Transcranial Magnetic Stimulation Group Research Articles

Effects of different mylohyoid muscle stimulations on swallowing cortex excitability in healthy subjects

BackgroundDysphagia has been recognized by the World Health Organization as a medical disability. Improving mylohyoid muscle function plays an important role in pharyngeal dysphagia. The aim of this study was to evaluate the treatment of transcranial magnetic stimulation (TMS), peripheral magnetic stimulation (PMS), and electrical stimulation (ES) for dysphagia. MethodsForty healthy subjects were randomly divided into four groups: TMS+PMS, TMS, PMS, and ES. TMS stimulated the cortical representative area of the mylohyoid muscle and the PMS was directly stimulating the mylohyoid muscle, both of them at a frequency of 10 Hz for a total of 1,800 pulses. The intensity of ES was based on the subject’s tolerance level, usually 2–5 mA. Functional near infrared spectroscopy (fNIRS) and motor evoked potential (MEP) of the mylohyoid muscle were used to evaluate the immediate effects of stimulation on swallowing cortex excitability of healthy subjects before and after intervention. ResultsThe fNIRS results revealed notable activation across multiple channels in the four groups of healthy subjects both pre- and post- the intervention. Among these channels, the activation levels were most pronounced in the TMS+PMS group, followed by the TMS, PMS, and ES groups, respectively. Regarding the MEP results, post-intervention observations indicated a reduction in bilateral latency and an increase in bilateral amplitude in the TMS+PMS group. Additionally, the left amplitude exhibited an increase in the TMS group. ConclusionsIn fNIRS, all four stimulation methods significantly activated the swallowing cortex of healthy subjects, and the activation of TMS+PMS was the most obvious, followed by TMS, PMS, and ES.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for post-stroke cognitive impairment: Protocol of a pilot randomized controlled double-blind trial.

Intermittent theta burst stimulation (iTBS), a novel mode of transcranial magnetic stimulation (TMS), has curative effects on patients with post-stroke cognitive impairment (PSCI). However, whether iTBS will be more applicable in clinical use than conventional high-frequency repetitive transcranial magnetic stimulation (rTMS) is unknown. Our study aims to compare the difference in effect between iTBS and rTMS in treating PSCI based on a randomized controlled trial, as well as to determine its safety and tolerability, and to further explore the underlying neural mechanism. The study protocol is designed as a single-center, double-blind, randomized controlled trial. Forty patients with PSCI will be randomly assigned to two different TMS groups, one with iTBS and the other with 5 Hz rTMS. Neuropsychological evaluation, activities of daily living, and resting electroencephalography will be conducted before treatment, immediately post-treatment, and 1 month after iTBS/rTMS stimulation. The primary outcome is the change in the Montreal Cognitive Assessment Beijing Version (MoCA-BJ) score from baseline to the end of the intervention (D11). The secondary outcomes comprise changes in resting electroencephalogram (EEG) indexes from baseline to the end of the intervention (D11) as well as the Auditory Verbal Learning Test, the symbol digit modality test, the Digital Span Test findings, and the MoCA-BJ scores from baseline to endpoint (W6). In this study, the effects of iTBS and rTMS will be evaluated using cognitive function scales in patients with PSCI as well as data from resting EEG, which allows for an in-depth exploration of underlying neural oscillations. In the future, these results may contribute to the application of iTBS for cognitive rehabilitation of patients with PSCI.

Excitatory brain stimulation over the left dorsolateral prefrontal cortex enhances voluntary distraction in depressed patients.

While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients. Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task. Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction. These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.

