Intermittent theta burst stimulation of the left dorsolateral prefrontal cortex has no additional effect on the efficacy of virtual reality exposure therapy for acrophobia. A randomized double-blind placebo-controlled study.

Anxiety disorders are among the most common mental disorders. Treatment guidelines recommend pharmacotherapy and cognitive behavioral therapy as standard treatment. Although cognitive behavioral therapy is an effective therapeutic approach, not all patients benefit sufficiently from it. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, have been investigated as promising adjuncts in the treatment of affective disorders. The aim of this study is to investigate whether a combination of intermittent theta burst stimulation (iTBS) and virtual reality exposure therapy leads to a significantly greater reduction in acrophobia than virtual reality exposure with sham stimulation. In this randomized double-blind placebo-controlled study, 43 participants with acrophobia received verum or sham iTBS over the left dorsolateral prefrontal cortex prior to two sessions of virtual reality exposure therapy. Stimulation of the left dorsolateral prefrontal cortex with iTBS was motivated by an experimental study showing a positive effect on extinction memory retention. Acrophobic symptoms were assessed using questionnaires and two behavioral approach tasks one week before, after treatment and six months after the second diagnostic session. The results showed that two sessions of virtual reality exposure therapy led to a significant reduction in acrophobic symptoms, with an overall remission rate of 79 %. However, there was no additional effect of iTBS of the left dorsolateral prefrontal cortex on the therapeutic effects. Further research is needed to determine how exactly a combination of transcranial magnetic stimulation and exposure therapy should be designed to enhance efficacy.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study.

BACKGROUND: Disorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies. METHODS: Twenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated. RESULTS: One-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031). CONCLUSIONS: Applying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05187000.

Impact of a mandibular advancement device on corticomotor plasticity in patients with obstructive sleep apnea.

BACKGROUND: Neuroplasticity induced by mandibular advancement appliance (MAD) in patients with obstructive sleep apnoea (OSA) is poorly documented. OBJECTIVE: This randomised placebo-controlled crossover mechanistic study assessed the effects of short-term use of a MAD on corticomotor excitability of the masseter and tongue in patients with OSA. METHODS: Adults (n = 28) with mild or moderate OSA were randomly allocated to sleep with a MAD for 2-weeks with 40% of the maximal protrusion (MAD active position) and without any jaw protrusion (MAD placebo position). The outcomes were assessed at baseline, and after 2 and 6 weeks, with a 2-week washout period. The primary outcome was the amplitude of motor evoked potential (MEP) assessed on the right masseter, right side of tongue and right first dorsal interosseous with transcranial magnetic stimulation. Corticomotor map volume of the same muscles was also assessed. Repeated-measures ANOVAs followed by Tukey test were applied to the data (p < .050). RESULTS: There was a significant increase in the MEP amplitude of the masseter and tongue following the MAD active position compared with the baseline and MAD placebo (Tukey: p < .001). There were no significant MEP amplitude differences between the baseline and placebo positions (p > .050). Moreover, there was a significant increase in corticomotor map volume for the masseter and tongue muscles following the MAD active position compared with baseline and MAD placebo (Tukey: p < .003). CONCLUSION: Excitability of the masseter and tongue motor pathways is, at least transiently, increased in patients with OSA following a short-term use of MAD. This novel finding of MAD-induced neuroplasticity in corticomotor pathways may contribute to a further understanding of the mechanisms of oral appliances for treating OSA.

Transcranial magnetic stimulation for obsessive-compulsive disorder and post-traumatic stress disorder: A comprehensive systematic review and analysis of therapeutic benefits, cortical targets, and psychopathophysiological mechanisms.

