The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

Tinkhauser G
Pogosyan A
Little S
Beudel M
Herz DM
Tan H
Brown P

We show that a form of pathological nerve cell activity called beta oscillations come in prolonged bursts in the brains of people with Parkinson’s disease. The duration of these ‘beta bursts’ is important because more nerve cells are recruited into them over time. A new type of Deep Brain Stimulation selectively targets the prolonged beta bursts, improving its usefulness and reducing side-effects.

Scientific Abstract

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered.

One important effect of adaptive Deep Brain Stimulation (aDBS) is to prematurely terminate long bursts of beta oscillations in the brain in Parkinson’s disease.
One important effect of adaptive Deep Brain Stimulation (aDBS) is to prematurely terminate long bursts of beta oscillations in the brain in Parkinson’s disease.
2017. Brain, 140(4):1053-1067.
Tinkhauser G, Torrecillos F, Duclos Y, Tan H, Pogosyan A, Fischer P, Carron R, Welter ML, Karachi C, Vandenberghe W, Nuttin B, Witjas T, Régis J, Azulay JP, Eusebio A, Brown P
2018. Neurobiol. Dis., 117(Sept):217-225.
Tinkhauser G, Pogosyan A, Tan H, Herz DM, Kühn AA, Brown P
2017. Brain, 140(11):2968-2981.
Duchet B, Ghezzi F, Weerasinghe G, Tinkhauser G, Kühn AA, Brown P, Bick C, Bogacz R
2021. PLoS Comput. Biol., 17(7):e1009116.
Muthuraman M, Bange M, Koirala N, Ciolac D, Pintea B, Glaser M, Tinkhauser G, Brown P, Deuschl G, Groppa S
2020. Brain, 143(11):3393-3407.
Torrecillos F, Tinkhauser G, Fischer P, Green AL, Aziz TZ, Foltynie T, Limousin P, Zrinzo L, Ashkan K, Brown P, Tan H
2018. J. Neurosci., 38(41):8905-8917.