Low-frequency transcranial magnetic stimulation protects cognition in mice with chronic unpredictable mild stress through autophagy regulation

Although transcranial magnetic stimulation (TMS) has been approved for the treatment of major depression, few studies have analyzed the ability of low-frequency TMS (LF-TMS) to treat depressive symptoms. Our study confirmed that LF-TMS protects the cognitive function,which can play a certain reference role in the future clinical treatment. The effectiveness of high-frequency TMS therapy has been well documented. However, the use of low-frequency TMS (LF-TMS) in the treatment of depression is rarely reported. This study aims to evaluate whether LF-TMS can reverse depression-induced cognitive impairment. We created a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Male C57BL/6J mice,6–8 weeks old,were randomly divided into four groups: a CON (control) group, a CUMS group, a CUMS+LF-TMS group, and a CUMS+LF-TMS+RAP (rapamycin) group. The CUMS was maintained for 28 days. LF-TMS (1 Hz) and Rap were administered for 28 days from the first day of CUMS. The mice in all groups except the control demonstrated evidence of anhedonia, anxiety, and cognitive decline on behavioral tests during the four weeks of CUMS.All the experiments were carried out under a 12-h light/dark cycle (lights on at 7 a.m.) except for the dark/light cycle reversal stimulation of CUMS. LF-TMS at 20 Mt, 1 Hz for 1 min alleviated damage to spatial cognition and synaptic plasticity in the hippocampus. Western blot analysis showed that LF-TMS reduced the down-regulation of autophagy signals in the CUMS+LF-TMS group, and enhanced the expression of synaptic plasticity-related factors, thereby improving the spatial cognitive impairment resulting from the CUMS. We concluded that LF-TMS can effectively relieve depressive behavior and cognitive dysfunction in mice subjected to CUMS by regulating autophagy signals and synaptic proteins.

Management of Children with Speech Disorders via Transcranial Magnetic Stimulation: Non-Randomized Controlled Study

Background. Speech development impairment is urgent and common problem in pediatric neurology. Transcranial magnetic stimulation (TMS) is one of the promising treatment variants for children with speech disorders. Objective. The aim of the study is to evaluate efficacy and safety of the developed approaches to TMS usage in the management of children with speech disorders. Methods. It was non-randomized controlled study. It included 46 children with speech disorders aged from 3 to 6.5 years. All children were divided into two groups comparable by gender and age: 26 children of the treatment group received TMS course, 20 children of the control group received treatment with hopantenic acid. All patients with speech disorders underwent psychological and pedagogical evaluation of speech and cognitive development, electroencephalography (EEG) before and after treatment. Moreover, comparative analysis of TMS and nootropic therapy efficacy was carried out. Specialized examination of speech and cognitive development was also performed via E.A. Strebeleva method for psychological and pedagogical diagnosis of children development. Furthermore, we carried out side reactions / adverse events registration according to patients and/or their parents complaints confirmed by physical examination, patient’s behavior observation, data from specially developed questionnaire for assessing child’s behavior and well-being (filled up by parents). Finally, we evaluated brain bioelectric activity recorded by EEG. Results. The study results have shown that it is possible to achieve significant positive dynamics in cognitive and speech development in preschool children with speech disorders in both groups (TMS course and medical treatment). But hereby, TMS treatment has demonstrated significantly higher positive dynamics in two out of the three evaluated parameters. There were no cases of adverse events in TMS group leading to early course discontinuation. Conclusion. TMS is non-invasive and safe method for treatment of children with speech disorders. This study has demonstrated the efficacy of the method in the field of personalized management of children with impaired speech and cognitive development.

Effect of transcranial magnetic stimulation in combination with citalopram on patients with post-stroke depression.

BackgroundAmelioration of depression in patients with post-stroke depression (PSD) remains challenging.ObjectiveThe primary vision was to explore the effect of transcranial magnetic stimulation (TMS) in combination with citalopram on patients with PSD.MethodsOne hundred eligible patients who were diagnosed with PSD were recruited and randomly assigned to the control group (n = 50) or the TMS group (n = 50). The controls were given citalopram (10 mg/d for consecutive 8 weeks), while, in addition to citalopram, patients in the TMS group were also given TMS at 5 Hz once a workday for 8 weeks. The primary outcome was patient depression status as reflected by 17-item Hamilton Rating Scale for Depression (HAMD-17) score, and the secondary outcome was patient neuropsychological score determined by Mini-Mental State Examination (MMSE) and Wisconsin Card Sorting Test (WCST).ResultsPatients treated with TMS in combination with citalopram had a drastic decrease in HAMD-17 score during treatment. Bigger changes in HAMD-17 score between baseline and 2 weeks as well as between baseline and 8 weeks in the TMS group were observed (P < 0.01). Patients in both groups had increased MMSE scores after treatment. Data of WCST revealed patients with TMS treatment completed more categories (P < 0.01) and had a lower RPP in comparison to patients in the control group (P < 0.0001). Additionally, TMS in combination with citalopram strikingly improved patients' MMSE scores when compared with those taking citalopram alone. Last, there was no striking difference in side effects between the two groups (P > 0.05).ConclusionOur study found TMS in combination with citalopram is conducive to improving depression status and neuropsychological function, which holds great promise for treating PSD.