Transcranial magnetic stimulation (TMS) is a safe non-invasive treatment technique. We systematically reviewed randomised controlled trials (RCTs) applying TMS in obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) to analyse its therapeutic benefits and explore the relationship between cortical target and psychopathophysiology. We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were investigated for OCD and four for PTSD, yielding similar results. Bilateral dlPFC-TMS exhibited the greatest symptom change (32.3 % for OCD, N = 4 studies; 35.7 % for PTSD, N = 1 studies), followed by right dlPFC-TMS (24.4 % for OCD, N = 8; 26.7 % for PTSD, N = 10), and left dlPFC-TMS (22.9 % for OCD, N = 6; 23.1 % for PTSD, N = 1). mPFC-TMS showed promising results, although evidence is limited (N = 2 studies each for OCD and PTSD) and findings for PTSD were conflicting. Despite clinical improvement, reviewed reports lacked a consistent and solid rationale for cortical target selection, revealing a gap in TMS research that complicates the interpretation of findings and hinders TMS development and optimisation. Future research should adopt a hypothesis-driven approach rather than relying solely on correlations from imaging studies, integrating neurobiological processes with affective, behavioural, and cognitive states, thereby doing justice to the complexity of human experience and mental illness.

The effect of repetitive transcranial magnetic stimulation on the Hamilton Depression Rating Scale-17 criterion in patients with major depressive disorder without psychotic features: a systematic review and meta-analysis of intervention studies.

AIM: In line with the publication of clinical information related to the therapeutic process of repetitive transcranial magnetic stimulation (rTMS) and the updating of relevant treatment guidelines, the present meta-analysis study was designed and conducted to determine the effect of repetitive transcranial magnetic stimulation (rTMS) on the Hamilton Depression Rating Scale-17 (HDRS-17) criterion in patients with major depressive disorder (MDD) without psychotic features. METHODS: In this study, a systematic search was conducted in electronic databases such as PubMed [Medline], Scopus, Web of Science, Embase, Ovid, Cochrane Library, and ClinicalTrials. gov using relevant keywords. The search period in this study was from January 2000 to January 2022, which was updated until May 2023. Randomized controlled trials (RCTs) that determined the effect of repetitive transcranial magnetic stimulation (rTMS) on the Hamilton Depression Rating Scale-17 (HDRS-17) criterion in patients with major depressive disorder (MDD) without psychotic features were included in the analysis. The quality of the included RCTs was assessed using the Cochrane Risk of Bias checklist. Statistical analyses were performed using STATA (Version 16) and RevMan (Version 5). RESULTS: Following the combination of results from 16 clinical trial studies in the present meta-analysis, it was found that the mean Hamilton Depression Rating Scale-17 (HDRS-17) in patients with major depressive disorder (MDD) decreases by an average of 1.46 units (SMD: -1.46; % 95 CI: -1.65, -1.27, I square: 45.74%; P heterogeneity: 0.56). Subgroup analysis results indicated that the standardized mean difference of Hamilton Depression Rating Scale-17 (HDRS-17) varied based on the number of treatment sessions: patients receiving 10 or fewer repetitive transcranial magnetic stimulation (rTMS) sessions showed a mean Hamilton Depression Rating Scale-17 (HDRS-17) reduction of 2.60 units (SMD: -2.60; % 95 CI: -2.86, -2.33, I square: 55.12%; P heterogeneity: 0.55), while those receiving 11 to 20 sessions showed a mean Hamilton Depression Rating Scale-17 (HDRS-17) reduction of 0.28 units (SMD: -0.28; % 95 CI: -0.65, -0.09, I square: 39.91%; P heterogeneity: 0.89). CONCLUSION: In conclusion, our meta-analysis demonstrates the efficacy of repetitive transcranial magnetic stimulation (rTMS) in reducing depressive symptoms in major depressive disorder (MDD) patients. The complex results of subgroup analysis revealed insight on the possible benefits of a more focused strategy with fewer sessions, as well as the impact of treatment session frequency. These findings add to our understanding of repetitive transcranial magnetic stimulation (rTMS) as a therapeutic intervention for the treatment of major depressive illnesses.

Optimizing antidepressant benefits: Effect of theta burst stimulation treatment in physically active people with treatment-resistant depression.

