Correlated activity in globus pallidus and thalamus during voluntary reaching movement in three children with primary dystonia

Abstract

Classical models of the physiology of dystonia suggest that involuntary muscle contractions are caused by inappropriately low activity in Globus Pallidus internus (GPi) that fails to adequately inhibit thalamic inputs to cortex. We test this prediction in three children with primary dystonia undergoing depth electrode recording in basal ganglia and thalamus during selection of targets for deep brain stimulation (DBS) implantation. We compare muscle activity to the power in the spectrogram of the local field potential, as well as to counts of identified spikes in GPi, subthalamic nucleus (STN), and the Ventral oralis (VoaVop) and Ventral Anterior (VA) subnuclei of the thalamus, while subjects are at rest or attempting to make active voluntary arm or leg reaching movements. In all three subjects, both spectrogram power and spike activity in GPi, STN, VoaVop, and VA are significantly positively correlated with movement. In particular, GPi and STN both increase activity during attempted movement. These results contradict the classical rate model of the physiology of dystonia, and support more recent models that propose abnormalities in the detailed pattern of activity rather than the overall lumped activity of pallidum and thalamus.

Globus pallidus internus activity increases during voluntary movement in children with dystonia

“…They were then asked to perform the task with either of their upper limb while contralateral depth electrode signals were recorded. 57 In all cases, dystonia was present in the tested limb, as evidenced by the presence of dystonic postures interfering with expected performance of the task. The reaching task consisted of 108 s of voluntary reaching followed by 30 seconds of resting period, for a total of four consecutive trials ( Figure S2 , Video S1 ).…”

Deep brain stimulation in globus pallidus internus travels to thalamus and subthalamic nuclei along physiological pathways

“…When the resulting signals are added, the opposite artifact polarities cancel out while the evoked response polarity is augmented. The experimental protocol, movement-LFP synchronization, and the stimualtion protocol are detailed in our previously published works, Kasiri et al [4], Hernandez-Martin et al [20], and Vidmark, Hernandez-Martin, and Sanger [16]. In order to primarily evaluate responses to monosynaptic transmission, we used recordings from GPi, VO, VA, and STN, as illustrated in Figure 1.…”

“…Dystonia is a movement disorder characterized by involuntary movements and repetitive muscle contractions, resulting in abnormal posture and motion [1]. In cases that medication and other medical interventions do not improve the dystonic symptoms, deep brain stimulation (DBS) is an alternative proven to be effective in the treatment of various neurological and movement disorders such as dystonia [1][2][3][4], and Parkinson's disease [5]. DBS is a neuromodulation method that involves implantation of depth electrodes at potential DBS targets, through which electrical pulses are transmitted to modulate neuronal activity [6], potentially by interrupting or distorting intrinsic abnormal activity.…”

Improvement of speed-accuracy tradeoff during practice of a point to point task in children with secondary dystonia

“…We test this in both healthy children and in children with secondary dystonia 10,11 . Dystonia is a disorder characterized by increased variability of movement and increased signal-dependent noise 5,6,[10][11][12] . Children with dystonia are aware of their increased noise and compensate appropriately in a ballistic target task [3][4][5][6]13 .…”