The ultrastructure of muscle fibers and satellite cells in experimental autoimmune encephalomyelitis after treatment with transcranial magnetic stimulation

ABSTRACT In this study, we investigated the effect of transcranial magnetic stimulation (TMS) on the ultrastructure of muscle fibers and satellite cells in rats with experimental autoimmune encephalomyelitis (EAE). EAE-induced animals were treated with TMS (60 Hz at 0.7 mT) for 2 hours in the morning, once a day, 5 days a week, for 3 weeks, starting on day 15 post-immunization. The rats were sacrificed on day 36 post-immunization, and the soleus muscles were evaluated by light microscopy and transmission electron microscopy. Findings were compared with a non-treated EAE group. Electron microscopy analysis showed the presence of degenerated mitochondria, autophagic vacuoles, and altered myofibrils in non-treated EAE group. This correlates with the presence of acid phosphatase activity in muscle fibers and core-targetoid lesions with desmin immunohistochemistry. Most myonuclei in the EAE group showed apoptotic features. In contrast, EAE induced-TMS treated animals had less ultrastructural changes in the mitochondria and the myofibrils, together with less frequent apoptotic nuclear features. Peripheral desmin+ protrusions, as a marker of active satellite cells, were significantly increased in TMS-treated group. This correlates ultrastructurally with the presence of active features in satellite cells in the TMS group. In conclusion, the attenuation of ultrastructural alterations in muscle fibers and activation response of satellite cells caused by EAE indicated that skeletal muscle had a regenerative response to TMS.

Randomized comparative study of 1-Hz transcranial magnetic stimulation (TMS), continuous theta-burst stimulation (cTBS) and sham-TMS for treatment-refractory auditory hallucinations (AH) in schizophrenia

IntroductionInsufficient efficacy of conventional treatment of auditory hallucinations (AH) in schizophrenia supports rising interest to brain stimulation techniques including transcranial magnetic stimulation (TMS). Left temporo-parietal cortex (TP3) is involved in emergence of AH, thus neuromodulation of this area might be reasonable.ObjectivesComparison of efficacy and tolerability of 2 protocols of TMS (1 Hz and cTBS) over TP3 and sham-TMS for treatment resistant AH in schizophrenia.Methods76 schizophrenia (ICD-10 - F20) patients with prominent AH (PANSS P3 ≥ 4, AHRS ≥ 15), who had failed to respond to previous antipsychotic treatment, were randomized into 3 groups: 1) 1 Hz TMS (30 patients); 2) cTBS (25 patients); 3) Sham-TMS (21 patients). Sessions were performed 5 days a week for 3 weeks. Antipsychotic medication was continued throughout the study. Patients were assessed weekly with PANSS, AHRS, CDSS, CGI-S by blinded raters. The criterion of efficacy was 30% AHRS score reduction after 3 weeks of treatment.ResultsThe number of responders were 13 (43,3%) in 1 Hz TMS group, 14 (56%) – in cTBS group, 4 (19,1%) in sham-TMS group. There was no statistically significant difference in efficacy between 1 Hz TMS and cTBS, but each of the active protocols was more effective than sham-TMS. Treatment was generally well tolerated in all groups, nobody was discontinued the study due to adverse events.ConclusionsBoth protocols of TMS (1 Hz and cTBS) over TP3 are safe and effective in the treatment of schizophrenic patients with pharmacotherapy resistant AH. Further studies are needed.DisclosureNo significant relationships.

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members.

