M. Klirova

Effect of Low-Frequency rTMS on Electromagnetic Tomography (LORETA) and Regional Brain Metabolism (PET) in Schizophrenia Patients with Auditory Hallucinations

Background: Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (≤1Hz) repetitive transcranial magnetic stimulation (rTMS) diminishes treatment-resistant auditory hallucinations. A neuroimaging study elucidating the effect of rTMS in auditory hallucinations has yet to be published. Objective: To evaluate the distribution of neuronal electrical activity and the brain metabolism changes after low-frequency rTMS in patients with auditory hallucinations. Methods: Low-frequency rTMS (0.9 Hz, 100% of motor threshold, 20 min) applied to the left temporoparietal cortex was used for 10 days in the treatment of medication-resistant auditory hallucinations in schizophrenia (n = 12). The effect of rTMS on the low-resolution brain electromagnetic tomography (LORETA) and brain metabolism (18FDG PET) was measured before and after 2 weeks of treatment. Results: We found a significant improvement in the total and positive symptoms (PANSS), and on the hallucination scales (HCS, AHRS). The rTMS decreased the brain metabolism in the left superior temporal gyrus and in interconnected regions, and effected increases in the contralateral cortex and in the frontal lobes. We detected a decrease in current densities (LORETA) for the beta-1 and beta-3 bands in the left temporal lobe whereas an increase was found for beta-2 band contralaterally. Conclusion: Our findings implicate that the effect is connected with decreased metabolism in the cortex underlying the rTMS site, while facilitation of metabolism is propagated by transcallosal and intrahemispheric connections. The LORETA indicates that the neuroplastic changes affect the functional laterality and provide the substrate for a metabolic effect.

Individualized rTMS neuronavigated according to regional brain metabolism ( 18 FGD PET) has better treatment effects on auditory hallucinations than standard positioning of rTMS: a double-blind, sham-controlled study

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of the left temporo-parietal cortex (LTPC) has been proposed as a useful therapeutic method for auditory hallucinations (AHs). Stereotactic neuronavigation enables the magnetic coil to be targeted according to the individual parameters obtained from neuroimaging. Individualized rTMS neuronavigated according to 18-fluorodeoxyglucose positron emission tomography (18FDG PET) allows us to focus the coil explicitly on a given area with detected maxima of specific abnormalities, thus presuming a higher therapeutic effect of the method. The objective of this study is to test clinical efficacy of neuronavigated LF-rTMS administered according to the local maxima of 18FDG PET uptake of LTPC and to compare it with treatment effects of standard and sham rTMS. In a double-blind, sham-controlled design, patients with AHs underwent a 10-day series of LF-rTMS using (1) 18FDG PET-guided “neuronavigation,” (2) “standard” anatomically guided positioning, and (3) sham coil. The effect of different rTMS conditions was assessed by the Auditory Hallucinations Rating Scale (AHRS) and the Positive and Negative Syndrome Scale (PANSS). Fifteen patients were randomized to a treatment sequence and ten of them completed all three treatment conditions. The intention-to-treat analysis of AHRS score change revealed superiority of the 18FDG PET-guided rTMS over both the standard and the sham rTMS. The analyses of the PANSS scores failed to detect significant difference among the treatments. Our data showed acute efficacy of 18FDG PET-guided rTMS in the treatment of AHs. Neuronavigated rTMS was found to be more effective than standard, anatomically guided rTMS.

Genetic variation in FOXP2 alters grey matter concentrations in schizophrenia patients

FOXP2, the first gene known to be involved in the development of speech and language, can be considered to be, a priori, a candidate gene in schizophrenia, given the mounting evidence that the underlying core deficit in this disease could be a failure of structures relevant to normal language processing. To investigate the potential link between grey matter concentration (GMC) changes in patients with schizophrenia and the FOXP2 rs2396753 polymorphism previously reported to be associated with hallucinations in schizophrenia, we analysed high-resolution anatomical magnetic resonance images of 40 genotyped patients with schizophrenia and 36 healthy controls, using optimised voxel-based morphometry (VBM). Here we show that the common SNP rs2396753 (C>A) gene variant of the FOXP2 gene has significant effects on GMC in patients with schizophrenia, within regions of the brain known to be affected by this disease. Our data suggest that GMC reductions in schizophrenia may be driven by C allele carriers of the FOXP2 gene variant.

