Parkinson Disease: Stein JF

Stein JF. · Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3PT, UK. · Exp Neurol. · Pubmed #18977223 No free full text.

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Jenkinson N, Nandi D, Aziz TZ, Stein JF. · University Laboratory of Physiology, Oxford University, UK. · Neuroreport. · Pubmed #16272870 No free full text.

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Aziz TZ, Nandi D, Parkin S, Liu X, Giladi N, Bain P, Gregory RG, Joint C, Scott RB, Stein JF. · University Laboratory of Physiology, Department of Neurosurgery, Radcliffe Infirmary, Oxford, UK. · Stereotact Funct Neurosurg. · Pubmed #12378062 No free full text.

Abstract: The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.

Ray NJ, Jenkinson N, Wang S, Holland P, Brittain JS, Joint C, Stein JF, Aziz T. · Department of Anatomy, Physiology and Genetics, University of Oxford, Parks Road, OX1 3PT, USA. · Exp Neurol. · Pubmed #18619592 No free full text.

Abstract: Parkinson's disease is treated pharmacologically with dopamine replacement medication and, more recently, by stimulating basal-ganglia nuclei such as the subthalamic nucleus (STN). Depth recordings after this procedure have revealed excessive activity at frequencies between 8 and 35 Hz (Brown et al., 2001; Kuhn et al., 2004; Priori et al., 2004) that are reduced by dopamine therapy in tandem with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006). It has also been shown that improvements in motor symptoms after dopamine correlate with single unit activity in the beta range (Weinberger et al., 2006). We recorded local field potentials (LFPs) from the subthalamic nucleus of patients with Parkinson's disease (PD) after surgery to implant deep brain stimulating electrodes while they were on and off dopaminergic medication. As well as replicating Kuhn et al., using the same patients we were able to extend Weinberger et al. to show that LFP beta oscillatory activity correlated with the degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine medication. We also found that the power of beta oscillatory activity uniquely predicted improvements in bradykinesia/rigidity, but again not tremor, after stimulation of the STN in a regression analysis. However improvements after STN stimulation related inversely to beta power, possibly reflecting the accuracy of the electrode placement and/or the limits of STN stimulation in patients with the greatest levels of beta oscillatory activity.

Muthusamy KA, Aravamuthan BR, Kringelbach ML, Jenkinson N, Voets NL, Johansen-Berg H, Stein JF, Aziz TZ. · Department of Physiology, Anatomy and Genetics, University of Oxford, UK. · J Neurosurg. · Pubmed #17937229 No free full text.

Abstract: OBJECT: The pedunculopontine nucleus (PPN) region of the brainstem has become a new stimulation target for the treatment of gait freezing, akinesia, and postural instability in advanced Parkinson disease (PD). Because PD locomotor symptoms are probably caused by excessive gamma-aminobutyric acidergic inhibition of the PPN, low-frequency stimulation of the PPN may overcome this inhibition and improve the symptoms. However, the anatomical connections of this region in humans are not known in any detail. METHODS: Diffusion weighted magnetic resonance (MR) images were acquired at 1.5 teslas, and probabilistic tractography was used to trace the connections of the PPN region in eight healthy volunteers. A single seed voxel (2 x 2 x 2 mm) was chosen in the PPN just lateral to the decussation of the superior cerebellar peduncle, and the Diffusion Toolbox of the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain was used to process the acquired MR images. The connections of each volunteer's PPN region were analyzed using a human brain MR imaging atlas. RESULTS: The PPN region was connected with the cerebellum and spinal cord below and to the thalamus, pallidum, subthalamic nucleus, and motor cortex above. The regions of the primary motor cortex that control the trunk and upper and lower extremities had the highest connectivity compared with other parts of motor cortex. CONCLUSIONS: These findings suggest that connections of the PPN region with the primary motor cortex, basal ganglia, thalamus, cerebellum, and spinal cord may play important roles in the regulation of movement by the PPN region. Diffusion tensor imaging tractography of the PPN region may be used preoperatively to optimize placement of stimulation electrodes and postoperatively it may also be useful to reassess electrode positions.

