Antiparkinson medication and subthalamic nucleus deep brain stimulation (STN-DBS), two common treatments of Parkinson's disease (PD), effectively improve skeletomotor movements. However, evidence ...suggests that these treatments may have differential effects on eye and limb movements, although both movement types are controlled through the parallel basal ganglia loops.
Using a task that requires both eye and upper limb movements, we aimed to determine the effects of medication and STN-DBS on eye and upper limb movement performance.
Participants performed a visually-guided reaching task. We collected eye and upper limb movement data from participants with PD who were tested both OFF and ON medication (
= 34) or both OFF and ON bilateral STN-DBS while OFF medication (
= 11). We also collected data from older adult healthy controls (
= 14).
We found that medication increased saccade latency, while having no effect on reach reaction time (RT). Medication significantly decreased saccade peak velocity, while increasing reach peak velocity. We also found that bilateral STN-DBS significantly decreased saccade latency while having no effect on reach RT, and increased saccade and reach peak velocity. Finally, we found that there was a positive relationship between saccade latency and reach RT, which was unaffected by either treatment.
These findings show that medication worsens saccade performance and benefits reaching performance, while STN-DBS benefits both saccade and reaching performance. We explore what the differential beneficial and detrimental effects on eye and limb movements suggest about the potential physiological changes occurring due to treatment.
•Right unilateral STN-DBS is not significantly different from OFF stimulation at impacting rightward saccades.•Left unilateral and bilateral STN-DBS benefit the motor aspects of rightward ...visually-guided saccades.•Left unilateral and bilateral STN-DBS only benefits saccade latency when the fixation-related attentional system is not engaged.
We aimed to gain further insight into previously reported beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on visually-guided saccades by examining the effects of unilateral compared to bilateral stimulation, paradigm, and target eccentricity on saccades in individuals with Parkinson’s disease (PD).
Eleven participants with PD and STN-DBS completed the visually-guided saccade paradigms with OFF, RIGHT, LEFT, and BOTH stimulation. Rightward saccade performance was evaluated for three paradigms and two target eccentricities.
First, we found that BOTH and LEFT increased gain, peak velocity, and duration compared to OFF stimulation. Second, we found that BOTH and LEFT stimulation decreased latency during the gap and step paradigms but had no effect on latency during the overlap paradigm. Third, we found that RIGHT was not different compared to OFF at benefiting rightward saccade performance.
Left unilateral and bilateral stimulation both improve the motor outcomes of rightward visually-guided saccades. Additionally, both improve latency, a cognitive-motor outcome, but only in paradigms when attention does not require disengagement from a present stimulus.
STN-DBS primarily benefits motor and cognitive-motor aspects of visually-guided saccades related to reflexive attentional shifting, with the latter only evident when the fixation-related attentional system is not engaged.
•Saccade latency is prolonged as disease severity increases, irrespective of whether participants were off or on medication.•Medication effects interact with task manipulations, such as paradigm and ...target eccentricity.•Medication has adverse effects on saccade latency, gain, and peak velocity; medication may impair rapid shifts of attention.
We examined whether previous inconsistent findings about the effect of anti-Parkinsonian medication on visually-guided saccades (VGS) were due to the use of different paradigms, which change the timing of fixation offset and target onset, or different target eccentricities.
Thirty-three participants with Parkinson’s disease (PD) completed the VGS tasks OFF and ON medication, along with 13 healthy controls. Performance on 3 paradigms (gap, step, and overlap) and 2 target eccentricities was recorded. We used mixed models to determine the effect of medication, paradigm, and target eccentricity on saccade latency, gain, and peak velocity.
First, we confirmed known paradigm effects on latency, and target eccentricity effects on gain and peak velocity in participants with PD. Second, latency was positively associated with OFF medication Movement Disorders Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score in PD. Third, medication prolonged latency for the larger target eccentricity across the 3 paradigms, while decreasing gain and peak velocity in the step paradigm across target eccentricities.
Medication adversely affected and was not therapeutically beneficial for VGS. Previous inconsistencies may have resulted from chosen target eccentricity.
The negative medication effect on VGS may be clinically significant, as many activities in daily life require oculomotor control, inhibitory control, and visually-guided shifts of attention.
An inflammation-driven model of PD has been proposed based on the endotoxin lipopolysaccaride (LPS), a potential source of inflammation in the gastrointestinal system linked to neurotoxicity. ...Systemic exposure to bacterial endotoxin (LPS) can be determined by measuring plasma LPS binding protein (LBP). We aimed to evaluate whether lipopolysaccharide binding protein (LBP) can be used to distinguish PD subjects from control subjects and to assess whether LBP levels correlate with PD disease severity.
We measured plasma LBP (ng/ml) using an ELISA kit in 94 PD subjects of various stages and 97 control subjects. Disease severity was assessed using the UPDRS and Hoehn and Yahr staging. The LBP level between the PD and control groups was compared using analysis of covariance. Spearman correlation was used to explore the relationship between LBP level and disease severity.
The mean LBP level in PD subjects (n = 94) was significantly different from control subjects (n = 95, p = 0.018). In PD subjects, we did not find a correlation between mean LBP level and disease severity.
Our data suggests that LBP is one GI biomarker related to LPS induced neurotoxicity. However, there was significant variability in LBP levels within the PD and control groups, limiting its utility as a stand-alone biomarker. This study supports the role of LPS induced neurotoxicity in PD and further exploration of this pathway may be useful in developing sensitive and specific biomarkers for PD.
Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). G
(
) mutation carriers, compared to sporadic PD, present ...with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between
and non-
mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-
and
mutation carriers with PD.
STN (left and right) resting state local field potentials were recorded intraoperatively from 4
and 5 non-
patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity.
Peak beta ratio was significantly different between the left and the right STN for the
group (
< 0.01) but not the non-
group (
= 0.56) after co-varying for age, age of disease onset, and disease severity.
Peak beta ratio in
mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that
mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.
Memory-guided movements, vital to daily activities, are especially impaired in Parkinson's disease (PD). However, studies examining the effects of how information is encoded in memory and the effects ...of common treatments of PD, such as medication and subthalamic nucleus deep brain stimulation (STN-DBS), on memory-guided movements are uncommon and their findings are equivocal. We designed two memory-guided sequential reaching tasks, peripheral-vision or proprioception encoded, to investigate the effects of encoding type (peripheral-vision vs. proprioception), medication (on- vs. off-), STN-DBS (on- vs. off-, while off-medication), and compared STN-DBS vs. medication on reaching amplitude, error, and velocity. We collected data from 16 (analyzed
= 7) participants with PD, pre- and post-STN-DBS surgery, and 17 (analyzed
= 14) healthy controls. We had four important findings. First, encoding type differentially affected reaching performance: peripheral-vision reaches were faster and more accurate. Also, encoding type differentially affected reaching deficits in PD compared to healthy controls: peripheral-vision reaches manifested larger deficits in amplitude. Second, the effect of medication depended on encoding type: medication had no effect on amplitude, but reduced error for both encoding types, and increased velocity only during peripheral-vision encoding. Third, the effect of STN-DBS depended on encoding type: STN-DBS increased amplitude for both encoding types, increased error during proprioception encoding, and increased velocity for both encoding types. Fourth, STN-DBS was superior to medication with respect to increasing amplitude and velocity, whereas medication was superior to STN-DBS with respect to reducing error. We discuss our findings in the context of the previous literature and consider mechanisms for the differential effects of medication and STN-DBS.
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