S-07-01

The role of genetic factors in modulating neuroplastic processes

F. Thome. School of Medicine, Dept, of Psychiatry, University of Wales, Swansea, United Kingdom

Objective: Neural plasticity represents an important factor which is most likely involved in the pathogenesis and therapy of several psychiatric disorders. The modulation of neuroplastic processes depends on a plethora of genes and their regulation via signalling cascades and transcription factors. Some gene families such as neurotrophic factors and synaptic vesicle proteins have been identified as key players in neural and synaptic plasticity. However, there is increasing evidence that neuroplastic processes result from the interaction of such genetic factors with environmental and behavioural factors.

S-07-02

Detection of neural plasticity offered by positron emission tomography (PET)

J. Horacek, T. Novak, M. Kopecek, F. Spaniel, C. Dockery, C. Hoschl. Prague Psychiatrc Center, Praha, Czech Republic

Objective: The neuroplastic changes are supposed to be the underlying mechanism for the long lasting clinical effect of the modem neuropsychiatric treatment modalities as psychotropics, psychotherapy or repetitive transcranial magnetic stimulation (rTMS). The use of 18FDG PET in the resting state reflects the regional glutamate turnover at the synaptic level and is the probe for relative synaptic strength and consequent functional and metabolic activity of the brain regions.

Methods: rTMS (0.9Hz, 100% of motor threshold, 20 min.) applied to the left temporo-parietal cortex was used for ten days in © 2005 Elsevier SAS. All rights reserved. treatment of medication-resistant auditory hallucinations in schizophrenia (N=ll). We detected the changes in 18fluoro- deoxyglucose (18FDG) uptake (PET) followed the low frequency rTMS (SPM99).

Results: We found a significant improvement in the total and positive symptoms (PANSS) and in hallucinations (HCS, AHRS). The rTMS decreased the brain metabolism (18FDG PET) in the left superior temporal gyrus and effected increases in the contralateral temporal cortex and in the frontal lobes bilaterally.

Conclusion: Our findings confirm the effect of rTMS in this indication and the neuroplastic changes in the cortex underlying the rTMS site (inhibition). The facilitation of metabolism is likely compensatory to the rTMS induced suppression in the left temporal cortex and would be mediated by interhemispheric transcallosal connections (to the right temporal cortex) and by intrahemispheric long superior fascicule (to the frontal lobe). This research was supported by the grant NF/7578 - 3 form MZCR and the project CNS 1M0002375201 MSMT CR.

S-07-03

Investigating subtle region-specific changes in grey and white matter by using voxel-based morphometry (VBM)

G. Hajak, P. Eichhammer, B. Langguth. University of Regensburg, Regensburg, Germany

Voxel-based morphometry is a sophisticated objective whole-brain technique to investigate subtle, region specific changes in gray and white matter. This method bases on high-resolution, threedimensional magnetic-resonance imaging, registered in a common stereotactic space and is designed to find significant regional differences by applying voxel-wise statistics in the context of Gaussian random fields. Using this approach a variety of changes in grey matter could be detected in schizophrenic patients as well as in patients with affective disorder. These results point to the fact that neuropsychiatric diseases can be interpreted as a result of maladaptive neuroplasticity. These findings are supported by our own studies, demonstrating that patients with chronic tinnitus show alterations in grey matter, restricted to specific areas involved in auditory processing. Taken together, voxel-based morphometry seems to be an ideal imaging technique to detect neuroplastic processes associated with neuropsychiatric diseases. New insights into the neurobiology of these disorders may also help to develop new treatment strategies

S-07-04

The contribution of modem neurophysiologic methods to our understanding of cortical neuroplasticity

P. Eichhammer, B. Langguth, G. Hajak. University of Regensburg Dep. of Psychiatry, Regensburg, Germany

In the last decade, transcranial magnetic stimulation (TMS) has been used increasingly as a tool to explore the mechanisms and consequences of cortical plasticity in the human cortex. Depending on the stimulation frequency, TMS can induce neurobiological effects resembling those used in animal studies of neuroplasticity in which electrical stimulation was used. In rodent auditory cortex, known for learning-induced plasticity, rTMS from 1 to 10 Hz resulted in long-term potentiation (LTP)-like and more durable long-term depression (LTD)-like changes in evoked spike rate (Wang et al., 1996). In support of this study, low-frequency 1-Hz rTMS, targeting the left temporoparietal cortex, causes a remarkable and sustained reduction of auditory hallucinations in schizophrenia, which is interpreted as the result of TMS-induced lasting changes in synaptic efficacy. Based on these results, we studied whether structural neuroplasticity is involved in mediating clinical effects of low-frequency rTMS in a group of healthy volunteers by means of voxel-based morphometry, a magnetic- resonance imaging technique, which is able to detect subtle changes in cortical grey and white matter. Our results point to the fact that TMS may be able to induce regenerative neuroplastic processes in specific brain areas depending on the site of TMS stimulation. These findings are in line with current studies investigating the neurobiological effects of central acting agents like antidepressants and underscore that the induction of neuroplastic processes may be essential for a variety of different treatment strategies.