Navigating Visual Challenges: How Parkinson's Disease Alters Cognitive Priorities in Visual Search.

OBJECTIVE: Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. METHODS: We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real-world scenes. RESULTS: PD participants prolonged fixation on high-probability (high-prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high-probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. CONCLUSION: This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo-cognitive deficits in PD patients.

Does Vestibular Motion Perception Correlate with Axonal Pathways Stimulated by Subthalamic Deep Brain Stimulation in Parkinson's Disease?

Perception of our linear motion - heading - is critical for postural control, gait, and locomotion, and it is impaired in Parkinson's disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30° to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts' involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases, there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD.

The Black and African American Connections to Parkinson's Disease (BLAAC PD) study protocol.

Determining the genetic contributions to Parkinson's disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson's Disease (BLAAC PD) study is part of the Global Parkinson's Genetics Program, supported by the Aligning Science Across Parkinson's initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.

DNM1L variant presenting as adolescent-onset sensory neuronopathy, spasticity, dystonia, and ataxia.

DMN1L encodes for dynamin-like protein 1 (DLP1) which plays a key role in perixosomal and mitochondrial fission. Individuals with heterozygous variants in DNM1L present with a wide range of neurologic symptoms, including encephalopathy, epilepsy, and motor deficits. Here we report on a woman presenting with adolescence onset of sensory neuronopathy, spasticity, dystonia, and ataxia. Trio genome sequencing identified a heterozygous variant in DNM1L (NM_012062.3 c.121G>A/p.Val41Met) which was thought to be pathogenic. This case describes the latest known symptomatic onset of DMN1L-related disease described in literature. We highlight our approach to a challenging diagnostic workup and interpretation of a specific variant that has not been previously reported. Furthermore, the case highlights the diagnostic importance of utilizing genomic sequencing and research studies for patients with rare disease.

Temporal Patterns of Spontaneous Fixational Eye Movements: The Influence of Basal Ganglia.

BACKGROUND: Spontaneity is a unique feature of the nervous system. One of the fundamentally critical and recognized forms of spontaneous motor activity is witnessed in the visuomotor system. Microsaccades, the miniature spontaneous eye movements, are critical for the visual perception. We hypothesized that microsaccades follow specific temporal patterns that are modulated by the basal ganglia output. METHODS: We used high-resolution video-oculography to capture microsaccades in 48 subjects (31 healthy and 17 with Parkinson's disease) when subjects were asked to hold their gaze on a straight-ahead target projected on white background. We analyzed spontaneous discharge patterns of microsaccades. RESULTS: The first analysis considering coefficient of variation in intersaccadic interval distribution demonstrated that microsaccades in Parkinson's disease are more dispersed than the control group. The second analysis scrutinized microsaccades' temporal variability and revealed 3 distinct occurrence patterns: regular rhythmic, clustered, and randomly occurring following a Poisson-like process. The regular pattern was relatively more common in Parkinson's disease. Subthalamic DBS modulated this temporal pattern. The amount of change in the temporal variability depended on the DBS-induced volume of tissue activation and its overlap with the subthalamic nucleus. The third analysis determined the autocorrelations of microsaccades within 2-second time windows. We found that Parkinson's disease altered local temporal organization in microsaccade generation, and DBS had a modulatory effect. CONCLUSION: The microsaccades occur in 3 temporal patterns. The basal ganglia are one of the modulators of the microsaccade spontaneity.

Severity-Dependent Effects of Parkinson's Disease on Perception of Visual and Vestibular Heading.

OBJECTIVES: Parkinson's disease (PD) commonly affects visuospatial navigation causing postural instability and falls. Our overarching aim was to examine the visual and vestibular systems governing visuospatial navigation in PD. We hypothesize that PD affects vestibular and visual motion perception but to a different extent. The effects of PD on motion perception are dependent on the severity of the disease. METHODS: The two-alternative-forced-choice task objectively measured the motion perception during two experiments. One experiment examined the vestibular motion perception with en bloc movement of the platform. The second experiment tested the visual motion perception using an immersive virtual reality goggle. RESULTS: We found that accuracy, threshold, and precision of vestibular perception were more impaired in advanced-PD patients compared to those with a mild form of the disease. The parameters also correlated with the disease duration, overall axial motor impairment causing postural instability and falls, and subjective rating of the balance function. Such changes were present but less severe in visual motion perception. CONCLUSION: We conclude that PD affects motion perception in the visual and vestibular domains in a severity-dependent manner. The impact of the disease in the vestibular domain is more severe compared to the visual domain. © 2020 International Parkinson and Movement Disorder Society.

