Paper of the month

Bergman’s Lab: Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations

L. Iskhakova, P. Rappel, M. Deffains, G. Fonar, O. Marmor, R. Paz, Z. Israel, R. Eitan & H. Bergman

Nat Commun 12, 7026 (2021)

Lay summary:

Brain activity can sometimes have a wave-like pattern of activity, i.e. go up and down in a constant rhythm. Such brain waves can occur at different frequencies. One such frequency domain, called Beta, covers the range of 13-30Hz, and has been thought to preserve the present behavior and maintain a “status quo”, preventing a switch to new behaviors. Elevated levels of Beta waves were detected in people with Parkinson’s disease (PD) and in PD animal models, and are thought to contribute to the difficulty of PD patients to “switch” from non-movement to movement states. During PD, brain areas like the cortex and the basal ganglia experience a significant loss of a specific neurotransmitter called dopamine. Beta activity in PD patients and animals who lack dopamine has been correlated with motor deficits. Traditionally, it has been thought that the loss of dopamine leads to increases in Beta power (amount/strength) and that this increase in power could be used as a marker of the pathological PD state. However, Beta activity is also present in healthy and non-PD brains. To better understand the relationship between dopamine tone and Beta properties we recorded from the brains (cortex and a basal ganglia nucleus called the globus pallidus) of monkeys that had their dopamine levels up- or down-regulated. Furthermore, we recorded from the subthalamic nucleus (STN; another Basal Ganglia nucleus) of human PD patients for many months following deep brain stimulation (DBS) surgery. Recordings from PD patients allowed us to assess the Beta activity during progression of PD (when dopamine levels slowly went down) and while patients were on and off dopamine replacement drug therapy (DRT), changing artificially dopamine level in their brains. We found that dopamine level was monotonically correlated with the frequency of the Beta waves, rather than with their power. Thus, when dopamine levels were reduced, Beta waves were slower, and when dopamine levels were elevated, Beta waves were faster. Beta power, and synchrony within and between brain areas were not monotonically correlated with dopamine level so that high Beta power could also be achieved with high dopamine level.

“Working memory”