Theta burst stimulation (TBS) is a promising therapy for treatment-resistant major depressive disorder (MDD), but a significant proportion of individuals do not respond adequately, necessitating alternative approaches. This study explores whether individuals meeting minimum recommended physical activity levels demonstrate better responses to TBS compared to physically inactive individuals. Using data from a randomized controlled trial (n = 43), participants were categorized as physically active or inactive based on baseline International Physical Activity Questionnaire (IPAQ) scores. Depression scores (Hamilton Rating Scale for Depression, 17-item; HRSD-17) were assessed at baseline, 4, and 6 weeks of TBS treatment. A significant Time X Group effect adjusted for age and baseline depression was observed. Physically active individuals consistently exhibited lower depression scores across time points. At 4 and 6 weeks, there was a significant increase in between-group differences, indicating that the physically active group derived greater benefits from treatment. At 6 weeks, a significantly higher proportion of responders (≥50 % HRSD-17 reduction) were observed in the physically active compared to inactive group. Physical activity significantly contributed to regression and logistic models predicting treatment response. These findings support the potential role of baseline physical activity in enhancing TBS therapy for MDD.

Improving efficacy of repetitive transcranial magnetic stimulation for treatment of Parkinson disease gait disorders.

Parkinson disease (PD) is a neurodegenerative disorder that causes motor and cognitive deficits, presenting complex challenges for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a type of neuromodulation that can produce plastic changes in neural activity. rTMS has been trialed as a therapy to treat motor and non-motor symptoms in persons with Parkinson disease (PwP), particularly treatment-refractory postural instability and gait difficulties such as Freezing of Gait (FoG), but clinical outcomes have been variable. We suggest improving rTMS neuromodulation therapy for balance and gait abnormalities in PwP by targeting brain regions in cognitive-motor control networks. rTMS studies in PwP often targeted motor targets such as the primary motor cortex (M1) or supplementary motor area (SMA), overlooking network interactions involved in posture-gait control disorders. We propose a shift in focus toward alternative stimulation targets in basal ganglia-cortex-cerebellum networks involved in posture-gait control, emphasizing the dorsolateral prefrontal cortex (dlPFC), cerebellum (CB), and posterior parietal cortex (PPC) as potential targets. rTMS might also be more effective if administered during behavioral tasks designed to activate posture-gait control networks during stimulation. Optimizing stimulation parameters such as dosage and frequency as used clinically for the treatment of depression may also be useful. A network-level perspective suggests new directions for exploring optimal rTMS targets and parameters to maximize neural plasticity to treat postural instabilities and gait difficulties in PwP.

Non-invasive TMS attenuates neuropathic pain after spinal cord injury associated with enhancing brain functional connectivity and HPA axis activity.

Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain. Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.

Excitability Changes in Occipital Cortex After Continuous Theta-Burst Stimulation.

Introduction: Modulation of visual cortical structures by repetitive transcranial magnetic stimulation is rarely observed in literature. In this study; the researchers aimed to investigate the neurophysiological alterations by using continuous theta burst stimulation (cTBS) protocol over the occipital cortex in healthy subjects. Methods: Twenty-five (15 female, 10 male) (mean age 29.84±4.7 years) healthy individuals were included in sham and real cTBS occipital stimulation sessions. Before and after each session, neurophysiological studies including phosphene threshold and visual evoked potential (VEP) responses were recorded. The P100 latency values and maximum amplitude values between N75-P100 peaks of 100 responses of 1000 uninterrupted continuous visual stimuli were measured. The VEP habituation and phosphene thresholds were compared in sham and real cTBS sessions. Results: The phosphene threshold values increased to statistically significant levels after the real cTBS session. Visual evoked potential habituation was observed in both sham and real cTBS sessions in individuals without significant differences. Also, no difference between the P100 latencies and N75-P100 amplitude values in the sham and real cTBS sessions was observed. Conclusion: Phosphene threshold measurements demonstrated the modulation of the occipital cortex excitability via cTBS in healthy subjects.