Effects of subthalamic deep brain stimulation on fixational eye movements in Parkinson's disease.

Miniature yoked eye movements, fixational saccades, are critical to counteract visual fading. Fixational saccades are followed by a return saccades forming squarewaves. Present in healthy states, squarewaves, if too many or too big, affect visual stability. Parkinson's disease (PD), where visual deficits are not uncommon, is associated with the squarewaves that are excessive in number or size. Our working hypothesis is that the basal ganglia are at the epicenter of the abnormal fixational saccades and squarewaves in PD; the effects are manifested through their connections to the superior colliculus (affecting saccade frequency and amplitude) and the cerebellum (affecting velocity and amplitude). We predict that the subthalamic deep brain stimulation (DBS) variably affects the amplitude, frequency, and velocity of fixational saccade and that the effect depends on the electrode's proximity or the volume of activated tissue in the subthalamic nucleus' connections with the superior colliculus or the cerebellum. We found that DBS modulated saccade amplitude, frequency, and velocity in 11 PD patients. Although all three parameters were affected, the extent of the effects varied amongst subjects. The modulation was dependent upon the location and size of the electrically activated volume of the subthalamic region.

Effects of Parkinson Disease on Blur-Driven and Disparity-Driven Vergence Eye Movements.

ABSTRACT: Synchronous movements of the 2 eyes in the opposite direction, disconjugate movements such as vergence, facilitate depth perception. The vergence eye movements are affected in Parkinson disease (PD). Visual blur (accommodation) and fusion (retinal disparity) are important triggers for the vergence. The neural circuit responsible for blur-driven and disparity-driven vergence is tightly coupled. We investigated the effect of PD on these 2 vergence paradigms. In the experiment involving 14 patients with PD and 6 healthy controls, substantial differences between blur-driven and disparity-driven vergence were found. The gain (ratio of actual vs desired eye movements) was reduced in patients with PD in case of disparity-driven vergence but not in blur-driven vergence. The latency of disparity-driven vergence onset was significantly longer for patients with PD compared with healthy controls. Four strategies were used to drive disparity-driven vergence: a) pure disconjugate vergence, b) conjugate saccadic movements, c) disconjugate vergence followed by saccadic movements, and d) conjugate saccades followed by disconjugate vergence movements. Blur-driven vergence had only 2 strategies: a) conjugate saccades followed by disconjugate vergence and b) conjugate saccadic movements only. The results are consistent with the prediction that PD primarily affects disparity-driven vergence, but there are some effects on the strategies to execute blur-driven vergence. We speculate that the deep cerebellar nuclei and the supraoculomotor area of the midbrain that carry the disparity-driven and blur-driven vergence are affected in PD. It is possible to modulate their function through projections to the subthalamic nuclei.

Automated Computer Vision Assessment of Hypomimia in Parkinson Disease: Proof-of-Principle Pilot Study.

BACKGROUND: Facial expressions require the complex coordination of 43 different facial muscles. Parkinson disease (PD) affects facial musculature leading to "hypomimia" or "masked facies." OBJECTIVE: We aimed to determine whether modern computer vision techniques can be applied to detect masked facies and quantify drug states in PD. METHODS: We trained a convolutional neural network on images extracted from videos of 107 self-identified people with PD, along with 1595 videos of controls, in order to detect PD hypomimia cues. This trained model was applied to clinical interviews of 35 PD patients in their on and off drug motor states, and seven journalist interviews of the actor Alan Alda obtained before and after he was diagnosed with PD. RESULTS: The algorithm achieved a test set area under the receiver operating characteristic curve of 0.71 on 54 subjects to detect PD hypomimia, compared to a value of 0.75 for trained neurologists using the United Parkinson Disease Rating Scale-III Facial Expression score. Additionally, the model accuracy to classify the on and off drug states in the clinical samples was 63% (22/35), in contrast to an accuracy of 46% (16/35) when using clinical rater scores. Finally, each of Alan Alda's seven interviews were successfully classified as occurring before (versus after) his diagnosis, with 100% accuracy (7/7). CONCLUSIONS: This proof-of-principle pilot study demonstrated that computer vision holds promise as a valuable tool for PD hypomimia and for monitoring a patient's motor state in an objective and noninvasive way, particularly given the increasing importance of telemedicine.

Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism.

BACKGROUND: X-linked dystonia parkinsonism (XDP) causes adult-onset progressive dystonia and parkinsonism, which may not respond to pharmacotherapy. OBJECTIVE: Previous case reports have reported beneficial effects from bilateral pallidal (GPi) deep brain stimulation (DBS). Here, we report the long-term clinical outcomes of 3 patients treated at our center. METHODS: All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Adverse events were recorded. RESULTS: The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other. CONCLUSION: Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms.

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

BACKGROUND: Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. METHODS: Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. RESULTS: Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). CONCLUSIONS: Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

Improved Side-Effect Stimulation Thresholds and Postoperative Transient Confusion With Asleep, Image-Guided Deep Brain Stimulation.

BACKGROUND AND OBJECTIVES: Asleep, image-guided deep brain stimulation (DBS) is a modern alternative to awake, microelectrode recording (MER) guidance. Studies demonstrate comparable efficacy and complications between techniques, although some report lower stimulation thresholds for side effects with image guidance. In addition, few studies directly compare the risk of postoperative transient confusion (pTC) across techniques. The purpose of this study was to compare clinical efficacy, stimulation thresholds for side effects, and rates of pTC with MER-guided DBS vs intraoperative 3D-fluoroscopy (i3D-F) guidance in Parkinson's disease and essential tremor. METHODS: Consecutive patients from 2006 to 2021 were identified from the departmental database and grouped as having either MER-guided DBS or i3D-F-guided DBS insertion. Directional leads were used once commercially available. Changes in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, levodopa equivalent daily dose, Fahn-Tolosa-Marin scores, and stimulation thresholds were assessed, as were rates of complications including pTC. RESULTS: MER guidance was used to implant 487 electrodes (18 globus pallidus interna, GPi; 171 subthalamic nucleus; 76 ventrointermediate thalamus, VIM) in 265 patients. i3D-F guidance was used in 167 electrodes (19 GPi; 25 subthalamic nucleus; 41 VIM) in 85 patients. There were no significant differences in Unified Parkinson's Disease Rating III Scale, levodopa equivalent daily dose, or Fahn-Tolosa-Marin between groups. Stimulation thresholds for side effects were higher with i3D-F guidance in the subthalamic nucleus (MER, 2.80 mA ± 0.98; i3D-F, 3.46 mA ± 0.92; P = .002) and VIM (MER, 2.81 mA ± 1.00; i3D-F, 3.19 mA ± 1.03; P = .0018). Less pTC with i3D-F guidance (MER, 7.5%; i3D-F, 1.2%; P = .034) was also found. CONCLUSION: Although clinical efficacy between MER-guided and i3D-F-guided DBS was comparable, thresholds for stimulation side effects were higher with i3D-F guidance and the rate of pTC was lower. This suggests that image-guided DBS may affect long-term side effects and pose a decreased risk of pTC.

A Genetics Pearl for Counseling Patients with Epsilon-Sarcoglycan Myoclonus-Dystonia.

Background: Epsilon-sarcoglycan (SGCE) myoclonus-dystonia is autosomal dominant (AD) with reduced penetrance due to maternal imprinting 95% of the time. Patients may lack family history delaying diagnosis and treatment. Additionally, counseling patients on their risk of passing on the variant differs for females versus males. Case Report: A woman in her thirties with typical phenotype of myoclonus-dystonia but lacking an AD pedigree was found to have a pathogenic variant in the SGCE gene. She was counseled that her daughters each have a 2.5% chance of expressing the phenotype. Discussion: Understanding the genetics of SGCE-myoclonus-dystonia enables effective genetic counseling and arrival at a timely diagnosis and treatment. Summary: In an era of advancing genetic analysis and precision medicine-based treatments, neurologists will be faced with increasing responsibility to properly counsel patients on the results of genetic testing. This case highlights a genetics pearl for counseling patients with epsilon-sarcoglycan myoclonus-dystonia, an autosomal dominant condition with penetrance differing by sex.

Objective assessment of eye alignment and disparity-driven vergence in Parkinson's disease.

