A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD). Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly. OBJECTIVE: We compared the efficacy and tolerability of a twice-daily versus once-daily iTBS protocol in patients with TRD. We hypothesized that twice-daily iTBS would result in a greater improvement in depression scores compared to once-daily iTBS. METHODS: 208 participants (131 females) with TRD were randomized to receive either iTBS (600 pulses) delivered twice-daily with a 54-min interval between treatments or once-daily (1200 pulses) with 1 sham treatment with the same interval between treatments, to ensure equal levels of daily therapeutic contact and blinding of patients and raters. The primary outcome measure was change in depression scores on the Hamilton Rating Scale for Depression (HRSD-17) after 10 days of treatment and 30 days of treatments. RESULTS: HRSD-17 scores improved in both the twice-daily and once-daily iTBS groups; however, these improvements did not significantly differ between the two groups at either the 10-day or 30-day timepoints. Response and remission rates were low (<10%) in both groups after 10 days and consistent with prior reports at 30 days; these rates did not differ between the treatment groups. CONCLUSIONS: These results suggest that twice-daily iTBS does not accelerate response to iTBS and is not different from once-daily treatment in terms of improving depressive symptoms in patients with TRD. Clinicaltrials.gov ID: NCT02729792 (https://clinicaltrials.gov/ct2/show/NCT02729792).

Monitoring Migraine Cycle Dynamics with an Easy-to-Use Electrophysiological Marker-A Pilot Study.

Migraine attacks can cause significant discomfort and reduced functioning for days at a time, including the pre-ictal and post-ictal periods. During the inter-ictsal period, however, migraineurs seem to function normally. It is puzzling, therefore, that event-related potentials of migraine patients often differ in the asymptomatic and inter-ictal period. Part of the electrophysiological dynamics demonstrated in the migraine cycle are attention related. In this pilot study we evaluated an easy-to-use new marker, the Brain Engagement Index (BEI), for attention monitoring during the migraine cycle. We sampled 12 migraine patients for 20 days within one calendar month. Each session consisted of subjects' reports of stress level and migraine-related symptoms, and a 5 min EEG recording, with a 2-electrode EEG device, during an auditory oddball task. The first minute of the EEG sample was analyzed. Repetitive samples were also obtained from 10 healthy controls. The brain engagement index increased significantly during the pre-ictal (p ≈ 0.001) and the ictal (p ≈ 0.020) periods compared with the inter-ictal period. No difference was observed between the pre-ictal and ictal periods. Control subjects demonstrated intermediate Brain Engagement Index values, that is, higher than inter-ictal, yet lower than pre-ictal. Our preliminary results demonstrate the potential advantage of the use of a simple EEG system for improved prediction of migraine attacks. Further study is required to evaluate the efficacy of the Brain Engagement Index in monitoring the migraine cycle and the possible effects of interventions.

A Pilot Study of Possible Easy-to-Use Electrophysiological Index for Early Detection of Antidepressive Treatment Non-Response.

INTRODUCTION: The evaluation of response to pharmacological treatment in MDD requires 4-8 weeks. Therefore, the ability to predict response, and especially lack of response to treatment, as early as possible after treatment onset or change, is of prime significance. Many studies have demonstrated significant results regarding the ability to use EEG and ERP markers, including attention-associated markers such as P300, for early prediction of response to treatment. But these markers are derived from long EEG/ERP samples, often from multiple channels, which render them impractical for frequent sampling. METHODS AND RESULTS: We developed a new electrophysiological attention-associated marker from a single channel (two electrodes), using 1-min samples with auditory oddball stimuli. This work presents an initial evaluation of the ability to use this marker's dynamics between repetitive measures for early (<2 weeks) differentiation between responders and non-responders to antidepressive treatment, in 26 patients with various levels of depression and heterogeneous treatment interventions. The slope of change in the marker between early consecutive samples was negative in the non-responders, but not in the responders. This differentiation was stronger for patients suffering from severe depression (p < 0.001). CONCLUSION: This pilot study supports the feasibility of the EEG marker for early recognition of treatment-resistant depression. If verified in large-scale prospective studies, it can contribute to research and clinical work.

Opposing effects of oxytocin on overt compliance and lasting changes to memory.

From infancy we learn to comply with societal norms. However, overt compliance is not necessarily accompanied by a change in internal beliefs. The neuromodulatory processes underlying these different phenomena are not yet understood. Here, we test the role of oxytocin in controlling overt compliance versus internalization of information delivered by a social source. After intranasal oxytocin administration, participants showed enhanced compliance to the erroneous opinion of others. However, this expression was coupled with a decrease in the influence of others on long-term memories. Our data suggest that this dissociation may result from reduced conflict in the face of social pressure, which increases immediate conforming behavior, but reduces processing required for deep encoding. These findings reveal a neurobiological control system that oppositely affects internalization and overt compliance.

The analgesic effect of botulinum-toxin A on postwhiplash neck pain.

BACKGROUND: The effectiveness of botulinum neurotoxin type A (BTXA) injections in relieving the neck pain and reduced motion that evolve after whiplash injury (WI) has been controversial. AIM OF STUDY: To test the long-term efficacy of a tender point injection of BTXA in relieving neck pain in patients with WI. METHODS: Twenty patients with cervical myofascial pain, 2 to 48 weeks after WI, were randomly assigned to receive either 200 U of BTXA or placebo at 4 tender points and were seen during the follow-ups 3, 6, 9, 12, and 24 weeks after the injections. Outcome measures included the intensity of pain as evaluated by a 10-cm Visual Analog Scale (VAS) and a 5-point Verbal Rating Scale (VRS), quality of life as evaluated by the SF-36 questionnaire, treatment efficacy as per the global assessment of the physician and patient, intensity of pain in response to mechanical pressure, range of cervical motion, and use of other therapies and their adverse effects. RESULTS: A time-dependent improvement in all the parameters was found in both groups, which was consistently larger in the BTXA-treated group, but mostly not at a significant level. Significant differences between the groups were found only in the percentages of patients who achieved 50% or more of reduction in intensity (VAS and average VRS) at 24 weeks (50% vs. 0%, P>0.05 and 70% vs. 11%, P>0.05, respectively). Systemic adverse effects tended to be more common in the BTXA-treated group (40% vs. 0%, P=0.07). CONCLUSIONS: Study results suggest that BTXA treatment has some efficacy when administered within 1 year of the WI. However, a large, well-designed clinical trial is needed to draw final conclusions.