BDNF Polymorphism and Differential rTMS Effects on Motor Recovery of Stroke Patients

BackgroundThe brain-derived neurotrophic factor (BDNF) gene often shows a single nucleotide polymorphism that is thought to influence synaptic plasticity. It also affects the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) on motor cortex excitability.ObjectiveThis study investigated whether BDNF polymorphism influences the effect of rTMS on the motor recovery of patients with stroke.MethodsForty-four patients (mean age 53.8 years) experiencing unilateral motor weakness after stroke were recruited. rTMS was applied over the primary motor cortex of the affected hemisphere at 10 Hz with 1000 pulses/day for 10 days. Each patient's motor functions were assessed using the Fugl-Meyer assessment (FMA) and the box and block test (BBT) before, immediately after and 2 months after the intervention. BDNF genotyping was performed via PCR assays of whole blood samples. The patients' data were grouped and analysed into Val/Val and Met allele groups according to the presence or absence of the BDNF polymorphism.ResultsNine patients (20.5%) were classified into the Val/Val group, and thirty-seven patients (79.5%) were classified into the Met allele group. The patients' baseline motor functions did not differ between the two groups. The FMA and BBT scores showed significant improvement immediately after and 2 months after rTMS in both groups. In addition, the time and groups were found to interact significantly, with the Val/Val group improving to a greater extent than the Met allele group in terms of their FMA and BBT scores.ConclusionsThe findings suggest that the BDNF gene polymorphism negatively influences the effect of rTMS on the motor recovery of upper extremities in stroke patients.     

Functional neuromuscular stimulation to improve severe hand dysfunction after stroke: does inhibitory rTMS enhance therapeutic efficiency?

Background

Novel strategies to improve hand function after stroke are needed. Electromyography-triggered functional neuromuscular stimulation (EMG-FNMS) and repetitive transcranial magnetic stimulation (rTMS) are promising techniques to facilitate recovery of sensory-motor hand dysfunction after stroke.

Objective

To investigate if 1 Hz rTMS over the contralesional primary motor cortex enhances the effectiveness of EMG-triggered FNMS of the hand and finger extensors to improve severe sensory-motor hand dysfunction after stroke.

Methods

24 subjects with a first stroke received 10 daily sessions of 20 min EMG-triggered FNMS of the hand and finger extensors of the affected forearm preceded by 15 min of either 1 Hz rTMS (rTMS group, n = 12) or sham rTMS (control group, n = 12) over the contralesional primary motor cortex. Prior to and after each intervention motor function and spasticity were rated at both hands, and cortical excitability of the contralesional primary motor cortex was assessed.

Results

Motor function and spasticity of the affected hand were significantly improved by either intervention, whereas behavioural measures of the unaffected hand did not change. There were no significant differences between both intervention groups. Improvement of motor function of the affected hand was positively correlated with cortical excitability of the contralesional primary motor cortex after EMG-triggered FNMS preceded by 1 Hz rTMS.

Conclusions

1 Hz rTMS does not enhance the general effectiveness of EMG-FNMS to the wrist and finger extensors of the affected forearm after stroke. Motor recovery of the severely affected hand after stroke appears to depend on excitability of the contralesional primary motor cortex.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: A randomized,multicentre, double-blind,clinical trial

BackgroundConstraint-induced movement therapy (CIMT) and transcranial direct current stimulation (tDCS) are used to reduce interhemispheric imbalance after stroke, which is why the combination of these therapies has been used for neurological recovery, but not in the acute phase.ObjectivesTo evaluate the effectiveness of combining active or sham bihemispheric tDCS with modified CIMT (mCIMT) for the recovery of the Upper Limb (UL) in hospitalized patients with acute and subacute stroke.MethodsThis randomized controlled, double-blind, placebo-controlled, parallel group clinical trial was executed between September 2018 to March 2021 recruited 70 patients. The patients were randomized to one of two groups to receive treatment for 7 consecutive days, which included 20 min of active or sham bihemispheric tDCS daily (anodal ipsilesional and cathodal contralesional), with an mCIMT protocol. The primary outcome was the difference in the evolution of motor and functional upper limb recovery with assessment on days 0, 5, 7, 10 and 90. The secondary outcomes were independence in activities of daily living (ADL) and quality of life.ResultsThe active group presented a statistically significant gap compared to the simulated group throughout the trend in the scores of the FMA (motor function and joint pain) and WMFT (functional ability and weight to box) (p < 0.05) and showed a minimal clinically important difference (FMA: difference between groups of 4.9 points [CI: 0.007- 9.799]; WMFT: difference between groups of 6.54 points [CI: 1.10-14.15]). In the secondary outcomes, there was a significant difference between the groups in ADL independence (Functional Independence Measure: difference of 8.63 [CI: 1.37-18.64]) and perceived recovery of quality of life evaluated at 90 days (p = 0.0176).ConclusionsCombining mCIMT with bihemispheric tDCS in patients hospitalized with acute-subacute stroke allows us to maximize the motor and functional recovery of the paretic upper limb in the early stages and independence in ADL, maintaining the effects over time.     

