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Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

ABSTRACT: The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12?Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (?13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli.

SUBMITTER: Anzak A

PROVIDER: S-EPMC3437023 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

Anzak Anam A Tan Huiling H Pogosyan Alek A Foltynie Thomas T Limousin Patricia P Zrinzo Ludvic L Hariz Marwan M Ashkan Keyoumars K Bogdanovic Marko M Green Alexander L AL Aziz Tipu T Brown Peter P

Brain : a journal of neurology 20120801 Pt 9

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be ...[more]

PMID: 22858550

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Project description:Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5-12 Hz (in the theta/alpha band) independently predicted better performance-reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55-375 Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13-23 Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5-12 Hz and 55-375 Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13-25 Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip.

Project description:Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson's disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson's disease, and that together these different states predict motor impairment with high fidelity. Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz. Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients' hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone. We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems.

Project description:The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. Here we investigated the relationship between frequency-specific oscillatory activities in the subthalamic nucleus (STN) and manual grips made with different efforts. The latter were self-rated using the 10 level Borg scale ranging from 0 (no effort) to 10 (maximal effort). STN LFP activities were recorded in patients with Parkinson's Disease (PD) who had undergone functional surgery. Patients were studied while motor performance was improved by dopaminergic medication. In line with previous studies we observed power increase in the theta/alpha band (4-12 Hz), power suppression in the beta band (13-30 Hz) and power increase in the gamma band (55-90 Hz) and high frequency band (101-375 Hz) during voluntary grips. Beta suppression deepened, and then reached a floor level as effort increased. Conversely, gamma and high frequency power increases were enhanced during grips made with greater effort. Multiple regression models incorporating the four different spectral changes confirmed that the modulation of power in the beta band was the only independent predictor of effort during grips made with efforts rated <5. In contrast, increases in gamma band activity were the only independent predictor of effort during grips made with efforts ?5. Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function is thought to be impaired in untreated PD where task-related reactivity in these two bands is deficient.

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Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

Publications

Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

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