TY - JOUR
T1 - Independently together
T2 - subthalamic theta and beta opposite roles in predicting Parkinson's tremor
AU - Asch, Nir
AU - Herschman, Yehuda
AU - Maoz, Rotem
AU - Auerbach-Asch, Carmel R.
AU - Valsky, Dan
AU - Abu-Snineh, Muneer
AU - Arkadir, David
AU - Linetsky, Eduard
AU - Eitan, Renana
AU - Marmor, Odeya
AU - Bergman, Hagai
AU - Israel, Zvi
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020
Y1 - 2020
N2 - Tremor is a core feature of Parkinson's disease and the most easily recognized Parkinsonian sign. Nonetheless, its pathophysiology remains poorly understood. Here, we show that multispectral spiking activity in the posterior-dorso-lateral oscillatory (motor) region of the subthalamic nucleus distinguishes resting tremor from the other Parkinsonian motor signs and strongly correlates with its severity. We evaluated microelectrode-spiking activity from the subthalamic dorsolateral oscillatory region of 70 Parkinson's disease patients who underwent deep brain stimulation surgery (114 subthalamic nuclei, 166 electrode trajectories). We then investigated the relationship between patients' clinical Unified Parkinson's Disease Rating Scale score and their peak theta (4-7 Hz) and beta (13-30 Hz) powers. We found a positive correlation between resting tremor and theta activity (r = 0.41, P < 0.01) and a non-significant negative correlation with beta activity (r = -0.2, P = 0.5). Hypothesizing that the two neuronal frequencies mask each other's relationship with resting tremor, we created a non-linear model of their proportional spectral powers and investigated its relationship with resting tremor. As hypothesized, patients' proportional scores correlated better than either theta or beta alone (r = 0.54, P < 0.001). However, theta and beta oscillations were frequently temporally correlated (38/70 patients manifested significant positive temporal correlations and 1/70 exhibited significant negative correlation between the two frequency bands). When comparing theta and beta temporal relationship (r θ β) to patients' resting tremor scores, we found a significant negative correlation between the two (r = -0.38, P < 0.01). Patients manifesting a positive correlation between the two bands (i.e. theta and beta were likely to appear simultaneously) were found to have lower resting tremor scores than those with near-zero correlation values (i.e. theta and beta were likely to appear separately). We therefore created a new model incorporating patients' proportional theta-beta power and r θ βscores to obtain an improved neural correlate of resting tremor (r = 0.62, P < 0.001). We then used the Akaike and Bayesian information criteria for model selection and found the multispectral model, incorporating theta-beta proportional power and their correlation, to be the best fitting model, with 0.96 and 0.89 probabilities, respectively. Here we found that as theta increases, beta decreases and the two appear separately - resting tremor is worsened. Our results therefore show that theta and beta convey information about resting tremor in opposite ways. Furthermore, the finding that theta and beta coactivity is negatively correlated with resting tremor suggests that theta-beta non-linear scale may be a valuable biomarker for Parkinson's resting tremor in future adaptive deep brain stimulation techniques.
AB - Tremor is a core feature of Parkinson's disease and the most easily recognized Parkinsonian sign. Nonetheless, its pathophysiology remains poorly understood. Here, we show that multispectral spiking activity in the posterior-dorso-lateral oscillatory (motor) region of the subthalamic nucleus distinguishes resting tremor from the other Parkinsonian motor signs and strongly correlates with its severity. We evaluated microelectrode-spiking activity from the subthalamic dorsolateral oscillatory region of 70 Parkinson's disease patients who underwent deep brain stimulation surgery (114 subthalamic nuclei, 166 electrode trajectories). We then investigated the relationship between patients' clinical Unified Parkinson's Disease Rating Scale score and their peak theta (4-7 Hz) and beta (13-30 Hz) powers. We found a positive correlation between resting tremor and theta activity (r = 0.41, P < 0.01) and a non-significant negative correlation with beta activity (r = -0.2, P = 0.5). Hypothesizing that the two neuronal frequencies mask each other's relationship with resting tremor, we created a non-linear model of their proportional spectral powers and investigated its relationship with resting tremor. As hypothesized, patients' proportional scores correlated better than either theta or beta alone (r = 0.54, P < 0.001). However, theta and beta oscillations were frequently temporally correlated (38/70 patients manifested significant positive temporal correlations and 1/70 exhibited significant negative correlation between the two frequency bands). When comparing theta and beta temporal relationship (r θ β) to patients' resting tremor scores, we found a significant negative correlation between the two (r = -0.38, P < 0.01). Patients manifesting a positive correlation between the two bands (i.e. theta and beta were likely to appear simultaneously) were found to have lower resting tremor scores than those with near-zero correlation values (i.e. theta and beta were likely to appear separately). We therefore created a new model incorporating patients' proportional theta-beta power and r θ βscores to obtain an improved neural correlate of resting tremor (r = 0.62, P < 0.001). We then used the Akaike and Bayesian information criteria for model selection and found the multispectral model, incorporating theta-beta proportional power and their correlation, to be the best fitting model, with 0.96 and 0.89 probabilities, respectively. Here we found that as theta increases, beta decreases and the two appear separately - resting tremor is worsened. Our results therefore show that theta and beta convey information about resting tremor in opposite ways. Furthermore, the finding that theta and beta coactivity is negatively correlated with resting tremor suggests that theta-beta non-linear scale may be a valuable biomarker for Parkinson's resting tremor in future adaptive deep brain stimulation techniques.
KW - Parkinson's disease
KW - beta oscillations
KW - subthalamic nucleus
KW - theta oscillations
KW - tremor
UR - http://www.scopus.com/inward/record.url?scp=85097531570&partnerID=8YFLogxK
U2 - 10.1093/braincomms/fcaa074
DO - 10.1093/braincomms/fcaa074
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AN - SCOPUS:85097531570
SN - 2632-1297
VL - 2
JO - Brain Communications
JF - Brain Communications
IS - 2
M1 - fcaa074
ER -