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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.

Alterations in the basal ganglia-thalamocortical "motor" circuit activity, have been proposed to explain many features associated with hypokinetic and hyperkinetic movement disorders. We describe the firing pattern of the globus pallidus pars interna in a Parkinson disease's patient who developed Hemichorea-Ballismus subsequent to ipsilateral subthalamotomy, and compare findings to those from PD patients submitted to pallidotomy while in the OFF-medication state. Single units obtained from extracellular recordings were extracted and mean discharge frequency, interspike interval and coefficient of variation (defined as Tonicity Score) were computed. Discharge density histograms, analysis of distribution and spectral analysis were also performed. Mean firing frequency showed no significant difference between PD patients in the OFF state and the patient we report. However, a significant difference in tonicity was found for this patient characterized by a regular, non-bursting firing pattern. The findings indicate that in HB caused by lesions to STN in the parkinsonian state, GPi firing rates can be similar to and firing pattern more regular than those observed in GPi of PD patients OFF-medication with intact STN.

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.

Exponential decay of the power spectrum is typically observed in turbulent flow patterns, as evidenced both in experiments and in the Navier-Stokes equations describing fluid dynamics. In this study, we present evidence on the exponential decay of power spectra belonging to interspike interval time series, registered in pallidal neurons from patients with Parkinson's disease. Extracellular neuronal recordings were obtained during functional neurosurgery and processed off-line. Interspike interval power spectra were calculated for single unit recordings. All power spectra analyzed were similar, presenting rapid decay of power with frequency. Regression coefficient (adjusted R squared) for exponential function fit was very high, over 0.99 (p<0.001) in every case. We therefore suggest that the neurons studied here show turbulent-like behavior from a spectral point of view, and theorize that Navier-Stokes-like equations may be potentially useful tools to model spectral patterns of firing activity in neurons of this type. We propose to classify neural systems according to the general form of their power spectrum into two major groups of physical systems: systems with scale invariance and a power-law behavior of the power spectrum, and systems with critical scale and an exponential decay of the power spectrum., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Motor imagery is thought to involve the same processes of movement preparation as actual movement. Imagination of a simple repetitive movement significantly decreased the firing rate of extracellular micro recording at sensorimotor neurons of globus pallidus internus in three patients with Parkinson's disease, who underwent microelectrode-guided posteroventral pallidotomy. These findings suggest, in agreement with previous clinical and functional neuroimaging studies that the motor corticostriatal circuit could be engaged in mental simulation.

The aim of this study was to analyse and compare published data during the last decade on the different approaches to Parkinson's disease surgery. Eighty-eight papers published between 1990 and 2001 fulfilled the inclusion criteria. Full-text and prospective papers on lesion and stimulation of GPi or STN were assessed. Descriptive analysis of surgery procedure and population under study was performed, as well as a meta-analysis of the most consistently reported variables. A total of 1702 patients underwent surgery with a mean age of 58.75 years (range 46.5 - 72.5), mean duration of illness 13.6 years (8.1 - 18.1) and a male:female ratio 1.5:1. Mean postoperative follow-up was 9 months (1 - 52). Single blind assessment was performed in two papers, while double blind evaluation was used in 6. In the GPi group, no difference was found between the pre- and postoperative levodopa equivalent daily dose (960.39 v. 943.13; p > 0.05), while the STN group showed a marked reduction (1104.8 v. 483.04; p < 0.05) of this dosage. Meta-analysis of the most consistently reported variables (UPDRS total score, UPDRS motor score, UPDRS ADL score and Schwab & England score showed that Nucleus, Bilaterality of Approach and Surgical Procedure were the best moderators for defining outcome. Bilateral DBS STN procedures proved to be associated with better outcome. Microelectrode recording was not found to be a moderator that influenced outcome. Although there was a significant improvement of dyskinesias among the different approaches described in the papers, the heterogeneity of data makes it impossible to perform a structured analysis on this item.

We studied 516 globus pallidus neurons in dystonic patients. The firing rate was analysed. We classified the burst activity into tonic, burst, and pause patterns. Mean +/- SD firing rates and tonicity score for internal globus pallidus (GPi) and external globus pallidus (GPe) were 54.6 +/- 28.6; 58.01 +/- 39.1 and 1.18 +/- 0.55; 0.95 +/- 0.43, respectively. Differences in percentage appearance of tonic, burst, or paused neurons were not statistically significant for GPi versus GPe. GPi firing features in dystonic patients were closely similar to those of GPe. This could suggest that the abnormally patterned output from GPi would not result from increased differential inhibitory/excitatory input arising from the direct/indirect pathway but rather be transmitted from GPe, striatum, or either centromedian nucleus., (Copyright 2003 Movement Disorder Society)