Effect of slow rTMS of motor cortex on the excitability of the Blink Reflex: A study in healthy humans

ObjectiveTo evaluate the after-effects of low frequency, sub-threshold repetitive Transcranial Magnetic Stimulation (rTMS) of primary motor cortex, on the excitability of Blink Reflex (BR) in healthy subjects.MethodsThe BR recovery cycle was carried out in 10 healthy volunteers in basal conditions, immediately after rTMS (30 s), 15 and 60 min later. A paired electric supraorbital stimulus paradigm with inter-stimulus intervals (ISI) of 100–600–1000–1500 ms was used. The “real” rTMS consisted of a 200 stimuli long train delivered at 1 Hz and intensity 80% of rest Motor Threshold of the FDI muscle, using a focal coil applied over the primary motor cortex region. The basal BR recovery cycle was also compared with that obtained after a “sham” rTMS.ResultsThe recovery of the R2 component of the BR was significantly suppressed 30 s after rTMS. This effect was also observed at 15 min, though of lower magnitude and only at long ISIs (1000-1500 ms). No significant effect on R2 recovery was observed 60 min after real rTMS as well as after sham rTMS.ConclusionsrTMS of motor cortex modulates the excitability of BR through its action on cortical excitability and on the cortical facilitatory drive to the brainstem reflex pathways.SignificanceSlow (1 Hz), sub-threshold rTMS of motor cortex determines a long-lasting reduction of excitability of BR.     

High frequency repetitive transcranial magnetic stimulation decreases cerebral vasomotor reactivity

ObjectiveRepetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR).MethodsTwenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before (T₀) and within 10 min (T₁) following rTMS. Four subjects underwent further VMR evaluations at 2 (T₂), 5 (T₃) and 24 h (T₄) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial.ResultsFollowing real rTMS on M1 (p = 0.002) and calcarine cortex (p < 0.001) VMR decreased with respect to T₀ in both hemispheres, while no change was observed after sham rTMS (p > 0.6). VMR tended to remain lower than T₀ until T_3. Cerebral VMR decreased independently of the stimulated side also in the patients’ group.ConclusionsHigh frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics.SignificanceThe effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients.     

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.     

Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5-45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen-Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen-Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials.     

The influence of high-frequency repetitive transcranial magnetic stimulation on endogenous estrogen in patients with disorders of consciousness

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising therapeutic intervention for neurological disorders. However, the precise mechanisms of rTMS in neural excitability remains poorly understood. Estradiol is known to have strong influence on cortical excitability. This study aimed to determine whether high-frequency (HF) rTMS influences endogenous estradiol in male patients with disorders of consciousness (DOC).MethodsA randomized controlled trial was conducted with a total of 57 male patients with DOC. Eventually, 50 patients completed the study. Twenty-five patients underwent real rTMS, and 25 patients underwent sham rTMS, which were delivered over the dorsolateral prefrontal cortex. The primary outcome measure was the change in serum estradiol from baseline to after 10 sessions of HF-rTMS. The improvement in the total score of the JFK Coma Recovery Scale-Revised (CRS-R) was also assessed.ResultsChanges in estradiol levels and CRS-R scores from pre-to post-treatment were significantly different between the active rTMS and sham stimulation conditions. A significant enhancement of CRS-R scores in the patients receiving rTMS stimulation was observed compared to the sham group. Serum estradiol levels in patients following HF-rTMS were significantly higher than their baseline levels, whereas no significant changes were found in the sham group from pre-to post-stimulation. The rise in estradiol levels was greater in responders than in non-responders. The changes in estradiol levels were significantly positively correlated with the improvement in CRS-R scores.ConclusionThese preliminary findings indicate that serum estradiol levels are affected by HF-rTMS and positively related to clinical responses in male patients with DOC. The elevation of estradiol levels may lay a physiological foundation for successful rTMS treatment for DOC patients by increasing cortical excitability.     

Paired inhibitory stimulation and gait training modulates supplemental motor area connectivity in freezing of gait

IntroductionFreezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if “inhibitory” repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity.MethodsTwo experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1 Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training.Results(Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (p_FDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7) = 3.87, p = 0.014).ConclusionsThe SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1 Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.     

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study

Background/ObjectivesRepetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke.Materials and MethodsTwelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20 Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded.ResultsNo participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham.ConclusionsThis exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.     

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain

ObjectiveThe role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity.MethodsCross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging.ResultsWe included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04).ConclusionThere is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity.SignificanceThese findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.     

