TY - JOUR
T1 - Mapping movement, mood, motivation and mentation in the subthalamic nucleus
AU - Gourisankar, Amritha
AU - Eisenstein, Sarah A.
AU - Trapp, Nicholas T.
AU - Koller, Jonathan M.
AU - Campbell, Meghan C.
AU - Ushe, Mwiza
AU - Perlmutter, Joel S.
AU - Hershey, Tamara
AU - Black, Kevin J.
N1 - Funding Information:
Ethics. The study was approved by the Human Research Protection Office at WUSM and was carried out in accordance with the principles expressed in the Declaration of Helsinki. All participants provided written informed consent. Data accessibility. The data for this study are deposited at Dryad: (http://dx.doi.org/10.5061/dryad.qq934j2) [33]. Authors’ contributions. A.G. participated in data analysis and in drafting and revising the manuscript. S.A.E. contributed to study design, data analysis and drafting and revising the manuscript. N.T.T. participated in data analysis and manuscript revision. J.M.K. participated in data analysis. M.C.C., J.S.P. and T.H. contributed to study design, data collection and manuscript revision. M.U. collected data and revised the manuscript. K.J.B. contributed to study design, data analysis, drafting and manuscript revision. All authors approved the final manuscript. Competing interests. The authors declare no competing interests. Funding. National Institutes of Health (NIH; R01 NS041509 and R01 NS075321 to J.S.P., R01 NS058797 to T.H.); Michael J. Fox Foundation for Parkinson’s Research to K.J.B.; American Parkinson Disease Association (APDA) Greater St. Louis chapter, APDA Advanced Research Center at Washington University and Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund) to J.S.P.; Brain & Behavior Research Foundation (NARSAD) Young Investigator Award to M.C.C.; American Brain Foundation/American Academy of Neurology Clinical Research Training Fellowship, Washington University Faculty Diversity Scholarship to M.U. Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding agencies. Acknowledgement. The authors thank Marisel Ponton for the help with data organization.
Funding Information:
National Institutes of Health (NIH; R01 NS041509 and R01 NS075321 to J.S.P., R01 NS058797 to T.H.); Michael J. Fox Foundation for Parkinson's Research to K.J.B.; American Parkinson Disease Association (APDA)Greater St. Louis chapter, APDA Advanced Research Center at Washington University and Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund)to J.S.P.; Brain & Behavior Research Foundation (NARSAD)Young Investigator Award to M.C.C.; American Brain Foundation/American Academy of Neurology Clinical Research Training Fellowship, Washington University Faculty Diversity Scholarship to M.U. Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS)of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding agencies.
Publisher Copyright:
© 2018 The Authors.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - The anatomical connections of the subthalamic nucleus (STN)have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS)contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hypothesis using a three-dimensional (3D)statistical method to interpret the acute effects of unilateral DBS at each patient's clinically optimized DBS settings and active contact. Here, we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral borders of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of three unilateral DBS conditions (ventral STN DBS, dorsal STN DBS and DBS off)for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Ventral STN DBS induced greater improvement in rigidity and anxiety than dorsal STN DBS. In the 3D analysis, contact location was significant for body hypokinesia, rigidity and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. The 3D results provide new, direct functional evidence for the anatomically derived model of STN, in which motor function is best represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, because locations that induced improvements in motor function and mood overlapped substantially.
AB - The anatomical connections of the subthalamic nucleus (STN)have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS)contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hypothesis using a three-dimensional (3D)statistical method to interpret the acute effects of unilateral DBS at each patient's clinically optimized DBS settings and active contact. Here, we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral borders of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of three unilateral DBS conditions (ventral STN DBS, dorsal STN DBS and DBS off)for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Ventral STN DBS induced greater improvement in rigidity and anxiety than dorsal STN DBS. In the 3D analysis, contact location was significant for body hypokinesia, rigidity and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. The 3D results provide new, direct functional evidence for the anatomically derived model of STN, in which motor function is best represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, because locations that induced improvements in motor function and mood overlapped substantially.
KW - Deep brain stimulation
KW - Emotions
KW - Inhibition (psychology)
KW - Parkinson's disease
KW - Short-term memory
KW - Subthalamic nucleus
UR - http://www.scopus.com/inward/record.url?scp=85051225890&partnerID=8YFLogxK
U2 - 10.1098/rsos.171177
DO - 10.1098/rsos.171177
M3 - Article
C2 - 30109035
AN - SCOPUS:85051225890
SN - 2054-5703
VL - 5
JO - Royal Society Open Science
JF - Royal Society Open Science
IS - 7
M1 - 171177
ER -