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Median nerve somatosensory evoked potentials (SEPs) were recorded in three parkinsonian patients who underwent electrode implant in the subthalamic nucleus and/or globus pallidus for chronic deep brain stimulation (DBS). SEPs were evoked before surgery, in a medication-free condition, and after the functional stereotactic procedure, before beginning DBS. In order to evaluate the timing of the SEP changes after the electrode implant, in three further patients SEPs were recorded within the operating theater, before and immediately after the implantation. Patients' symptoms improved immediately after the electrode implant, and both N20 and N30 amplitudes increased in the postsurgical SEP recording. The clinical and neurophysiological effects observed after surgery, before commencing DBS, can be explained by microdamage in the target nucleus following the electrode implant. They occurred also in the patients studied in the operating theater, thus suggesting that they occur immediately after the stereotactic procedure. Our results suggest that the circuitries between the basal ganglia and the primary sensorimotor cortex may be modified not only by DBS but also by microdamage due to surgery and that they exert an important influence on SEP amplitude.

We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from macroelectrodes (MEs) inserted into the subthalamic nucleus (STN) in eight awake patients following functional neurosurgery for Parkinson's disease. An EEG was also recorded, as were the signals from MEs in the globus pallidus interna (GPi) in two of the cases. Coherence between EEG and ME potentials was apparent in three major frequency bands, 2-10 Hz, 10-30 Hz and 70-85 Hz. These rhythmic activities differed in their cortical topography, although coherence was always strongest over the midline. Coherence between EEG and ME potentials in the 70-85 Hz band was only recorded in patients treated with levodopa. Cortical activity phase led that in the basal ganglia in those oscillatory activities with frequencies <30 Hz. In contrast, STN and GPi phase led cortex in the 70-85 Hz band. The temporal differences in the way in which cortical activity led or lagged behind that in STN/GPi were similar, around 20 ms, regardless of the overall direction of information flow and frequency band. We conclude that the basal ganglia may receive multiple cortical inputs at frequencies <30 Hz and, in the presence of dopaminergic activity, produce a high frequency drive back to the cerebral cortex, in particular the supplementary motor area (SMA).

There is a wealth of data suggesting that behavioural events are reflected in the basal ganglia through phasic changes in the discharge of individual neurones. Here we investigate whether events are also reflected in momentary changes in the degree of synchronization between neuronal elements. We simultaneously recorded local potentials (LPs) from the subthalamic nucleus (STN) and/or ipsilateral globus pallidus interna (GPi) or scalp EEG during voluntary movements of a hand-held joystick in six awake patients following neurosurgery for Parkinson's disease. Without medication the power within the STN and the coherence between the STN and the GPi were dominated by activity with a frequency of <30 Hz. This coupling was attenuated by movement. In the presence of exogenous dopaminergic stimulation, power within the STN and coherence between the STN and the GPi was dominated by activity at 70-85 Hz, which increased with movement. The movement-related changes in coherence between the STN and EEG showed a similar pattern of pharmacological dependence, as seen subcortically. Movement-related frequency-specific changes in synchronization occur in the basal ganglia and extend to involve subcortico-cortical motor loops. The dynamic organization of activities in the frequency domain might provide a means for temporal co-ordination within and across different processing streams in the basal ganglia. This organization is critically dependent on the level of dopaminergic activity.

Background: Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. Results: To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics. We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort to simulate large scale networks. For this reason we considered a reduced order model, the Izhikevich one, which is computationally much lighter. The comparison between neural lattices built using both neuron models provided comparable results, both without traditional stimulation and in presence of all the stimulation protocols. This was a first result toward the study and simulation of the large scale neural networks involved in pathological dynamics. Using the reduced order model an inspection on the activity of two neural lattices was also carried out at the aim to analyze how the stimulation in one area could affect the dynamics in another area, like the usual medical treatment protocols require. The study of population dynamics that was carried out allowed us to investigate, through simulations, the positive effects of the stimulation signals in terms of desynchronization of the neural dynamics. Conclusions: The results obtained constitute a significant added value to the analysis of synchronization and desynchronization effects due to neural stimulation. This work gives the opportunity to more efficiently study the effect of stimulation in large scale yet computationally efficient neural networks. Results were compared both with the other mathematical models, using Morris Lecar and Izhikevich neurons, and with simulated Local Field Potentials (LFP). [ABSTRACT FROM AUTHOR]

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]

To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92–3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs. [ABSTRACT FROM AUTHOR]

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson''s disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing. [Copyright &y& Elsevier]