alternating blocks of resting and mental rotation tasks before, during, and after stimulation. During the stimulation blocks, participants received 20 min of stimulation adjusted to their individual alpha frequency (IAF). We assessed shifts in resting state alpha power, event‐related desynchronization (ERD) of alpha activity during mental rotation, as well as resulting improvements in behavioral performance. Our results indicate tTIS and tACS to be effective in modulating cortical alpha activity during mental rotation, leading to an increase in ERD from pre‐ to poststimulation as well as compared to sham stimulation. However, this increase in ERD was not correlated with enhanced mental rotation performance, and resting state alpha power remained unchanged. Our findings underscore the complex nature of tTIS and tACS efficacy, indicating that stimulation effects are more observable during active cognitive tasks, while their impacts are less pronounced on resting neuronal systems. Our study adds to the limited human research on the novel tTIS technique, which holds the potential for non‐invasive deep brain stimulation. We show that while tTIS and tACS can modulate cortical alpha activity during an active cognitive task, they do not improve behavioral performance or affect resting state alpha power. This underscores the task‐specific effectiveness of these techniques, suggesting their therapeutic potential is most effective during active cognitive engagement. [ABSTRACT FROM AUTHOR]

Past research has illuminated pivotal roles of dopamine D 3 receptors (D 3 R) in the rewarding effects of cocaine and opioids. However, the cellular and neural circuit mechanisms that underlie these actions remain unclear. We employed Cre-LoxP techniques to selectively delete D 3 R from presynaptic dopamine neurons or postsynaptic dopamine D 1 receptor (D 1 R)–expressing neurons in male and female mice. We utilized RNAscope in situ hybridization, immunohistochemistry, real-time polymerase chain reaction, voltammetry, optogenetics, microdialysis, and behavioral assays (n ≥ 8 animals per group) to functionally characterize the roles of presynaptic versus postsynaptic D 3 R in cocaine and opioid actions. Our results revealed D 3 R expression in ∼25% of midbrain dopamine neurons and ∼70% of D 1 R-expressing neurons in the nucleus accumbens. While dopamine D 2 receptors (D 2 R) were expressed in ∼80% dopamine neurons, we found no D 2 R and D 3 R colocalization among these cells. Selective deletion of D 3 R from dopamine neurons increased exploratory behavior in novel environments and enhanced pulse-evoked nucleus accumbens dopamine release. Conversely, deletion of D 3 R from D 1 R-expressing neurons attenuated locomotor responses to D 1 -like and D 2 -like agonists. Strikingly, deletion of D 3 R from either cell type reduced oxycodone self-administration and oxycodone-enhanced brain-stimulation reward. In contrast, neither of these D 3 R deletions impacted cocaine self-administration, cocaine-enhanced brain-stimulation reward, or cocaine-induced hyperlocomotion. Furthermore, D 3 R knockout in dopamine neurons reduced oxycodone-induced hyperactivity and analgesia, while deletion from D 1 R-expressing neurons potentiated opioid-induced hyperactivity without affecting analgesia. We dissected presynaptic versus postsynaptic D 3 R function in the mesolimbic dopamine system. D 2 R and D 3 R are expressed in different populations of midbrain dopamine neurons, regulating dopamine release. Mesolimbic D 3 R are critically involved in the actions of opioids but not cocaine. [ABSTRACT FROM AUTHOR]