Green AL, Wang S, Purvis S, Owen SL, Bain PG, Stein JF, Guz A, Aziz TZ, Paterson DJ. · Department of Neurosurgery, Radcliffe Infirmary, Oxford OX2 6HE, UK. · J Physiol. · Pubmed #17082229 links to  free full text

Abstract: For almost one hundred years, the exact role of human brain structures controlling the cardiorespiratory response to exercise ('central command') has been sought. Animal experiments and functional imaging studies have provided clues, but the underlying electrophysiological activity of proposed relevant neural sites in humans has never been measured. In this study, local field potentials were directly recorded in a number of 'deep' brain nuclei during an exercise task designed to dissociate the exercise from peripheral feedback mechanisms. Several patient groups had electrodes implanted sterotaxically for the treatment of movement disorder or chronic pain. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental spectral frequencies. Anticipation of exercise resulted in increases in heart rate, blood pressure and ventilation. The greatest neural changes were found in the periaqueductal grey area (PAG) where anticipation of exercise was accompanied by an increase of 43% in the power of the 12-25 Hz frequency band (P = 0.007). Exercise increased the activity by 87% compared to rest (P = 0.006). Changes were also seen in the 60-90 Hz band when anticipation or exercise increased power by 32% (P = 0.006) and 109% (P < 0.001), respectively. In the subthalamic nucleus there was a reduction in the power of the beta frequency during both anticipation (7.6 +/- 0.68% P = 0.001) and exercise (17.3 +/- 0.96% P < 0.001), whereas an increase was seen with exercise only at higher frequencies (93 +/- 1.8% P = 0.007). No significant changes were seen in the globus pallidus during anticipation of exercise. We provide direct electrophysiological evidence highlighting the PAG as an important subcortical area in the neural circuitry of the cardiorespiratory response to exercise, since stimulation of this structure is known to alter blood pressure in awake humans.

Wang S, Aziz TZ, Stein JF, Bain PG, Liu X. · Department of Physiology, Anatomy, and Genetics, University of Oxford, and Department of Neurosurgery, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. · Clin Neurophysiol. · Pubmed #16737846 No free full text.

Abstract: OBJECTIVE: To differentiate physiological from harmonic components in coherence analysis of the tremor-related neural and muscular signals by comparing power, cross-power and coherence spectra. METHODS: Influences of waveform, burst-width and additional noise on generating harmonic peaks in the power, cross-power and coherence spectra were studied using simulated signals. The local field potentials (LFPs) of the subthalamic nucleus (STN) and the EMGs of the contralateral forearm muscles in PD patients with rest tremor were analysed. RESULTS: (1) Waveform had significant effect on generating harmonics; (2) noise significantly decreased the coherence values in a frequency-dependent fashion; and (3) cross-spectrum showed high resistance to harmonics. Among six examples of paired LFP-EMG signals, significant coherence appeared at the tremor frequency only, both the tremor and double tremor frequencies and the double-tremor frequency only. CONCLUSIONS: In coherence analysis of neural and muscular signals, distortion in waveform generates significant harmonic peaks in the coherence spectra and the coherence values of both physiological and harmonic components are modulated by extra noise or non-tremor related activity. SIGNIFICANCE: The physiological or harmonic nature of a coherence peak at the double tremor frequency may be differentiated when the coherence spectra are compared with the power and in particular the cross-power spectra.

Nandi D, Jenkinson N, Stein JF, Aziz TZ. · University Laboratory of Physiology, Oxford University, Parks Road, Oxford OX1 3PT, UK. · Suppl Clin Neurophysiol. · Pubmed #16623323 No free full text.

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Liu X, Ford-Dunn HL, Hayward GN, Nandi D, Miall RC, Aziz TZ, Stein JF. · University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK. · Clin Neurophysiol. · Pubmed #12417218 No free full text.

