Efficacy of low and high frequency Deep Brain Stimulation in epilepsy

Purpose: Deep brain stimulation using a neurocybernetic device and intracranially implanted electrodes is currently being investigated as a treatment for refractory epilepsy. Several brain structures such as the cerebellum and the thalamus have been targeted. At Ghent University Hospital a pilot trial in patients using hippocampal DBS has shown a significant reduction in seizure frequency in patients with temporal lobe epilepsy. The current stimulation parameters that are being used are not evidence based. Further improvement of clinical efficacy may result from research towards the identificition of optimal stimulation parameters in specific seizure types. This study investigated the efficacy of hippocampal DBS using two different stimulation frequencies in a validated animal model for temporal lobe epilepsy. Methods: Twenty rats were transformed into epileptic rats using the alternate day rapid kindling model, that makes use of electrical stimuli in the amygdala. When fully kindled, these rats have a seizure each time an electrical stimulus is administered in the hippocampus. For therapeutic hippocampal stimulation rats were devided into a 130 Hz (HFS) group and a 5 Hz (LFS) stimulation group. Rats received 10 days of therapeutic hippocampal DBS. During and after termination of therapeutic DBS, seizures were evoked in all rats using the amygdalar electrical stimulation. Typical seizure characteristics such as afterdischarge (AD) threshold, latency and duration were compared between both treatment groups. Results: During HFS, AD threshold and AD latency showed a significantly larger increase (P<0.05 and p<0.005 respectively) compared to the rats that received LFS (p=0.48 and p<0.05 respectively).In the HFS group the AD duration was shorter (p<0.05) compared to baseline. This was not observed in the LFS group. After termination of DBS, effects faded out slowly. Discussion and Conclusion: Both HFS and LFS of the hippocampus in epileptic rats resulted in reduced excitability that is typical for epileptic seizures. When HFS and LFS were compared, HFS was more efficacious the n LFS as reflected in a higher AD threshold and AD latency and a shorter AD duration during treatment. This study is the first to show clear evidence in favour of HFS of the hippocampus to treat seizures

Rat brain normalization templates for robust regional analysis of [<tex>^{11}C$</tex>]ABP688 positron emission tomography/computed tomography

A methodology to generate rat brain templates for spatial normalization of positron emission tomographic (PET)/computed tomographic (CT) images is described and applied to generate three different templates for imaging of [ 11 C]ABP688, a PET ligand binding to the metabotropic glutamate 5 receptor. The templates are based on functional (PET), structural (CT), and combined PET and CT information, respectively. The templates are created from a test–retest study under normal conditions and are used to assess the different templates by using them in the analysis pipeline of a test–retest and a blocking experiment. The resulting average nondisplaceable binding potentials (BP ND ) show significant (analysis of variance, p < .05) and substantial (up to 23%) differences between the different approaches in several brain regions. The highest BP ND values in receptor-rich regions are obtained using the PET-based approach. This approach also had the smallest variability in all tested regions (standard error of measurement of 9% versus 14% [PET/CT] and 20% [CT]). All approaches showed similar relative changes in BP ND values with increased blocking. Taken together, these results suggest that the use of the tracer-specific PET-based template outperforms the other approaches with the performance of the combined PET/CT template between those of the PET and the tracer-independent CT template

Rat Brain Normalization Templates for Robust Regional Analysis of [11C]ABP688 Positron Emission Tomography/Computed Tomography

A methodology to generate rat brain templates for spatial normalization of positron emission tomographic (PET)/computed tomographic (CT) images is described and applied to generate three different templates for imaging of [11C]ABP688, a PET ligand binding to the metabotropic glutamate 5 receptor. The templates are based on functional (PET), structural (CT), and combined PET and CT information, respectively. The templates are created from a test–retest study under normal conditions and are used to assess the different templates by using them in the analysis pipeline of a test–retest and a blocking experiment. The resulting average nondisplaceable binding potentials (BPND) show significant (analysis of variance, p < .05) and substantial (up to 23%) differences between the different approaches in several brain regions. The highest BPND values in receptor-rich regions are obtained using the PET-based approach. This approach also had the smallest variability in all tested regions (standard error of measurement of 9% versus 14% [PET/CT] and 20% [CT]). All approaches showed similar relative changes in BPND values with increased blocking. Taken together, these results suggest that the use of the tracer-specific PET-based template outperforms the other approaches with the performance of the combined PET/CT template between those of the PET and the tracer-independent CT template