Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Double-pulse transcranial magnetic stimulation over the frontal eye field facilitates triggering of memory-guided saccades.

The study investigated the influence of double-pulse transcranial magnetic stimulation (dTMS) on memory-guided saccade triggering. Double pulses with interstimulus intervals (ISIs) of 35, 50, 65 or 80 ms were applied over the right frontal eye field (FEF) and as control over the occipital cortex. A significant dTMS effect was found exclusively for contralateral saccades; latency of memory-guided saccades was reduced after FEF stimulation with an ISI of 50 ms compared to latency without stimulation. This effect proved to be specific for the ISI of 50 ms over the FEF because control stimulation with the same ISI over the occipital cortex had no significant effect on latency of memory-guided saccades. The results of our study showed that, by using an appropriate ISI, dTMS is able to facilitate contralateral saccade triggering by stimulating the FEF. This suggests that TMS interferes specifically with saccade triggering mechanisms, probably by acting on presaccadic neurons of the FEF.

High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral cortex: EEG topography during waking and subsequent sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young (age range 21-25 years) right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night (sham stimulation) and an experimental night (rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design), were scheduled. In each subject, 40 trains of 2-s duration of rTMS (inter-train interval 28 s) were applied at a frequency of 20 Hz (i.e. 1600 pulses per session) and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals approximately 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode (23.00-07.00 h). The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 (in min and percentage of total sleep time) over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.

Mood effects of repetitive transcranial magnetic stimulation of left prefrontal cortex in healthy volunteers.

This study investigated the effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left prefrontal cortex (LPFC) on mood in a sham-controlled crossover design. Twenty-five healthy male subjects received HF-rTMS of the LPFC in real and sham conditions. Forty trains (frequency 20 Hz, stimulation intensity 100% of individual motor threshold, train duration 2 s, intertrain interval 28 s) were applied in each session. Mood change from baseline was measured with five visual analog scales (VAS) for sadness, anxiety, happiness, tiredness and pain/discomfort. We were unable to demonstrate significant mood changes from baseline on visual analog scales after either sham or real stimulation of LPFC. There is insufficient evidence to support the general conclusion that HF-rTMS of LPFC has mood effects in healthy volunteers. Future studies should be sham-controlled, have larger sample sizes, and strictly stimulate one single region per session in order to exclude interaction effects with the previous stimulation.

Purchase decision-making is modulated by vestibular stimulation

Purchases are driven by consumers’ product preferences and price considerations. Using caloric vestibular stimulation (CVS), we investigated the role of vestibular-affective circuits in purchase decision-making. CVS is an effective noninvasive brain stimulation method, which activates vestibular and overlapping emotional circuits (e.g., the insular cortex and the anterior cingulate cortex (ACC)). Subjects were exposed to CVS and sham stimulation while they performed two purchase decision-making tasks. In Experiment 1 subjects had to decide whether to purchase or not. CVS significantly reduced probability of buying a product. In Experiment 2 subjects had to rate desirability of the products and willingness to pay (WTP) while they were exposed to CVS and sham stimulation. CVS modulated desirability of the products but not WTP. The results suggest that CVS interfered with emotional circuits and thus attenuated the pleasant and rewarding effect of acquisition, which in turn reduced purchase probability. The present findings contribute to the rapidly growing literature on the neural basis of purchase decision-making.

Refractory chronic pelvic pain syndrome in men: can transcutaneous electrical nerve stimulation help?

Objective To evaluate the effect of transcutaneous electrical nerve stimulation (TENS) for treating men with refractory chronic pelvic pain syndrome (CPPS). Patients and Methods A consecutive series of 60 men treated with TENS for refractory CPPS was evaluated prospectively at an academic tertiary referral centre. The effects of treatment were evaluated by a pain diary and by the quality of life item of the National Institutes of Health Chronic Prostatitis Symptom Index at baseline, after 12 weeks of TENS treatment, and at last known follow-up. Adverse events related to TENS were also assessed. Results The mean (95% confidence interval, CI; range) age of the 60 men was 46.9 (43.5–50.3; 21–82) years. TENS was successful after 12 weeks of treatment in 29 (48%) patients and a positive effect was sustained during a mean (95%, CI; range) follow-up of 43.6 (33.2–56; 6–88) months in 21 patients. After 12 weeks of TENS treatment, mean (95% CI) pain visual analogue scale decreased significantly (P < 0.001) from 6.6 (6.3–6.9) to 3.9 (3.2–4.6). Patients' quality of life changed significantly after TENS treatment (P < 0.001). Before TENS, all 60 patients felt mostly dissatisfied (n = 17; 28%), unhappy (n = 28; 47%) or terrible (n = 15; 25%). After 12 weeks of TENS treatment, 29 (48%) patients felt mostly satisfied (n = 5), pleased (n = 18) or delighted (n = 6). No adverse events related to TENS were noted. Conclusion TENS may be an effective and safe treatment for refractory CPPS in men, warranting randomized, placebo-controlled trials.

Transcutaneous electrical nerve stimulation: an effective treatment for refractory non-neurogenic overactive bladder syndrome?

PURPOSE: To assess the effect of transcutaneous electrical nerve stimulation (TENS) for treating refractory overactive bladder syndrome (OAB). PATIENTS AND METHODS: A consecutive series of 42 patients treated with TENS for refractory OAB was prospectively investigated at an academic tertiary referral centre. Effects were evaluated using bladder diary for at least 48 h and satisfaction assessment at baseline, after 12 weeks of TENS treatment, and at the last known follow-up. Adverse events related to TENS were also assessed. RESULTS: Mean age of the 42 patients (25 women, 17 men) was 48 years (range, 18-76). TENS was successful following 12 weeks of treatment in 21 (50 %) patients, and the positive effect was sustained during a mean follow-up of 21 months (range, 6-83 months) in 18 patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h decreased significantly from 15 to 11 (p < 0.001) and mean voided volume increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS completely restored continence in 7 (39 %) of the 18 incontinent patients. Before TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p < 0.001). No adverse events related to TENS were noted. CONCLUSIONS: TENS seems to be an effective and safe treatment for refractory OAB warranting randomized, placebo-controlled trials.

Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction

Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regulatory (Treg) cytokine profiles of RAO-associated antigen- and parasite-antigen-stimulated peripheral blood mononuclear cells (PBMC) differ between RAO-affected and healthy horses depending on their genetic background. In our study, PBMC from 17 RAO-affected and 14 healthy control horses of F1 and F2 were stimulated for 24h with antigens relevant to RAO [hay dust extract (HDE), Aspergillus fumigatus extract (AFE) and lipopolysaccharids (LPS)]; cyathostomin extract (CE) and recombinant cyathostomin antigen (RCA) or with concanavalin A (ConA). Total mRNA levels of IL-4, IL-4R, IL-13, interferon (INF)-γ and IL-10 were examined by qRT-PCR. Stimulation with either HDE or RCA resulted in significant differences in IL-4R mRNA levels between RAO-affected and control horses in F1, but not in F2. For IL-10 mRNA expression, a significant difference between RAO-affected and control horses in F1 but not in F2 was observed only following stimulation with HDE. In contrast to HDE, stimulation with CE resulted in a significant difference of IL-10 mRNA expression level between RAO-affected horses of F2 and healthy horses of F1. No significant differences were detected upon stimulation with any of the other challenge agents. These findings indicate that the immunological response, specifically IL-4R expression, in response to hay dust and cyathostomin antigens, differs between RAO-affected and healthy horses depending on their genetic background. This study shows that analysis of PBMC reveals systemic changes associated with RAO and helps to elucidate immunological pathways involved in this disease.

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study

One Hertz (1 Hz) repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for auditory verbal hallucinations (AVH). Theta burst protocols (TBS) show longer after-effects. This single-blind, randomized controlled study compared continuous TBS with 1Hz rTMS in a 10-day treatment. Patients were diagnosed with schizophrenia or schizoaffective disorder. TBS demonstrated equal clinical effects compared to 1Hz TMS.

Effects of amygdala-hippocampal stimulation on synchronization.

Changes in EEG synchronization, i.e., spatio-temporal correlation, with amygdala-hippocampal stimulation were studied in patients with temporal lobe epilepsy. Synchronization was evaluated for high frequency, 130Hz, pseudo-monophasic or biphasic charge-balanced pulses. Desynchronization was most frequently induced by stimulation. There was no correlation between the changes in synchronization and the changes in interictal epileptiform discharge rates. Changes in synchronization do not appear yet to be a marker of stimulation efficiency in reducing seizures.

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy

PURPOSE To study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. METHODS Eight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. RESULTS The distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. CONCLUSION Decrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Analysis of fractal electrodes for efficient neural stimulation

Planar electrodes are increasingly used in therapeutic neural stimulation techniques such as functional electrical stimulation, epidural spinal cord stimulation (ESCS), and cortical stimulation. Recently, optimized electrode geometries have been shown to increase the efficiency of neural stimulation by increasing the variation of current density on the electrode surface. In the present work, a new family of modified fractal electrode geometries is developed to enhance the efficiency of neural stimulation. It is shown that a promising approach in increasing the neural activation function is to increase the "edginess" of the electrode surface, a concept that is explained and quantified by fractal mathematics. Rigorous finite element simulations were performed to compute electric potential produced by proposed modified fractal geometries. The activation of 256 model axons positioned around the electrodes was then quantified, showing that modified fractal geometries required a 22% less input power while maintaining the same level of neural activation. Preliminary in vivo experiments investigating muscle evoked potentials due to median nerve stimulation showed encouraging results, supporting the feasibility of increasing neural stimulation efficiency using modified fractal geometries.

Validation of targeting the ventrointermediate thalamic nucleus using Q-ball calculation in deep brain stimulation for tremor

Objective: Identification of the ventrointermediate thalamic nucleus (Vim) in modern 3T high-field MRI for image-based targeting in deep brain stimulation (DBS) is still challenging. To evaluate the usefulness and reliability of analyzing the connectivity with the cerebellum using Q-ball-calculation we performed a retrospective analysis. Method: 5 patients who underwent bilateral implantation of electrodes in the Vim for treatment of Essential Tremor between 2011 and 2012 received additional preoperative Q-ball imaging. Targeting was performed according to atlas coordinates and standard MRI. Additionally we performed a retrospective identification of the Vim by analyzing the connectivity of the thalamus with the dentate nucleus. The exact position of the active stimulation contact in the postoperative CT was correlated with the Vim as it was identified by Q-ball calculation. Results: Localization of the Vim by analysis of the connectivity between thalamus and cerebellum was successful in all 5 patients on both sides. The average position of the active contacts was 14.6 mm (SD 1.24) lateral, 5.37 mm (SD 0.094 posterior and 2.21 mm (SD 0.69) cranial of MC. The cranial portion of the dentato-rubro-thalamic tract was localized an average of 3.38 mm (SD 1.57) lateral and 1.5 mm (SD 1.22) posterior of the active contact. Conclusions: Connectivity analysis by Q-ball calculation provided direct visualization of the Vim in all cases. Our preliminary results suggest, that the target determined by connectivity analysis is valid and could possibly be used in addition to or even instead of atlas based targeting. Larger prospective calculations are needed to determine the robustness of this method in providing refined information useful for neurosurgical treatment of tremor.