Functional repetitive transcranial magnetic stimulation increases motor cortex excitability in survivors of stroke

ObjectiveTo determine if repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex with simultaneous voluntary muscle activation, termed functional-rTMS, will promote greater neuronal excitability changes and neural plasticity than passive-rTMS in survivors of stroke.MethodsEighteen stroke survivors were randomized into functional-rTMS (EMG-triggered rTMS) or passive-rTMS (rTMS only; control) conditions. Measures of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), force steadiness (coefficient of variation, CV) at 10% of maximum voluntary contraction, and pinch task muscle activity were assessed before and after rTMS. Functional-rTMS required subjects to exceed a muscle activation threshold to trigger each rTMS train; the passive-rTMS group received rTMS while relaxed.ResultsSignificant interactions (time × condition) were observed in abductor pollicis brevis (APB) SICI, APB ICF, CV of force, and APB muscle activity. Functional-rTMS decreased APB SICI (p < 0.05) and increased ICF (p < 0.05) after stimulation, whereas passive-rTMS decreased APB muscle activity (p < 0.01) and decreased CV of force (p < 0.05). No changes were observed in FDI measures (EMG, ICF, SICI).Conclusion(s)Functional-rTMS increased motor cortex excitability, i.e., less SICI and more ICF for the APB muscle. Passive stimulation significantly reduced APB muscle activity and improved steadiness.SignificanceFunctional-rTMS promoted greater excitability changes and selectively modulated agonist muscle activity.     

Effects of paired associated stimulation with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction

ObjectiveTo investigate the effects of paired associated stimulation (PAS) with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction.MethodA total of 120 volunteers with cerebral infarction were randomly divided into four groups. Based on conventional rehabilitation treatment, the PAS stimulation group was given the corresponding position of PAS treatment once a day for 28 consecutive days. The MEP amplitude and RMT of both hemispheres were assessed before and after treatment, and a simple upper limb Function Examination Scale (STEF) score, simplified upper limb Fugl–Meyer score (FMA), and improved Barthel Index (MBI) were used to assess upper limb motor function in the four groups.ResultsFollowing PAS, the MEP amplitude decreased, and the RMT of abductor pollicis brevis (APB) increased on the contralesional side, while the MEP amplitude increased and the RMT of APB decreased on the ipsilesional side. After 28 consecutive days the scores of STEF, FMA, and MBI in the bilateral stimulation group were significantly better than those in the ipsilesional stimulation group and the contralesional stimulation group, but there was no significant difference in the scores of STEF, FMA, and MBI between the ipsilesional stimulation group and the contralesional stimulation group.ConclusionThe excitability of the motor cortex can be changed when the contralesional side or the ipsilesional side was given the corresponding PAS stimulation, while the bilateral PAS stimulation can more easily cause a change of excitability of the motor cortex, resulting in better recovery of the upper limb function.     

Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke

Objective –  Although there is evidence for short term benefits of rTMS in stroke, longer term effects have not been reported. The aim of the study was to evaluate the effect of two different frequencies of rTMS on motor recovery and on cortical excitability up to 1 year post-treatment.
Methods –  Forty-eight patients with acute ischemic stroke were randomly classified into three groups. The first two groups received real rTMS over motor cortex (3 and 10 Hz respectively) of the affected hemisphere and the third group received sham stimulation of the same site, daily for five consecutive days. Disability was assessed before, after fifth sessions, and then after 1, 2, 3 and 12 months. Cortical excitability was assessed for both hemispheres before and after the second and fifth sessions.
Results –  A significant 'rTMS × time' interaction was obtained indicating that real and sham rTMS had different effects on rating scales. This was because real rTMS produced greater improvement than sham that was evident even at one year follow-up. These improvements were associated with changes in cortical excitability over the period of treatment.
Conclusion –  These results confirm that real rTMS over motor cortex can enhance and maintain recovery and may be a useful add on therapy in treatment of acute stroke patients.     

Characterizing the Mechanisms of Central and Peripheral Forms of Neurostimulation in Chronic Dysphagic Stroke Patients

BackgroundSwallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration.Objective/hypothesisOur hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response.MethodsIn 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy.ResultsCorticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F_1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = −2.79) was observed compared to sham.ConclusionsIn this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = −.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.     

