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Depth recordings in patients with Parkinson’s disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of ∼70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at ∼70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep–wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at ∼70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at ∼70 Hz may be involved in movement and arousal. [ABSTRACT FROM AUTHOR]

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the β (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local β activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP β activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the β band over the same time period. The reduction in LFP β activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of β activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological β activity in PD. [ABSTRACT FROM AUTHOR]

Abstract: Enhanced oscillatory local field potential (LFP) activities over a broad frequency range (5–30 Hz) have been consistently reported from the basal ganglia in patients with Parkinson''s disease (PD) and in animal models of this disease. Here we test the hypothesis that these activities may have different functional connotations according to their frequency, by seeking a relatively differentiated distribution within the different functional territories of the subthalamic nucleus (STN). To this end we made intra-operative microelectrode recordings of LFP activities within the STN of 8 PD patients undergoing functional neurosurgery. A significantly larger beta (13–30 Hz) power was found in the dorsolateral part of STN, which is related to motor cortical areas, compared to the ventral (associative/limbic) part of STN. This specific topography was not observed for low frequency activity (5–12 Hz). Our data suggest that the relative distribution of oscillatory activity within the STN of patients with PD may differ according to frequency and confirm previously reported findings that beta activity may provide a functional marker for the ‘motor’ STN in functional neurosurgery. [Copyright &y& Elsevier]

Abstract: Depth recordings in patients with Parkinson''s disease (PD) have demonstrated oscillatory activity in the gamma frequency (60–100 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesised to contribute to movement preparation, it is unclear to what extent these LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded LFPs and neuronal activity from microelectrodes inserted into the STN in PD patients during functional neurosurgery. Eight sides in seven patients out of 15 sides in 12 patients were identified that had peaks in the gamma band in spectra of LFPs. As microelectrodes descended towards STN, there was a pronounced increase in gamma frequency band LFP activity 1 mm above the line joining the anterior and posterior commissures and 2 mm above the microelectrode defined dorsal border of the STN. Gamma activity dropped again 3 mm below the microelectrode defined dorsal border of the STN. Spike-triggered averages of LFP activity suggested that the discharges of neurons in this region were locked to gamma oscillations in the LFP. Gamma band oscillations in the LFP are therefore likely to represent synchronous activity in populations of neurons in the upper STN and bordering zona incerta of patients with PD. [Copyright &y& Elsevier]

Abstract: Depth recordings in patients with Parkinson''s disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13–35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD. [Copyright &y& Elsevier]

The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following acoustic stimulation occurs at the level of the motor cortex through reticulo-cortical projections or subcortically, perhaps through reticulo-spinal projections. We compared the influence of acoustic stimulation on motor effects elicited by TMS over motor cortical areas to those evoked with subcortical electrical stimulation (SES) through depth electrodes in five patients treated with deep brain stimulation for Parkinson’s disease. SES bypasses the motor cortex, demonstrating any interaction with acoustic stimuli at the subcortical level. EMG was recorded from the contralateral biceps brachii muscle. Acoustic stimulation was delivered binaurally through headphones and used as a conditioning stimulus at an interstimulus interval of 50 ms. When TMS was used as the test stimulus, the area and amplitude of the conditioned motor response was significantly inhibited (area: 57.5±12.9%, amplitude: 47.9±7.4%, as percentage of unconditioned response) whereas facilitation occurred with SES (area: 110.1±4.3%, amplitude: 116.9±6.9%). We conclude that a startle-evoked activation of reticulo-cortical projections transiently inhibits the motor cortex. [ABSTRACT FROM AUTHOR]

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia. [ABSTRACT FROM AUTHOR]

Abstract: Local field potential (LFP) gamma (55–95 Hz) activity has been recorded in the vicinity of the subthalamic nucleus with both microelectrodes and macroelectrodes in patients with Parkinson''s disease undergoing functional neurosurgery. Although this activity increases with movement its functional significance remains unknown. We hypothesised that elevations in local gamma activity might be associated with an increase in the capacity of individual spike trains to code information. Changes in the median firing frequency, entropy and baud were determined during spontaneous variations in the level of simultaneously recorded LFP gamma activity in a sample of 31 neurons. The latter were recorded from the zona incerta (n =5) and subthalamic nucleus (n =26) in 10 parkinsonian patients. Although 19% of neurons showed a decrease in firing rate, overall there was a net increase in spike frequency and baud of 18.0±5.5% and 16.9±5.3%, when periods of high gamma were compared to periods of low gamma LFP activity. In contrast, entropy dropped by only 0.8±0.2% across the sampled neuronal population during periods of high gamma. All net changes were significant. We conclude that overall there was a net elevation in firing rate and potential information coding capacity, assessed in terms of baud, amongst neurons during periods of elevated gamma LFP activity in the subthalamic region. [Copyright &y& Elsevier]

Abstract: Several studies have confirmed that subthalamic and pallidal local field potential activity in the beta frequency band (13–30 Hz) is exaggerated in untreated patients with Parkinson''s disease (PD) and is suppressed by dopaminergic treatment. This particular spectral pattern differs from that in patients with dystonia in whom pallidal activity is prominent at low frequencies (<12 Hz). Here we demonstrate that tetrabenazine induced monoamine depletion and dopamine blockade is associated with increased activity in the low beta band (13–20 Hz) in the internal pallidum of patients with dystonia. Beta activity was elevated in six patients treated with tetrabenazine compared to six patients in whom this drug was not used. Our findings suggest that beta activity is enhanced in the chronically dopamine-depleted and blocked state irrespective of the underlying pathology, consistent with the idea that excessive synchrony in the beta band is directly related to dopaminergic hypofunction, rather than some degenerative disease-specific attribute of Parkinson''s disease. [Copyright &y& Elsevier]

Abstract: Excessive synchronisation of basal ganglia activity at frequencies &#60;30Hz is a hallmark of the parkinsonian state, and may contribute to bradykinesia. Accordingly, we electrically stimulated chronically implanted subthalamic macroelectrodes in 10 Parkinson''s disease patients, after overnight withdrawal of anti-parkinsonian medication. We compared the effects of stimulation at 0, 5, 10, 15, 20, 25, 30, and ca. 130Hz by measuring kinesia time (KT) in a tapping task. Although the effects of direct stimulation were small, frequency–response curves demonstrated local peaks at 5–10Hz and at 20–25Hz, superimposed upon an overall tendency for KT to reduce with increasing stimulation frequency. This is consistent with the hypothesis that spontaneous activities in these bands might promote bradykinesia. [Copyright &y& Elsevier]