CiteULike: nelmor parkinson

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Nicolas Mallet — 2008-05-02T08:52:58-00:00

J. Neurosci., Vol. 28, No. 18. (30 April 2008), pp. 4795-4806.

In the subthalamic nucleus (STN) of Parkinson's disease (PD) patients, a pronounced synchronization of oscillatory activity at beta frequencies (15-30 Hz) accompanies movement difficulties. Abnormal beta oscillations and motor symptoms are concomitantly and acutely suppressed by dopaminergic therapies, suggesting that these inappropriate rhythms might also emerge acutely from disrupted dopamine transmission. The neural basis of these abnormal beta oscillations is unclear, and how they might compromise information processing, or how they arise, is unknown. Using a 6-hydroxydopamine-lesioned rodent model of PD, we demonstrate that beta oscillations are inappropriately exaggerated, compared with controls, in a brain-state-dependent manner after chronic dopamine loss. Exaggerated beta oscillations are expressed at the levels of single neurons and small neuronal ensembles, and are focally present and spatially distributed within STN. They are also expressed in synchronous population activities, as evinced by oscillatory local field potentials, in STN and cortex. Excessively synchronized beta oscillations reduce the information coding capacity of STN neuronal ensembles, which may contribute to parkinsonian motor impairment. Acute disruption of dopamine transmission in control animals with antagonists of D1/D2 receptors did not exaggerate STN or cortical beta oscillations. Moreover, beta oscillations were not exaggerated until several days after 6-hydroxydopamine injections. Thus, contrary to predictions, abnormally amplified beta oscillations in cortico-STN circuits do not result simply from an acute absence of dopamine receptor stimulation, but are instead delayed sequelae of chronic dopamine depletion. Targeting the plastic processes underlying the delayed emergence of pathological beta oscillations after continuing dopaminergic dysfunction may offer considerable therapeutic promise. 10.1523/JNEUROSCI.0123-08.2008

Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism

Michael Frank — 2007-11-20T16:59:08-00:00

Science (25 October 2007), 1146157.

Deep brain stimulation (DBS) of the subthalamic nucleus dramatically improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. Here we show that DBS selectively interferes with the normal ability to slow down when faced with decision conflict. While on DBS, patients actually sped up under high conflict conditions. This form of impulsivity was not affected by dopaminergic medication status. Instead, medication impaired patients' ability to learn from negative decision outcomes. These findings implicate independent mechanisms leading to impulsivity in treated Parkinson's patients, and were predicted by a single neurocomputational model of the basal ganglia. 10.1126/science.1146157

Re-emergence of striatal cholinergic interneurons in movement disorders

Antonio Pisani — 2007-10-06T11:16:25-00:00

Trends in Neurosciences, Vol. In Press, Corrected Proof

Twenty years ago, striatal cholinergic neurons were central figures in models of basal ganglia function. But since then, they have receded in importance. Recent studies are likely to lead to their re-emergence in our thinking. Cholinergic interneurons have been implicated as key players in the induction of synaptic plasticity and motor learning, as well as in motor dysfunction. In Parkinson's disease and dystonia, diminished striatal dopaminergic signalling leads to increased release of acetylcholine by interneurons, distorting network function and inducing structural changes that undoubtedly contribute to the symptoms. By contrast, in Huntington's disease and progressive supranuclear palsy, there is a fall in striatal cholinergic markers. This review gives an overview of these recent experimental and clinical studies, placing them within the context of the pathogenesis of movement disorders.

Pathological synchronization in Parkinson's disease: networks, models and treatments

Constance Hammond — 2007-07-03T08:13:20-00:00

Trends in Neurosciences, Vol. 30, No. 7. (July 2007), pp. 357-364.

Parkinson's disease is a common and disabling disorder of movement owing to dopaminergic denervation of the striatum. However, it is still unclear how this denervation perverts normal functioning to cause slowing of voluntary movements. Recent work using tissue slice preparations, animal models and in humans with Parkinson's disease has demonstrated abnormally synchronized oscillatory activity at multiple levels of the basal ganglia-cortical loop. This excessive synchronization correlates with motor deficit, and its suppression by dopaminergic therapies, ablative surgery or deep-brain stimulation might provide the basic mechanism whereby diverse therapeutic strategies ameliorate motor impairment in patients with Parkinson's disease. This review is part of the INMED/TINS special issue, Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).