Abstract: OBJECTIVES: To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation. METHODS: During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinson's disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN. RESULTS: Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity. CONCLUSIONS: We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Aravamuthan BR, Stein JF, Aziz TZ. · Department of Physiology, Anatomy and Genetics, University of Oxford, UK. · Br J Neurosurg. · Pubmed #19085350 No free full text.

Abstract: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has recently been shown to effectively ameliorate medically intractable axial symptoms of Parkinson's disease (PD). The effects of DBS are not limited to the targeted structure, but will affect the distributed anatomical networks to which the target structure belongs. Therefore, understanding the anatomical connections of the PPN will help elucidate treatment effects. Furthermore, establishing the topography of cortical and sub-cortical connections of the PPN in the human brain could aid accurate targeting of critical pathways in DBS. This article summarizes the connections of the PPN and the distribution of these connections within this nucleus (topography) as previously determined using diffusion tensor imaging (DTI) in healthy human volunteers and in a primate Macaca mulatta brain. These findings highlight DTI as a useful tool for surgical targeting for DBS of the PPN, and also show that DTI can be used to accurately probe the anatomy of the human and monkey brain in vivo.

Aravamuthan BR, Muthusamy KA, Stein JF, Aziz TZ, Johansen-Berg H. · Department of Physiology, Anatomy, and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, OX1 3PT, UK. · Neuroimage. · Pubmed #17644361 No free full text.

Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common surgical therapy for Parkinson' s disease (PD). DBS of the pedunculopontine nucleus (PPN) is emerging as a promising surgical therapy for PD as well. In order to better characterize these nuclei in humans, we determined the anatomical connections of the PPN and STN and the topography of these connections using probabilistic diffusion tractography. Diffusion tractography was carried out in eight healthy adult subjects using diffusion data acquired at 1.5 T MRI (60 directions, b=1000 s/mm(2), 2 x 2 x 2 mm(3) voxels). The major connections that we identified from single seed voxels within STN or PPN were present in at least half the subjects and the topography of these connections within a 36-voxel region surrounding the initial seed voxel was then examined. Both the PPN and STN showed connections with the cortex, basal ganglia, cerebellum, and down the spinal cord, largely matching connections demonstrated in primates. The topography of motor and associative brain areas in the human STN was strikingly similar to that shown in animals. PPN Topography has not been extensively demonstrated in animals, but we showed significant topography of cortical and subcortical connections in the human PPN. In addition to demonstrating the usefulness of PDT in determining the connections and topography of small grey matter structures in vivo, these results allow for inference of optimal DBS target locations and add to our understanding of the role of these nuclei in PD.

Wang SY, Aziz TZ, Stein JF, Liu X. · University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK. · J Neurosci Methods. · Pubmed #15922033 No free full text.

Abstract: In order to investigate the dynamic change in transient neuromuscular events and the functional correlation between the neural and muscular activity, local field potentials (LFPs) of the subthalamic nucleus (STN) and surface electromyograms (sEMGs) over several episodes of transient resting tremor from a patient with Parkinson's disease were quantitatively characterised in time-frequency domain using short-time Fourier transform and continuous wavelet transform. Events of onset and cessation of the tremor-related activity in the STN and muscles were correlated to reveal the temporal relationship between the two signals. A significant suppression in the power of the STN LFPs in the beta band (10-30 Hz) preceded the onset of resting tremor, which was presented as the increases in the power at the tremor frequency (3.0-4.5 Hz) in both STN LFPs and surface EMGs. Over the episodes of the intermittent resting tremor, the power of the STN LFPs in the beta band and the power of sEMGs in the tremor frequency band change in an alternating pattern with a significant exponential correlation (P(STN) = 16.8+62.3 x exp(-P(EMG)/6270.7); R2 = 0.72; p < 0.05). Significant linear correlation in the power values at the tremor frequency appears between STN LFPs and sEMGs (P(STN) = 65.1 + 2.1 x 10(-4)P(EMG); R2 = 0.41; p < 0.05). In comparison with short-time Fourier transform, similar results could be achieved using continuous wavelet transform of an appropriate wavelet with a higher temporal resolution but larger distortion in the high frequency.

