On-line flexibility of the cognitive tuning of corticospinal excitability: a TMS study in human gait

Human subjects have been found to be able to cognitively prepare themselves to resist to a TMS-induced central perturbation by selectively modulating the corticospinal excitability (CS). The aim of this study was to investigate the on-line adaptability of this cognitive tuning of CS excitability during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability before the movement was evoked. TMS was applied at mid-stance (evoking additional hip extension) or at the beginning of the swing (evoking hip flexion) with a random phase, thus evoking unpredictable flexion or extension movement. This was compared to a condition of fixed phase, in which the subjects knew in advance the direction of the evoked movement. In both conditions, we compared the amplitude of the TMS-evoked movement and the motor-evoked potentials (MEPs) of the muscles acting at the hip joint (RF/BF) according to two opposite instructions, either to cognitively prepare to "let go", or to cognitively prepare to "compensate" for the evoked movements. The results showed that the subjects were able to compensate for random TMS-evoked movements, but with a lower performance level in comparison to the fixed TMS-evoked movements. When they succeeded in the random-phase condition, the subjects used the same preparation strategy as in the fixed-phase condition; preparing to compensate resulted in a selective increase in the CS excitability to those muscles which would be involved in counteracting the possible central perturbation. This requires continuous change in the tuning of CS excitability within the stride and thus reveals the high flexibility of the cognitive tuning of CS excitability during gait.     

TMS with fast and accurate electronic control: Measuring the orientation sensitivity of corticomotor pathways

BackgroundTranscranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing.ObjectiveWe aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability.MethodsWe designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custom-made electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3° steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude.ResultsThe two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity.ConclusionThe developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols.     

Atlas of optimal coil orientation and position for TMS: A computational study

Background

Transcranial magnetic stimulation (TMS) activates target brain structures in a non-invasive manner. The optimal orientation of the TMS coil for the motor cortex is well known and can be estimated using motor evoked potentials. However, there are no easily measurable responses for activation of other cortical areas and the optimal orientation for these areas is currently unknown.

Right prefrontal TMS versus sham treatment of mania: a controlled study

Objective:  Left prefrontal transcranial magnetic stimulation (TMS) has been reported to have ECT-like effects in depression and we therefore planned a study of TMS in mania. Sixteen patients completed trial of right versus left prefrontal TMS at 20 Hz, 2-sec duration per train, 20 trains per day for 10 treatment days. Mania was evaluated using the Mania Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impression. Significantly more improvement was observed in patients treated with right prefrontal TMS than with left prefrontal. We now report a follow-up study of right active TMS versus right sham TMS with the same indications and parameters.
Methods:  Twenty-five patients entered and 19 completed right TMS versus sham right TMS.
Results:  Right TMS was no more effective than sham TMS.
Conclusions:  It is possible that the previous results were due to an effect of left TMS to worsen mania. Alternatively, it is noted that the present patient group had much more psychosis than the previous study of TMS in mania, and depression studies have reported that psychosis is a poor prognostic sign for TMS response.     

Effectiveness of a second deep TMS in depression: a brief report

Objectives

Deep transcranial magnetic stimulation (DTMS) is an emerging and promising treatment for major depression. In our study, we explored the effectiveness of a second antidepressant course of deep TMS in major depression. We enrolled eight patients who had previously responded well to DTMS but relapsed within 1 year in order to evaluate whether a second course of DTMS would still be effective.

Methods

Eight depressive patients who relapsed after a previous successful deep TMS course expressed their wish to be treated again. Upon their request, they were recruited and treated with 20 daily sessions of DTMS at 20 Hz using the Brainsway's H1 coil. The Hamilton depression rating scale (HDRS), Hamilton anxiety rating scale (HARS) and the Beck depression inventory (BDI) were used weekly to evaluate the response to treatment.

Results

Similar to the results obtained in the first course of treatment, the second course of treatment (after relapse) induced significant reductions in HDRS, HARS and BDI scores, compared to the ratings measured prior to treatment. The magnitude of response in the second course was smaller relative to that obtained in the first course of treatment.

Conclusions

Our results suggest that depressive patients who previously responded well to deep TMS treatment are likely to respond again. However, the slight reduction in the magnitude of the response in the second treatment raises the question of whether tolerance or resistance to this treatment may eventually develop.     