Dual-mode non-invasive brain stimulation using repetitive transcranial magnetic stimulation and transcranial direct current stimulation is known to help neurorehabilitation in patients with stroke. However, this neuromodulation effect may vary depending on the lesion location of patients with stroke, and the basis in lesion location for this is insufficient. This study aims to investigate the difference in neuromodulation effectiveness according to the lesion location after dual-mode brain stimulation using electroencephalography signals. Eight patients with ischemic subacute stroke and 11 healthy controls participated in this study. Brain stimulation was conducted in one session per day for a total of 10 days over the motor cortex, electroencephalography was measured for 5 min with eyes closed, and motor function was evaluated before and after dual-mode stimulation. The lesion location was divided into an infratentorial stroke (ITS) and a supratentorial stroke (STS) based on tentorium cerebelli. In addition, we focused on the mu and beta bands related to motor function. In terms of intrahemispheric connectivity, the mu weighted phase lag index over the contralesional primary motor cortex was significantly higher in only ITS before stimulation compared to healthy controls, and mu Granger causality over the ipsilesional primary motor cortex was significantly higher in both ITS and STS after stimulation compared to healthy controls. In contrast, from the perspective of interhemispheric connectivity, the laterality of beta Granger causality before stimulation in ITS was lower than that of healthy controls and significantly increased after stimulation. The effect of brain stimulation may vary depending on the lesion location of patients with stroke, and these findings provide indicative insights into effective dual-mode stimulation interventions for neurorehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear. Methods: To further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based eventrelated potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory thetaburst stimulation--a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)--over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices. Results: The results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials ("Gratton effect") that was only accomplished with an intact DLPFC (i.e., following placebo stimulation). Discussion: Because non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has long been the conventional method for targeting deep brain structures, but noninvasive alternatives like transcranial Temporal Interference Stimulation (tTIS) are gaining traction. Research has shown that alternating current influences brain oscillations through neural modulation. Understanding how neurons respond to the stimulus envelope, particularly considering tTIS's high-frequency carrier, is vital for elucidating its mechanism of neuronal engagement. This study aims to explore the focal effects of tTIS across varying amplitudes and modulation depths in different brain regions. An excitatory-inhibitory network using the Izhikevich neuron model was employed to investigate responses to tTIS and compare them with transcranial Alternating Current Stimulation (tACS). We utilized a multi-scale model that integrates brain tissue modeling and network computational modeling to gain insights into the neuromodulatory effects of tTIS on the human brain. By analyzing the parametric space, we delved into phase, amplitude, and frequency entrainment to elucidate how tTIS modulates endogenous alpha oscillations. Our findings highlight a significant difference in current intensity requirements between tTIS and tACS, with tTIS requiring notably higher intensity. We observed distinct network entrainment patterns, primarily due to tTIS's high-frequency component, whereas tACS exhibited harmonic entrainment that tTIS lacked. Spatial resolution analysis of tTIS, conducted via computational modeling and brain field distribution at a 13 Hz stimulation frequency, revealed modulation in deep brain areas, with minimal effects on the surface. Notably, we observed increased power within intrinsic and stimulation bands beneath the electrodes, attributed to the high stimulus signal amplitude. Additionally, Phase Locking Value (PLV) showed slight increments in non-deep areas. Our analysis indicates focal stimulation using tTIS, prompting further investigation into the necessity of high amplitudes to significantly affect deep brain regions, which warrants validation through clinical experiments. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI. Methods: The meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis. Results: This meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87-3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31-3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30-5.24; executive function: SMD = -0.52, 95% CI = -3.17-2.12; language: SMD = 3.43, 95% CI = 1.50-5.36; memory: SMD = 3.52, 95% CI = 1.74-5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61-6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = -0.30-1.55; executive function: SMD = 2.15, 95% CI = 0.87-3.43; memory: SMD = 0.99, 95% CI = -0.81-2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04-4.23). Conclusion: In conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI. [ABSTRACT FROM AUTHOR]

Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel technique for noninvasive brain stimulation (NIBS). TUS delivered in a theta (5 Hz) burst pattern (tbTUS) induces plasticity in the human primary motor cortex (M1) for 30–60 min, showing promise for therapeutic development. Metaplasticity refers to activity-dependent changes in neural functions governing synaptic plasticity; depotentiation is the reversal of long-term potentiation (LTP) by a subsequent protocol with no effect alone. Metaplasticity can enhance plasticity induction and clinical efficacy of NIBS protocols. In our study, we compared four NIBS protocol combinations to investigate metaplasticity on tbTUS in humans of either sex. We delivered four interventions: (1) sham continuous theta burst stimulation with 150 pulses (cTBS150) followed by real tbTUS (tbTUS only), (2) real cTBS150 followed by sham tbTUS (cTBS only), (3) real cTBS150 followed by real tbTUS (metaplasticity), and (4) real tbTUS followed by real cTBS150 (depotentiation). We measured motor-evoked potential amplitude, short-interval intracortical inhibition, long-interval intracortical inhibition, intracortical facilitation (ICF), and short-interval intracortical facilitation before and up to 90 min after plasticity intervention. Plasticity effects lasted at least 60 min longer when tbTUS was primed with cTBS150 compared with tbTUS alone. Plasticity was abolished when cTBS150 was delivered after tbTUS. cTBS150 alone had no significant effect. No changes in M1 intracortical circuits were observed. Plasticity induction by tbTUS can be modified in manners consistent with homeostatic metaplasticity and depotentiation. This substantiates evidence that tbTUS induces LTP-like processes and suggests that metaplasticity can be harnessed in the therapeutic development of TUS. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To investigate the effects of directional subthalamic deep brain stimulation (STN‐dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).We included 10 participants who underwent STN‐DBS and presented severe preoperative FOG, in a randomized, double‐blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non‐directional (ring‐mode) STN‐DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre‐operative structural and diffusion‐weighted imaging to model individual VTAs and to examine cortico‐subthalamic connectivity. We used linear mixed‐effects models to contrast the effects of central STN‐dDBS, posterior STN‐dDBS, and ring‐mode STN‐DBS.Central STN‐dDBS produced significantly better improvement in gait and balance control compared to posterior STN‐dDBS (p = 0.027), with fewer FOG episodes (p < 0.001). Conversely, ring‐mode STN‐DBS resulted in worsened postural control compared to central STN‐dDBS (p = 0.009). The cortico‐subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico‐STN connectivity with ring‐mode STN‐DBS.Central STN‐dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN‐DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Recent findings suggest that prism adaptation can extend its effects beyond spatial attention, modulating the performance of different cognitive tasks by acting on cerebellar, parietal and temporal-frontal networks. We tested groups of healthy subjects to investigate the effects of rightward vs. leftward prism adaptation vs. neutral lenses exposure in a series of memory tasks, probing either short-term (Digit span, Corsi span) or long-term memory (Supraspan verbal and spatial learning). In the short-term memory tasks, leftward prism adaptation selectively increased verbal span, while rightward prism adaptation increased spatial span. In the long-term memory tasks, leftward prism adaptation selectively increased verbal supraspan, i.e., increased the number of digits in the correct sequence reproduced and reduced the number of repetitions needed to learn the supraspan sequence. On the other hand, rightward prism adaptation selectively increased spatial supraspan, i.e. it increased the number of spatial positions in the correct sequence reproduced and reduced the number of repetitions needed to learn the supraspan sequence. Moreover, rightward, but not leftward, prism adaptation selectively increased supraspan recall after a delay interval, regardless of the stimulus material, i.e., it increased the number of digits or spatial positions recalled after a delay interval. Neutral lenses exposure did not influence any memory task. These findings suggest that prism adaptation can induce both modality/hemispheric-specific and process-specific effects on short-term and long-term explicit memory. [ABSTRACT FROM AUTHOR]

Background/Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that shows promise as a potential treatment for depression. However, the clinical efficacy of tDCS varies, possibly due to individual differences in head anatomy affecting tDCS dosage. While functional changes in brain activity are more commonly reported in major depressive disorder (MDD), some studies suggest that subtle macroscopic structural differences, such as cortical thickness or brain volume reductions, may occur in MDD and could influence tDCS electric field (E-field) distributions. Therefore, accounting for individual anatomical differences may provide a pathway to optimize functional gains in MDD by formulating personalized tDCS dosage. Methods: To address the dosing variability of tDCS, we examined a subsample of sixteen active-tDCS participants' data from the larger ELECT clinical trial (NCT01894815). With this dataset, individualized neuroimaging-derived computational models of tDCS current were generated for (1) classifying treatment response, (2) elucidating essential stimulation features associated with treatment response, and (3) computing a personalized dose of tDCS to maximize the likelihood of treatment response in MDD. Results: In the ELECT trial, tDCS was superior to placebo (3.2 points [95% CI, 0.7 to 5.5; P = 0.01]). Our algorithm achieved over 90% overall accuracy in classifying treatment responders from the active-tDCS group (AUC = 0.90, F1 = 0.92, MCC = 0.79). Computed precision doses also achieved an average response likelihood of 99.981% and decreased dosing variability by 91.9%. Conclusion: These findings support our previously developed precision-dosing method for a new application in psychiatry by optimizing the statistical likelihood of tDCS treatment response in MDD. [ABSTRACT FROM AUTHOR]

