Olfaction and early detection of Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to Erwin B Montgomery.
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OBJECTIVE: The neuronal elements mediating the effects of deep brain stimulation (DBS) are unknown. The objective was to determine the strength-duration properties of the neuronal elements that mediate paresthesias evoked by thalamic microstimulation. METHODS: The strength-duration properties of the neuronal elements causing paresthesias were measured using intraoperative microstimulation of the human thalamus. The sample included both concordant (reported in the same region as the mapped sensory receptive fields) and discordant paresthesias (reported in a region different than the mapped sensory receptive fields). RESULTS: There were no significant differences between the chronaxies of concordant and discordant paresthesias. There was no significant correlation between chronaxie and rheobase for concordant paresthesias, but a strong negative correlation existed for discordant paresthesias. CONCLUSIONS: Chronaxies did not distinguish the neuronal elements mediating concordant and discordant paresthesias, but correlations between chronaxie and rheobase suggest that concordant paresthesias were produced by activation of local cells while discordant paresthesias were caused by activation of axons of passage. SIGNIFICANCE: The similarity between the strength-duration properties of paresthesias evoked by thalamic stimulation, tremor reduction evoked by thalamic DBS, and EMG responses to thalamic DBS does not mean that these effects are caused by the same neural elements.
We studied different patterns of deep brain stimulation (DBS), but same average rate, in seven Parkinson disease patients performing a wrist flexion/extension task. Movement times were shorter with regular (continuous) stimulation than cycled 'on' and 'off' for 0.1s (mean difference 0.129 s; 95% confidence interval [CI], 0.228-0.029 s; P < 0.007) and tended to be shorter than cycling at 0.5s (mean difference 0.076 s, 95% CI, 0.171 to -0.020 s; P < 0.6). Movement times under stimulation cycling at 0.5 s tended to be shorter than cycling at 0.1 s (mean difference, 0.083 s, 95% CI, 0.188 to -0.022 s, P < 0.12). Any therapeutic mechanisms of action of DBS must account for patterns of stimulation.
Cluster analysis is an important tool for classifying data. Established techniques include k-means and k-median cluster analysis. However, these methods require the user to provide a priori estimations of the number of clusters and their approximate location in the parameter space. Often these estimations can be made based on some prior understanding about the nature of the data. Alternatively, the user makes these estimations based on visualization of the data. However, the latter is problematic in data sets with large numbers of dimensions. Presented here is an algorithm that can automatically provide these estimates without human intervention based on the inherent structure of the data set. The number of dimensions does not limit it.
Recent successes in treating neurological disorders with electrical stimulation of the brain have spurred interest in studying the neuronal mechanisms by which such therapies work. However, microelectrode recordings can be confounded by stimulation artifact. Also, large microelectrode arrays now allow recording amounts of data that would otherwise overwhelm current analytic methods that depend heavily on human intervention and interpretation. A set of algorithms is described for automatically removing stimulus artifacts that minimize signal loss with minimum human involvement. Other algorithms automatically differentiate between the extracellular action potentials of individual neurons.
Deep brain stimulation (DBS) has a record of safety and efficacy for an expanding range of indications. Recently,the Food and Drug Administration provided approval through a Humanitarian Device Exemption for DBS of the globus pallidus internus and subthalamic nucleus for the treatment of dystonia. There is increasing clinical experience demonstrating that DBS is also effective for other hyperkinetic disorders such as chorea from a variety of causes. The selection criteria, intraoperative targeting, and the postoperative management of DBS for hyperkinetic disorders are discussed.
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Many sources of disability impact on quality of life and some are likely to remain relatively refractory to pharmacological or surgical treatment. Rehabilitative approaches may help despite the paucity of randomized control studies. There is increasing evidence from neuroscience, reviewed here, that supports current rehabilitative approaches and most importantly, can be the basis for future rehabilitative approaches. Parkinson's disease is complex and the disabilities not absolute but relative. These disabilities can be affected by the environment or context in which the motor activities occur. These observations can be exploited and argue for the potential of rehabilitative approaches.