Pre-supplementary motor area strengthens reward sensitivity in intertemporal choice.

Previous investigations on the causal neural mechanisms underlying intertemporal decision making focused on the dorsolateral prefrontal cortex as neural substrate of cognitive control. However, little is known, about the causal contributions of further parts of the frontoparietal control network to delaying gratification, including the pre-supplementary motor area (pre-SMA) and posterior parietal cortex (PPC). Conflicting previous evidence related pre-SMA and PPC either to evidence accumulation processes, choice biases, or response caution. To disentangle between these alternatives, we combined drift diffusion models of decision making with online transcranial magnetic stimulation (TMS) over pre-SMA and PPC during an intertemporal decision task. While we observed no robust effects of PPC TMS, perturbation of pre-SMA activity reduced preferences for larger over smaller rewards. A drift diffusion model of decision making suggests that pre-SMA increases the weight assigned to reward magnitudes during the evidence accumulation process without affecting choice biases or response caution. Taken together, the current findings reveal the computational role of the pre-SMA in value-based decision making, showing that pre-SMA promotes choices of larger, costly rewards by strengthening the sensitivity to reward magnitudes.

Site- and frequency-specific enhancement of visual search performance with online individual alpha frequency (IAF) repetitive transcranial magnetic stimulation (rTMS) to the inferior frontal junction.

In this study, repetitive transcranial magnetic stimulation was applied to either the right inferior frontal junction or the right inferior parietal cortex during a difficult aerial reconnaissance search task to test its capacity to improve search performance. Two stimulation strategies previously found to enhance cognitive performance were tested: The first is called "addition by subtraction," and the second condition utilizes a direct excitatory approach by applying brief trains of high-frequency repetitive transcranial magnetic stimulation immediately before task trials. In a within-subjects design, participants were given active or sham repetitive transcranial magnetic stimulation at either 1 Hz or at 1 Hz above their individual peak alpha frequency (IAF + 1, mean 11.5 Hz), delivered to either the right inferior frontal junction or the right inferior parietal cortex, both defined with individualized peak functional magnetic resonance imaging (fMRI) activation obtained during the visual search task. Results indicated that among the 13 participants who completed the protocol, only active IAF + 1 stimulation to inferior frontal junction resulted in significant speeding of reaction time compared to sham. This site- and frequency-specific enhancement of performance with IAF + 1 repetitive transcranial magnetic stimulation applied immediately prior to task trials provides evidence for the involvement of inferior frontal junction in guiding difficult visual search, and more generally for the use of online repetitive transcranial magnetic stimulation directed at specific functional networks to enhance visual search performance.

Lasting effects of transcranial direct current stimulation on the inducibility of synaptic plasticity by paired-associative stimulation in humans.

BACKGROUND: Transcranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications. OBJECTIVE: The study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics. METHODS: Amplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each). RESULTS: tDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects. CONCLUSIONS: tDCS is capable of inducing lasting changes in the brain's capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules.

Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study.

BACKGROUND: New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. METHODS: This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. RESULTS: Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point's reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. CONCLUSION: rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. TRIAL REGISTRATION: CTRI/2023/05/053247.