This study presents data for using accelerated transcranial magnetic stimulation (TMS) as an intervention for suicidal crisis (SC). This prospective, single-site, randomized, double-blind trial enrolled active-duty military participants with SC to receive either active TMS (n = 59) or sham TMS (n = 61) 3 times per day for 3 consecutive days. Our primary outcome, the Beck Scale for Suicidal Ideation-current (SSI-C), was measured before each session of TMS. Secondary outcomes measured both the SSI-C and the Beck Scale for Suicidal Ideation-total daily for the 3 intervention days and at 1, 3, and 6 months of follow-up. In the modified intention to treat (mITT) analysis of SSI-C changes over treatment sessions, the TMS active group had accelerated decline in suicidal ideation as compared with sham: β for interaction was 0.12 points greater SSI-C decline per session (standard error [SE], 0.06) in TMS versus sham (P = 0.04). In both the mITT and per-protocol active TMS groups, the mean final SSI-C scores were below 3. These scores remained below 3 for the entire 6-month follow-up period. In this military trial of suicidal patients, we found that both active and sham accelerated TMS rapidly reduces SC. Moreover, in the mITT analysis, there was a statistically significant antisuicidal benefit of active TMS versus sham TMS in the primary outcome. Both the mITT and per-protocol groups moved from higher to approximately 7 times lower suicide risk strata and remained there for the duration of the study. Further studies are warranted to understand accelerated TMS' full potential as a treatment for SC.

Participation of visual association areas in social processing emerges when rTPJ is inhibited.

During a social evaluation, the right temporo-parietal junction (rTPJ) plays an important role according to its contribution in making inferences about the mental states of others. However, what is the neural response if rTPJ function is inhibited during a mentalizing task? In this study, participants played the Dictator Game with two confederates: one playing cooperation (C) and other playing non-cooperation (NC) role and then they were scanned during a mentalizing test. However, we inhibited rTPJ using transcranial magnetic stimulation (TMS) after they played the game and before they were scanned. In this test, participants read negative (Neg) or positive (Pos) personal situations and then they watched confederate's pictures. Images from the TMS group were compared against controls with no TMS stimulation. After statistical comparison, we found a significantly higher activity in right and left visual association areas (BA 18) during the NCPos > NCNeg condition in the TMS group compared with the No-TMS group. Same visual association areas have been described before when participants are processing visual emotional information or when making a fast social categorization. This could reflect a neural mechanism of socio - emotional categorization that emerges after rTPJ inhibition.

Effects of short-term upper limb immobilization on sensory information processing and corticospinal excitability.

Several studies have reported the effects of short-term immobilization of the upper limb on the excitability of the primary motor cortex. In a report examining the effects of upper limb immobilization on somatosensory information processing using somatosensory-evoked potentials (SEPs), short-term upper limb immobilization reduced the amplitude and increased the latency of the P45 component recorded over the contralateral sensorimotor cortex of SEPs. However, the effects of upper limb immobilization on other regions involved in somatosensory information processing are unknown. Therefore, we investigated the effects of short-term right upper limb immobilization on sensory information processing, particularly in motor-related areas, by measuring the cortical components of SEPs. We also evaluated the excitability of the primary motor cortex and corticospinal tract as well as motor performance (visual simple reaction time and pinch force) related to these areas. All subjects were divided into two groups: the SEP group, in which the effects of upper limb immobilization on the excitability of somatosensory processing were investigated, and the transcranial magnetic stimulation (TMS) group, in which the effects of upper limb immobilization on the excitability of the corticospinal tract and primary motor cortex were investigated. Motor performance was evaluated in all subjects. We showed that 10-h right upper limb immobilization increased the cortical component of SEPs (N30) in the SEP group and decreased the excitability of the corticospinal tract, but not of the primary motor cortex, in the TMS group. The pinch force decreased after upper limb immobilization. However, the visual simple reaction time did not change between pre- and post-immobilization. The supplementary motor area and premotor cortex are believed to be the source of the N30. Therefore, these results suggest that upper limb immobilization affected somatosensory information processing in motor-related areas. Moreover, 10-h right upper limb immobilization reduced the excitability of corticospinal tracts but not that of the primary motor cortex, suggesting that circuits outside the M1, such as the intra- and inter-hemispheric inhibitory and facilitatory circuits rather than circuits within the M1, may be responsible for the reduced excitability of the central nervous system after restraint.

