Pre-treatment anterior cingulate activity as a predictor of antidepressant response to repetitive transcranial magnetic stimulation (rTMS).

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which has received increasing attention as an antidepressant treatment. However available studies are characterized by a substantial variability in response. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Therefore we investigated whether either alterations of regional cerebral blood flow (rCBF) or clinical characteristics may predict antidepressant response to rTMS. DESIGN: 24 patients with major depression and stable medication received high frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex (DLPFC) for two weeks as add-on treatment. ECD-Single photon emission computed tomographay (SPECT) imaging was performed 1 to 2 days before rTMS. SETTING: Tertial referral center RESULTS: After two weeks of rTMS a mean reduction of 30% of the initial Hamilton Depression Rating Score (HAMD) was observed. Using a multivariate regression model with simultaneous evaluation of the relative impact of a-priori chosen potential factors influencing treatment outcome, two variables, the pretreatment anterior cingulate rCBF and the former response to antidepressant agents proved significant. High pretreatment anterior cingulate activity and low treatment resistance to pharmacologic therapy were positive predictors for treatment response to rTMS. CONCLUSIONS: Pretreatment anterior cingulate activity seems to be a useful prognostic marker of rTMS treatment response, which is in line with other treatment strategies, like sleep deprivation, electroconvulsive therapy or antidepressant medication.

Comparison perception of singular transcranial magnetic stimuli by subjectively electrosensitive subjects and general population controls.

Transcranial magnetic stimulation of the dorsolateral prefrontal cortex by single pulses of varying field intensities was used to measure thresholds of individual perception and motor response in three groups of subjects: subjectively electrosensitive people, general population controls with a high burden of complaints related to electromagnetic field (EMF) exposure in the literature (highest decile in complaint burden), and general population controls with a low burden of complaints (lowest decile in complaint burden). The major study endpoint was the ability of the subjects to differentiate between real magnetic stimulation and a sham condition. There were no significant differences between groups in the thresholds, neither of detecting the real magnetic stimulus nor in motor response. But the three groups differed significantly in differentiating between stimulation and sham condition, with the subjectively electrosensitive people having the lowest ability to differentiate and the control group with high level of EMF-related complaints having the best ability to differentiate. Differences between groups were mostly due to false alarm reactions in the sham condition reported by subjectively electrosensitives (SES). We found no objective correlate of the self perception of being "electrosensitive." Overall, our experiment does not support the hypothesis that subjectively electrosensitive patients suffer from a physiological hypersensitivity to EMFs or stimuli. Further research should focus on disposing factors explaining the unspecific sensory hyperresponsiveness of subjectively electrosensitive subjects.

Cortical excitability in neuroleptic-naive first-episode schizophrenic patients.

Transcranial magnetic stimulation (TMS) provides an intriguing in vivo method to investigate motor cortex excitability in men. This offers new insights into the neurophysiological basis of neuropsychiatric diseases. Earlier TMS studies in patients with schizophrenia revealed inconsistent results, probably due to major confounding variables like state of medication and stage of illness. To control for these effects, we studied two TMS paradigms in 21 drug-naive first-episode schizophrenic patients and 21 age- and sex-matched healthy controls. The patient group demonstrated a significant lower resting motor threshold as compared with healthy controls, whereas TMS paradigms of intracortical inhibition and intracortical facilitation failed to show significant differences between patients and controls. This pattern of TMS parameters is similar to that obtained in healthy volunteers investigated under increasing doses of ketamine, a central acting drug known to produce psychosis-like effects. In agreement with recent results of functional imaging, our neurophysiological findings suggest that drug-induced and naturally occurring psychosis may share a common pathway, which may base on dysfunctional glutamatergic mechanisms.

[Transcranial magnetic stimulation for nicotine dependence]. / Transkranielle Magnetstimulation bei Nikotinabhängigkeit.

70-80% of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120,000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30% after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebo-stimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

[Repetitiv Transcranial Magnetic Stimulation in Nicotine Dependence] / Transkranielle Magnetstimulation bei Nikotinabhängigkeit.

70 - 80 % of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120 000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30 % after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebostimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment.

Clinical, neurophysiological and neuroimaging data suggest that chronic tinnitus resembles neuropsychiatric syndromes characterised by focal brain activation. Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an efficient method in treating brain hyperexcitability disorders. In one patient suffering from chronic tinnitus, [18F]deoxyglucose PET revealed increased metabolic activity in a circumscript area of the left primary auditory cortex (PAC). The effect of MRI and PET guided neuronavigated 1 Hz rTMS of this area was evaluated in a single-blind, sham-controlled, cross-over manner, followed by a 4-week open treatment. Following active stimulation there was a remarkable effect, enduring several weeks, on tinnitus sensation, which was paralleled by altered cortical excitability. These findings suggest that neuronavigated rTMS of increased PAC activity might offer a new option for treating auditory phantom perceptions like chronic tinnitus.

Allelic variation in the serotonin transporter promoter affects neuromodulatory effects of a selective serotonin transporter reuptake inhibitor (SSRI).

RATIONALE: Antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) has been shown to depend on functional polymorphisms within the promoter region of the serotonin transporter gene (5-HTTLPR). This gene gives rise to a biallelic polymorphism designated long (l) and short (s). Homozygosity for the long variant (ll-genotype) is associated with a two times more efficient 5-HT uptake compared to the s/l- or s/s-genotype. Paired pulse transcranial magnetic stimulation is a feasible tool in detecting changes of motor cortex excitability induced by SSRIs. OBJECTIVE: Our study aimed to measure neuromodulatory effects of SSRIs on cortical excitability in healthy volunteers characterized by distinct genotypes of the 5-HTTLPR. METHODS: Cortical excitability was determined in eight genetically defined subjects pre- and post-ingestion of 60 mg citalopram. RESULTS: Subjects with the ll-genotype of the 5-HTTLPR showed a significant enhancement of a particular component of motor cortex excitability (intracortical inhibition) as compared to volunteers without the ll-genotype. CONCLUSION: Distinct neuromodulatory effects after intake of citalopram based on allelic variations of the 5-HTTLPR may explain variable response of patients treated with SSRIs.