Neuronal firing patterns outweigh circuitry oscillations in parkinsonian motor control

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Abstract

<p class="first" id="d10665978e266">Neuronal oscillations at beta frequencies (20–50 Hz) in the cortico-basal ganglia circuits have long been the leading theory for bradykinesia, the slow movements that are cardinal symptoms in Parkinson’s disease (PD). The beta oscillation theory helped to drive a frequency-based design in the development of deep brain stimulation therapy for PD. However, in contrast to this theory, here we have found that bradykinesia can be completely dissociated from beta oscillations in rodent models. Instead, we observed that bradykinesia is causatively regulated by the burst-firing pattern of the subthalamic nucleus (STN) in a feed-forward, or efferent-only, mechanism. Furthermore, STN burst-firing and beta oscillations are two independent mechanisms that are regulated by different NMDA receptors in STN. Our results shift the understanding of bradykinesia pathophysiology from an interactive oscillatory theory toward a feed-forward mechanism that is coded by firing patterns. This distinct mechanism may improve understanding of the fundamental concepts of motor control and enable more selective targeting of bradykinesia-specific mechanisms to improve PD therapy. </p>

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Boosting Cortical Activity at Beta-Band Frequencies Slows Movement in Humans

Alek Pogosyan, Louise Doyle Gaynor, Alexandre Eusebio … (2009)

Summary Neurons have a striking tendency to engage in oscillatory activities. One important type of oscillatory activity prevalent in the motor system occurs in the beta frequency band, at about 20 Hz. It is manifest during the maintenance of tonic contractions and is suppressed prior to and during voluntary movement [1–7]. This and other correlative evidence suggests that beta activity might promote tonic contraction, while impairing motor processing related to new movements [3, 8, 9]. Hence, bursts of beta activity in the cortex are associated with a strengthening of the motor effects of sensory feedback during tonic contraction and with reductions in the velocity of voluntary movements [9–11]. Moreover, beta activity is increased when movement has to be resisted or voluntarily suppressed [7, 12, 13]. Here we use imperceptible transcranial alternating-current stimulation to entrain cortical activity at 20 Hz in healthy subjects and show that this slows voluntary movement. The present findings are the first direct evidence of causality between any physiological oscillatory brain activity and concurrent motor behavior in the healthy human and help explain how the exaggerated beta activity found in Parkinson's disease can lead to motor slowing in this illness [14].

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Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.

Matthieu Bastide, Wassilios G Meissner, Barbara Picconi … (2015)

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.

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Baseline brain activity fluctuations predict somatosensory perception in humans.

Mary Phillips, G Moonen, M Boly … (2007)

In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium-yttrium/aluminum-garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity somatosensory stimuli and immediately preceding levels of baseline activity in medial thalamus and the lateral frontoparietal network, respectively, which are thought to relate to vigilance and "external monitoring." Conversely, there was a negative correlation between subsequent reporting of conscious perception and baseline activity in a set of regions encompassing posterior cingulate/precuneus and temporoparietal cortices, possibly relating to introspection and self-oriented processes. At nociceptive levels of stimulation, pain-intensity ratings positively correlated with baseline fluctuations in anterior cingulate cortex in an area known to be involved in the affective dimension of pain. These results suggest that baseline brain-activity fluctuations may profoundly modify our conscious perception of the external world.