One of the key challenges in Big Data for clinical research and healthcare is how to integrate new sources of data, whose relation to disease processes are often not well understood, with multiple classical clinical measurements that have been used by clinicians for years to describe disease processes and interpret therapeutic outcomes. Without such integration, even the most promising data from emerging technologies may have limited, if any, clinical utility. This paper presents an approach to address this challenge, illustrated through an example in Parkinson's Disease (PD) management. We show how data from various sensing sources can be integrated with traditional clinical measurements used in PD; furthermore, we show how leveraging Big Data frameworks, augmented by Artificial Intelligence (AI) algorithms, can distinctively enrich the data resources available to clinicians. We showcase the potential of this approach in a cohort of 50 PD patients who underwent both evaluations with an Integrated Motion Analysis Suite (IMAS) composed of a battery of multimodal, portable, and wearable sensors and traditional Unified Parkinson's Disease Rating Scale (UPDRS)-III evaluations. Through techniques including Principal Component Analysis (PCA), elastic net regression, and clustering analysis we demonstrate how this combined approach can be used to improve clinical motor assessments and to develop personalized treatments. The scalability of our approach enables systematic data generation and analysis on increasingly larger datasets, confirming the integration potential of IMAS, whose use in PD assessments is validated herein, within Big Data paradigms. Compared to existing approaches, our solution offers a more comprehensive, multi-dimensional view of patient data, enabling deeper clinical insights and greater potential for personalized treatment strategies. Additionally, we show how IMAS can be integrated into established clinical practices, facilitating its adoption in routine care and complementing emerging methods, for instance, non-invasive brain stimulation. Future work will aim to augment our data repositories with additional clinical data, such as imaging and biospecimen data, to further broaden and enhance these foundational methodologies, leveraging the full potential of Big Data and AI. [ABSTRACT FROM AUTHOR]

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions. [ABSTRACT FROM AUTHOR]

Background: Biomarkers of Alzheimer's disease (AD) and mild cognitive impairment (MCI, or prodromal AD) are highly significant for early diagnosis, clinical trials and treatment outcome evaluations. Electroencephalography (EEG), being noninvasive and easily accessible, has recently been the center of focus. However, a comprehensive understanding of EEG in dementia is still needed. A primary objective of this study is to investigate which of the many EEG characteristics could effectively differentiate between individuals with AD or prodromal AD and healthy individuals. Methods: We collected resting state EEG data from individuals with AD, prodromal AD, and normal cognition. Two distinct preprocessing pipelines were employed to study the reliability of the extracted measures across different datasets. We extracted 41 different EEG features. We have also developed a stand-alone software application package, Feature Analyzer, as a comprehensive toolbox for EEG analysis. This tool allows users to extract 41 EEG features spanning various domains, including complexity measures, wavelet features, spectral power ratios, and entropy measures. We performed statistical tests to investigate the differences in AD or prodromal AD from age-matched cognitively normal individuals based on the extracted EEG features, power spectral density (PSD), and EEG functional connectivity. Results: Spectral power ratio measures such as theta/alpha and theta/beta power ratios showed significant differences between cognitively normal and AD individuals. Theta power was higher in AD, suggesting a slowing of oscillations in AD; however, the functional connectivity of the theta band was decreased in AD individuals. In contrast, we observed increased gamma/alpha power ratio, gamma power, and gamma functional connectivity in prodromal AD. Entropy and complexity measures after correcting for multiple electrode comparisons did not show differences in AD or prodromal AD groups. We thus catalogued AD and prodromal AD-specific EEG features. Conclusions: Our findings reveal that the changes in power and connectivity in certain frequency bands of EEG differ in prodromal AD and AD. The spectral power, power ratios, and the functional connectivity of theta and gamma could be biomarkers for diagnosis of AD and prodromal AD, measure the treatment outcome, and possibly a target for brain stimulation. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated changes in athletes brain imaging across a competitive season due to repeated head impacts during collision sports. However, there is no data reporting cortical activity in elite female rugby sevens players. There is scant literature on the effects of high-definition (HD)-transcranial direct current stimulation (tDCS) on cortical activity responses at different time points (TP) across the competitive season on the responsiveness of spectral band frequencies for HD-tDCS stimulation. This study examined the cortical activity of elite female rugby sevens players prior to pre-season (TP1) and following five months of training and competition (TP2), and the acute effects of HD-tDCS on cortical activity parameters. For each TP, the squad was randomly allocated to the HD-tDCS sham or the HD-tDCS anodal (active) stimulation groups. The Stroop task was performed for approximately 15 min prior to HD-tDCS (Stroop task-PRE). Following completion of the Stroop task-PRE, participants received 20-minutes of HD-tDCS stimulation and then performed the Stroop task (Stroop task-POST). A diminished responsiveness of cortical activity to the perturbation (HD-tDCS) for TP2 (vs. TP1) was observed, with cortical rhythms exhibiting a relative decline in faster bands (alpha, beta, and gamma), while slower bands (delta and theta) increased its proportional contribution to cortical activity. This discovery implies a potential alteration in the neural substrate's responsiveness to neuromodulation, likely influenced by the cumulative effects of repeated head impacts. The diminished responsiveness to HD-tDCS prompts significant considerations for the application of neuromodulation techniques in athletes participating in contact/collision sports. [ABSTRACT FROM AUTHOR]

