Neural code alterations and abnormal time patterns in Parkinson's disease.

OBJECTIVE: The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson's disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. APPROACH: We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. MAIN RESULTS: At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson's disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. SIGNIFICANCE: We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson's disease.

Neuronal Entropy Depends on the Level of Alertness in the Parkinsonian Globus Pallidus in vivo.

A new working hypothesis of Parkinson's disease (PD) proposes to focus on the central role of entropy increase in the basal ganglia (BG) in movement disorders. The conditions necessary for entropy increase in vivo are, however, still not fully described. We recorded the activity of single globus pallidus pars interna neurons during the transition from deep anesthesia to full alertness in relaxed, head-restrained, control, and parkinsonian (6-hydroxydopamine-lesioned group-lesioned) rats. We found that during awakening from anesthesia, the variation of neuronal entropy was significantly higher in the parkinsonian than in the control group. This implies in our view that in PD the entropy of the output neurons of the BG varies dynamically with the input to the network, which is determined by the level of alertness. Therefore, entropy needs to be interpreted as a dynamic, emergent property that characterizes the global state of the BG neuronal network, rather than a static property of parkinsonian neurons themselves. Within the framework of the "entropy hypothesis," this implies the presence of a pathological feedback loop in the parkinsonian BG, where increasing the network input results in a further increase of neuronal entropy and a worsening of akinesia.

Finite dimensional structure of the GPI discharge in patients with Parkinson's disease.

Stochastic systems are infinitely dimensional and deterministic systems are low dimensional, while real systems lie somewhere between these two limit cases. If the calculation of a low (finite) dimension is in fact possible, one could conclude that the system under study is not purely random. In the present work we calculate the maximal Lyapunov exponent from interspike intervals time series recorded from the internal segment of the Globus Pallidusfrom patients with Parkinson's disease. We show the convergence of the maximal Lyapunov exponent at a dimension equal to 7 or 8, which is therefore our estimation of the embedding dimension for the system. For dimensions below 7 the observed behavior is what would be expected from a stochastic system or a complex system projecting onto lower dimensional spaces. The maximal Lyapunov exponent did not show any differences between tremor and akineto-rigid forms of the disease. However, it did decay with the value of motor Unified Parkinson's Disease Rating Scale -OFF scores. Patients with a more severe disease (higher UPDRS-OFF score) showed a lower value of the maximal Lyapunov exponent. Taken together, both indexes (the maximal Lyapunov exponent and the embedding dimension) remark the importance of taking into consideration the system's non-linear properties for a better understanding of the information transmission in the basal ganglia.