Biology subjects

McKay, J. L.

Publications and source records attributed to McKay, J. L..

13 recordsLinked to original sources

bioRxiv2024

Cortically-mediated muscle responses to balance perturbations increase with perturbation magnitude in older adults with and without Parkinson's disease

We lack a clear understanding of how cortical contributions to balance are altered in aging and Parkinsons disease (PD), which limits development of rehabilitation strategies. Processes like balance control are typically mediated through brainstem circuits, with higher-order circuits becoming engaged as needed. Using reactive balance recovery, we investigated how hierarchical neural mechanisms shape balance- correcting muscle activity across task difficulty in older adults (OAs) with and without PD. We hypothesize that feedback loops involving brainstem and cortical circuits contribute to balance control, and cortical engagement increases with challenge, aging, and PD. We decomposed perturbation-evoked agonist and antagonist muscle activity into hierarchical components based on latency using neuromechanical models consisting of two feedback loops with different delays to reflect different neural conduction and processing times. Agonist muscle activity was decomposed into two components that both increased with balance challenge in both groups. The first component occurred [~]120ms and the second occurred [~]210ms, consistent with the latencies of brainstem and transcortical circuits, respectively. Exploratory comparisons to young adults revealed larger transcortical components in OA and PD groups at lower balance challenge levels, consistent with increased cortical involvement with aging. Antagonist muscle activity included destabilizing and stabilizing components, with the destabilizing component correlating to balance ability in OAs but not in PD. These findings demonstrate that neuromechanical models can identify changes in the hierarchical control of balance without direct brain measurements. Identifying cortical contributions during balance control may complement clinical measures of balance ability to inform balance rehabilitation and assistive devices. NEW & NOTEWORTHYA neuromechanical model can decompose perturbation evoked muscle activity into components attributed to brainstem and higher-order sensorimotor feedback based on latency. In older adults with and without PD contributions from higher-order neural circuits increase with balance challenge and are related to clinical measures of balance ability. Interpreting the neural substrates of motor output for balance may reveal individual differences in the hierarchical control of balance, that could inform rehabilitation.

neuroscience↗

bioRxiv2023

Associations between music and dance relationships, rhythmic proficiency, and spatiotemporal movement modulation ability in adults with and without mild cognitive impairment

BackgroundPersonalized dance-based movement therapies may improve cognitive and motor function in individuals with mild cognitive impairment (MCI), a precursor to Alzheimers disease. While age- and MCI-related deficits reduce individuals abilities to perform dance-like rhythmic movement sequences (RMS)--spatial and temporal modifications to movement--it remains unclear how individuals relationships to dance and music affect their ability to perform RMS. ObjectiveCharacterize associations between RMS performance and music or dance relationships, as well as the ability to perceive rhythm and meter (rhythmic proficiency) in adults with and without MCI. MethodsWe used wearable inertial sensors to evaluate the ability of 12 young adults (YA; age=23.9{+/-}4.2 yrs; 9F), 26 older adults without MCI (OA; age=68.1{+/-}8.5 yrs; 16F), and 18 adults with MCI (MCI; age=70.8{+/-}6.2 yrs; 10F) to accurately perform spatial, temporal, and spatiotemporal RMS. To quantify self-reported music and dance relationships and rhythmic proficiency, we developed Music (MRQ) and Dance Relationship Questionnaires (DRQ), and a rhythm assessment (RA), respectively. We correlated MRQ, DRQ, and RA scores against RMS performance for each group separately. ResultsThe OA and YA groups exhibited better MRQ and RA scores than the MCI group (p<0.006). Better MRQ and RA scores were associated with better temporal RMS performance for only the YA and OA groups (r2=0.18-0.41; p<0.045). DRQ scores were not associated with RMS performance in any group. ConclusionsCognitive deficits in adults with MCI likely limit the extent to which music relationships or rhythmic proficiency improve the ability to perform temporal aspects of movements performed during dance-based therapies.

neuroscience↗

bioRxiv2023

Precise cortical contributions to feedback sensorimotor control during reactive balance

The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships between hierarchical control mechanisms and their engagement across balance tasks of increasing difficulty in young adults. We hypothesize that parallel sensorimotor feedback loops engaging subcortical and cortical circuits contribute to balance-correcting muscle activity, and that the involvement of cortical circuits increases with balance challenge. We decomposed balance-correcting muscle activity based on hypothesized subcortically- and cortically-mediated feedback components driven by similar sensory information, but with different loop delays. The initial balance-correcting muscle activity was engaged at all levels of balance difficulty. Its onset latency was consistent with subcortical sensorimotor loops observed in the lower limb. An even later, presumed, cortically-mediated burst of muscle activity became additionally engaged as balance task difficulty increased, at latencies consistent with longer transcortical sensorimotor loops. We further demonstrate that evoked cortical activity in central midline areas measured using electroencephalography (EEG) can be explained by a similar sensory transformation as muscle activity but at a delay consistent with its role in a transcortical loop driving later cortical contributions to balance-correcting muscle activity. These results demonstrate that a neuromechanical model of muscle activity can be used to infer cortical contributions to muscle activity without recording brain activity. Our model may provide a useful framework for evaluating changes in cortical contributions to balance that are associated with falls in older adults and in neurological disorders such as Parkinsons disease.

neuroscience↗

bioRxiv2022

Motor and cognitive deficits limit the ability to flexibly modulate spatiotemporal gait features in older adults with mild cognitive impairment

IntroductionDance-based therapies are an emerging form of movement therapy aiming to improve motor and cognitive function in older adults with mild cognitive impairments (MCIs). Despite promising effects of dance-based therapies on function, it remains unclear how age-related declines in motor and cognitive function affect movement capacity and influence which movements and rhythms maximize dance therapy efficacy. Here, we evaluated the effects of age and MCI on the ability to accurately modulate spatial (i.e., joint kinematics), temporal (i.e., step timing), and spatiotemporal features of gait to achieve spatial and temporal targets during walking. MethodsWe developed novel rhythmic movement sequences - nine spatial, nine temporal, and four spatiotemporal - that deviated from typical spatial and temporal features of walking. Healthy young adults (HYA), healthy older adults (HOA), and adults with MCI were trained on each gait modification before performing the modification overground, with kinematic data recorded using wearable sensors. ResultsHOA performed spatial (p = 0.010) and spatiotemporal (p = 0.048) gait modifications less accurately than HYA. Individuals with MCI performed spatiotemporal gait modifications less accurately than HOA (p = 0.017). Spatial modifications to the swing phase of gait (p = 0.006, Cohens d = -1.3), and four- and six-step Duple rhythms during temporal modifications (p < 0.030, Cohens d > 0.9) elicited the largest differences in gait performance in HYA vs. HOA and HOA vs. MCI, respectively. DiscussionThese findings suggest that age-related declines in strength and balance reduce the ability to accurately modulate spatial gait features, while declines in working memory in individuals with MCI may reduce the ability to perform longer temporal gait modification sequences. Differences in rhythmic movement sequence performance highlight motor and cognitive factors potentially underlying deficits in gait modulation capacity, which may guide therapy personalization and provide more sensitive indices to track intervention efficacy.

synthetic biology↗

bioRxiv2022

Distinct features of the cortical N1 response to balance perturbation are associated with balance and cognitive impairments in Parkinson's disease

Mechanisms underlying associations between balance and cognitive impairments in older adults with and without Parkinsons disease are poorly understood. Balance disturbances evoke a cortical N1 response that is associated with both balance and cognitive abilities in unimpaired populations. We hypothesized that the N1 response reflects neural mechanisms that are shared between balance and cognitive function, and would therefore be associated with both balance and cognitive impairments in Parkinsons disease. Although N1 responses did not differ at the group level, they showed different associations with balance and cognitive function in the Parkinsons disease vs. control groups. In the control group, higher N1 amplitudes were correlated with lower cognitive set shifting ability and lower balance confidence. However, in Parkinsons disease, narrower N1 widths (i.e., shorter durations) were associated with greater parkinsonian motor symptom severity, lower balance ability and confidence, lower mobility, and lower overall cognitive function. Despite different relationships across populations, the present results suggest the N1 response reflects neural processes related to both balance and cognitive function. A better understanding of neural mechanisms linking balance and cognitive function could provide insight into associations between balance and cognitive decline in aging populations.

neuroscience↗

bioRxiv2021

Lower cognitive set shifting ability is associated with stiffer balance recovery behavior and larger perturbation-evoked cortical responses in older adults

1.The mechanisms underlying associations between cognitive set shifting impairments and balance dysfunction are unclear. Cognitive set shifting refers to the ability to flexibly adjust behavior to changes in task rules or contexts, which could be involved in flexibly adjusting balance recovery behavior to different contexts, such as the direction the body is falling. Prior studies found associations between cognitive set shifting impairments and severe balance dysfunction in populations experiencing frequent falls. The objective of this study was to test whether cognitive set shifting ability is expressed in successful balance recovery behavior in older adults with high clinical balance ability (N=19, 71 {+/-} 7 years, 6 female). We measured cognitive set shifting ability using the Trail Making Test and clinical balance ability using the miniBESTest. For most participants, cognitive set shifting performance (Trail Making Test B-A = 37 {+/-} 20s) was faster than normative averages (46s for comparable age and education levels), and balance ability scores (miniBESTest = 25 {+/-} 2 / 28) were above the threshold for fall risk (23 for people between 70-80 years). Reactive balance recovery in response to support-surface translations in anterior and posterior directions was assessed in terms of body motion, muscle activity, and brain activity. Across participants, lower cognitive set shifting ability was associated with smaller peak center of mass displacement during balance recovery, lower directional specificity of late phase balance-correcting muscle activity (i.e., greater antagonist muscle activity 200-300ms after perturbation onset), and larger cortical N1 responses (100-200ms). None of these measures were associated with clinical balance ability. Our results suggest that cognitive set shifting ability is expressed in balance recovery behavior even in the absence of profound clinical balance disability. Specifically, our results suggest that lower flexibility in cognitive task performance is associated with lower ability to incorporate the directional context into the cortically-mediated later phase of the motor response. The resulting antagonist activity and stiffer balance behavior may help explain associations between cognitive set shifting impairments and frequent falls.

neuroscience↗

bioRxiv2020

Abnormal center of mass control during balance is associated with falls in Parkinson's disease

Although Parkinson disease (PD) causes profound balance impairments, we know very little about how PD impacts the sensorimotor networks we rely on for automatically maintaining balance control. In young healthy people and animals, muscles are activated in a precise temporal and spatial organization when the center of body mass (CoM) is unexpectedly moved that is largely automatic and determined by feedback of CoM motion. Here, we show that PD alters the sensitivity of the sensorimotor feedback transformation. Importantly, sensorimotor feedback transformations for balance in PD remain temporally precise, but become spatially diffuse by recruiting additional muscle activity in antagonist muscles during balance responses. The abnormal antagonist muscle activity remains precisely time-locked to sensorimotor feedback signals encoding undesirable motion of the body in space. Further, among people with PD, the sensitivity of abnormal antagonist muscle activity to CoM motion varies directly with the number of recent falls. Our work shows that in people with PD, sensorimotor feedback transformations for balance are intact but disinhibited in antagonist muscles, likely contributing to balance deficits and falls.

neuroscience↗

bioRxiv2019

Perception of whole-body motion during balance perturbations is impaired in Parkinson’s disease and is associated with balance impairment

BackgroundIn addition to motor deficits, Parkinsons disease (PD) may cause perceptual impairments. The role of perceptual impairments in sensorimotor function is unclear, and has typically been studied in single-joint motions. Research Question: We hypothesized that perception of whole-body motion is impaired in PD and contributes to balance impairments. We tested 1) whether directional acuity to whole body perturbations during standing was worse in people with PD compared to neurotypical older adults (NOA), and 2) whether balance ability, as assessed by the MiniBESTest, was associated with poor directional acuity in either group.\n\nMethodsParticipants were exposed to pairs of support-surface translation perturbations in a two-alternative forced choice testing paradigm developed previously in a young healthy population. The first perturbation of each pair was directly backward and the second deviated to the left or right (1{degrees}-44{degrees}). Participants judged and reported whether the perturbations in each pair were in the \"same\" or \"different\" direction. This information was used to calculate directional acuity thresholds corresponding to \"just-noticeable differences\" in perturbation direction. Linear mixed models determined associations between directional thresholds and clinical variables including MDS UPDRS-III score, age, and MiniBESTest score. Results: 20 PD (64{+/-}7 y, 12 male, [>=]12 hours since last intake of antiparkinsonian medications) and 12 NOA (64{+/-}8, 6 male) were assessed. Directional thresholds were higher (worse) among PD participants (17.6{+/-}5.9{degrees} vs. 12.8{+/-}3.3{degrees}, P<0.01). Linear mixed models further showed that higher thresholds were associated with MDS UPDRS-III score (P<0.01), and were associated with poorer balance ability among PD participants (P<0.01), but not among NOA participants (P=0.40). Significance: Perception of whole-body motion is impaired in PD and may contribute to impaired balance and falls.

neuroscience↗

bioRxiv2019

Levodopa Responsiveness Subtypes of Freezing of Gait: Results Using a Levodopa Challenge

ObjectiveTo demonstrate that levodopa-unresponsive freezing of gait (ONOFF-FOG), which is a disabling untreatable feature of Parkinsons disease (PD), is distinct from responsive/OFF only FOG (OFF-FOG) and potentially has a distinct pathophysiology.\n\nMethodsFifty-five PD patients completed levodopa challenges after >12 hours OFF with supratherapeutic doses to classify them as NOFOG, OFF-FOG or ONOFF-FOG. Serum levodopa levels ensured threshold levels were met. An \"ON\" response was defined as [≥]20% improvement in MDS-UPDRS-III score. Main outcome measure was MDS-UPDRS-III based on clinical exam, timed-up-and-go tests and 360{degrees} turns.\n\nResults45 patients exhibited an \"ON\" response to the challenge. Levodopa-equivalent-dose was 142{+/-}56% of patients typical morning doses. Patients could be classified as: 19 ONOFF-FOG, 11 OFF-FOG, 15 NOFOG. The ONOFF-FOG group exhibited significantly higher NFOG-Q, MDS-UPDRS-II/III scores compared to the OFF-FOG group. MDS-UPDRS-III total varied significantly across medication response states (P<0.01) and groups (P=0.03). Among MDS-UPDRS-III subdomains, significant effects of group (highest in ONOFF-FOG group) were identified for measures of lower extremities and gait. Linear mixed models revealed a highly significant association between serum levodopa level and MDS-UPDRS-III score that did not vary across the groups. There was a highly significant group interaction effect on the association between serum levodopa level with MDS-UPDRS-III item 11 \"Freezing of Gait\" (P<0.001).\n\nConclusionsONOFF-FOG is a distinct subtype of FOG in PD, as opposed to OFF-FOG. This is an important step in demonstrating that FOG is not a single entity and, in turn, could lead to better understanding of pathophysiology and development of effective therapies.

neuroscience↗

bioRxiv2019

Lower-limb rigidity is associated with frequent falls in Parkinson disease

BACKGROUND AND OBJECTIVEThe role of muscle rigidity as an etiological factor of falls in Parkinson disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. METHODS: We examined associations between UPDRS-III (motor) rigidity subscores and history of monthly or more frequent falls in N=216 individuals with PD (age, 66{+/-}10 y; 36% female, disease duration, 7{+/-}5 y) with logistic regression. RESULTS: N=35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P=0.01) after controlling for age, sex, PD duration, total UPDRS-III score, and presence of FOG. No significant associations (P[≥]0.14) were identified for total, arm, or neck rigidity. CONCLUSION: Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.\n\nFinancial Disclosures/Conflict of Interest concerning the research related to the manuscript: None\n\nFundingNIH K25HD086276, R01HD046922, R21HD075612, UL1TR002378, UL1TR000454; Department of Veterans Affairs R&D Service Career Development Awards E7108M and N0870W, Consolidated Anti-Aging Foundation, and the Sartain Lanier Family Foundation.

neuroscience↗

bioRxiv2018

Antagonist muscle activity during reactive balance responses is elevated in Parkinson’s disease and in balance impairment

BACKGROUND: Abnormal antagonist leg muscle activity could indicate increased muscle co-contraction and clarify mechanisms of balance impairments in Parkinsons disease (PD). Prior studies in carefully selected patients showed PD patients demonstrate earlier, longer, and larger antagonist muscle activation during reactive balance responses to perturbations. RESEARCH QUESTION: Here, we tested whether antagonist leg muscle activity was abnormal in a group of PD patients who were not selected for phenotype, and most of whom had volunteered for exercise-based rehabilitation. METHODS: We compared antagonist activation during reactive balance responses to multidirectional support-surface translation perturbations in 31 patients with mild-moderate PD (age 68{+/-}9; H&Y 1-3; UPDRS -III 32{+/-}10) and 13 matched individuals (age 65{+/-}9). We quantified modulation of muscle activity (i.e., the ability to activate and inhibit muscles appropriately according to the perturbation direction) using modulation indices (MI) derived from minimum and maximum EMG activation levels observed across perturbation directions. RESULTS: Antagonist leg muscle activity was abnormal in unselected PD patients compared to controls. Linear mixed models identified significant associations between impaired modulation and PD (P<0.05), PD severity (P<0.01), and balance ability (P<0.05), but not age (P=0.10). SIGNIFICANCE: Antagonist activity is increased during reactive balance responses in PD patients of varying phenotypes who are candidates for rehabilitation. Abnormal antagonist activity may contribute to balance impairments in PD and be a potential rehabilitation target or outcome measure.\n\nFunding SourcesThis work was supported by the National Institutes of Health (NIH) KL2 TR000455, K25 HD086276, R01 HD46922, R21 HD075612, TL1TR000456, and UL1 TR000424. The study sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.\n\nDeclaration of InterestConflicts of interest: None.\n\nAuthor ContributionsResearch project: Conception, JLM, LHT, MEH; Organization, JLM, KCL, LHT, MEH; Execution, JLM, KCL, LHT, MEH.\n\nStatistical Analysis: Design and Execution, JLM, KCL; Review and Critique, LHT, MEH. Manuscript Preparation: Writing of the first draft, KCL; Review and Critique: JLM, LHT, MEH.\n\nHighlights O_LIWe quantified abnormal antagonist muscle activation during balance in PD.\nC_LIO_LIAbnormalities were related to PD severity as well as to overall balance ability.\nC_LIO_LIAbnormalities were similar across PD phenotypes with and without tremor.\nC_LIO_LIBalance antagonist activation may be a useful rehabilitative outcome measure.\nC_LI