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: a pilot study

Our aim was to assess the potential of navigated transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) responses in studying neuronal reactivity and cortical connectivity in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). We studied 14 right-handed subjects: five patients with AD, five patients with MCI and four healthy controls. Fifty TMS-pulses at an intensity of 110% of individually determined motor threshold were delivered to the hand area of primary motor cortex (M1) with navigated brain stimulation (NBS). Spreading of primary NBS-evoked neuronal activity was monitored with a compatible 60-channel EEG, and analyzed in time, frequency and spatial-domains. We found significantly reduced TMS-evoked P30 (time-locked response 30 ms after the magnetic stimulation) in the AD subjects. This reduction was seen in the temporo-parietal area ipsilateral to stimulation side as well as in the contralateral fronto-central cortex corresponding to the sensorimotor network, which is anatomically interconnected with the stimulated M1. In addition, there was a significant decrease in the N100 amplitude in the MCI subjects when compared with the control subjects. Thus, the combination of NBS and EEG revealed prominent changes in functional cortical connectivity and reactivity in the AD subjects. This pilot study suggests that the method may provide a novel tool for examining the degree and progression of dementia.     

Human dorsolateral prefrontal cortex is involved in visual search for conjunctions but not features: A theta TMS study

Functional neuroimaging studies have shown that the detection of a target defined by more than one feature (for example, a conjunction of colour and orientation) amongst distractors is associated with the activation of a network of brain areas. Dorsolateral prefrontal cortex (DLPFC), along with areas such as the frontal eye fields (FEF) and posterior parietal cortex (PPC), is a component of this network. While transcranial magnetic stimulation (TMS) had shown that both FEF and PPC are necessary for, and not just correlated with, successful conjunction search, this is not the case for DLPFC. To test the hypothesis that this area is also necessary for efficient conjunction search, TMS was applied over DLPFC and the effects on conjunction and feature (in this case colour) search performance compared with those when TMS was delivered over area MT/V5 and a vertex control stimulation condition. DLPFC TMS impaired performance on the conjunction search task but was without effect on feature search, similar to findings when TMS is delivered over PPC or FEF. Vertex TMS had no effects whereas MT/V5 TMS significantly improved performance with a time course that may indicate that this was due to modulation of V4 activity. These findings illustrate that, like FEF and PPC, DLPFC is necessary for fully effective conjunction visual search performance.     

Evidence for an occipito-temporal tract underlying visual recognition in picture naming

A 24-year-old male underwent awake surgery for a lesion in the left dominant basal temporo-occipital junction.     

Static Field Influences on Transcranial Magnetic Stimulation: Considerations for TMS in the Scanner Environment

BackgroundTranscranial magnetic stimulation (TMS) can be combined with functional magnetic resonance imaging (fMRI) to simultaneously manipulate and monitor human cortical responses. Although tremendous efforts have been directed at characterizing the impact of TMS on image acquisition, the influence of the scanner's static field on the TMS coil has received limited attention.Objective/hypothesisThe aim of this study was to characterize the influence of the scanner's static field on TMS. We hypothesized that spatial variations in the static field could account for TMS field variations in the scanner environment.MethodsUsing an MRI-compatible TMS coil, we estimated TMS field strengths based on TMS-induced voltage changes measured in a search coil. We compared peak field strengths obtained with the TMS coil positioned at different locations (B₀ field vs fringe field) and orientations in the static field. We also measured the scanner's static field to derive a field map to account for TMS field variations.ResultsTMS field strength scaled depending on coil location and orientation with respect to the static field. Larger TMS field variations were observed in fringe field regions near the gantry as compared to regions inside the bore or further removed from the bore. The scanner's static field also exhibited the greatest spatial variations in fringe field regions near the gantry.ConclusionsThe scanner's static field influences TMS fields and spatial variations in the static field correlate with TMS field variations. Coil orientation changes in the B0 field did not result in substantial TMS field variations. TMS field variations can be minimized by delivering TMS in the bore or outside of the 0–70 cm region from the bore entrance.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

认知刺激疗法对蛛网膜下腔出血患者急性期认知功能障碍的疗效

目的 观察认知刺激疗法对蛛网膜下腔出血(SAH)患者急性期认知功能障碍的疗效。方法收集30例Hunt - Hess Ⅰ～Ⅱ级动脉瘤性SAH患者,随机分为两组。实验组15例,行认知刺激治疗;对照组15例,未行认知刺激治疗。患者分别在介入治疗前、治疗后第14天各完成一次认知功能检查。检查项目：简易精神状态检查量表( MMSE)、词语流畅性测验、视觉再生、连线测验。结果(1)两组患者性别、年龄比较差异无统计学意义(P＞0.05);术前Hunt - Hess分级比较差异无统计学意义(P＞0.05)。(2)术前两组患者MMSE、词语流畅性测验、视觉再生、连线测验A及B各项测试结果比较差异无统计学意义(P＞0.05)。(3)术后两组患者MMSE、词语流畅性测验、连线测验A及B各项测试结果比较实验组优于对照组(P＜0.05);两组视觉再生评分比较差异无统计学意义(P＞0.05)。结论认知刺激治疗可以辅助改善急性期SAH患者的部分认知功能。     

Dissociating cognitive from affective theory of mind: A TMS study

Introduction

“Theory of Mind” (ToM), i.e., the ability to infer other persons' mental states, is a key function of social cognition. It is increasingly recognized to form a multidimensional construct. One differentiation that has been proposed is that between cognitive and affective ToM, whose neural correlates remain to be identified. We aimed to ascertain the possible role of the right dorsolateral prefrontal cortex (DLPFC) for cognitive ToM as opposed to affective ToM processes.

