Retinal Tear Following Low-Frequency Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation that uses magnetic pulses to stimulate specific brain regions. Retina is being investigated whether the retina, which is also known as the brain's window to the outside world, is affected by the treatment. METHODS: Magventure X100 device was used for the procedure. The bilateral supplementary motor area was targeted. Procedure protocol: power: 47%, repetitive rate (frequency): 1 Hz, pulses in train duration: 300, intertrain interval (waiting time): 120 seconds, number of trains: 4, total pulses: 1200. Twenty sessions of rTMS were planned for the patient. The patient was informed about the procedure, and her consent was obtained. RESULTS: The Yale-Brown Obsessive-Compulsive Disorder Scale (YBOCS) score before the first session was 31, and the Brown Assessment Beliefs Scale (BABS) score was 5. The patient's YBOCS score after the 15th session was 14, and the BABS score was 0. After the implementation of the 15th session of the patient's treatment, retinal detachment developed in the right eye, and the treatment was terminated. As a result of the eye examination of the patient, it was determined that there was 1 horseshoe rupture and 2 hole-shaped ruptures in the lower half of the left eye. CONCLUSIONS: Patients at risk for retinal detachment may require specialized treatment and close monitoring to prevent the condition from worsening. It is important to consult with an ophthalmologist for patients at risk for retinal detachment before TMS application.

A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression.

LEARNING OBJECTIVES: After participating in this CME activity, the psychiatrist should be better able to:• Compare and contrast therapies used in combination with transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treating MDD. BACKGROUND: Noninvasive neuromodulation, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has emerged as a major area for treating major depressive disorder (MDD). This review has two primary aims: (1) to review the current literature on combining TMS and tDCS with other therapies, such as psychotherapy and psychopharmacological interventions, and (2) to discuss the efficacy, feasibility, limitations, and future directions of these combined treatments for MDD. METHOD: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three databases: PubMed, PsycInfo, and Cochrane Library. The last search date was December 5, 2023. RESULTS: The initial search revealed 2,519 records. After screening and full-text review, 58 studies (7 TMS plus psychotherapy, 32 TMS plus medication, 7 tDCS plus psychotherapy, 12 tDCS plus medication) were included. CONCLUSIONS: The current literature on tDCS and TMS paired with psychotherapy provides initial support for integrating mindfulness interventions with both TMS and tDCS. Adding TMS or tDCS to stable doses of ongoing medications can decrease MDD symptoms; however, benzodiazepines may interfere with TMS and tDCS response, and antipsychotics can interfere with TMS response. Pairing citalopram with TMS and sertraline with tDCS can lead to greater MDD symptom reduction compared to using these medications alone. Future studies need to enroll larger samples, include randomized controlled study designs, create more uniform protocols for combined treatment delivery, and explore mechanisms and predictors of change.

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. METHODS: Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. RESULTS: We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction).Limitations: The linear model was constructed separately for each region of interest. CONCLUSION: This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS.

Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing.

The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex-a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS's ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm [Formula: see text]. Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( 1.060±0.155 %) was markedly higher than that in the TUS group ( 0.560±0.114 %) and sham group ( 0.570±0.088 %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial.

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis.

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. Data Sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. Study Selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. Data Extraction and Synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. Conclusions and Relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

Gray matter volume of functionally relevant primary motor cortex is causally related to learning a hand motor task.

Variability in brain structure is associated with the capacity for behavioral change. However, a causal link between specific brain areas and behavioral change (such as motor learning) has not been demonstrated. We hypothesized that greater gray matter volume of a primary motor cortex (M1) area active during a hand motor learning task is positively correlated with subsequent learning of the task, and that the disruption of this area blocks learning of the task. Healthy participants underwent structural MRI before learning a skilled hand motor task. Next, participants performed this learning task during fMRI to determine M1 areas functionally active during this task. This functional ROI was anatomically constrained with M1 boundaries to create a group-level "Active-M1" ROI used to measure gray matter volume in each participant. Greater gray matter volume in the left hemisphere Active-M1 ROI was related to greater motor learning in the corresponding right hand. When M1 hand area was disrupted with repetitive transcranial stimulation (rTMS), learning of the motor task was blocked, confirming its causal link to motor learning. Our combined imaging and rTMS approach revealed greater cortical volume in a task-relevant M1 area is causally related to learning of a hand motor task in healthy humans.