The causal role of the bilateral ventrolateral prefrontal cortices on emotion regulation of social feedback.

The ventrolateral prefrontal cortices (VLPFC) are crucial regions involved in voluntary emotion regulation. However, the lateralization of the VLPFC in downregulating negative emotions remains unclear; and whether the causal role of the VLPFC is generalizable to upregulating positive emotions is unexplored. This study used transcranial magnetic stimulation (TMS) to examine the causal relationship between the left/right VLPFC and social emotion reappraisal. One hundred and twenty participants were randomly assigned to either active (left and right VLPFC groups, n = 40/40) or sham (vertex, n = 40) TMS groups. Participants were instructed to passively receive social feedback or use reappraisal strategies to positively regulate their emotions. While the subjective emotional rating showed that the bilateral VLPFC facilitated the reappraisal success, the electrophysiological measure of the late positive potential (LPP) demonstrated a more critical role of the right VLPFC on social pain relief (decreased LPP amplitudes) and social reward magnification (enhanced LPP amplitudes). In addition, the influence of emotion regulation on social evaluation was found to be mediated by the memory of social feedback, indicating the importance of memory in social behavioral shaping. These findings suggest clinical protocols for the rehabilitation of emotion‐regulatory function in patients with affective and social disorders.

The Efficacy of High- or Low-Frequency Transcranial Magnetic Stimulation in Alzheimer's Disease Patients with Behavioral and Psychological Symptoms of Dementia.

Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown. A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment. After 2weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2week's treatment and 17.33 ± 3.11 at 4week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups. These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.

Study of the role of the transcranial magnetic stimulation on language progress in autism spectrum disorder

BackgroundChildren with autism spectrum disorder (ASD) are almost universally delayed in the acquisition of spoken language as primary means of communication so they tend to have restricted outcomes in terms of independence and integration. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study (study and modulate excitability and plasticity, applied in single pulses to investigate corticospinal excitability, pairs of pulses to study intracortical inhibition and facilitation) and potential treatment of ASD. The purpose of this study is to evaluate the role of repetitive TMS in language progress in children with ASD.ResultsThere was a statistically significant clinical improvement in patients receiving active TMS (group I) comparing baseline Childhood Autism Rating Scale (CARS) assessment and after treatment (P ≤ 0.05). There was mild improvement with no significant difference between the patients receiving active TMS (group I) and those of sham TMS (group II), and both groups received language therapy as regard post-treatment CARS. There was significant difference in improvement between the two groups according to eye contact (P ≤ 0.05). There was significant improvement in response to examiner (P ≤ 0.05). There was mild improvement with no statistically significant difference in attention between the two groups. There was significant difference in improvement between the two groups according to active expressive language. There was no statistically significant difference in passive vocabulary between the two groups.ConclusionRepetitive transcranial magnetic stimulation (rTMS) over left inferior frontal gyrus may be a safe and effective way of improving language of ASD. The joint application of rTMS and standard language therapy may lead to more rapid improvement in the language progress of children with ASD.

The prediction of need of using ankle-foot orthoses in stroke patients based on findings of a transcranial magnetic stimulation study.

Ankle-foot orthoses (AFOs) are widely prescribed for stroke rehabilitation. We investigated the potential of transcranial magnetic stimulation (TMS) at an early stage, after stroke, to predict the need of using AFOs in stroke patients. We recruited 35 patients who could walk with intermittent support of one person or independently 3 months after onset of stroke. The patients included in the study were classified into two groups: a TMS (+) group (n = 10), in which motor-evoked potential (MEP) in the affected tibialis anterior (TA) was present, and a TMS (-) group (n = 25), in which the MEP in the affected TA was absent. Three months after the onset of stroke, we investigated whether patients were using AFOs or not. We also checked the motor function of the affected lower extremity using the Medical Research Council (MRC) scale. After 3 months of onset of stroke in the TMS (+) group, 4 patients (40%) were using an AFO during ambulation. In the TMS (-) group, 21 patients (84%) were using an AFO. The probability of using AFOs in the 2 groups were significantly different. Additionally, 3 months after the onset of stroke, the MRC scores of ankle dorsiflexor power, on the affected side, were significantly higher in the TMS (+) group. Early TMS evaluation of the corticospinal tract to the TA appears to be useful for predicting the need of using AFOs in stroke patients during the recovery phase.

