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Perception of our linear motion - heading - is critical for postural control, gait, and locomotion, and it is impaired in Parkinson's disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30° to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts' involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases, there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Perception of our linear motion, heading, relies on convergence from multiple sensory systems utilizing visual and vestibular signals. Multisensory convergence takes place in the visuo-vestibular areas of the cerebral cortex and posterior cerebellar vermis. Latter closely connected with the inferior olive may malfunction in disorders of olivo-cerebellar hypersynchrony, such as the syndrome of oculopalatal tremor (OPT). We had recently shown an impairment in vestibular heading perception in the subjects with OPT. Here we asked whether the hypersynchrony in the inferior-olive cerebellar circuit also affects the visual perception of heading, and the impairment is coupled with the deficits in vestibular heading perception. Three subjects with OPT and 11 healthy controls performed a two-alternative forced-choice task in two separate experiments; one when they were moved en bloc in a straight-ahead forward direction or at multiple heading angles to the right or the left; and second when under virtual reality goggle they experienced the movement of star cloud leading to the percept of heading straight, left or to the right at the heading angles similar to those utilized in the vestibular task. The resultant psychometric function curves, derived from the two-alternative-forced-choice task, revealed abnormal threshold to perceive heading direction, abnormal sensitivity to the change in heading direction compared to straight ahead, and a bias towards one side. Although the impairment was present in both visual and vestibular heading perception, the deficits were not coupled., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Multisensory integration is critical for resolving ambiguities in isolated sensory systems assuring accurate perception of one's own linear motion, i.e., heading. The vestibular signal, a critical source of information for heading perception, is transformed in appropriate coordinates suitable for multisensory integration-such transformation takes place under cerebellar supervision. Deficiency in cerebellar function due to Purkinje cell loss results in inaccurate multisensory integration and impaired heading perception. Here, we predict that a classic movement disorder, the syndrome of oculopalatal tremor (OPT), also presents with inaccurate heading direction perception. The characteristic feature of oculopalatal tremor is pseudohypertrophic inferior olive that constantly sends spontaneous, hypersynchronous, abnormal, and meaningless signals to the cerebellum. Such malicious olive signal can impair heading perception. We examined vestibular heading perception in 6 individuals with OPT and 9 age-matched healthy controls (HC). We used a two-alternative forced choice task performed during passive en bloc translation. Compared with age-matched HC, OPT group had significantly higher heading direction perception threshold indicating a less sensitive vestibular system to variations in heading direction. Using computational simulations, we show that the addition of the abnormal noise into the cerebellar system results in decreased spatiotemporal tuning behavior of the cerebellar output. Such impairment in spatiotemporal tuning causes reduced ability to perceive heading direction. Hyperactivity in the inferior-olive cerebellar pathway impairs the heading direction perception. We suggest that this impairment stems from abnormal noise into the cerebellum due to hypersynchronized inferior olive., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

The relationship between two common movement disorders, dystonia and tremor, is controversial. Both deficits have correlates in the network that includes connections between the cerebellum and the basal ganglia. In order to assess the physiological relationship between tremor and dystonia, we measured the activity of 727 pallidal single-neurons during deep brain stimulation surgery in patients with cervical dystonia without head oscillations, cervical dystonia plus jerky oscillations, and cervical dystonia with sinusoidal oscillations. Cluster analyses of spike-train recordings allowed classification of the pallidal activity into burst, pause, and tonic. Burst neurons were more common, and number of spikes within spike and inter-burst intervals was shorter in pure dystonia and jerky oscillation groups compared to the sinusoidal oscillation group. Pause neurons were more common and irregular in pure tremor group compared to pure dystonia and jerky oscillation groups. There was bihemispheric asymmetry in spontaneous firing discharge in pure dystonia and jerky oscillation groups, but not in sinusoidal oscillation group. These results demonstrate that the physiology of pallidal neurons in patients with pure cervical dystonia is similar to those who have cervical dystonia combined with jerky oscillations, but different from those who have cervical dystonia combined with sinusoidal oscillations. These results imply distinct mechanistic underpinnings for different types of head oscillations in cervical dystonia.