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Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk–benefit ratio. [ABSTRACT FROM PUBLISHER]

In this prospective double blind randomised "N of 1" study, a patient with a severe form of burette's syndrome was treated with ,bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe turns of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-paullido-thalamo-cortical systems in this disorder. [ABSTRACT FROM AUTHOR]

Abstract Saccade adaptation can be experimentally induced by systematically displacing a visual cue during a targeting saccade. Non-human primate studies have highlighted the crucial role of the cerebellum for saccade adaptation, but its neural substrates in humans are poorly understood. Recent physiological experiments suggest that, in addition to cerebellar structures, cortical areas may be involved as well. We have therefore hypothesized that saccade adaptation may rely on a cerebello-cerebral network, in which the cerebellar thalamus may link cerebellar and cerebral structures. To test this hypothesis, we studied saccade adaptation in a group of four patients with a thalamic lesion, with (n = 2) or without (n = 2) involvement of the cerebellar thalamus. Compared to healthy subjects, saccade adaptation was reduced in patients with associated cerebellar syndrome, but normal in patients without cerebellar syndrome. These results are consistent with the hypothesis that cerebello-thalamic pathways contribute to saccade adaptation in humans and suggest that the thalamus relays adaptation-related information from the cerebellum to cerebral cortical oculomotor areas. [ABSTRACT FROM AUTHOR]

Abstract Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In parallel, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity. [ABSTRACT FROM AUTHOR]

The striatopallidonigral connection was studied by injecting anterograde tracers into either the associative or the sensorimotor striatum in ten macaques. The results were analyzed using a precise cartographic method. Injections into various parts of the associative striatum (caudate nucleus and ventromedial putamen) produced a labeling of axons in the dorsomedial and ventral pallidal regions. These associative regions occupied two-thirds of the lateral pallidum and one-third of the medial pallidum. Bands of labeled axons from the sensorimotor striatum (dorsolateral putamen) were found in the remaining, central part of the two pallidal nuclei. In the substantia nigra, the rostral associative striatum projected medially to the pars reticulata, while the caudal parts projected laterally. The whole pars reticulata and lateralis thus appeared to receive associative striatal inputs. The sensorimotor striatal territory projected to the central part of the pars reticulata/lateralis. It was concluded that the two functional territories remain separate in the two pallidal nuclei but overlap in the middle third of the substantia nigra. However, due to their great size, the pallidal neurons located at the border of the two territories may receive striatal inputs from both the associative and the sensorimotor components in the same way that nigral neurons do. [ABSTRACT FROM AUTHOR]

Abstract The pathophysiology of parkinsonian tremor remains a matter of debate with two opposing hypotheses proposing a peripheral and a central origin, respectively. A central origin of tremor could arise either from a rhythmic activity of the internal segment of the globus pallidus (GPi) or from a structure such as the thalamus, outside the basal ganglia. In this study, single-unit recordings were performed in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys within the GPi and within three territories of the motor thalamus (delimited by their afferent inputs from the GPi, the substantia nigra and the cerebellum, respectively). For each recorded neuron, we compared the variations in firing rate and pattern in tremor and no tremor periods. Tremor either occurred spontaneously or was induced by external stimulation. When the animals entered into a tremor period we observed: (i) an increase in the mean firing rate in about half of the recorded neurons of the motor thalamus; and (ii), a change from an irregular to a rhythmic discharge within the range of tremor frequency (5–7 Hz) in about 10% of the recorded neurons of the motor thalamus (pallidal and cerebellar territories) and the GPi. Most of the thalamic neurons that exhibited a rhythmic discharge during tremor were found to be sensitive to external stimulation. Because the changes in firing rate occurred predominantly in the motor thalamus and not in the GPi, and because a fast rhythmic discharge of 10–15 Hz was frequently observed in the GPi and not in the motor thalamus, we conclude that thalamic activity is not a simple reproduction of basal ganglia output. Moreover, we suggest that thalamic processing of basal ganglia outputs could participate in the genesis of tremor, and that this thalamic processing could be influenced by sensory inputs and/or changes in attentional level elicited by external stimulation. [ABSTRACT FROM AUTHOR]