Background: Self-reported diplopia is described in up to one-third of Parkinson's disease (PD) patients. Objective: The purpose of our study was to expand our understanding of the mechanistic underpinnings of diplopia in PD. We hypothesize that the time-based control of eye alignment and increased eye deviation under binocular viewing will be related to the fusion-initiating and fusion-maintaining component deficits of disparity-driven vergence in PD. Methods: We used high-resolution video-oculography to measure eye alignment under binocular and monocular viewing and disparity-driven vergence in 33 PD and 10 age-matched healthy participants. We computed eye deviation and time-based control of eye alignment, occurrence of conjugate saccadic eye movements, latency and gain of vergence (fusion initiation), and variance of eye position at the end of dynamic vergence (fusion maintenance). Results: We categorized PD subjects into three groups, considering their time-based control of eye alignment as compared to healthy controls in binocular viewing. Group 1 = 45% had good control and spent >80% of the time when the eyes were well-aligned, Group 2 = 26% had intermediate control and spent <80% but greater >5% of the time when the eyes were well-aligned, and Group 3 = 29% had very poor control with increased eye deviation majority of the times (<5% of the time when the eyes were well-aligned). All three groups exhibited greater eye deviation under monocular viewing than controls. PD subjects exhibited fusion-initiating and fusion-maintaining vergence deficits (prolonged latencies, reduced vergence gain, increased variance of fusion-maintaining component) with a greater probability of saccadic movements than controls. Group 2 and Group 3 subjects were more likely to exhibit failure to initiate vergence (>20%) than Group 1 (13%) and controls (0%) trials. No significant difference was found in the Unified Parkinson's Disease Rating Scale (UPDRS-a tool to measure the severity of PD) values between the three PD groups (Group 1 = 33.69 ± 14.22, Group 2 = 38.43 ± 22.61, and Group 3 = 23.44 ± 1, p > 0.05). Conclusion: The majority of PD subjects within our cohort had binocular dysfunction with increased eye deviation under monocular viewing and disparity-driven vergence deficits. PD subjects with intermediate or poor control of eye deviation under binocular viewing had greater fusion-initiating and fusion-maintaining vergence deficits. The study highlights the importance of assessing binocular dysfunction in PD subjects independent of the severity of motor symptoms.

Physiological measures and anatomical correlates of subthalamic deep brain stimulation effect on gait in Parkinson's disease.

We examined whether conflicting visual and non-visual information leads to gait abnormalities and how the subthalamic deep brain stimulation (STN DBS) influences gait dysfunction in Parkinson's disease (PD). We used a motion capture system to measure the kinematics of the lower limbs during treadmill walking in immersive virtual reality. The visual information provided in the virtual reality paradigm was modulated to create a mismatch between the optic-flow velocity of the visual scene and the walking speed on the treadmill. In each mismatched condition, we calculated the step duration, step length, step phase, step height, and asymmetries. The key finding of our study was that mismatch between treadmill walking speed and the optic-flow velocity did not consistently alter gait parameters in PD. We also found that STN DBS improved the PD gait pattern by changing the stride length and step height. The effects on phase and left/right asymmetry were not statistically significant. The DBS parameters and location also determined its effects on gait. Statistical effects on stride length and step height were noted when the DBS volume of activated tissue (VTA) was in the dorsal aspect of the subthalamus. The statistically significant effects of STN DBS was present when VTA significantly overlapped with MR tractogrphically measured motor and pre-motor hyperdirect pathways. In summary, our results provide novel insight into ways for controlling walking behavior in PD using STN DBS.

Dystonia Due to GM3 Synthase Deficiency.

BACKGROUND: Gangliosides are expressed in neuronal membranes, and play roles in neuronal differentiation and cell regulation during brain development. The ST3GAL5 gene encodes the enzyme GM3 synthase, and its deficiency causes a rare condition described to cause refractory epilepsy, profound intellectual disability, quadriplegia, choreoathetosis, and pigmentary skin changes. GM3 synthase deficiency is rarely reported to cause dystonia. We report five cases of GM3 synthase deficiency involving a dystonic phenotype. CASES: The five reported individuals were born of unaffected consanguineous parents from Old Order Amish families. They all developed refractory epilepsy and developmental regression within the first few months of life. They exhibit variable degrees of extrapyramidal movements, including orofacial, cervical, and limb dystonia, as well as choreoathetosis. CONCLUSIONS: We report five individuals with GM3 synthase deficiency who developed dystonic features. Dystonia has previously been reported in only one case of GM3 synthase deficiency.

Eye movements in Parkinson's disease during visual search.