Impairments in postural responses to perturbation are common in people with Parkinson's disease (PwPD) and lack effective treatment. We recently showed that a single session of transcranial direct current stimulation (tDCS) promotes acute improvement of postural response to perturbation in PwPD. However, the effects of multiple tDCS sessions remain unclear. What is the efficacy of eight sessions of anodal tDCS on postural responses to external perturbation in PwPD? Twenty-two PwPD participated in this randomized, double-blind, parallel-arm, and sham-controlled study. Participants were randomly distributed into active (a-tDCS; n=11) or sham stimulation (s-tDCS; n=11). Eight tDCS sessions were applied over the primary motor cortex (M1), with the a-tDCS group receiving 2 mA for 20 minutes. Postural responses to external perturbations were assessed before, 48 hours after, and one month after (follow-up) the completion of tDCS sessions. Primary outcome measures included the onset latency of medial gastrocnemius (MG) muscle and range of center of pressure. Secondary outcomes included electromyography and CoP parameters, and prefrontal cortex (PFC) activity. ANOVA revealed a trend for Group*Moment interaction for MG onset latency (p=0.058). a-tDCS tended to have shorter MG onset latency at post-test (p=0.040; SRM = −0.63) compared to pre-test. For the secondary outcomes, only a-tDCS decreased the time taken to recover balance after the perturbation at post-test and follow-up compared to pre-test (both p<0.001; SRM=-1.42 and −1.53, respectively). Also, only a-tDCS demonstrated lower PFC activity at post-test compared to pre-test (p=0.017; SRM = −0.82) and follow-up (p=0.001). Eight sessions of tDCS over M1 improved postural response to perturbation in PwPD. Some benefits lasted for at least a month. Neuromuscular and behavioral changes observed after the intervention were accompanied by decreased PFC activity (executive-attentional control), suggesting that tDCS applied over M1 can improve movement automaticity. • A tendency to decreased MG onset latency was evidenced in a-tDCS at post vs. pre-test. • tDCS over M1 decreased the recovery time after perturbation in PwPD. • tDCS over M1 decreased the PFC activity after perturbation in PwPD. • Effects of tDCS on postural response were sustained for at least a month in PwPD. [ABSTRACT FROM AUTHOR]

The relationship between working memory (WM) and neuronal oscillations can be studied in detail using brain stimulation techniques, which provide a method for modulating these oscillations and thus influencing WM. The endogenous coupling between the amplitude of gamma oscillations and the phase of theta oscillations is crucial for cognitive control. Theta/gamma peak-coupled transcranial alternating current stimulation (TGCp-tACS) can modulate this coupling and thus influence WM performance. This study investigated the effects of TGCp-tACS on WM in older adults and compared their responses with those of younger participants from our previous work who underwent the same experimental design. Twenty-eight older subjects underwent both TGCp-tACS and sham stimulation sessions at least 72 h apart. Resting-state electroencephalography (EEG) was recorded before and after the interventions, and a WM task battery with five different WM tasks was performed during the interventions to assess various WM components. Outcomes measured included WM task performance (e.g., accuracy, reaction time (RT)) and changes in power spectral density (PSD) in different frequency bands. TGCp-tACS significantly decreased accuracy and RT on the 10- and 14-point Sternberg tasks and increased RT on the Digit Symbol Substitution Test in older adults. In contrast, younger participants showed a significant increase in accuracy only on the 14-item Sternberg task. Electrophysiological analysis revealed a decrease in delta and theta PSD and an increase in high gamma PSD in both younger and older participants after verum stimulation. In conclusion, theta-gamma coupling is essential for WM and modulation of this coupling affects WM performance. The effects of TGCp-tACS on WM vary with age due to natural brain changes. To better support older adults, the study suggests several strategies to improve cognitive function, including: Adjusting stimulation parameters, applying stimulation to two sites, conducting multiple sessions, and using brain imaging techniques for precise targeting. [ABSTRACT FROM AUTHOR]