Cortical plasticity is correlated with cognitive improvement in Alzheimer’s disease patients after rTMS treatment

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has been widely used in non-invasive treatments for different neurological disorders. Few biomarkers are available for treatment response prediction. This study aims to analyze the correlation between changes in long-term potentiation (LTP)-like cortical plasticity and cognitive function in patients with Alzheimer’s disease (AD) that underwent rTMS treatment.MethodsA total of 75 AD patients were randomized into either 20 Hz rTMS treatment at the dorsolateral prefrontal cortex (DLPFC) group (n = 37) or a sham treatment group (n = 38) for 30 sessions over six weeks (five days per week) with a three-month follow-up. Neuropsychological assessments were conducted using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment-Cognitive Component (ADAS-Cog). The cortical plasticity reflected by the motor-evoked potential (MEP) before and after high-frequency repetitive TMS to the primary motor cortex (M1) was also examined prior to and after the treatment period.ResultsThe results showed that the cognitive ability of patients who underwent the MMSE and ADAS-Cog assessments showed small but significant improvement after six weeks of rTMS treatment compared with the sham group. The cortical plasticity improvement correlated to the observed cognition change.ConclusionsCortical LTP-like plasticity could predict the treatment responses of cognitive improvements in AD patients receiving rTMS intervention. This warrants future clinical trials using cortical LTP as a predictive marker.     

The Effect of Sham Controlled Continuous Theta Burst Stimulation and Low Frequency Repetitive Transcranial Magnetic Stimulation on Upper Extremity Spasticity and Functional Recovery in Chronic Ischemic Stroke Patients

ObjectiveThis randomized controlled study examined the effect of continuous theta burst stimulation (cTBS) and low frequency repetitive transcranial magnetic stimulation (rTMS) on upper extremity spasticity and functional recovery in chronic ischemic stroke patients.Materials and MethodsTwenty chronic ischemic stroke patients were randomized into three groups as real rTMS group (n = 7), real cTBS group (n = 7) and sham cTBS group (n = 6), in which real rTMS with physical therapy (PT), real cTBS with PT and sham cTBS with PT were applied in 10 sessions, respectively. The evaluation parameters were assessed at pre-treatment, post-treatment and follow up at 4 weeks.ResultsTen sessions of real rTMS or real cTBS combined with PT were found beneficial in motor functional recovery and daily living activities both at post-treatment and follow up at 4 weeks (p ? 0.05). In the sham cTBS group, functional improvement was not significant (p > 0.05). In addition, in the real rTMS group, elbow flexor, pronator, wrist flexor and finger flexor spasticity were significantly decreased; in the real cTBS group, significant decrease was observed in the elbow flexor and wrist flexor spasticity (p ? 0.05). In comparison with sham cTBS group, only in the real cTBS group, significant improvement was observed in the level of wrist flexor spasticity at follow up at 4 weeks (p ? 0.017).ConclusionsIn this study, it was observed that real cTBS or real rTMS combined with PT provided improvement on upper extremity motor functions and daily living activities in chronic ischemic stroke patients, but improvement in spasticity was limited.     

Changes of cortico-cortical neural connections associated with motor functional recovery after stroke

ObjectivesDuring functional recovery after stroke, some neural connections in the brain are augmented and new neural networks are constructed to compensate for impaired neurological functions. Recently, it was reported that the extent of cortico-cortical neural connections can be estimated by correlation analysis based on electroencephalography (EEG). The purpose of this study was to investigate changes of correlation coefficients in the cerebral cortex with motor functional recovery after stroke.Materials and methodsTwenty-two post-stroke hemiparetic patients admitted to our rehabilitation ward (mean age at admission: 71.4 ± 12.9 years old), were studied. For the evaluation of hemiparesis, Fugl-Meyer Assessment (FMA) was applied. All subjects underwent EEG with electrodes placed according to the international 10-20 system for correlation analysis, on admission to our ward and 4 weeks after admission. EEG data were analyzed with the program software FOCUS (NIHON KOHDEN, Japan), and squared correlation coefficients in some cortico-cortical areas of the cerebral cortex were calculated.ResultsThe correlation coefficients in some cortico-cortical areas of the lesional hemisphere, such as C3-F3 or C4-F4, C3-F7 or C4-F8, and F3-F7 or F4-F8, significantly increased with rehabilitation training. The change of the correlation coefficient in F3-F7 or F4-F8 and F7-T3 or F8-T4 in the lesional hemisphere was significantly correlated with the change of the upper-limb FMA.ConclusionsThe augmentation of cortico-cortical connections, represented by an increase of the correlation coefficient in the lesional hemisphere, may contribute to motor functional recovery, especially in hemiparetic upper limbs, after stroke.     

Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers

The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS. In contrast the aim of this randomised sham-controlled study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and six Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”. We found a significant reduction of the BDI sum score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI sum score were caused by sham stimulation (GLM, p = 0.109). The BDI single item analyses revealed within and between group differences supporting the modifying effect of rTMS on BDI. According to the employed VAS we did not find significant differences caused by active or sham stimulation in five of six VAS. In the VAS labelled lively/gloomy the active group was found to be more “gloomy” (p = 0.0111) immediately after stimulation. Our data show that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men, whereas no significant long-term changes were found in VAS.