Visual spatial dysfunction is not uncommon in Parkinson's disease. We hypothesized that visual search behavior is impaired in Parkinson's disease and the deficits correlate with changes in the amplitudes and frequency of fixational and non-fixational rapid eye movements. We measured eye movements, the horizontal and vertical angular position vectors of the right and left eye using high-resolution video oculography, in the Parkinsonian cohort who viewed a blank scene and pictures with real-life scene. Latter was associated with a task of searching an object hidden in a clutter, either at an expected or an unexpected location. Parkinsonian cohort took longer initial time to reach the region of interest. The ultimate response time was comparable in both Parkinson's disease and their healthy peers. The fixation duration was comparable in two cohorts but there was a trend wise decline for the ones located at unexpected locations. Parkinson's disease participants made more fixational saccades with significantly larger amplitude and less non-fixational saccades with significantly smaller amplitude during blank scene viewing. However, overall scanned area of the blank scene was not affected in Parkinson's disease. The Parkinson's disease participants made less non-fixational saccades with amplitudes comparable to healthy control during the visual search of a target object. Fixational saccades during visual search were larger in Parkinson's disease particularly when target was placed at an unexpected location, but the frequency was unchanged.

Does visuospatial motion perception correlate with coexisting movement disorders in Parkinson's disease?

Postural instability and balance impairment are common in Parkinson's disease (PD). Multiple factors, such as increased tone, bradykinesia, freezing of gait, posture, axial stiffness, and involuntary appendicular movements, can affect balance. The recent studies found that PD patients have abnormal perception of self-motion in vestibular domain. We asked whether measures of balance function, such as perception of one's motion, correlate with specific movement disorders seen in PD. Moving retinal image or self-motion in space triggers the perception of self-motion. We measured one's linear motion (heading) perception when subjects were moved en bloc using a moving platform (vestibular heading). Similar motion perception was generated in the visual domain (visual heading) by having the subjects view a 3D optical flow with immersive virtual reality goggles. During both tasks, the subjects reported the motion direction in the two-alternative-forced-choice paradigm. The accuracy of perceived motion direction was calculated from the responses fitted to the psychometric function curves to estimate how accurately and precisely the subjects can perceive rightward versus leftward motion (i.e., threshold and slope). Response accuracies and psychometric parameters were correlated with the disease duration, disease severity (total Unified Parkinson's Disease Rating Scale-III, UPDRS-III), and tremor, rigidity, axial, gait/posture components of UPRDS-III. We also correlated heading perception with the number of falls and subjective assessment of balance confidence using the Activities-Specific Balance Component (ABC) Scale. Accuracy, threshold, and sensitivity of vestibular heading perception significantly correlated with the disease duration and severity, particularly the tremor. Correlations were stronger for leftward heading perception in the vestibular domain. The visual heading perception was correlated with ABC Scale, especially with its items concerning optic-flow processing. There was asymmetry in leftward versus rightward vestibular heading perception. The level of asymmetry correlated with the axial component of UPDRS-III. Differences in the clinical parameters that correlate with visual versus vestibular heading perception suggest that two heading perception processes have different mechanistic underpinnings. The correlation of discordance between vestibular and visual heading perception with disease severity and duration suggests that visual function can be utilized for balance rehab in PD patients.

Subthalamic deep brain stimulation affects heading perception in Parkinson's disease.

Parkinson's disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates visuospatial perception. We hypothesized that DBS has different effects on visual and vestibular perception of linear motion (heading), a critical aspect of visuospatial navigation; and such effects are specific to modulated STN location. Two-alternative forced-choice experiments were performed in 14 PD patients with bilateral STN DBS and 19 age-matched healthy controls (HC) during passive en bloc linear motion and 3D optic-flow in immersive virtual reality measured vestibular and visual heading. Objective measure of perception with Weibull psychometric function revealed that PD has significantly lower accuracy [L: 60.71 (17.86)%, R: 74.82 (17.44)%] and higher thresholds [L: 16.68 (12.83), R: 10.09 (7.35)] during vestibular task in both directions compared to HC (p < 0.05). DBS significantly improved vestibular discrimination accuracy [81.40 (14.36)%] and threshold [4.12 (5.87), p < 0.05] in the rightward direction. There were no DBS effects on the slopes of vestibular psychometric curves. Visual heading perception was better than vestibular and it was comparable to HC. There was no significant effect of DBS on visual heading response accuracy or discrimination threshold (p > 0.05). Patient-specific DBS models revealed an association between change in vestibular heading perception and the modulation of the dorsal STN. In summary, DBS may have different effects on vestibular and visual heading perception in PD. These effects may manifest via dorsal STN putatively by its effects on the cerebellum.