Objectives: Non-invasive vagus nerve stimulation (nVNS) is an emerging neuromodulation technique in recent years, which plays a role in nervous system diseases, psychiatric diseases, and autoimmune diseases. However, there is currently no comprehensive analysis of all the literature published in this field. Therefore, in this article, a bibliometric analysis will be conducted on all the literature published in the field of nVNS in the past 20 years. Methods: All articles and reviews published in this field from 2004 to 2023 were extracted from the WOS core database. VOSviewer 1.6.18.0, Scimago Graphica, CiteSpace 6.2.R2, and Excel 2021 were used to analyze the number of publications, participating countries, institutions, authors, references, and research hotspots in this field. Results: A total of 843 articles were included in the bibliometric analysis of nVNS. Over the past 20 years, the number of publications in this field has gradually increased, reaching a peak in 2023. The United States and China ranked top two in terms of publication volume, and institutions from these two countries also ranked high in terms of publication volume, citation count, and collaboration intensity. Rong Peijing is the author with the most publications, while Bashar W Badran is the most cited author. Articles in the field of nVNS were most frequently published in Frontiers in Neuroscience, while Brain Stimulation had the most citations. Currently, research hotspots in nVNS mainly focus on its application in diseases and related mechanisms. Conclusion: We conducted a comprehensive analysis of the field of nVNS, clarifying the previous research directions, which is helpful to expand its indications and promote clinical application. [ABSTRACT FROM AUTHOR]

Background: Stroke frequently results in upper limb motor dysfunction, with traditional therapies often failing to yield sufficient improvements. Emerging technologies such as virtual reality (VR) and noninvasive brain stimulation (NIBS) present promising new rehabilitation possibilities. Objectives: This study systematically reviews and meta-analyses the effectiveness of VR and NIBS in improving upper limb motor function in stroke patients. Methods: Registered with PROSPERO (CRD42023494220) and adhering to the PRISMA guidelines, this study conducted a thorough search of databases including PubMed, MEDLINE, PEDro, REHABDATA, EMBASE, Web of Science, Cochrane, CNKI, Wanfang, and VIP from 2000 to December 1, 2023, to identify relevant studies. The inclusion criterion was stroke patients receiving combined VR and NIBS treatment, while exclusion criteria were studies with incomplete articles and data. The risk of bias was assessed using the Cochrane Collaboration tool. Statistical analysis was performed using Stata SE 15.0, employing either a fixed-effects model or a random-effects model based on the level of heterogeneity. Results: A total of 11 studies involving 493 participants were included, showing a significant improvement in Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores in the combined treatment group compared to the control group (SMD = 0.85, 95% CI [0.40, 1.31], p = 0.017). The Modified Ashworth Scale (MAS) scores significantly decreased (SMD = − 0.51, 95% CI [− 0.83, − 0.20], p = 0.032), the Modified Barthel Index (MBI) scores significantly increased (SMD = 0.97, 95% CI [0.76, 1.17], p = 0.004), and the Wolf Motor Function Test (WMFT) scores also significantly increased (SMD = 0.36, 95% CI [0.08, 0.64], p = 0.021). Subgroup analysis indicated that the duration of treatment influenced the outcomes in daily living activities. Conclusions: The combination of VR and NIBS demonstrates significant improvements in upper limb motor function in stroke patients. The duration of treatment plays a critical role in influencing the outcomes, particularly in activities of daily living. This systematic review has limitations, including language bias, unclear randomization descriptions, potential study omissions, and insufficient follow-up periods. Future studies should focus on exploring long-term effects and optimizing treatment duration to maximize the benefits of combined VR and NIBS therapy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Age-related decline in balance and postural control is common in healthy elders and is escalated in aging adults with stroke. Transcranial direct current stimulation (tDCS) has emerged as one of the promising brain stimulations adjoining therapeutic exercise to enhance the recovery of balance and motor functions in persons with and without neurological disorders. This review aims to summarize and compare the available evidence of the tDCS on improving balance in the older adults without neurological disorders and the older adults with stroke. Methods: The Ovid (Medline) database was searched from its inception through to 06/15/2024 for randomized controlled trials investigating tDCS for improving balance in older adults with and without stroke. Results: Overall, 20 appropriate studies (including 271 stroke subjects and 259 healthy older adults) were found. The data indicate mixed results of tDCS for improving balance in older adults with and without stroke. Conclusions: Based on current research evidence, we have not found a specific tDCS protocol that is more effective than other tDCS protocols for improving balance and postural control in healthy older adults and older adults with stroke. Further research should explore the ideal tDCS approach, possibly in conjunction with standard interventions, to optimize postural control and balance in healthy older adults and older adults with stroke. [ABSTRACT FROM AUTHOR]