Repetitive Transcranial Magnetic Stimulation on individualized spots based on task fMRI improves swallowing function in post-stroke dysphagia.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not previously been used to localize the swallowing functional area in repetitive transcranial magnetic stimulation (rTMS) treatment for post-stroke dysphagia; Traditionally, the target area for rTMS is the hotspot, which is defined as the specific region of the brain identified as the optimal location for transcranial magnetic stimulation (TMS). This study aims to compare the network differences between the TMS hotspot and the saliva swallowing fMRI activation to determine the better rTMS treatment site and investigate changes in functional connectivity related to post-stroke dysphagia using resting-state fMRI. METHODS: Using an information-based approach, we conducted a single case study to explore neural functional connectivity in a patient with post-stroke dysphagia before, immediately after rTMS, and four weeks after rTMS intervention. 20 healthy participants underwent fMRI and TMS hotspot localization as a control group. Neural network alterations were assessed , and functional connections related to post-stroke dysphagia were examined using resting-state fMRI. RESULTS: Compared to the TMS-induced hotspots, the fMRI activation peaks were located significantly more posteriorly and exhibited stronger functional connectivity with bilateral postcentral gyri. Following rTMS treatment, this patient developed functional connection between the brainstem and the bilateral insula, caudate, anterior cingulate cortex, and cerebellum. CONCLUSION: The saliva swallowing fMRI activation peaks show more intense functional connectivity with bilateral postcentral gyri compared to the TMS hotspots. Activation peak-guided rTMS treatment improves swallowing function in post-stroke dysphagia. This study proposes a novel and potentially more efficacious therapeutic target for rTMS, expanding its therapeutic options for treating post-stroke dysphagia.

Effect of repetitive transcranial magnetic stimulation on trigeminal-mediated headshaking in 17 horses.

BACKGROUND: Trigeminal-mediated headshaking is a neuropathic facial pain condition in horses. No treatment has been entirely successful. Repetitive transcranial magnetic stimulation (rTMS) is used in human medicine as a treatment for various neuropathic pain conditions, and good results have been achieved in cases of trigeminal neuralgia. OBJECTIVES: Apply rTMS to horses with trigeminal-mediated headshaking (TMHS) and to evaluate tolerability, application of the setting, and success rate. ANIMALS: Seventeen horses with nonseasonal signs of TMHS. METHODS: Other underlying causes of headshaking were ruled out. The rTMS was performed under standing sedation on 5 consecutive days applying 3 sets of 500 stimulations each, with a stimulation strength of 5 Hz. Horses were evaluated on Day 1 (t0) and Day 5 (t1) of the treatment and 2 (t2) and 4 weeks (t3) afterwards using a special scoring system. RESULTS: The rTMS was well tolerated. Headshaking signs during exercise were decreased by 70% (Day 5; t1). Four weeks after rTMS, signs were still decreased (mean reduction of 50%) during exercise. Improvement of mean resting and exercise scores was significant (P < .05) and effect sizes between pretreatment and all time points after treatment (t1, t2, t3) were large (>±0.8). CONCLUSIONS AND CLINICAL IMPORTANCE: Repetitive transcranial magnetic stimulation may be a promising treatment for neuropathic pain and headshaking in affected horses. Pain-free periods after treatment differ individually, and repeated treatment may be necessary. More studies should be performed to determine ideal settings for horses.

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex.

OBJECTIVE: Transcranial focused ultrasound (TUS) can suppress human motor cortical excitability. However, it is unclear whether the TUS may interact with transcranial magnetic stimulation (TMS) when they co-delivered in multiple trials. METHODS: Nineteen subjects received three different TUS-TMS co-stimulation protocols to the motor cortex including concurrent stimulation (TUS-TMS-C), separated stimulation (TUS-TMS-S), and TMS only. In each condition, two runs of 30 stimulation trials were conducted with a five-minute rest between runs. Motor-evoked potentials (MEP) were recorded during stimulation and at 0, 10, 20, and 30 min after stimulation. The MEP amplitudes after intervention were normalized to the mean pre-intervention MEP amplitude and expressed as MEP ratios. An additional test with TUS alone was applied to all participants to assess whether TUS itself can elicit after-effects. RESULTS: There were no significant after-effects of all three interventions on MEP ratios. However, 11 subjects who showed online inhibition (OI + ) during the TUS-TMS-C protocol, defined as having MEP ratio less than 1 during TUS-TMS-C, showed significant MEP suppression at 10, 20 and 30 min after TUS-TMS-C. In 8 subjects did not show online inhibition (OI-), defined as having MEP ratios greater than 1 during TUS-TMS-C, showed no significant inhibitory after-effects. OI + and OI- status did not change in a follow-up repeat TUS-TMS-C test. TUS alone did not generate inhibitory after-effects in either OI + or OI- participants. CONCLUSIONS: Our results showed that co-delivery of TUS and TMS can elicit inhibitory after-effect in subjects who showed online inhibition, suggesting that TUS and TMS may interact with each other to produce plasticity effects. SIGNIFICANCE: TUS and TMS may interact with each other to modulate cortical excitability.

