Metabolic Alterations in Parkinson's Disease after Thalamotomy, as Revealed by 1H MR Spectroscopy

Objective: To determine, using proton magnetic resonance spectroscopy ( 1H MRS) whether thalamotomy in patients with Parkinson\u27s disease gives rise to significant changes in regional brain metabolism. Materials and Methods: Fifteen patients each underwent stereotactic thalamotomy for the control of medically refractory parkinsonian tremor. Single-voxel 1H MRS was performed on a 1.5T unit using a STEAM sequence (TR/TM/TE, 2000/14/20 msec), and spectra were obtained from substantia nigra, thalamus and putamen areas, with volumes of interest of 7-8ml, before and after thalamotomy. NAA/Cho, NAA/Cr and Cho/Cr metabolite ratios were calculated from relative peak area measurements, and any changes were recorded and assessed. Results: In the substantia nigra and thalamus, NAA/Cho ratios were generally low. In the substantia nigra of 80% of patients (12/15) who showed clinical improvement, decreased NAA/Cho ratios were observed in selected voxels after thalamic surgery (\u3c 0.05). In the thalamus of 67% of such patients (10/15), significant decreases were also noted (\u3c 0.05). Conclusion: Our results suggest that the NAA/Cho ratio may be a valuable criterion for the evaluation of Parkinson\u27s disease patients who show clinical improvement following surgery. By highlighting variations in this ratio, 1H MRS may help lead to a better understanding of the pathophysiologic processes occurring in those with Parkinson\u27s disease

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit