Lisa Graham

Background: Postural instability is one of the most debilitating symptoms of Parkinson’s disease (PD). Moreover, older adults (OA) often show issues with postural control leading to increased fall-risk. However, the current understanding of the neural underpinnings of standing postural control remains limited. This study aims to investigate cortical control of postural control in OA, younger adults (YA), and people with PD (PwPD), using functional near-infrared spectroscopy (fNIRS). Methods: A total of four 2-minute standing conditions were performed. Postural control and cortical activity were recorded in 80 PwPD, 33 OA, and 38 YA. A wireless fNIRS system recorded changes in relative oxygenated haemoglobin (∆HbO ₂ ) across cortical regions including the prefrontal cortex (PFC), supplementary motor area (SMA), primary motor cortex (M1), primary somatosensory cortex (S1), and primary visual cortex (V1). Six wearable sensors provided sway outcome measures (area, jerkiness velocity, root mean square, and frequency). Results: Sway outcomes were greater across several conditions in PwPD. Significant group effects were found with increased ∆HbO ² in the PFC in PD compared to OA. Moreover, YA had increased ∆HbO ₂ in the S1 compared to OA and PD. Conclusions: PwPD showed greater PFC recruitment, indicating reliance on executive-attentional resources for balance. In contrast, YA engaged somatosensory regions more strongly, suggesting that ageing may affect the integration of sensory information for postural control. Findings support interventions that (a) reduce executive load during balance in PD and (b) bolster somatosensory integration in ageing.

Ocular microtremor (OMT) is an involuntary fixational eye movement linked to brainstem activity. OMT is thought to have a mean frequency range of 70–90 Hz in healthy adults. Previous research suggests OMT may be reduced in neurological diseases like Parkinson’s Disease. Historically, OMT has been measured invasively in specialist laboratories using lengthy and expensive protocols. Developments now allow for OMT measurement quickly and non-invasively using hand-held technology (i.e., iTremor ONE). This pilot study aimed to examine the analytical and clinical validation of OMT measurement via the iTremor ONE in people with Parkinson’s Disease (PwPD). 33 PwPD and 31 age matched healthy controls participated in this study. For analytical validation, 22 PwPD completed a test re-test reliability assessment of OMT measurement, assessed using interclass correlation coefficients (ICC). For clinical validation, OMT frequency in PwPD (n = 33) was compared to controls. Correlations were explored with demographics and clinical scales. Additionally, 24 PwPD were tested ‘OFF’ (12hr withdrawal) and ‘ON’ their anti-Parkinson’s (dopaminergic) medication to compare OMT response to a known intervention. The iTremor ONE demonstrated excellent test-retest reliability (ICC > 0.9) for measuring OMT frequency in PwPD. Mean OMT frequency was significantly lower in PwPD (63.78 ± 4.82 Hz) compared to controls (69.44 ± 6.47 Hz, p < .001), with good discriminative ability (AUC 0.75-0.77). OMT frequency correlated with age in both groups and with specific motor features (speech, facial expression, gait) in PwPD. No significant differences in OMT frequency were observed between ‘OFF’ and ‘ON’ dopaminergic medication states. This is the first study to demonstrate that a non-invasive hand-held device can reliably measure OMT in PwPD and presents OMT analytical and clinical validation evidence. OMT frequency may provide a supporting measure for diagnosis or screening. Further research is required to understand the neural mechanisms underpinning OMT in PwPD and the role it could play in clinical practice.

Pupil response may be a useful biomarker in Parkinson’s disease (PD) due to links with autonomic function and cognitive load. However, research has focused on static tasks, missing functional demands during real-world activities like walking. Methods: We recruited 38 people with PD and 16 healthy controls who walked for 2 min under single- and dual-task conditions while wearing mobile eye-tracking glasses (Tobii Pro Glasses 2, 100 Hz). Pupil response outcomes (velocity, size, difference between eyes) were extracted alongside gait characteristics from inertial sensors. Known groups validity compared PD and controls; convergent/divergent validity examined relationships with cognitive, visual, clinical, and gait measures. Results: People with PD had significantly altered pupil constriction/dilation velocity (p = 0.01), a larger difference between their left and right pupils (p = 0.04), and a larger mean and minimum pupil size (p ≤ 0.01) compared to controls during walking. Pupil response correlated with cognitive function (JLO, CLOX1, TMTB), visual acuity, disease severity (MDS-UPDRS-III), and gait characteristics in both groups. No dual-task effects were observed. Conclusions: Pupil response during walking demonstrates known groups and convergent validity, indicating potential as a clinical biomarker for PD. Following this initial study, more research is required to further validate pupil response in PD (e.g., analytical validation and testing within real-world ecologically valid environments).

