Stimulation of the Subthalamic Nucleus Changes Cortical-Subcortical Blood Flow Patterns During Speech: A Positron Emission Tomography Study

Abstract

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD) but can have an adverse effect on speech. In normal speakers and in those with spinocerebellar ataxia, an inverse relationship between regional cerebral blood flow (rCBF) in the left inferior frontal (IFG) region and the right caudate (CAU) is associated with speech rate. This pattern was examined to determine if it was present in PD, and if so, whether it was altered by STN-DBS.Methods: Positron Emission Tomography (PET) measured rCBF during speech in individuals with PD not treated with STN-DBS (n = 7), and those treated with bilateral STN-DBS (n = 7). Previously reported results from non-PD control subjects (n = 16) were reported for comparison. The possible relationships between speech rate during scanning and data from the left and right IFG and CAU head regions were investigated using a step-wise multiple linear regression to identify brain regions that interacted to predict speech rate.Results: The multiple linear regression analysis replicated previously reported predictive coefficients for speech rate involving the left IFG and right CAU regions. However, the relationships between these predictive coefficients and speech rates were abnormal in both PD groups. In PD who had not received STN-DBS, the right CAU coefficient decreased normally with increasing speech rate but the left IFG coefficient abnormally decreased. With STN-DBS, this pattern was partially normalized with the addition of a left IFG coefficient that increased with speech rate, as in normal controls, but the abnormal left IFG decreasing coefficient observed in PD remained. The magnitudes of both cortical predictive coefficients but not the CAU coefficient were exaggerated with STN-DBS.Conclusions: STN-DBS partially corrects the abnormal relationships between rCBF and speech rate found in PD by introducing a left IFG subregion that increases with speech rate, but the conflicting left IFG subregion response remained. Conflicting IFG responses may account for some of the speech problems observed after STN-DBS. Cortical and subcortical regions may be differentially affected by STN-DBS.

Cerebral Blood Flow Is Not a Direct Surrogate of Behavior: Performance Models Suggest a Role for Functional Meta-Networks

“…The graph on the right presents the linear regression weights for the two regions that predict speech rate [ F (2,81) = 6.87; p = 0.002]. The standardized coefficient value is −0.29 for the right caudate and–0.24 for the left inferior frontal region ( Sidtis et al, 2021 ). The negatively weighted left inferior frontal region is adjacent and inferior to the positively weighted left inferior region found in the New York normal group.…”

“…The graph on the left presents the mean normalized CBF (± SEM) for the head of the caudate nuclei, and the inferior frontal region, bilaterally. The graph on the right presents the linear regression weights for the two predictor regions ( Sidtis et al, 2021 ). The negatively weighted left inferior frontal region is adjacent and inferior to the left inferior predictor region in the NY normal group.…”

“…The positively weighted inferior frontal region is the same region found in the New York normal group. It is interesting to note that the significant left greater than right CBF in the lower inferior frontal region is negatively weighted in the regression model ( Sidtis et al, 2021 ). This may reflect an effect of DBS.…”

“…The initial observation in normal speakers ( Sidtis et al, 2003 ) was replicated in a different group of normal speakers in a different scanner ( Sidtis et al, 2018 ) using the normalized CBF approach. This pattern was also identified in three genotypes of hereditary spinocerebellar ataxia ( Sidtis et al, 2006 , 2010 ), in an impaired form in individuals with Parkinson’s disease not treated with deep brain stimulation (DBS), and in a modified form in individuals with Parkinson’s disease treated with DBS of the subthalamic nucleus ( Sidtis et al, 2021 ).…”

Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation

“…For example, positron emission tomography (PET) is feasible in parallel to all three brain stimulation methods described in this review (TMS [ 85 , 89 ], DBS [ 252 , 253 ], and tES [ 254 , 255 ]). In the past, however, PET was mainly used to investigate how brain activity changes in response to brain stimulation, i.e., regional cerebral blood flow was assessed [ 256 ]. It is, however, also possible to investigate how brain stimulation changes the binding of very specialized ligands to certain neurotransmitters and their receptors [ 257 ].…”