Methods

1 Hz repetitive transcranial magnetic stimulation (rTMS) was used to interfere offline with cortical function of the right DLPFC in healthy male subjects who subsequently had to perform a computerized task assessing cognitive and affective ToM.

Results

RTMS over the right DLPFC induced a selective effect on cognitive but not affective ToM. More specifically, a significant acceleration of reaction times in cognitive ToM compared to affective ToM and control items was observed in the experimental (right DLPFC) compared to the control (vertex) rTMS stimulation condition.

Conclusions

Our findings provide evidence for the functional independence of cognitive from affective ToM. Furthermore, they point to an important role of the right DLPFC within neural networks mediating cognitive ToM. Possible underlying mechanisms of the acceleration of cognitive ToM processing under rTMS are discussed.     

Comparative efficacy of non-invasive neurostimulation therapies for poststroke dysphagia: A systematic review and meta-analysis

ObjectiveTo explore the effect of non-invasive neurostimulation therapies on dysphagia patients after stroke.MethodsWe searched MEDLINE (Ovid), PubMed, Embase, Web of Science, ScienceDirect, and Cochrane library databases until April 22, 2020. All published and unpublished randomized controlled trials (RCT) were included. Full texts were independently reviewed. The risk of RCT bias was evaluated by two independent assessors using the Cochrane risk of bias tool. The primary outcome measure was swallowing function before and after neurostimulation therapy. The effect sizes are calculated from the extracted data and combined into a comprehensive summary statistic.ResultA total of 27 randomized controlled trials were included in this study, involving 914 stroke patients (27 intervention groups and 20 control groups). Meta-analysis showed that compared with the control group, noninvasive neurostimulation therapies (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), surface neuromuscular electrical stimulation (sNMES) or pharyngeal electrical stimulation (PES)) had a better effect (SMD = 0.91; 95% CI: 0.54–1.27; Z = 4.84; P < 0.00001; I² = 86%). In the subgroup analysis based on type of stimulus, rTMS appeared to perform better. In the subgroup analysis based on clinical phase, stimulation applied in the acute phase may be more effective. In the subgroup analysis based on the site of injury, the brainstem injury group seemed to achieve better outcomes. In the subgroup analysis based on stroke type, the cerebral infarction group had better outcomes than the cerebral infarction/hemorrhage mixed group.ConclusionsNon-invasive neurostimulation therapies can effectively promote the recovery of dysphagia after stroke.     

Classification accuracy of TMS for the diagnosis of mild cognitive impairment

ObjectiveTo evaluate the performance of a Random Forest (RF) classifier on Transcranial Magnetic Stimulation (TMS) measures in patients with Mild Cognitive Impairment (MCI).MethodsWe applied a RF classifier on TMS measures obtained from a multicenter cohort of patients with MCI, including MCI-Alzheimer’s Disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), and healthy controls (HC). All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The primary outcome measures were the classification accuracy, precision, recall and F1-score of TMS in differentiating each disorder.Results160 participants were included, namely 64 patients diagnosed as MCI-AD, 28 as MCI-FTD, 14 as MCI-DLB, and 47 as healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.72 to 0.86), high precision (0.72–0.90), high recall (0.75–0.98), and high F1-scores (0.78–0.92), in differentiating each neurodegenerative disorder. By computing a new classifier, trained and validated on the current cohort of MCI patients, classification indices showed even higher accuracy (ranging from 0.83 to 0.93), precision (0.87–0.89), recall (0.83–1.00), and F1-scores (0.85–0.94).ConclusionsTMS may be considered a useful additional screening tool to be used in clinical practice in the prodromal stages of neurodegenerative dementias.     

The effect of meninges on the electric fields in TES and TMS. Numerical modeling with adaptive mesh refinement

BackgroundWhen modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs.ObjectiveWe investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model.MethodWe use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas ($\text{M}{1}_{\text{HAND}}$ and $\text{DLPFC}$) and for several distinct TES and TMS setups.ResultsMaximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (～6%) decrease on average when the meninges are included.ConclusionOur results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online.