Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities

2021 ◽  
pp. 1-8
Author(s):  
Jauhtai Cheng ◽  
J. Kaci Fairchild ◽  
Margaret W. McNerney ◽  
Art Noda ◽  
J. Wesson Ashford ◽  
...  

Background: Despite decades of research efforts, current treatments for Alzheimer’s disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition. Objective: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities. Methods: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group). Results: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up. Conclusion: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

Author(s):  
T. Hebel ◽  
M. A. Abdelnaim ◽  
M. Deppe ◽  
P. M. Kreuzer ◽  
A. Mohonko ◽  
...  

Abstract Introduction The effect of concomitant medication on repetitive transcranial magnetic stimulation (rTMS) outcomes in depression remains understudied. Recent analyses show attenuation of rTMS effects by antipsychotic medication and benzodiazepines, but data on the effects of antiepileptic drugs and lithium used as mood stabilizers or augmenting agents are sparse despite clinical relevance. Preclinical electrophysiological studies suggest relevant impact of the medication on treatment, but this might not translate into clinical practice. We aimed to investigate the role of lithium (Li), lamotrigine (LTG) and valproic acid (VPA) by analyzing rTMS treatment outcomes in depressed patients. Methods 299 patients with uni- and bipolar depression treated with rTMS were selected for analysis in respect to intake of lithium, lamotrigine and valproic acid. The majority (n = 251) were treated with high-frequency (10–20 Hz) rTMS of the lDLPFC for an average of 17 treatment sessions with a figure-of-8 coil with a MagVenture system aiming for 110% resting motor threshold, and smaller groups of patients were being treated with other protocols including intermittent theta-burst stimulation and bilateral prefrontal and medial prefrontal protocols. For group comparisons, we used analysis of variance with the between-subjects factor group or Chi-Square Test of Independence depending on the scales of measurement. For post-hoc tests, we used least significant difference (LSD). For differences in treatment effects between groups, we used an ANOVA with the between-subjects factor group (groups: no mood stabilizer, Li, LTG, VPA, Li + LTG) the within-subjects factor treatment (pre vs. post treatment with rTMS) and also Chi-Square Tests of independence for response and remission. Results Overall, patients showed an amelioration of symptoms with no significant differences for the main effect of group and for the interaction effect treatment by group. Based on direct comparisons between the single groups taking mood stabilizers against the group taking no mood stabilizers, we see a superior effect of lamotrigine, valproic acid and combination of lithium and lamotrigine for the response and remission rates. Motor threshold was significantly and markedly higher for patients taking valproic acid. Conclusion Being treated with lithium, lamotrigine and valproic acid had no relevant influence on rTMS treatment outcome. The results suggest there is no reason for clinicians to withhold or withdraw these types of medication from patients who are about to undergo a course of rTMS. Prospective controlled work on the subject is encouraged.


2021 ◽  
Vol 15 ◽  
Author(s):  
Islam Halawa ◽  
Katharina Reichert ◽  
Aman S. Aberra ◽  
Martin Sommer ◽  
Angel V. Peterchev ◽  
...  

Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations.Objectives: To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses.Methods: We stimulated the hand motor cortex with 5 Hz rTMS applying 1,200 bidirectional pulses with the main component durations of 80, 100, and 120 μs using a controllable pulse stimulator TMS (cTMS). Fourteen healthy subjects were investigated in nine sessions with 80% resting motor threshold (RMT) for posterior-anterior (PA) and 80 and 90% RMT anterior-posterior (AP) induced current direction. We used a model approximating neuronal membranes as a linear first order low-pass filter to estimate the strength–duration time constant and to simulate the membrane polarization produced by each waveform.Results: PA and AP 5 Hz rTMS at 80% RMT produced no significant excitation. An exploratory analysis indicated that 90% RMT AP stimulation with 100 and 120 μs pulses but not 80 μs pulses led to significant excitation. We found a positive correlation between the plastic outcome of each session and the simulated peak neural membrane depolarization for time constants >100 μs. This correlation was strongest for neural elements that are depolarized by the main phase of the AP pulse, suggesting the effects were dependent on pulse direction.Conclusions: Among the tested conditions, only 5 Hz rTMS with higher intensity and wider pulses appeared to produce excitatory aftereffects. This correlated with the greater depolarization of neural elements with time constants slower than the directly activated neural elements responsible for producing the motor output (e.g., somatic or dendritic membrane).Significance: Higher intensities and wider pulses seem to be more efficient in inducing excitation. If confirmed, this observation could lead to better results in future clinical studies performed with wider pulses.


CNS Spectrums ◽  
2020 ◽  
pp. 1-6
Author(s):  
Chiara Arici ◽  
Beatrice Benatti ◽  
Rita Cafaro ◽  
Laura Cremaschi ◽  
Luca Degoni ◽  
...  

Abstract Background Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates. Methods Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Results Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed. Conclusion Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.


2006 ◽  
Vol 101 (2) ◽  
pp. 500-505 ◽  
Author(s):  
Gabrielle Todd ◽  
Stanley C. Flavel ◽  
Michael C. Ridding

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (∼1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5–20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of ∼1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for ∼30 min ( P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.


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