Background: Gait impairment in Parkinson’s disease (PD) occurs early and pharmaceutical interventions do not fully restore this function. Visual cueing has been shown to improve gait and alleviate freezing of gait (FOG) in PD. Technological development of digital laser shoe visual cues now allows for visual cues to be used continuously when walking. This study aimed to investigate the effects of laser shoe visual cueing on gait in people with PD across different disease severity (i.e., Hoehn & Yahr [H&Y] stages I-III) and FOG status. Methods: Eighty people with PD (H&YI = 20, H&YII = 30 [15 FOG, 15 noFOG], H&YIII = 30 [15 FOG, 15 noFOG]) walked a 10 m straight path (back and forth) self-paced for 80 seconds without and then with laser shoe cues (participants were allowed 1-2 walks to familiarize with the cues). Inertial sensors were used to measure gait metrics. Laser cue line was set to usual step length for individuals based on their usual walk data from the inertial sensors. Results: Laser shoe cueing did not improve gait in PD regardless of disease severity or FOG status. Across all groups, participants decreased gait speed ( P < .001), cadence ( P < .001), arm range of motion ( P < .005), and increased stride time, double support time ( P < .001), elevation at midswing ( P < .001), and gait variability ( P < .001) with the laser shoes compared to usual walking. Conclusion: Digital laser shoe visual cues do not improve gait in people with PD across disease severity or FOG status. Further investigation is required to examine different cue settings or exposure periods.

Background: Internal and external cueing strategies are often applied to alleviate gait deficits in Parkinson’s disease (PD). However, it remains unclear which type of cueing strategy is most effective at different disease stages. The underlying neural mechanisms of response to cueing are also unknown. Objective: To investigate the immediate response of multiple brain cortical regions and gait to internal and external cueing in people at different stages of PD. Methods: People with PD (n = 80) were split into groups dependent on their disease stage (Hoehn and Yahr [H&Y] stage I to III). Participants performed a baseline walk without cues followed by randomized cued walking conditions (internal and external [visual, auditory and tactile] cues). A combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) system assessed cortical brain activity while walking. Wearable inertial sensors assessed gait. Results: Cue-related gait improvements were not influenced by H&Y stage; moderate or large effect sizes were only observed for internal cueing and external visual cueing. fNIRS findings suggested cortical response was similar across H&Y stages, with increased activity in the prefrontal cortex with internal cues; and increased activity in the primary motor and visual cortices with external cues. However, EEG showed that people with PD in H&YIII had higher parietal alpha power than those in H&YI in the auditory, tactile, and visual cueing conditions. Conclusion: Gait improvement with cueing was similar across PD stages and underpinned by cognitive, motor, and/or sensory neural processing within selective brain regions that may be influenced by PD stage (i.e., parietal cortex).

Ocular microtremor (OMT) is a fixational eye movement that cannot be seen with the naked eye but is always present, even when the eye appears motionless/still. The link between OMT and brain function provides a strong rationale for investigation as there lies potential for its use as a biomarker in populations with neurological impairments. OMT frequency is typically 70-80Hz in healthy adults and research suggests that this will be reduced in those with neurological disease such as Parkinson’s Disease (PD). This study aims to examine OMT in people with PD compared to healthy older adults. This is an exploratory, observational study that will use a novel handheld device–The iTremor ONE, which has been developed to rapidly, non-invasively assess and evaluate OMT frequency. This device uses incident laser technology directed at the sclera. People with PD who meet the inclusion criteria will participate in a home-based assessment involving cognitive, motor (using the UPDRS-III) and OMT measures. With OMT as the primary outcome, assessment with the iTremor is quick, taking just three seconds to obtain a reading. People with PD will be invited into the laboratory to perform extensive cognitive assessments along with an assessment of balance, gait, and turning using wearable sensors. People with PD will be assessed both off, and on, their anti-parkinsonian medication following a 12 hour washout period. We will recruit 30 People with PD, 30 people with suspected PD and 30 age-matched healthy control participants for assessment of OMT. 20 People with PD will complete a test-retest reliability assessment at the same approximate time, exactly one week after their initial visit under the same conditions to explore consistency. This will be the first study of its kind to non-invasively investigate OMT frequency as a marker/monitor for PD with advanced technology that could be used within the clinic, laboratory, or home. Identifying OMT as a PD biomarker could better support clinical assessment, enabling improved provision of care to patients with advanced disease monitoring. Clinical trial registration: This trial is registered at clinicaltrials.gov (NCT06051877; September 2023).