Introduction: Treatment‐resistant depression (TRD) is a condition in which patients suffering from depression no longer respond to common methods of treatment, such as anti‐depressant medication. Neurosurgical procedures such as ablative surgery, deep brain stimulation, and vagus nerve stimulation have been used in efforts to overcome TRD. Objectives: This review aims to provide an overview of the side effects of neurosurgery performed in clinical studies related to depression. Methods: A literature search was conducted through PubMed, MEDLINE, EMBASE, Ovid, and ClinicalTrials.gov databases. Results: This review selected 10 studies for ablative surgery, 12 for deep brain stimulation, and 10 for vagus nerve stimulation, analyzing their side effect profiles of neurosurgery for TRD. The major side effects of each type of neurosurgery were identified, such as incontinence and confusion for ablative surgery, headaches and increased suicide ideation for deep brain stimulation, and voice hoarseness and dyspnea for vagus nerve stimulation. Conclusion: The review discusses the merits and demerits of neurosurgery as a treatment option for TRD. It also suggests new insights into decreasing the burden of these neurosurgical side effects so that they can be a viable, high‐efficacy treatment method for TRD. [ABSTRACT FROM AUTHOR]

Background: Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. Objective: This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. Methods: Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). Results: The intervention had high rates of adherence and completion (98% of participants completed at least 18 of 20 sessions). The active tDCS group demonstrated significant improvement for the left hand compared with baseline in 9-HPT (−5.85 ± 6.19 vs −4.23 ± 4.34, p = 0.049) and DMMPUT (−10.62 ± 8.46 vs −8.97 ± 6.18, p = 0.049). The active tDCS group reported improvements in multiple sclerosis (MS)-related quality of life (mean increase: 5.93 ± 13.04 vs −0.05 ± −8.27; p = 0.04). Conclusion: At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity. [ABSTRACT FROM AUTHOR]

The overlap between motor and cognitive signs resulting from posterior parietal cortex (PPC) and cerebellar lesions can mask their relative contribution in the sensorimotor integration process. This study aimed to identify distinguishing motor and cognitive features to disentangle PPC and cerebellar involvement in two sensorimotor-related functions: gait and body schema representation. Thirty healthy volunteers were enrolled and randomly assigned to PPC or cerebellar stimulation. Sham stimulation and 1 Hz-repetitive-Transcranial-Magnetic-Stimulation were delivered over P3 or cerebellum before a balance and a walking distance estimation task. Each trial was repeated with eyes open (EO) and closed (EC). Eight inertial measurement units recorded spatiotemporal and kinematic variables of gait. Instability increased in both groups after real stimulation: PPC inhibition resulted in increased instability in EC conditions, as evidenced by increased ellipse area and range of movement in medio-lateral and anterior–posterior (ROMap) directions. Cerebellar inhibition affected both EC (increased ROMap) and EO stability (greater displacement of the center of mass). Inhibitory stimulation (EC vs. EO) affected also gait spatiotemporal variability, with a high variability of ankle and knee angles plus different patterns in the two groups (cerebellar vs parietal). Lastly, PPC group overestimates distances after real stimulation (EC condition) compared to the cerebellar group. Stability, gait variability, and distance estimation parameters may be useful clinical parameters to disentangle cerebellar and PPC sensorimotor integration deficits. Clinical differential diagnosis efficiency can benefit from this methodological approach. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30–70 Hz) coupled with lower theta band power (4–8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts. [ABSTRACT FROM AUTHOR]

