Physiological changes in the pallidum in a progressive model of Parkinson's disease: Are oscillations enough?

Abstract

Neurophysiological changes in the basal ganglia thalamo-cortical circuit associated with the development of parkinsonian motor signs remain poorly understood. Theoretical models have ranged from those emphasizing changes in mean discharge rate to increased oscillatory activity within the beta range. The present study characterized neuronal activity within and across the internal and external segments of the globus pallidus as a function of motor severity using a staged, progressively severe 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinsonism in three rhesus monkeys. An increase in coherence between neuronal pairs across the external and internal globus pallidus was present in multiple frequency bands in the parkinsonian state; both the peak frequency of oscillatory coherence and the variability were reduced in the parkinsonian state. The incidence of 8-20 Hz oscillatory activity in the internal globus pallidus increased with the progression of the disease when pooling the data across the three animals; however it did not correlate with motor severity when assessed individually and increased progressively in only one of three animals. No systematic relationship between mean discharge rates or the incidence or structure of bursting activity and motor severity was observed. These data suggest that exaggerated coupling across pallidal segments contribute to the development of the parkinsonian state by inducing an exaggerated level of synchrony and loss of focusing within the basal ganglia. These data further point to the lack of a defined relationship between rate changes, the mere presence of oscillatory activity in the beta range and bursting activity in the basal ganglia to the motor signs of Parkinson's disease.

Dynamical Role of Pivotal Brain Regions in Parkinson Symptomatology Uncovered with Deep Learning

“…During the first year, those are the Pallidum and the Subcallosal Area. The Parkinsonian state is indeed characterized by alterations in the temporal-spatial processing of information within the Pallidum [40]. For fourth year predictions, the Caudate Nucleus become significant, consistent with descriptions of its key involvement in motor responses [41][42][43][44][45][46].…”

Circuit Mechanisms of Parkinson’s Disease

“…Despite accumulating evidence for such activity changes, investigators are now trying to determine whether patterned activity actually causes different symptoms of PD. Many experiments are consistent with the idea that pattern is a key causal mechanism, but there are some data suggesting that these markers of patterned activity do not consistently correlate with motor impairments in both rodent and nonhuman primate models (Leblois et al, 2007;Muralidharan et al, 2016).…”

“…Though changes in these measures have been reported across many nuclei in the basal ganglia circuit, their functional contribution to PD symptoms remains unclear. At the level of basal ganglia output, several groups have found altered bursting activity in GPi neurons in human PD patients (Hutchison et al, 1994;Starr et al, 2005), as well as parkinsonian nonhuman primates (Miller and DeLong, 1988;Boraud et al, 1998;Muralidharan et al, 2016). Bursting has also been observed in the GPe and STN of both PD patients and parkinsonian nonhuman primates (Bergman et al, 1994;Soares et al, 2004).…”

Understanding Parkinson’s disease and deep brain stimulation: Role of monkey models

“…Supported by monkey studies, PD is increasingly recognized as a network disorder involving changes in synchronized oscillatory activity and coupling within and between cortical and subcortical brain areas. Enhanced synchronization between pallidal segments has been demonstrated in the MPTP monkey model of PD as well as changes in synchronized oscillatory activity within and across nodal points in the BGTC circuit (84)(85)(86)(87)(88)(89). Unique to these monkey studies, and unfeasible in humans, is the ability to examine neuronal changes within the same subject in normal and diseased states while varying the pattern of stimulation as well as the target site.…”