Assessment of the Effectiveness of Transcranial Magnetic Stimulation in Subjective Tinnitus.

Introduction Increases in spontaneous activity in the neurons of the auditory cortex are presumed as the pathophysiology of tinnitus. Objective To investigate the effectiveness of transcranial magnetic stimulation (TMS) in the treatment of tinnitus. Methods A total of 62 patients between the ages of 22 and 74 with chronic subjective tinnitus were enrolled in the study. The inclusion criteria were normal findings on an otolaryngologic examination and normal ranges of complete blood count, routine biochemical parameter levels, thyroid function, air-bone gap on pure-tone audiometry, and middle-ear pressure and stapedial reflex on tympanometry. The patients were randomized into 2 groups: 40 patients were placed in the treatment for TMS (tTMS) group, and the rest (22 patients) were placed in the sham TMS group. The frequency and severity of the tinnitus, as well as the tinnitus handicap inventory (THI) score of each patient were measured before and one month after the treatment, and the values were statistically evaluated. Results We observed a statistically significant improvement in the tTMS group ( p < 0.05 and p < 0.05 respectively) regarding the THI and tinnitus severity scores. The sham TMS group showed no significant improvement in terms of the THI ( p > 0.05). However, the tinnitus severity showed a significant increase in this group ( p < 0.05). The comparison of differences in the changes in the THI and the tinnitus severity scores showed a significant statistical improvement in the tTMS group compared with the sham TMS group ( p < 0.05 and p < 0.05 respectively). Conclusion Transcranial magnetic stimulation was found to be effective in the treatment of tinnitus, and may be adopted as a treatment for tinnitus after further comprehensive studies.

Effects of transcranial magnetic stimulation on the performance of the activities of daily living and attention function after stroke: a randomized controlled trial

Objective: We aimed to interrogate the effects of transcranial magnetic stimulation (TMS) on the performance in activities of daily living (ADL) and attention function after stroke. Design: Randomized controlled trial. Setting: Inpatient rehabilitation hospital. Subjects: We randomized 62 stroke patients with attention dysfunction who were randomly assigned into two groups, and two dropped out from each group. The TMS group (n = 29) and a sham group (n = 29), whose mean (SD) was 58.12 (6.72) years. A total of 33 (56.9%) patients had right hemisphere lesion while the rest 25 (43.1%) patients had left hemisphere lesion. Interventions: Patients in the TMS group received 10 Hz, 700 pulses of TMS, while those in the sham group received sham TMS for four weeks. All the participants underwent comprehensive cognitive training. Main measures: At baseline, and end of the four-week treatment, the performance in the activities of daily living was assessed by Functional Independence Measure (FIM). On the other side, attention dysfunction was screened by Mini-Mental State Examination (MMSE), while the attention function was assessed by the Trail Making Test-A (TMT-A), Digit Symbol Test (DST) and Digital Span Test (DS). Results: Our data showed a significant difference in the post-treatment gains in motor of Functional Independence Measure (13.00 SD 1.69 vs 4.21 SD 2.96), cognition of Functional Independence Measure (4.69 SD 1.56 vs 1.52 SD 1.02), total of Functional Independence Measure (17.69 SD 2.36 vs 5.72 SD 3.12), Mini-Mental State Examination (3.07 SD 1.36 vs 1.21 SD 0.62), time taken in Trail Making Test-A (96.67 SD 25.18 vs 44.28 SD 19.45), errors number in Trail Making Test-A (2.72 SD 1.03 vs 0.86 SD 1.03), Digit Symbol Test (3.76 SD 1.09 vs 0.76 SD 0.87) or Digital Span Test (1.69 SD 0.54 vs 0.90 SD 0.72) between the TMS group and the sham group (P < 0.05). Conclusions: Taken together, we demonstrate that TMS improves the performance in the activities of daily living and attention function in patients with stroke.

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials

The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta-analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%-3.2%) and 2.7% (95% CI 2.0%-3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%-22.6%) and 13.6% (95% CI 11.6%-15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75-3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta-analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14-7.40) and 2.93 times higher (95% CI 1.41-6.07), respectively, in the active treatment groups compared to placebo. TMS is a safe and well-tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice.

Changes in the Spatial Organization of Brain Activity after Combined Antidepressive Therapy Including Transcranial Magnetic Stimulation

In order to reveal changes in the spatial organization of brain activity after a course of combined antidepressive therapy, including antidepressants and high-frequency (20 Hz) rhythmic transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) of the left hemisphere, a multidisciplinary clinical psycho-neurophysiological study was performed on two groups of patients suffering from depression that were receiving a purely medication (control group), or combined (TMS group) therapy. It was shown that after the course of therapy an improvement of the clinical state occured in both groups, although the psychological state and general condition were better in the ТМS group. After the course of therapy, small changes in the spatial organization of brain activity were found in both groups, as reflected in the values of the EEG coherence (Coh), rather than of the spectral power of the EEG. The main changes of Coh in the control group were observed in the α2 (9–11 Hz), α3 (11–13 Hz), and θ1 (4–6 Hz) EEG subbands, while in the ТМS group the changes were seen in the β2 (20–30 Hz) subband, including the area of direct ТМS action. The results suggest that the therapeutic effect of the combined antidepressive therapy, including high frequency ТМS of the DLPFC of the left hemisphere, was manifested as a more pronounced improvement of psychological and cognitive conditions in the patients of the TMS group, which resulted from activation of not only this cortical area itself as a zone of direct influence of ТМS, but also of other areas of the cortex and subcortical regions that are closely connected with it. The increase of the Coh in lower-frequency EEG bands (α and θ) in other cortical areas may be based on strengthening of inhibitory influences from the prefrontal and orbito-frontal cortices.

Effect of Paired Associative Stimulation on Motor Cortex Excitability in Rats.

Paired associative stimulation (PAS), combining transcranial magnetic stimulation (TMS) with electrical peripheral nerve stimulation (PNS) in pairs with an optimal interstimulus interval (ISI) in between, has been shown to influence the excitability of the motor cortex (MC) in humans. However, the underlying mechanisms remain unclear. This study was designed to explore an optimal protocol of PAS, which can modulate the excitability of MC in rats, and to investigate the underlying mechanisms. The resting motor thresholds (RMTs) of TMS-elicited motor evoked potentials (MEPs) recorded from the gastrocnemius muscle and the latency of P1 component of somatosensory evoked potentials (SEPs) induced by electrical tibial nerve stimulation were determined in male Sprague-Dawley rats (n=10). Sixty rats were then randomly divided into 3 groups: a PAS group (further divided into 10 subgroups at various ISIs calculated by using the latency of P1, n=5, respectively), a TMS (only) group (n=5) and a PNS (only) group (n=5). Ninety repetitions of PAS, TMS and PNS were administered to the rats in the 3 groups, respectively, at the frequency of 0.05 Hz and the intensity of TMS at 120% RMT and that of PNS at 6 mA. RMTs and motor evoked potentials' amplitude (MEPamp) were recorded before and immediately after the interventions. It was found that the MEPamp significantly decreased after PAS at ISI of 5 ms (P<0.05), while the MEPamp significantly increased after PAS at ISI of 15 ms, as compared with those before the intervention (P<0.05). However, the RMT did not change significantly after PAS at ISI of 5 ms or 15 ms (P>0.05). PAS at other ISIs as well as the sole use of TMS and PNS induced no remarkable changes in MEPamp and RMT. In conclusion, PAS can influence motor cortex excitability in rats. Neither TMS alone nor PNS alone shows significant effect.