This document presents a case study of a 17-year-old male with isolated dystonia, a condition characterized by involuntary twisting movements and posturing. The patient had a mutation in the COL6A3 gene, which is believed to contribute to the development of dystonia. Traditional treatments were ineffective, and the patient also experienced mood and social disturbances. However, bilateral deep brain stimulation (DBS) surgery resulted in significant improvement in motor symptoms and quality of life. The study suggests that genetic screening before DBS surgery may be important in identifying potential genetic factors contributing to dystonia. The authors also highlight the therapeutic value of DBS for isolated dystonia and call for further research in this area. [Extracted from the article]

The quality space hypothesis about conscious experience proposes that conscious sensory states are experienced in relation to other possible sensory states. Recent empirical findings suggest that subjective quality space can be explained in terms of similarities in neural activation patterns; however, computational theories of consciousness have had little to say about this qualitative aspect of experience. Localist, global workspace, and higher-order theories of consciousness can all accommodate a quality space in which subjects experience relations between actually instantiated experiences. Different theories make distinct predictions for inactivation and stimulation experiments on both local (sensory) and nonlocal (e.g., prefrontal) neural activity patterns. If experiments find that the whole structure of activation space affects the qualitative character of experience, this can be accommodated by localist and lean workspace/higher-order theories, but is more challenging for full-content global workspace and higher-order theories that require the whole structure to be re-represented. The quality space hypothesis about conscious experience proposes that conscious sensory states are experienced in relation to other possible sensory states. For instance, the colour red is experienced as being more like orange, and less like green or blue. Recent empirical findings suggest that subjective similarity space can be explained in terms of similarities in neural activation patterns. Here, we consider how localist, workspace, and higher-order theories of consciousness can accommodate claims about the qualitative character of experience and functionally support a quality space. We review existing empirical evidence for each of these positions, and highlight novel experimental tools, such as altering local activation spaces via brain stimulation or behavioural training, that can distinguish these accounts. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), and transcranial direct current stimulation (tDCS), is an emerging intervention that has been used to treat various mental illnesses. However, previous studies have not comprehensively compared the efficacies of various NIBS modalities in alleviating anxiety symptoms among patients with generalized anxiety disorder (GAD). Therefore, this study conducted a systematic review and meta-analysis to assess the efficacy of NIBS for patients with GAD. A systematic search of four major bibliographic databases (Embase, PubMed, Web of Science and The Cochrane Library) was conducted from inception dates to November 26, 2023 to identify eligible studies. The data were analyzed using a random-effects model. Seven randomized controlled trials (RCTs) were included in the meta-analysis. Significant differences were found in changes in Hamilton anxiety rating scale (HARS) scores, study-defined response, and remission between the intervention and control groups. Moreover, the intervention groups experienced a significantly higher frequency of headaches. The results revealed that interventions improved GAD compared to control groups. cTBS and rTMS exhibited better treatment efficacy than tDCS, which did not appear to have a significant therapeutic effect. Longer follow-up periods and larger sample sizes are required in future RCTs. This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/ , CRD42023466285). • Systematic review and meta-analysis of NIBS techniques, including cTBS, rTMS, and tDCS, for treating GAD. • NIBS significantly reduces anxiety symptoms and improves response and remission rates. • The efficacy is notably contingent on the stimulation types employed. • Discerning headaches as an adverse event exhibited notable statistical disparities. [ABSTRACT FROM AUTHOR]

We conducted a meta-analysis and qualitative review on the randomized controlled trials investigating the effects of transcranial direct current stimulation and transcranial magnetic stimulation on fear extinction and the return of fear in non-primate animals and humans. The meta-analysis was conducted by searching PubMed, Web of science, PsycINFO, and Cochrane Library and extracting fear response in the active and sham groups in the randomized controlled trials. The pooled effect size was quantified by Hedges' g using a three-level meta-analytic model in R. We identified 18 articles on the tDCS effect and 5 articles on the TMS effect, with 466 animal subjects and 621 human subjects. Our findings show that tDCS of the prefrontal cortex significantly inhibit fear retrieval in animal models (Hedges' g = -0.50). In human studies, TMS targeting the dorsolateral/ventromedial prefrontal cortex has an inhibiting effect on the return of fear (Hedges' g = -0.24). The limited number of studies and the heterogeneous designs of the selected studies made cross-study and cross-species comparison difficult. Our findings shed light on the optimal non-invasive brain stimulation protocols for targeting the neural circuitry of threat extinction in humans. [ABSTRACT FROM AUTHOR]