The neurophysiological correlates of motor tics following focal striatal disinhibition

Abstract

The cortico-basal ganglia pathway is involved in normal motor control and implicated in multiple movement disorders. Brief repetitive muscle contractions known as motor tics are a common symptom in several basal ganglia related motor disorders. We used focal micro-injections of the GABA-A antagonist bicuculline to the sensorimotor putamen of behaving primates to induce stereotyped tics similar to those observed in human disorders. This focal disruption of GABA transmission in the putamen led to motor tics confined to a single or a few muscles. The temporal and structural properties of the tics were identified using electromyogram and frame-by-frame analysis of multi-camera video recordings. During experimental sessions the tics would wax and wane, but their size and shape remained highly stereotyped within the session. Neuronal spiking activity and local field potentials were recorded simultaneously from multiple locations along the cortico-basal ganglia pathway: motor cortex, putamen and globus pallidus external and internal segments. The local field potentials displayed stereotyped tic-related voltage transients lasting several hundred milliseconds. These 'local field potential spikes', which appeared throughout the cortico-basal ganglia pathway, were consistently observed in close temporal association to the motor tics. During tic expression, neuronal activity was altered in most of the recorded neurons in a temporally focal manner, displaying phasic firing rate modulations time locked to the tics. Consistent with theoretical models of tic generation, transient inhibition of the basal ganglia output nucleus prior to and during tic expression was observed. The phasic reduction of basal ganglia output was correlated with a disinhibition of cortical activity, manifesting as short bursts of activity in motor cortex. The results demonstrate that the basal ganglia provide a finely timed disinhibition in the output nuclei of the basal ganglia. However, a large fraction of the neurons were simultaneously inhibited during tics, although tics were only manifested in a small confined muscle group. This suggests that rather than representing a specific action within the basal ganglia itself, these nuclei provide a temporally exact but spatially distributed release signal. The tics induced by striatal disinhibition bear a striking resemblance to motor tics recognized in human pathologies associated with basal ganglia dysfunction. The neuronal changes observed during tic formation may provide valuable insights into the underlying mechanism of tic disorders, as well as into basic information processing in the cortico-basal ganglia loop.

Deep brain stimulation: from neurology to psychiatry?

“…The general rationale for modulating (or ablating) these areas is based on the assumption that tics and abnormal behaviour are associated with dysfunction of corticostriatal-thalamocortical circuitry involving frontal associative and limbic areas of the basal ganglia and thalamus (Table 2). Focal disruption of different functional striatal territories results in abnormal activation of neocortical motor and non-motor areas, producing repeated stereotypical movements and elaborated stereotypical behaviour, which supports the notion that both tics and OCD in GTS are related to BG-thalamocortical loop dysfunction [83][84][85][86][87]. Anecdotal improvements in GTS patients treated with DBS have been reported, but controlled studies currently include only very small numbers of patients [88,89].…”

Spatial and Temporal Properties of Tic-Related Neuronal Activity in the Cortico-Basal Ganglia Loop

“…Specifically, structural and functional imaging studies have found abnormalities in the striatum (Singer and Minzer, 2003), which is the main input structure of the basal ganglia (BG). The direct involvement of the striatum in tics is further supported by findings that disruption of striatal information transmission by localized application of a GABA A antagonist induces motor tics (Tarsy et al, 1978;Crossman et al, 1988;McCairn et al, 2009;Worbe et al, 2009).…”

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

“…In two cynomolgus monkeys, focal disinhibition of the sensorimotor putamen, using the GABA A antagonist bicuculline, produced repetitive motor tics predominantly in the orofacial region (McCairn et al, 2009). Local field potential spikes, which correlated with tics, were identified throughout the cortico-basal ganglia pathway.…”