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Neuropsychological changes in individuals with Parkinson's disease (PD) were studied longitudinally. Sixty-nine idiopathic PD patients, with Mini-Mental State Examination (MMSE) scores falling within normal range, and 37 elderly control participants were given neuropsychological tests twice approximately two years apart. The PD group performed poorer than the control group on Semantic Fluency, Letter Fluency, Modified Wisconsin Card Sorting Task, and Block Design at test time 1. Two years later, the PD group showed significant decline in Semantic and Letter Fluency. A subset of 12 PD patients declined in mental status by second testing (> or =4 MMSE points). Cox proportional-hazards models were used to see if any baseline measures were associated with relative risk of decline in mental status. In the final model, Repetition performance and Age were significantly associated with cognitive decline. Consistent with previous studies, executive function tasks were those most susceptible to disease progression.
The effect of subthalamic nucleus (STN) stimulation on cortical electroencephalographic activity was examined in 10 patients with Parkinson's disease and 4 patients with epilepsy. Evoked potentials were created by time-locking electroencephalography to the onset of electrical stimulation delivered through the lead implanted in the STN of patients who had previously undergone deep brain stimulation (DBS) surgery. The effect of different patterns of stimulation on the evoked response, including single- and paired-pulse as well as burst stimulation, was explored. Cortical evoked potentials to single pulses were observed with latencies as short as 1 to 2 msec after a single pulse of stimulation, with activity continuing, in some cases, for up to 400 msec. Paired-pulse experiments revealed refractory periods on the order of 0.5 msec, suggesting that stimulation of axons contributed to the generation of at least some portion of the evoked potential waveform. Evoked potentials were also present in response to 100-msec bursts of stimulation, with some evidence that the potential was initiated within the burst artifact. The potential implications of the types of responses observed as well as potential applications are discussed.
OBJECTIVES: The substantia nigra in the animal model has been implicated in the control of epilepsy. The substantia nigra pars reticulata (SNpr) receives afferents from the subthalamic nucleus (STN), which thus may have an effect on the control of epilepsy. There is evidence in the animal model of a direct connection from the cortex to the STN. High-frequency STN stimulation is being used in experimental trial for the management of intractable epilepsy. Our primary objective in this study was to determine if there was epileptiform activity recorded from the STN in association with scalp recorded epileptiform activity to support the presence of a pathway from the cortex to the STN in humans as described in animals that may be important for the management of epilepsy. This article describes the interictal and ictal electroencephalographic (EEG) findings as well as evoked potential recordings from the STN in these patients with intractable epilepsy. METHODS: Four patients (3 males) ranging from 19 to 45 years with intractable focal epilepsy refractory to anti-epileptic drugs were studied. Two patients failed vagal nerve stimulation and one patient had previous epilepsy surgery. Depth electrodes were implanted stereotactically in the STN bilaterally. A comparative analysis of the interictal and ictal activities recorded from the scalp and STN electrodes was performed. Median nerve somatosensory evoked potentials (SEPs) and auditory evoked potentials (AEPs) were also recorded. RESULTS: Interictal sharp waves recorded in the scalp EEG were always negative in polarity. These sharp waves were always associated with sharp waves recorded at the ipsilateral STN electrode contacts that were always positive in polarity. In addition repetitive spikes were recorded independently at the left or right STN electrode contacts, with no reflection at the scalp. These spikes were extremely stereotyped, of high amplitude and short duration, and were positive or negative in polarity. Focal scalp EEG seizures were also recorded at the ipsilateral STN electrodes. In 3 patients SEPs were recorded from the contralateral STN electrodes corresponding to the P14/N18 far-field complex. In two patients AEPs were recorded, and wave V (near-field) and wave VII (far-field) from the contralateral STN electrodes. CONCLUSIONS: This study demonstrates that scalp recorded epileptiform activity is reflected at the ipsilateral STN either following or preceding the scalp sharp waves. The STN sharp waves are most probably an expression of the direct cortico-STN glutamatergic pathways that have been demonstrated previously in animals. This pathway in man may be important with regard to a possible mechanism for the treatment of epilepsy with STN stimulation.
Levodopa should generally be avoided early in the course of Parkinson disease; dopamine agonists, particularly second-generation agents such as ropinirole (Requip) and pramipexole (Mirapex), carry a smaller long-term risk of dyskinesia and should be used instead. Deep brain stimulation is remarkably effective in refractory cases and may well usher in a new era in the treatment of chronic neurologic disease.