AS21-03 - Effect of low-frequency rtms on electromagnetic tomography (LORETA) and regional brain metabolism (PET) in schizophrenia patients with auditory hallucinations

BACKGROUND Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (<or=1 Hz) repetitive transcranial magnetic stimulation (rTMS) diminishes treatment-resistant auditory hallucinations. A neuroimaging study elucidating the effect of rTMS in auditory hallucinations has yet to be published. OBJECTIVE To evaluate the distribution of neuronal electrical activity and the brain metabolism changes after low-frequency rTMS in patients with auditory hallucinations. METHODS Low-frequency rTMS (0.9 Hz, 100% of motor threshold, 20 min) applied to the left temporoparietal cortex was used for 10 days in the treatment of medication-resistant auditory hallucinations in schizophrenia (n = 12). The effect of rTMS on the low-resolution brain electromagnetic tomography (LORETA) and brain metabolism ((18)FDG PET) was measured before and after 2 weeks of treatment. RESULTS We found a significant improvement in the total and positive symptoms (PANSS), and on the hallucination scales (HCS, AHRS). The rTMS decreased the brain metabolism in the left superior temporal gyrus and in interconnected regions, and effected increases in the contralateral cortex and in the frontal lobes. We detected a decrease in current densities (LORETA) for the beta-1 and beta-3 bands in the left temporal lobe whereas an increase was found for beta-2 band contralaterally. CONCLUSION Our findings implicate that the effect is connected with decreased metabolism in the cortex underlying the rTMS site, while facilitation of metabolism is propagated by transcallosal and intrahemispheric connections. The LORETA indicates that the neuroplastic changes affect the functional laterality and provide the substrate for a metabolic effect.

P02-549 - Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Medication-Resistant Neuropatic Pain

Introduction Transcranial magnetic stimulation (TMS) is a non-invasive method that induces functional changes in a relatively small area of the cerebral cortex. It is supposed that the effect of the method in therapy of neuropatic pain is based on the induction of spinothalamic tract inhibiton, which leads to the symptom withdrawal. Aim To prove the clinical and electrophysiological effect of rTMS in the therapy of chronic neuropatic pain. Methods 29 patients with medication-resistant neuropatic pain were examined by Visual analog scale (VAS), McGill Pain Questionnaire (MPQ) and QST(Quantitative sensory Testing, consisted of von Frey and thermic treshold examination),then treated by high frequency rTMS in the study using double-blind randomized sham-controlled parallel design. rTMS parameters: 5 rTMS sessions (2 weeks treatment), where each session consisted of three 10 Hz rTMS series using: 1) 85%MT (motor treshold), 2) 90%MT and 3) 95%MT. Each rTMS serie consisted of 20 pulses in 12 trains. Location of the active coil was administered over the contralateral motor cortex, directed specifically to facial area of homunculus (according to funcional location). Sham coil was angled 90° degrees away from the skull. Results Confirmation of a significant decrease of VAS item in active group, trend to improvement in tactile sensation of severed patient faces. The changes of thermic treshold were not found. Sham rTMS did not show any trend for improvement. Conclusion Although no general recommendations can be drawn based on our result, our study is another one that suggest rTMS should be considered as an effective and safe treatment option for chronic neuropatic pain.

P02-83 Clinical response of neuronavigated rTMS in the treatment of auditory hallucinations

Aim To prove the clinical effect rTMS neuronavigation vs. standard coil positioning vs. controlls in the therapy of madication-resistant auditory hallucinations. Materials and methods 10 patients with medication-resistant auditory hallucinations on stabile antipsychotic medication, examined by MRI, PET, then treated by 1) neuronavigated, 2) standard positioning and 3) sham rTMS (controlls). Double-blind randomized sham-controlled parallel design was used in the study. rTMS parameters: 0.9Hz, 100%MT, 1080 pulses/session, 10 rTMS sessions within 2 weeks: 1. Neuronavigated rTMS: coil focused over the highest contrast of metabolic activity in the left temporo-parietal (T-P) area (according to the SPM analyse 18FDG PET data). 2. Standard rTMS: coil administered over the left T-P region defined as the midway between the T3 and P3 sites according to the international 10/20 EEG electrode system. 3. Sham: coil angled 90° away from the skullPsychometric measurement: PANSS, Hallucination Change Scale (HCS) and the Auditory Hallucination rating scale (AHRS). Results and conclusion Confirmation of a significant decrease in the Hallucination item as well as in the total of the positive score of PANSS, HCS and AHRS. Sham rTMS did not show a trend for improvement over time. Between-group comparisons of AHRS scores revealed significant differences, which confirmed efficiency of using neuronavigated rTMS. Compared to standard positioning in future studies, we believe to find rTMS neuronavigation more precise and effective. Studies monitoring a continuing effect of rTMS over long time periods are needed. Supported by the CNS, MZC;R MZ0PCP2005 and MSMT 1M0517, VZ 00 216 208 16.