Switching off: disruptive TMS reveals distinct contributions of the posterior middle temporal gyrus and angular gyrus to bilingual speech production.

The role of the left temporoparietal cortex in speech production has been extensively studied during native language processing, proving crucial in controlled lexico-semantic retrieval under varying cognitive demands. Yet, its role in bilinguals, fluent in both native and second languages, remains poorly understood. Here, we employed continuous theta burst stimulation to disrupt neural activity in the left posterior middle-temporal gyrus (pMTG) and angular gyrus (AG) while Italian-Friulian bilinguals performed a cued picture-naming task. The task involved between-language (naming objects in Italian or Friulian) and within-language blocks (naming objects ["knife"] or associated actions ["cut"] in a single language) in which participants could either maintain (non-switch) or change (switch) instructions based on cues. During within-language blocks, cTBS over the pMTG entailed faster naming for high-demanding switch trials, while cTBS to the AG elicited slower latencies in low-demanding non-switch trials. No cTBS effects were observed in the between-language block. Our findings suggest a causal involvement of the left pMTG and AG in lexico-semantic processing across languages, with distinct contributions to controlled vs. "automatic" retrieval, respectively. However, they do not support the existence of shared control mechanisms within and between language(s) production. Altogether, these results inform neurobiological models of semantic control in bilinguals.

An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness.

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortex.

Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control.

Transcutaneous auricular vagus nerve stimulation enhances short-latency afferent inhibition via central cholinergic system activation.

The present study examined the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on short-latency afferent inhibition (SAI), as indirect biomarker of cholinergic system activation. 24 healthy adults underwent intermittent taVNS (30 s on/30 s off, 30 min) or continuous taVNS at a frequency of 25 Hz (15 min) along with earlobe temporary stimulation (15 min or 30 min) were performed in random order. The efficiency with which the motor evoked potential from the abductor pollicis brevis muscle by transcranial magnetic stimulation was attenuated by the preceding median nerve conditioning stimulus was compared before taVNS, immediately after taVNS, and 15 min after taVNS. Continuous taVNS significantly increased SAI at 15 min post-stimulation compared to baseline. A positive correlation (Pearson coefficient = 0.563, p = 0.004) was observed between baseline SAI and changes after continuous taVNS. These results suggest that 15 min of continuous taVNS increases the activity of the cholinergic nervous system, as evidenced by the increase in SAI. In particular, the increase after taVNS was more pronounced in those with lower initial SAI. This study provides fundamental insight into the clinical potential of taVNS for cholinergic dysfunction.

Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

Role of the left posterior middle temporal gyrus in shape recognition and its reconstruction during drawing: A study combining transcranial magnetic stimulation and functional near infrared spectroscopy.

There are numerous reports of enhanced or emerged visual arts abilities in patients with semantic impairment. These reports led to the theory that a loss of function on the language side of the brain can result in changes of ability to draw and/or to paint. Further, the left posterior middle temporal gyrus (l-pMTG) has been revealed to contribute to the higher control semantic mechanisms with objects recognition and integration of visual information, within a widely distributed network of the left hemisphere. Nevertheless, the theory has not been fully studied in neural bases. The aim of this study is to examine role of the l-pMTG on shape recognition and its reconstruction within drawing behavior, by using a combining method of the repetitive transcranial magnetic stimulation (rTMS) and functional near-infrared spectroscopy (fNIRS). Eighteen healthy participants received a low frequency inhibitory rTMS to their l-pMTG during the drawing task of the Benton Visual Retention Test (BVRT). There was a significant decrease of the mean accuracy of reproductions in the Complex designs of the BVRT, compared to the Simple and Medium designs. The fNIRS data showed strong negative correlations with the results of the BVRT. Though our hypothesis had a contradiction that rTMS would have inhibited the brain activity in the stimulated site, the results suggest that shape recognition and its reconstruction such as the BVRT require neural activations of the l-TL as well as that of the l-pMTG.

