Effect of Pulse Duration and Direction on Plasticity Induced by 5 Hz Repetitive Transcranial Magnetic Stimulation in Correlation With Neuronal Depolarization.

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.

Less Might Be More: Conduction Failure as a Factor Possibly Limiting the Efficacy of Higher Frequencies in rTMS Protocols.

Introduction: rTMS has been proven effective in the treatment of neuropsychiatric conditions, with class A (definite efficacy) evidence for treatment of depression and pain (Lefaucheur et al., 2014). The efficacy in stimulation protocols is, however, quite heterogeneous. Saturation of neuronal firing by HFrTMS without allowing time for recovery may lead to neuronal response failures (NRFs) that compromise the efficacy of stimulation with higher frequencies. Objectives: To examine the efficacy of different rTMS temporal stimulation patterns focusing on a possible upper stimulation limit related to response failures. Protocol patterns were derived from published clinical studies on therapeutic rTMS for depression and pain. They were compared with conduction failures in cell cultures. Methodology: From 57 papers using protocols rated class A for depression and pain (Lefaucheur et al., 2014) we extracted Inter-train interval (ITI), average frequency, total duration and total number of pulses and plotted them against the percent improvement on the outcome scale. Specifically, we compared 10 Hz trains with ITIs of 8 s (protocol A) and 26 s (protocol B) in vitro on cultured cortical neurons. Results: In the in vitro experiments, protocol A with 8-s ITIs resulted in more frequent response failures, while practically no response failures occurred with protocol B (26-s intervals). The HFrTMS protocol analysis exhibited no significant effect of ITIs on protocol efficiency. Discussion: In the neuronal culture, longer ITIs appeared to allow the neuronal response to recover. In the available human dataset on both depression and chronic pain, data concerning shorter ITIs is does not allow a significant conclusion. Significance: NRF may interfere with the efficacy of rTMS stimulation protocols when the average stimulation frequency is too high, proposing ITIs as a variable in rTMS protocol efficacy. Clinical trials are necessary to examine effect of shorter ITIs on the clinical outcome in a controlled setting.

Frontal theta/beta ratio changes during TOVA in Egyptian ADHD children.

OBJECTIVE: To spot the frontal theta/beta ratio alterations during Tests of Variance of Attention (TOVA) in Egyptian attention deficit hyperactivity disorder (ADHD) children. METHODS: This is a cross sectional study performed in Clinical Neurophysiology Unit, Cairo University, Egypt. It included 2 groups, each of 52 children (one of them with ADHD and the other were normal control). EEG was recorded for every subject during normal relaxing circumstance with eyes opened as well as during TOVA. RESULTS: Comparing both groups revealed statistically significant difference in the theta/beta ratio in both state (normal relaxing with eyes opened and during TOVA), also we found that the theta/beta ratio decreased in normal group (during concentration) while in the ADHD group it increased with a specific pattern. CONCLUSION: The theta/beta ratio can be of value in helping for differential diagnosis in patients presenting with mild ADHD.

Results of the Dyslipidemia International Study (DYSIS)-Middle East: clinical perspective on the prevalence and characteristics of lipid abnormalities in the setting of chronic statin treatment.

BACKGROUND: Therapeutic intervention with low-density lipoprotein cholesterol-lowering agents known as statins has been demonstrated to reduce cardiovascular risk. However, many patients on statin treatment have persistent dyslipidemia and remain at a high risk of cardiovascular disease. Therefore, the objective of this study was to assess the frequency of lipid abnormalities in patients receiving chronic statin treatment. METHODS: As part of an international, cross-sectional, observational study, DYSIS-Middle East enrolled 2,182 patients in the United Arab Emirates (UAE), Saudi Arabia, Lebanon and Jordan. All patients were over 45 years of age and had been on statin treatment for at least three months. Data on demographics, lipid parameters and cardiovascular risk profile were recorded. Cardiovascular risk was defined according the guidelines of the European Society of Cardiology. RESULTS: The majority of patients (82.6%) were classified as being at very high risk of cardiovascular events, and 61.8% of all patients did not attain LDL-C target levels. Low high-density lipoprotein cholesterol levels and elevated triglyceride levels were noted in 55.5% and 48.5% of patients, respectively. Multivariate logistical regression modeling indicated that factors independently associated with LDL-C levels not being at goal were lifestyle choices, diabetes mellitus, ischemic heart disease, and blood pressure ≥ 140/90 mmHg. CONCLUSIONS: Almost two-thirds of statin-treated patients in the United Arab Emirates, Saudi Arabia, Lebanon and Jordan had inadequately controlled lipid levels. More comprehensive surveillance, awareness and treatment regimens, as well as modification of lifestyle choices, is necessary to halt the rise in cardiovascular disease-related mortality.