Wang SY, Liu X, Yianni J, Christopher Miall R, Aziz TZ, Stein JF. · University Laboratory of Physiology, University of Oxford, UK. · J Neurosci Methods. · Pubmed #15183272 No free full text.

Abstract: Application of coherence estimation needs not only to correctly estimate coherence values but also to efficiently test the statistical significance of the estimates. In the present report, we have explained the approach of optimising a coherence estimator by restricting its normalised bias error and random error. In addition to the commonly used independence threshold, two more tests based on the probability of detection and the exact confidence interval have been proposed for detecting the significance of the coherence estimates. All three methods have been used to evaluate the significant functional correlation between oscillatory field potentials (FPs) in the subthalamic nucleus (STN) and the surface electromyogram (EMG) of the forearm muscles during tremor in Parkinson's disease.

Liu X, Osterbauer R, Aziz TZ, Miall RC, Stein JF. · University Laboratory of Physiology, Parks Road, OX1 3PT, Oxford, UK. · Neurosci Lett. · Pubmed #11335046 No free full text.

Abstract: To investigate the response to visual feedback of involuntary movements which have a frequency composition similar to cerebellar tremor but are not caused by cerebellar damage, we have tested six advanced Parkinson's disease (PD) patients with drug-induced dyskinetic movements using visually guided wrist tracking tasks. Tracking performance was assessed under three visual conditions: (1) both guiding target and movement cursor were displayed continuously; (2) the target display was turned off for the second half of each trial; or (3) the cursor display, but not the target, was turned off for the second half of each trial. The response to visual feedback of drug-induced dyskinetic movements at 1-5 Hz in these advanced PD patients were significantly increased than in normal controls. This suggests that increased response to visual feedback might be a common feature of low frequency involuntary movements and not directly caused by cerebellar damages.

Munro-Davies LE, Winter J, Aziz TZ, Stein JF. · Oxford University Laboratory of Physiology, UK. · Exp Brain Res. · Pubmed #10638425 No free full text.

Abstract: The akinesia of Parkinsonism is relieved by pallidotomy and subthalamic nucleotomy, but not by thalamotomy. Therefore, this disabling symptom probably depends upon connections other than the pallidalthalamocortical tracts, possibly efferents of the medial pallidum descending to the upper brainstem. We have previously demonstrated akinesia in the normal monkey following radiofrequency lesioning in the region of the pedunculopontine nucleus (PPN), one of the primary targets for descending pallidal outflow. Here, we confirm that selectively destroying neurones in the PPN area, whilst sparing fibres of passage, results in an akinetic state in normal macaques.

Liu X, Tubbesing SA, Aziz TZ, Miall RC, Stein JF. · University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. · Exp Brain Res. · Pubmed #10591921 No free full text.

Abstract: Visual feedback is one of the key elements in on-line control of smooth manual tracking. To in- vestigate the effects basal ganglia dysfunction have on visual feedback control, we have tested six advanced Parkinson's disease (PD) patients in comparison with normal controls using visually guided wrist tracking tasks. Tracking performance was assessed under three visual conditions: (1) both guiding target and movement cursor were displayed continuously; (2) the target display was turned off for the second half of each trial; or (3) the cursor display, but not the target, was turned off for the second half of each trial. Thus, for the second half of each trial under conditions 2 and 3, no visual feedback of the relationship between the target and the cursor was available. Results showed that although PD patients had significantly larger tracking errors than controls, and errors significantly increased in both PD patients and controls after withdrawing either visual cue, increases in tracking errors in PD were not significantly different from those in controls. Nor were any significant changes found in the frequency (6-8 Hz) or magnitude of the PD patient's action tremor after withdrawing visual feedback. These results suggest that on-line movement control of wrist tracking movements in advanced PD is not especially reliant on visual feedback. In conjunction with our previous study of multiple sclerosis (MS) patients, the present results confirm that the basal ganglia is less involved in visual guidance of smooth manual tracking than the cerebellar circuits.