Lessons learned from an fMRI-guided rTMS study on performance in a numerical Stroop task.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

Effectiveness of Personalized Hippocampal Network-Targeted Stimulation in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe and promising intervention for Alzheimer disease (AD). Objective: To investigate the effect of a 4-week personalized hippocampal network-targeted rTMS on cognitive and functional performance, as well as functional connectivity in AD. Design, Setting, and Participants: This randomized clinical trial, which was sham-controlled and masked to participants and evaluators, was conducted between May 2020 and April 2022 at a single Korean memory clinic. Eligible participants were between ages 55 and 90 years and had confirmed early AD with evidence of an amyloid biomarker. Participants who met the inclusion criteria were randomly assigned to receive hippocampal network-targeted rTMS or sham stimulation. Participants received 4-week rTMS treatment, with assessment conducted at weeks 4 and 8. Data were analyzed between April 2022 and January 2024. Interventions: Each patient received 20 sessions of personalized rTMS targeting the left parietal area, functionally connected to the hippocampus, based on fMRI connectivity analysis over 4 weeks. The sham group underwent the same procedure, excluding actual magnetic stimulation. A personalized 3-dimensional printed frame to fix the TMS coil to the optimal target site was produced. Main Outcomes and Measures: The primary outcome was the change in the AD Assessment Scale-Cognitive Subscale test (ADAS-Cog) after 8 weeks from baseline. Secondary outcomes included changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Seoul-Instrumental Activity Daily Living (S-IADL) scales, as well as resting-state fMRI connectivity between the hippocampus and cortical areas. Results: Among 30 participants (18 in the rTMS group; 12 in the sham group) who completed the 8-week trial, the mean (SD) age was 69.8 (9.1) years; 18 (60%) were female. As the primary outcome, the change in ADAS-Cog at the eighth week was significantly different between the rTMS and sham groups (coefficient [SE], -5.2 [1.6]; P = .002). The change in CDR-SOB (-4.5 [1.4]; P = .007) and S-IADL (1.7 [0.7]; P = .004) were significantly different between the groups favoring rTMS groups. The fMRI connectivity analysis revealed that rTMS increased the functional connectivity between the hippocampus and precuneus, with its changes associated with improvements in ADAS-Cog (r = -0.57; P = .005). Conclusions and Relevance: This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and the plastic changes in the hippocampal-cortical network. Our results support the consideration of rTMS as a potential treatment for AD. Trial Registration: ClinicalTrials.gov Identifier: NCT04260724.

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial.

INTRODUCTION: Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA. METHODS AND ANALYSIS: This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: The study has been registered on ClinicalTrials.gov (NCT05957445).

The effects of music combined to paired associative stimulation on motor-evoked potentials and alertness in spinal cord injury patients and healthy subjects.

Paired associative stimulation (PAS) consisting of high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral nerve stimulation (known as high-PAS) induces plastic changes and improves motor performance in patients with incomplete spinal cord injury (SCI). Listening to music during PAS may potentially improve mood and arousal and facilitate PAS-induced neuroplasticity via auditory-motor coupling, but the effects have not been explored. This pilot study aimed to determine if the effect of high-PAS on motor-evoked potentials (MEPs) and subjective alertness can be augmented with music. Ten healthy subjects and nine SCI patients received three high-PAS sessions in randomized order (PAS only, PAS with music synchronized to TMS, PAS with self-selected music). MEPs were measured before (PRE), after (POST), 30 min (POST30), and 60 min (POST60) after stimulation. Alertness was evaluated with a questionnaire. In healthy subjects, MEPs increased at POST in all sessions and remained higher at POST60 in PAS with synchronized music compared with the other sessions. There was no difference in alertness. In SCI patients, MEPs increased at POST and POST30 in PAS only but not in other sessions, whereas alertness was higher in PAS with self-selected music. More research is needed to determine the potential clinical effects of using music during high-PAS.