neuroscience↗

bioRxiv2017

The Influence of Parkinson’s Disease and Neurotypical Aging on Cognitive Performance Among Volunteers for an Exercise-based Rehabilitative Intervention

PURPOSETo determine the impact of aging versus combined aging and disease on cognition in older adults with and without Parkinsons disease (PD) who were volunteers for exercise based rehabilitation research.\n\nMETHODSWe used a multiple linear regression approach to analyze cognitive outcome measures of rehabilitation volunteers with and without PD.\n\nRESULTSSignificant associations were identified between increased age and decreased performance on 8 of the 14 outcomes analyzed after controlling for false discovery rate. Of those 8 outcomes, multivariate regression analyses demonstrated an effect of disease on performance in only 4/8. In all cases, PD was associated with superior, rather than decreased performance after controlling for age. Results were unaffected by sex and education. Post-hoc comparison with available age norms demonstrated that differences between PD and Non-PD volunteers could be primarily attributed to the Non-PD group substantially underperforming versus age norms.\n\nCONCLUSIONSIn rehabilitative exercise studies using volunteers, many cognitive domains decline with increasing age, consistent with previous neuropsychological studies without a rehabilitation component. However, older \"neurotypical\" volunteers may potentially underperform PD volunteers after controlling for age. This may be an important design consideration for rehabilitation studies with cognitive outcomes.\n\nIMPLICATIONS FOR REHABILITATIONO_LIAn increasing number of rehabilitation studies incorporate cognitive outcomes.\nC_LIO_LIWhether the overall cognitive profile of rehabilitation volunteers differs from that of neurotypical aging remains to be established.\nC_LIO_LIRehabilitation volunteers with Parkinsons disease may outperform putatively neurotypical volunteers after controlling for covariates.\nC_LIO_LICognitive impairments associated with PD in neuropsychological studies may not generalize to exercise rehabilitation volunteers.\nC_LI

neuroscience↗

bioRxiv2017

Agreement between measurements of stance width using motion capture and center of pressure in individuals with and without Parkinson’s disease

BackgroundMany individuals with Parkinsons disease exhibit narrow stance width during balance and gait. Because of this, stance width is an important biomechanical variable in many studies. Measuring stance width accurately using kinematic markers in parkinsonian patients can be problematic due to occlusions by research staff who must closely guard patients to prevent falls.\n\nMethodsWe investigated whether a measure of stance width based on the mediolateral distance between the center of pressure under each foot could approximate stance width measured with kinematic data. We assessed the agreement between estimates of stance width obtained from simultaneous kinematic and center of pressure measures during quiet standing in 15 individuals (n=9 parkinsonian, n=6 age-similar neurotypical). The source data (1363 unique trials) contained observations of stance width varying between 75-384 mm ({approx}25-150% of hip width).\n\nFindingsStance width estimates using the two measures were strongly correlated (r = 0.98). Center of pressure estimates of stance width were 48 mm wider on average than kinematic measures, and did not vary across study groups (F2,12=1.81, P<0.21). The expected range of differences between the center of pressure and kinematic methods was 14-83 mm. Agreement increased as stance width increased (P<0.02).\n\nInterpretationIt is appropriate to define stance width based on center of pressure when it is convenient to do so in studies of individuals with and without Parkinsons disease. When comparing results across studies with the two methodologies, it is reasonable to assume a bias of 48 mm.

neuroscience↗