Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson''s disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double‐blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta‐burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long‐lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA‐GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA‐GP pathway.     

Probing the role of the right inferior frontal gyrus during Pain‐Related empathy processing: Evidence from fMRI and TMS

Recent studies have suggested that the right inferior frontal gyrus (rIFG) may be involved in pain‐related empathy. To verify the role of the rIFG, we performed a functional magnetic resonance imaging (fMRI) experiment to replicate previous research and further designed a noninvasive repetitive transcranial magnetic stimulation (rTMS) experiment to probe the causal role of the rIFG in pain‐related empathy processing. We assigned 74 volunteers (37 females) to three groups. Group 1 (n = 26) performed a task in which participants were required to perceive pain in others (task of pain: TP) and we used fMRI to observe the activity of the rIFG during pain‐related empathy processing. Then, we applied online rTMS to the rIFG and the vertex site (as reference site) to observe the performance of Group 2 (n = 24; performing TP) and Group 3 (n = 24; performing a control task of identifying body parts; task of body: TB). fMRI experiment demonstrated stronger activation in the rIFG than in the vertex during the perception of pain in others (p < .0001, Bonferroni‐corrected). rTMS experiment indicated that when the rIFG was temporarily disrupted, participants perceived pain in others significantly more slowly (p < .0001, Bonferroni‐corrected) than when the vertex was disrupted. Our results provide evidence that the rIFG is involved in pain‐related empathy processing, which yields insights into how the brain perceives pain in others.     

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review

A large body of molecular and neurophysiological evidence connects synaptic plasticity to specific functions and energy metabolism in particular areas of the brain. Furthermore, altered plasticity and energy regulation has been associated with a number of neuropsychiatric disorders. A favourable approach enabling the modulation of neuronal excitability and energy in humans is to stimulate the brain using transcranial direct current stimulation (tDCS) and then to observe the effect on neurometabolites using magnetic resonance spectroscopy (MRS). In this way, a well‐defined modulation of brain energy and excitability can be achieved using a dedicated tDCS protocol to a predetermined brain region. This systematic review was guided by the preferred reporting items for systematic reviews and meta‐analysis and summarises recent literature studying the effect of tDCS on neurometabolites in the human brain as measured by proton or phosphorus MRS. Limitations and recommendations are discussed for future research. The findings of this review provide clear evidence for the potential of using tDCS and MRS to examine and understand the effect of neurometabolites in the in vivo human brain.     

Mapping of multiple muscles with transcranial magnetic stimulation: absolute and relative test–retest reliability

The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within‐limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid‐based sulcus‐informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI‐based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within‐limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter‐muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

The Effects of Acute Transcranial Direct Current Stimulation on Attentional Bias in Pedophilic Disorder: A Preregistered Pilot Study

ObjectivesIndividuals with pedophilic disorder (PD) experience personal and interpersonal difficulties and are at risk of sexually offending against children. As such, innovative and empirically validated treatments are needed. Recent studies have indicated that men who have sexually offended against children (SOC) with PD display an automatic attention bias for child-related stimuli as well as reduced activity in the dorsolateral prefrontal cortex (dlPFC), a brain area involved in cognitive control, including control over sexual arousal. In this preregistered pilot study, we are the first to investigate whether acutely increasing prefrontal activity could reduce the putative pedophilic attention bias.Materials and MethodsWe delivered a single 20-min session of active anodal versus sham transcranial direct current stimulation (tDCS) over the left dlPFC to 16 SOC with PD and 16 matched healthy controls, while they performed a task requiring controlled attention to computer-generated images of clothed and nude children and adults. We collected responses unobtrusively by recording eye movements.ResultsOur results did not support the presence of the expected automatic attention bias across outcome measures. Nonetheless, we found a response facilitation with child targets in patients and, unexpectedly, in controls, likely due to unwanted salience effects. Active versus sham tDCS reduced this bias across groups, as indicated by a significant group*condition interaction (p = 0.04). However, no attentional bias and no tDCS effects on attentional responses to child and adult images emerged following tDCS.ConclusionsThese results suggest enhanced cognitive control in response to salient stimuli during active tDCS. Thus, to assist future studies on neuromodulation in PD, we provide suggestions for design improvement.     