We studied 12 non-demented PD patients in on state before and 3 months after posteroventral pallidotomy (PVP), in order to evaluate the effects of surgery upon an unconstrained, multijoint skilled movement as well as a single joint, repetitive, ballistic movement. A Selspot II System was used for three-dimensional data acquisition, processing and reconstruction of limb trajectories. Specific wrist kinematic features of spatial accuracy (linearity and planarity), temporal attributes (acceleration and velocity), spatiotemporal relationships (velocity-curvature coupling), and joint kinematic variables (relationships between wrist and elbow velocities and relative arm angle amplitudes) for each cycle of movement were graphically and numerically analysed. QMC was applied to single joint, repetitive, ballistic movements. QMC significantly improved after PVP (P < 0.0006). However, wrist as well as joint kinematic variables of the gestural movements failed to change significantly after PVP. The lack of improvement of the kinematic abnormalities of the gestural movement in PD patients would indicate that they are unrelated to the basic motor deficit; most likely they are the result of a disruption of a complex of sensorimotor integration processes due to abnormal parieto-frontal basal ganglia interaction., (Copyright 2002 Movement Disorder Society)

Objective: Posteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed., Methods: A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later., Results: The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement., Conclusion: Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Objectives: Over the past few years many reports have shown that posteroventral pallidotomy is an effective method for treating advanced cases of Parkinson's disease. The main differences with earlier descriptions were the use of standardised evaluation with new high resolution MRI studies and of single cell microrecording which can electrophysiologically define the sensorimotor portion of the internal globus pallidus (GPi). The present study was performed on a consecutive series of 40 patients with Parkinson's disease who underwent posteroventral pallidotomy to determine localisation discrepancies between the ventriculography based theoretical and the electrophysiologically defined target for posteroventral pallidotomy., Methods: The tentative location of the posteroventral GPi portion was defined according to the proportional Talairach system. Single cell recording was performed in all patients. The definitive target was chosen according to the feasibility of recording single cells with GPi cell features, including the presence of motor drive and correct identification of the internal capsule and of the optic tract by activity recording and microstimulation., Results: In all 40 patients the electrophysiologically defined sensorimotor portion of the GPi was lesioned, with significantly improved cardinal Parkinson's disease symptoms as well as levodopa induced dyskinesias, without damage to the internal capsule or optic tract. Significant differences between the localisation of the ventriculography based theoretical versus electrophysiological target were found in depth (p<0.0008) and posteriority (p<0.04). No significant differences were found in laterality between both approaches. Difference ranges were 8 mm for laterality, 6.5 mm for depth, and 10 mm for posteriority., Conclusions: Electrophysiologically defined lesion of GPi for posteroventral pallidotomy, shown to be effective for treating Parkinson's disease, is located at a significantly different site from the ventriculography based theoretical target.

We present a patient with clinically evident beginning-of-dose motor deterioration who had undergone posteroventral pallidotomy. This patient underwent an intrasurgical apomorphine test followed by single cell recording of the internal globus pallidus (GPi) to determine changes in GPi firing rate during the occurrence of such phenomenon. A significant increase in GPi firing rate coincident with worsening of patient disabilities prior to improvement was found. This finding suggests that beginning-of-dose motor deterioration may be mediated by enhanced thalamic inhibition.

Unlabelled: Many reports published during the past 5 years have shown evidence of the beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients for up to 3 years, but none of them have compared patients who underwent surgery with a control group., Objective: To compare the evolution of Parkinson's disease symptoms at 1-year follow-up between patients who underwent surgery and those who did not., Material and Methods: Ten patients with idiopathic Parkinson's disease refractory to treatment who were included in the Core Assessment for Intracerebral Transplantation program for PVP did not undergo surgery because financial support was lacking. These patients were followed up for 1 year as if they had been operated on and were finally compared with 10 patients having similar characteristics in whom PVP had been performed during the same period of time., Results: There were no significant differences at basal evaluation in the motor section scores of the Unified Parkinson's Disease Rating Scale between those patients who underwent surgery and those who did not, but a significant reduction in Unified Parkinson's Disease Rating Scale motor score in the group who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias, which was nonsignificantly different at basal evaluation, showed, at the 1-year follow-up, a significant reduction in the group who underwent surgery (P < 0.04). Scores from the subsets of the Unified Parkinson's Disease Rating Scale addressing rigidity, tremor, and bradykinesia also proved significantly different at the 1-year follow-up. The slope of the line generated by the two evaluations for each group showed a negative value in the group who underwent surgery (value of -0.21) and a positive value in the group who did not (value of 0.148)., Conclusion: At the 1-year follow-up, microelectrode-guided PVP produced significant changes in patient motor status and disease progression versus a comparable group of patients who did not undergo surgery during the same period of time.

