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  • Amplitude modulation of oscillatory activity in the subthalamic nucleus during movement.

    8 December 2017

    Depth recordings in patients with Parkinson's disease (PD) have demonstrated exaggerated local field potential (LFP) activity at frequencies between 10 and 30 Hz in the subthalamic nucleus (STN). This activity is modulated prior to single phasic movements, possibly as part of the feedforward organization of incipient voluntary movement, and after single phasic movements, as a consequence of afferent feedback processes. Here we test the hypothesis that this activity is also modulated during repetitive movements, reflecting a role in ongoing performance. Accordingly, we recorded LFP activity from the contralateral STN of seven patients with PD withdrawn from anti-parkinsonian medication while they performed repetitive index finger to thumb taps. Cross-correlograms of LFP activity at different frequencies in the 10-30 Hz band with finger position showed that LFP activity was modulated in amplitude by finger tapping. The modulation was higher at the beginning of each recording when tapping performance was better, and diminished as tapping became more bradykinetic over time. The best modulations were seen over those frequencies that were maximal in the power spectrum of the corresponding LFP, and for a given side were most marked at the contact pair that exhibited the highest power at these frequencies. In conclusion, subthalamic activity in the 10-30-Hz band is amplitude modulated during movement. This process fails as bradykinesia increases.

  • Reversal of hypertonic co-contraction after bilateral pallidal stimulation in generalised dystonia: a clinical and electromyogram case study.

    8 December 2017

    In a patient of generalised dystonia treated with bilateral pallidal stimulation, serial surface EMGs recorded from the neck muscles during alternating head movements revealed progressive reduction in hypertonic activity and reversal of co-contraction to reciprocal contraction, which preceded clinical improvement.

  • Field potentials - Response

    27 October 2017

  • Deep brain stimulation of the pedunculopontine region in the normal non-human primate.

    12 December 2017

    Lesions in the pedunculopontine nucleus (PPN) cause akinesia. The PPN degenerates in Parkinson's disease. Stimulation of the PPN region induces stepping movements in rats and cats. These findings suggest that the PPN may play an important role in akines ia and that stimulating it may alleviate akinesia.Therefore, we have stereotactically implanted a macroelectrode in the left PPN region in a normal macaque to investigate the effects of deep brain stimulation at different frequencies. Motor activity was recorded with an infra-red counter and behaviour videotaped. At frequencies above 45 Hz there was significantly more severe akinesia than at lower frequencies (paired t -test, n=15, P<0.005). At 100 Hz, there was gross impairment of postural control. At low frequencies (5-30 Hz), stimulation induced a 5-Hz tremor in the right arm. We conclude that stimulating the PPN region at high frequency causes akinesia, whereas low frequencies induce some positive motor effects.

  • Involvement of the medial pallidum in focal myoclonic dystonia: A clinical and neurophysiological case study.

    12 December 2017

    We successfully treated a patient with familial myoclonic dystonia (FMD), which primarily affected his neck muscles, with bilateral deep brain stimulation (DBS) to the medial pallidum, and investigated the role of the medial pallidum in FMD. A patient with FMD underwent bilateral implantation of DBS electrodes during which field potentials (FPs) in the medial pallidum and electromyograms (EMGs) from the affected neck muscles were recorded. The effects of high-frequency DBS to the medial pallidum on the FMD were also assessed by recording EMGs during and immediately after implantation, as well as 6 days and 8 weeks postoperatively. During spontaneous myoclonic episodes, increased FPs oscillating at 4 and 8 Hz were recorded from the medial pallidum; these correlated strongly with phasic EMG activity at the same frequencies in the contralateral affected muscles. The EMG activity was suppressed by stimulating the contralateral medial pallidum at 100 Hz during the operation and continuous bilateral DBS from an implanted stimulator abolished myoclonic activity even more effectively postoperatively. The phasic pallidal activity correlated with and led the myoclonic muscle activity, and the myoclonus was suppressed by bilateral pallidal DBS, suggesting that the medial pallidum was involved in the generation of the myoclonic activity. High-frequency DBS may suppress the myoclonus by desynchronising abnormal pallidal oscillations. This case study has significant clinical implications, because at present, there is no effective treatment for focal myoclonic dystonia.

  • Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity.

    8 December 2017

    Parkinson's disease (PD) is associated with exaggerated oscillatory synchrony in the basal ganglia at frequencies over 8-35 Hz. Studies have demonstrated a suppression of local field potential (LFP) activity in the subthalamic nucleus (STN) upon treatment with the dopamine prodrug, levodopa, with the degree of suppression of power in the 8-35 Hz band correlating with the improvement in combined measures of bradykinesia and rigidity. However, these studies do not explicitly address the question of what is more important in predicting clinical change - synchronisation of neuronal activity or the specific frequency within the 8-35 Hz band over which the latter occurs. In addition, they have not demonstrated a relationship between treatment-induced changes in synchronisation and changes in bradykinesia or rigidity on their own. To this end, we collected and analysed LFP and clinical data in 30 patients with PD. We found significant correlations between levodopa-induced power suppression and rigidity and bradykinesia, when these clinical features were considered separately, but only when power suppression profiles were re-aligned to the frequency of peak synchronisation. Under these circumstances correlations with rigidity persisted despite partialising out the effect of bradykinesia and vice versa. These data suggest that levodopa-induced improvements in both rigidity and bradykinesia scale with the degree of suppression of oscillatory power in the STN LFP, and that this is true irrespective of the frequency at which synchronisation occurs across a broad band from 8-35 Hz.

  • Effect of GPi DBS on functional imaging of the brain in dystonia.

    12 December 2017

    Five patients with idiopathic dystonic conditions, treated successfully with deep brain stimulation (DBS) of the globus pallidus internus (GPi), were studied using single-photon emission tomography (SPET) in order to evaluate brain perfusion in the presence and absence of DBS. Comparison was made between the "on" and "off" DBS scans on an individual basis and also as part of a group analysis. Whilst the individual data suggested great regional variation in cerebral perfusion between individuals, the results of the group analysis revealed several topographically similar areas of the brain where relative hyperperfusion in the absence of DBS was common to all patients. Based on these results we postulate on possible mechanisms for this phenomenon.