Transcranial Alternating Current Stimulation Reduces Network Hypersynchrony and Persistent Vertigo

ObjectivesPersistent oscillating vertigo that occurs after entrainment to periodic motion is known as Mal de Débarquement Syndrome (MdDS). Down-modulation of this oscillating vertigo is associated with reduction in long-range resting-state functional connectivity between fronto-parieto-occipital regions. In order to determine the association between this oscillating vertigo and hypersynchrony as measured by the auditory steady-state response (ASSR), we investigated the differences in ASSR between individuals with MdDS and healthy controls as well as the change in ASSR in individuals with MdDS before and after treatment with transcranial alternating current stimulation (tACS).Materials and MethodsIndividuals with treatment refractory MdDS lasting at least six months received single administrations of fronto-parieto-occipital tACS in an “n-of-1” double-blind randomized design: alpha-frequency in-phase, alpha-frequency antiphase, and gamma frequency antiphase control. The treatment protocol that led to the most acute reduction in symptoms and improved balance was administered for 10–12 sessions given over three days (each session 20-min at 2–4 mA).ResultsTwenty-four individuals with MdDS participated (mean age 53.0 ± 11.8 years [range: 22–66 years, median: 57.0 years]; mean duration of illness 38.6 ± 53.4 months [range: 6–240 months, median: 18.0 months]). Individuals with MdDS had elevated ASSR compared to healthy controls at baseline (t₁₁ = 5.95, p < 0.001). There was a significant decrease in the 40 Hz-ASSR response between responders compared to nonresponders to tACS (t-test, t₁₅ = −2.26, p = 0.04). Both in-phase and anti-phase alpha tACS lead to symptom improvement but only antiphase alpha-tACS led to a significant decrease of 40 Hz-ASSR (t-test, t₁₂ = −9.6, p < 0.001).ConclusionsOur findings suggest that tACS has the potential to reduce network-level hypersynchrony and pathological susceptibility to entrainment by sensory input. To the best of our knowledge, this is the first successful demonstration of desynchronization by noninvasive brain stimulation leading to reduced vertigo. Other disease states associated with pathological functional coupling of neuronal networks may similarly benefit from this novel approach.     

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis

Transcranial magnetic stimulation, a type of noninvasive brain stimulation, has become an ancillary therapy for motor function rehabilitation. Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS) on motor function in stroke patients. There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke. The MEDLINE, Embase, Cochrane Library, ISI Science Citation Index, Physiotherapy Evidence Database, China National Knowledge Infrastructure Library, and ClinicalTrials.gov databases were searched. Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke, published from inception to November 28, 2019, were included. Standard pairwise meta-analysis was conducted using R version 3.6.1 with the "meta" package. Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions. Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation. Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency r TMS or sham stimulation. These findings suggest that rTMS can improve motor function in patients with stroke, and that low-frequency rTMS mainly affects motor function, whereas high-frequency rTMS increases the amplitudes of motor evoked potentials. More highquality randomized controlled trials are needed to validate this conclusion. The work was registered in PROSPERO(registration No. CRD42020147055) on April 28, 2020.     

Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6‐month longitudinal investigation

The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal‐reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post‐anterior cruciate ligament reconstruction (ACLr). This longitudinal, case‐control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor‐evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal‐reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post‐surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post‐surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post‐surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal‐reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal‐reflexive excitability may help improve postoperative outcomes, while later‐stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.     

Effects of cilostazol on the progression and regression of symptomatic intracranial artery stenosis:it reduces the risk of ischemic stroke

OBJECTIVE: To assess the efficacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis.DATA RETRIVAL: We searched the main databases for eligible trials including Medline(from 1966 to June 2014), Embase(from 1980 to June 2014), Cochrane Library(Issue 6, 2014), Chinese National Knowledge Infrastructure(from 1995 to June 2014), Current Controlled Trials(http://controlled-trials.com), Clinical Trials.gov(http://clinicaltrials.gov), and Chinese Clinical Trial Registry(http://www.chictr.org). All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the English words: "cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke." No restrictions were put on publications or publication language.SELECTION CRITERIA: Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspirin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Rev Man 5.2 software was used for data analysis.MAIN OUTCOME MEASURES: Clinical efficacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnetic resonance angiography and transcranial Doppler.RESULTS: Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis(OR = 0.21, 95%CI: 0.09–0.47, P 0.01), it had no beneficial effect on symptom regression(OR = 1.42, 95%CI: 0.80–2.51, P = 0.24). During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients.CONCLUSION: Cilostazol may prevent the progression of symptomatic intracranial artery stenosis, which could reduce the incidence of ischemic stroke.