Eye-movement assessment is a key component of neurological evaluation, offering valuable insights into neural deficits and underlying mechanisms. This narrative review explores the emerging subject of digital eye-movement outcomes (DEMOs) and their potential as sensitive biomarkers for neurological impairment. Eye tracking has become a useful method for investigating visual system functioning, attentional processes, and cognitive mechanisms. Abnormalities in eye movements, such as altered saccadic patterns or impaired smooth pursuit, can act as important diagnostic indicators for various neurological conditions. The non-invasive nature, cost-effectiveness, and ease of implementation of modern eye-tracking systems makes it particularly attractive in both clinical and research settings. Advanced digital eye-tracking technologies and analytical methods enable precise quantification of eye-movement parameters, complementing subjective clinical evaluations with objective data. This review examines how DEMOs could contribute to the localisation and diagnosis of neural impairments, potentially serving as useful biomarkers. By comprehensively exploring the role of eye-movement assessment, this review aims to highlight the common eye-movement deficits seen in neurological injury and disease by using the examples of mild traumatic brain injury and Parkinson’s Disease. This review also aims to enhance the understanding of the potential use of DEMOs in diagnosis, monitoring, and management of neurological disorders, ultimately improving patient care and deepening our understanding of complex neurological processes. Furthermore, we consider the broader implications of this technology in unravelling the complexities of visual processing, attention mechanisms, and cognitive functions. This review summarises how DEMOs could reshape our understanding of brain health and allow for more targeted and effective neurological interventions.

Objective Vestibular/ocular deficits occur with mild traumatic brain injury (mTBI). The vestibular/ocular motor screening (VOMS) tool is used to assess individuals post-mTBI, which primarily relies upon subjective self-reported symptoms. Instrumenting the VOMS (iVOMS) with technology may allow for more objective assessment post-mTBI, which reflects actual task performance. This study aimed to validate the iVOMS analytically and clinically in mTBI and controls. Methods Seventy-nine people with sub-acute mTBI (2,1 0.85-0.99) in mTBI and controls. The iVOMS outcomes were clinically valid as there were significant differences between groups for convergence, vertical saccades, smooth pursuit, vestibular ocular reflex and visual motion sensitivity outcomes. However, there was no significant relationship between iVOMS outcomes and self-reported symptoms. Conclusion The iVOMS is analytically and clinically valid in mTBI and controls, but further work is required to examine the sensitivity of iVOMS outcomes across the mTBI spectrum. Findings also highlighted that symptom and physiological issue resolution post-mTBI may not coincide and relationships need further examination.

Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of cueing through prescribed auditory, visual, and/or tactile cues. Each has shown use to rectify abnormal gait patterns, improving mobility. Yet, a limitation remains, i.e., long-term engagement with cueing modalities. A paradigm shift towards personalised cueing approaches, considering an individual’s unique physiological condition, may bring a contemporary approach to ensure longitudinal and continuous engagement. Sonification could be a useful auditory cueing technique when integrated within personalised approaches to gait rehabilitation systems. Previously, sonification demonstrated encouraging results, notably in reducing freezing-of-gait, mitigating spatial variability, and bolstering gait consistency in people with Parkinson’s disease (PD). Specifically, sonification through the manipulation of acoustic features paired with the application of advanced audio processing techniques (e.g., time-stretching) enable auditory cueing interventions to be tailored and enhanced. These methods used in conjunction optimize gait characteristics and subsequently improve mobility, enhancing the effectiveness of the intervention. The aim of this narrative review is to further understand and unlock the potential of sonification as a pivotal tool in auditory cueing for gait rehabilitation, while highlighting that continued clinical research is needed to ensure comfort and desirability of use.

Background: Visual cues can improve gait in Parkinson’s disease (PD), including those experiencing freezing of gait (FOG). However, responses are variable and underpinning mechanisms remain unclear. Visuo-cognitive processing (measured through visual exploration) has been implicated in cue response, but this has not been comprehensively examined. Objective: To examine visual exploration and gait with and without visual cues in PD who do and do not self-report FOG, and healthy controls (HC). Methods: 17 HC, 21 PD without FOG, and 22 PD with FOG walked with and without visual cues, under single and dual-task conditions. Visual exploration (ie, saccade frequency, duration, peak velocity, amplitude, and fixation duration) was measured via mobile eye-tracking and gait (ie, gait speed, stride length, foot strike angle, stride time, and stride time variability) with inertial sensors. Results: PD had impaired gait compared to HC, and dual-tasking made gait variables worse across groups (all P < .01). Visual cues improved stride length, foot strike angle, and stride time in all groups ( P < .01). Visual cueing also increased saccade frequency, but reduced saccade peak velocity and amplitude in all groups ( P < .01). Gait improvement related to changes in visual exploration with visual cues in PD but not HC, with relationships dependent on group (FOG vs non-FOG) and task (single vs dual). Conclusion: Visual cues improved visual exploration and gait outcomes in HC and PD, with similar responses in freezers and non-freezers. Freezer and non-freezer specific associations between cue-related changes in visual exploration and gait indicate different underlying visuo-cognitive processing within these subgroups for cue response.