Y. Levkovitz

Positive effects of repetitive transcranial magnetic stimulation on attention in ADHD Subjects: A randomized controlled pilot study

Abstract Objectives. Repetitive transcranial stimulation (rTMS) affects dopaminergic secretion in the prefrontal cortex. Attention deficit hyperactivity disorder (ADHD) had been suggested to involve dopaminergic prefrontal abnormalities. Methods. In this crossover double-blind randomized, sham-controlled pilot study, patients diagnosed as having adult ADHD received either a single session of high-frequency rTMS directed to the right prefrontal cortex (real rTMS) or a single session of sham rTMS. Results. A total of 13 patients (seven males, six females) who fulfilled the criteria for adult ADHD, according to DSM-IV criteria gave informed consent and were enrolled. There was a specific beneficial effect on attention 10 minutes after a real rTMS course. The post-real rTMS attention score improved significantly (M=3.56, SD=0.39) compared to the pre-real rTMS attention score (M=3.31, SD=0.5) [t(12)=2.235, P < 0.05]. TMS had no effect on measures of mood and anxiety. The sham rTMS had no effect whatsoever. Conclusions. Our findings should encourage future research on the possibility of amelioration of attention difficulties in patients suffering from ADHD by using high frequency rTMS directed to the right dorsolateral prefrontal cortex. (NIH registry NCT00825708)

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 Brainsways 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.

Transcranial magnetic stimulation of the ventromedial prefrontal cortex impairs theory of mind learning

Imaging and lesion studies indicate that the prefrontal cortex plays a prominent role in mediating theory of mind (ToM) functioning. Particularly, the ventromedial prefrontal cortex (VMPFC) appears to be involved in mediating ToM functioning. This study utilized slow repetitive transcranial magnetic stimulation (rTMS) over the VMPFC in 13 healthy subjects in order to test whether normal functioning of the VMPFC is necessary for ToM functioning. We found that rTMS to the VMPFC, but not sham-rTMS, significantly disrupted ToM learning. Performance on a control task, not involving affective ToM functioning, was not significantly altered after applying rTMS to the VMPFC or sham-rTMS. In an additional experiment, rTMS to the vertex did not significantly affect ToM learning, confirming specificity of the VMPFC region. These findings indicate that the VMPFC is critical for intact ToM learning and shed further light on the concept and localization of ToM in particular and empathic functioning in general.

I think therefore I am: Rest-related prefrontal cortex neural activity is involved in generating the sense of self.

The sense of self has always been a major focus in the psychophysical debate. It has been argued that this complex ongoing internal sense cannot be explained by any physical measure and therefore substantiates a mind-body differentiation. Recently, however, neuro-imaging studies have associated self-referential spontaneous thought, a core-element of the ongoing sense of self, with synchronous neural activations during rest in the medial prefrontal cortex (PFC), as well as the medial and lateral parietal cortices. By applying deep transcranial magnetic stimulation (TMS) over human PFC before rest, we disrupted activity in this neural circuitry thereby inducing reports of lowered self-awareness and strong feelings of dissociation. This effect was not found with standard or sham TMS, or when stimulation was followed by a task instead of rest. These findings demonstrate for the first time a critical, causal role of intact rest-related PFC activity patterns in enabling integrated, enduring, self-referential mental processing.

Deep TMS augmentation treatment for fibromyalgia: A safety and feasibility study

Introduction: Fibromyalgia (FM) is a prevalent chronic pain syndrome, with limited therapeutic options. Repetitive Transcranial Magnetic Stimulation (rTMS) is emerging as a potential new treatment modality for FM. Deep TMS (dTMS) is a novel modification of standard rTMS, capable of delivering stimulation to a greater depth. This preliminary study is the first to explore the efficacy of dTMS as an augmentation treatment in FM. Method: Eleven FM patients completed a 20-day treatment protocol, in order to examine left dorsal-lateral prefrontal cortex (DLPFC) excitation via dTMS using the h-coil. Clinical and psychophysical measurements of pain were evaluated each week, and 2 weeks after study completion. The primary outcomemeasures were the changes in pain measures from baseline to visit 20: Short FormMcGill Pain Questionnaire (SF-Mcgill) and Brief Pain Inventory (BPI). Secondary outcomes were FM clinical measures such as the Fibromyalgia Pain Questionnaire (FIQ). Demographic and clinical measures are summarized in Table 1. Results: Patients demonstrated a significant reduction in pain symptoms (p1⁄4.024) and improved functioning (p1⁄4.022) at visit 20 (figure 1) Demographic and clinical measures are summarized in Table 1. A significant decrease in FM symptoms that are not directly linked to pain (sleep disturbances, cognitive impairments and tiredness) was found only at followup (p1⁄4.044). Depressive symptoms were not reduced, indicating that pain reduction among our subjects could not be attributed to the antidepressant effect of dTMS. Treatment was well tolerated and no significant side effects were reported. Discussion: dTMS was safe and tolerable as augmentation treatment for FM patients. It reduced pain intensity in FM, improved function, and may have induced changes in neuroplasticity. Further double-blinded controlled studies, with a larger sample, are required to confirm and more accurately assess the therapeutic utility of dTMS in FM.

P643: Safety and characterization of a novel multi-channel TMS stimulator

Background: Currently available TMS stimulators have a single channel operating a single coil. Objective: To outline and present physical and physiological benefits of a novel convenient multi-channel stimulator, comprising five channels, where the stimulation parameters of each channel are independently controllable. Methods: Simultaneous and sequential operation of various channels was tested in healthy volunteers. Paired pulses schemes with various inter-stimulus intervals (ISIs) were studied for the hand APB and the leg AH muscles. Energy consumption and coil heating rates with simultaneous operation of 4 channels was compared to a single figure-8 coil. Results: Repetitive operation of separate channels with different stimulation parameters is demonstrated. The operations of various channels can be combined simultaneously or sequentially to induce multiple pulses with ISIs of ms resolution. A universal pattern of inhibition and facilitation as a function of ISI was found, with some dependence on coils configurations and on pulse widths. A strong dependence of the induced inhibition on the relative orientation of the conditioning and test pulses was discovered. The ability of this method to induce inhibition in shallow brain region but not in deeper region, thus focusing the effect in the deep brain region, is demonstrated. A significant saving in energy consumption and a reduction in coil heating were demonstrated for several channels operated simultaneously compared to a standard single channel figure-8 coil. Conclusions: The multi-channel stimulator enables the synchronized induction of different excitability modulations to different brain regions using different stimulation patterns in various channels. Multiple pulses operation with coils with various depth profiles can increase the focality of TMS effect in deep brain regions.