Information in pallidal neurons increases with parkinsonian severity

Abstract

Introduction The motor symptoms of Parkinson's disease (PD) present with pathological neuronal activity in the basal ganglia. Although neuronal firing rate changes in the globus pallidus internus (GPi) and externus (GPe) are reported to underlie the development of PD motor signs, firing rates change inconsistently, vary confoundingly with some therapies, and are poor indicators of symptom severity. Methods We explored the relationship between parkinsonian symptom severity and the effectiveness with which pallidal neurons transmit information. We quantify neuronal entropy and information – alternatives to firing rate and correlations respectively – in and between GPe and GPi neurons using a progressive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, non-human primate model of PD. Results Neuronal entropy and symptom severity were not linearly correlated: in both pallidal segments, entropy increased from naive to moderate parkinsonism, but decreased with further progression to the severely parkinsonian condition. In contrast, information transmitted from GPe to GPi increased consistently with symptom severity. Furthermore, antidromic information from GPi to GPe increased substantially with symptom severity. Together, these findings suggest that as parkinsonian severity increases, more and more information enters GPe and GPi from common sources, diminishing the relative importance of the orthodromic GPe to GPi connection. Conclusions With parkinsonian progression, the direct and indirect pathways lose their independence and start to convey redundant information. We hypothesize that a loss of parallel processing impairs the ability of the network to select and implement motor commands, thus promoting the hypokinetic symptoms of PD.

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

“…Although the increase in incidence of coherence occurred predominately in low frequency bands, even in the absence of a significant change within a given pallidal segment, there was a marked and significant increase in paired neurons coherent in the gamma range across segments. This cross-segment increase in coherence was a predominant feature in both low and high frequency bands and is consistent with our previous observations that information transmitted from GPe to GPi increases with symptom severity (Dorval et al , 2015). Taken together these findings suggest that in the parkinsonian state the direct and indirect pathways receive input from a common source and lose independence (Dorval et al, 2015; Mink, 1996).…”

“…This cross-segment increase in coherence was a predominant feature in both low and high frequency bands and is consistent with our previous observations that information transmitted from GPe to GPi increases with symptom severity (Dorval et al , 2015). Taken together these findings suggest that in the parkinsonian state the direct and indirect pathways receive input from a common source and lose independence (Dorval et al, 2015; Mink, 1996). This loss of functional segregation leads to a loss of specificity, altered temporal spatial processing of information flow within the pallidum, and disruption in information transmission throughout the BGTC network.…”

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

“…This regularity can be quantified via the firing pattern entropy, which is calculated from the inter-spike intervals of single unit recordings. In the rodent GP and substantia nigra pars reticulata (SNr), entropy increases with parkinsonism and decreases back to near healthy levels with effective DBS (Dorval et al, 2008 , 2015 ; Dorval and Grill, 2014 ; Anderson et al, 2015 ).…”

Changes in Neuronal Entropy in a Network Model of the Cortico-Basal Ganglia during Deep Brain Stimulation

“…These signals are commonly referred to as disease 'biomarkers'. Clinical and experimental studies have identified several potential biomarkers for PD, such as increased oscillatory activity in the beta frequency band (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) recorded from the cortico-basal ganglia circuit [1], betagamma band (60-200 Hz) phase-amplitude coupling in the primary motor cortex [2], and changes in neuronal entropy in the basal ganglia network [3]. Deep brain stimulation is an effective treatment for PD which has been shown to have measurable effects on these biomarkers.…”

“…Firing pattern entropy quantifies an upper bound on the information embedded in a spike train. Spike trains from globus pallidus (GP) neurons are shown to have increased firing pattern entropy during PD, with this being reduced to near healthy levels during effective DBS [3]- [6]. Sample entropy is a measure for assessing the complexity of physiological time series signals.…”