Repetitive Transcranial Magnetic Stimulation for Motor Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Low Risk of Bias.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in enhancing motor recovery after stroke, but nuances regarding its use, such as the impact of the type and site of stimulation, are not yet established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) with low risk of bias to investigate the effect of rTMS on motor recovery after both ischemic and hemorrhagic stroke. MATERIALS AND METHODS: Three databases were searched systematically for all RCTs reporting comparisons between rTMS (including theta-burst stimulation) and either no stimulation or sham stimulation up to August 19, 2022. The primary outcome measure was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE). Secondary outcome measures comprised the Action Research Arm Test, Box and Block Test, Modified Ashworth Scale for the wrist, and modified Rankin Scale (mRS). RESULTS: A total of 37 articles reporting 48 unique comparisons were included. Pooled mean FMA-UE scores were significantly higher in the experimental group than the control group after intervention (MD = 5.4 [MD = 10.7 after correction of potential publication bias], p < 0.001) and at the last follow-up (MD = 5.2, p = 0.031). On subgroup analysis, the improvements in FMA-UE scores, both after intervention and at the last follow-up, were significant in the acute/subacute stage of stroke (within six months) and for patients with more severe baseline motor impairment. Both contralesional and ipsilesional stimulation yielded significant improvements in FMA-UE at the first assessment after rTMS but not at the last follow-up, while the improvements from bilateral rTMS only achieved statistical significance at the last follow-up. Among the secondary outcome measures, only mRS was significantly improved in the rTMS group after intervention (MD = -0.5, p = 0.013) and at the last follow-up (MD = -0.9, p = 0.001). CONCLUSIONS: Current literature supports the use of rTMS for motor recovery after stroke, especially when done within six months and for patients with more severe stroke at baseline. Future studies with larger sample sizes may be helpful in clarifying the potential of rTMS in poststroke rehabilitation.

TMS and tDCS as potential tools for the treatment of cognitive deficits in Parkinson's disease: a meta-analysis.

BACKGROUND: Cognitive deficits are common nonmotor symptoms in Parkinson's disease (PD). Non-Invasive Brain Stimulation (NIBS) could be a potential aid to prevent or delay dementia progression in this clinical population. However, previous studies reported controversial results concerning their efficacy on cognitive symptoms of PD. Hence, the present meta-analysis aims to systematically examine the effects of NIBS as possible treatments for PD cognitive impairments. Understanding NIBS' impact on these symptoms may be of outstanding importance to implement new therapeutic strategies and improve the patients' quality of life. METHODS: EMBASE, Scopus, and PubMed databases were systematically searched for consecutive studies published from 2000 to March 2023 describing Randomized Controlled Trials studies evaluating the effect of NIBS on PD cognitive symptoms. From the included studies, data concerning neuropsychological tests were extracted and grouped into six cognitive domains, separately analyzed. Hedge's method was computed as the effect size measure of the extracted data; heterogeneity among studies and publication bias were also assessed. The Cochrane's RoB2 tool was used to evaluate the risk of bias for each of the included studies. RESULTS: After database searching and screening of texts, sixteen studies met the inclusion criteria. No significant results emerged from any investigated cognitive domain when comparing NIBS and sham treatments. CONCLUSION: Several factors may have contributed to the lack of effects; among these, methodological choices, the small sample of studies, the high heterogeneity of data and stimulation protocols pose the need for more controlled studies to highlight the potentiality of NIBS as a future treatment for PD cognitive impairments.

A 3D-Printed helmet for precise and repeatable neuromodulation targeting in awake non-human primates.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.