Objective: To determine the effect of a single dose of apomorphine on internal globus pallidus (GPi) neuronal discharge in patients with Parkinson's disease (PD)., Patients and Methods: Nine PD patients who underwent microelectrode-guided posteroventral pallidotomy (PVP) were studied. After identification of a single GPi unit discharge with sufficient spike S/N ratio to allow reliable thresholding, basal recording was followed by a single 3-mg subcutaneous injection. One-minute samples were recorded 10', 30', and 60' after apomorphine., Results: In four patients, recording was lost after 5-10 minutes. In two, changes were observed at peak-of-dose but recording was then lost, whereas three completed recording and returned to baseline, all five showing significant reduction in GPi firing rate (mean +/- standard deviation for basal and post-apomorphine were 143+/-55.6 and 52+/-19.2, respectively; p <0.002)., Conclusion: In patients with PD, apomorphine induces changes in GPi spontaneous discharge and modifies firing rates resembling recordings in normal primates. These findings show that clinical improvement as well as induction of dyskinesias following DA administration could be mediated by reduction of GPi outflow.

Microelectrode-guided posteroventral pallidotomy (PVP) has shown to be an effective method in the treatment of a group of patients with advanced Parkinson's disease. A nonlesioning approach by means of deep brain electrodes connected to a programmable neuropacemaker has also been used to inhibit the internal segment of globus pallidus (posteroventral stimulation [PVS]) reporting comparable clinical efficacy to the one obtained with the ablative method. Nevertheless, no controlled studies have been performed to compare the efficacy of both procedures. A prospective series of 13 patients with a clinical indication for globus pallidus surgery was randomized either to a pallidotomy or stimulator implantation, and comparisons on motor and neuropsychologic measurements were made on a 3-month follow-up basis. Primary measurements of efficacy showed a comparable effect on Unified Parkinson's Disease Rating Scale and activities of daily living score after both procedures. Secondary measurements of efficacy showed that although both techniques improve hand tapping score and dyskinesia score, the bilateral improvement in the former was greater after PVS whereas the latter improved more significantly after PVP. No significant changes in neuropsychologic parameters were observed after either PVP or PVS. Side effects and surgery complications occurred in six of 13 patients (three after PVP and three after PVS): they were mild, transient, and unrelated to optic tract injury. In conclusion, the short-time effect and safety of both procedures is comparable.

We present a series of six consecutive Parkinson's disease patients undergoing posteroventral pallidotomy (PVP), who received an apomorphine injection after thermolesioning the posteroventral region of the internal globus pallidus (GPi) to evaluate the effect of the lesion on drug-induced dykinesias and therefore to proceed with further lesions or to conclude the surgery. Five of six patients failed to present dykinesias or did so to a significantly lesser degree (F [2,10] 42.6; p < 0.0001) so that surgery was concluded. One patient continued having contralateral dyskinesia despite an improvement in rigidity and bradykinesia, therefore, a new track was performed followed by a new lesion. No differences were found between intrasurgical and 1-month postoperative apomorphine test values. This report indicates that the use of an apomorphine test after thermolesioning may provide a reliable tool to check lesion efficacy on dyskinesia. The development of techniques that provide additional clinical information to the electrophysiological recording could help improve the outcome of patients undergoing pallidotomy.

To determine the effect of unilateral posteroventral pallidotomy (PVP) on latency and duration of response to L-dopa ipsilateral and contralateral to the side of the lesion, six severe fluctuating Hoehn-Yahr IV patients with Parkinson's disease were evaluated 2 days before and after unilateral PVP. After an overnight drug holiday in a fasting state, patients were challenged with a single dose of 200/50 mg of L-dopa/ carbidopa. Sequential tapping tests every 5 minutes in both hands were used to measure changes in motor status. Duration of L-dopa effect was significantly longer after PVP (p < 0.03). Mean latency of the effect improved by 50% without reaching statistical significance. Despite a clear, asymmetric improvement of cardinal Parkinson's disease symptoms after unilateral PVP, changes in the dose-response L-dopa profile occurred symmetrically, suggesting that mechanisms underlying the two effects are distinct.

Eight of the first 15 patients with advanced Parkinson's disease who underwent microelectrode guided posteroventral pallidotomy developed transient abnormal involuntary movements during thermolesion, four of whom also did so during high frequency macrostimulation. Abnormal involuntary movements found before thermolesion were choreic, ballistic, or choreoathetoid in nature, usually persisted less than 60 minutes, and were contralateral to the site of thermolesion in six and bilateral in two of them. The appearance of abnormal involuntary movements during macrostimulation or thermolesion of the internal globus pallidus correlated with better surgical outcome as measured by UPDRS motor items and CAPIT timed test, so that they seem to be of prognostic value.