Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

Associating white matter microstructural integrity and improvements in reactive stepping in people with Parkinson's Disease.

Reactive steps are rapid responses after balance challenges. People with Parkinson's Disease (PwPD) demonstrate impaired reactive stepping, increasing fall-risk. Although PwPD can improve steps through practice, the neural mechanisms contributing to improved reactive stepping are poorly understood. This study investigated white-matter correlates of responsiveness to reactive step training in PwPD. In an eighteen-week multiple-baseline study, participants (n = 22) underwent baseline assessments (B1 and B2 two-weeks apart), a two-week training protocol, and post-training assessments immediately (P1) and two-months (P2) post-training. Assessments involved three backward reactive step trials, measuring anterior-posterior margin of stability (AP MOS), step length, and step latency. Tract-Based Spatial Statistics correlated white-matter integrity (fractional anisotropy (FA) and radial diffusivity (RD)) with retained (P2-B2) and immediate improvements (P1-B2) in stepping. Significant and sustained improvements in step length and AP MOS were observed. Greater retention of step length improvement correlated with increased FA in the left anterior thalamic radiation (ATR), left posterior thalamic radiation (PTR), left superior longitudinal fasciculus (SLF), and right inferior longitudinal fasciculus (ILF). Step latency retention was associated with lower RD in the left posterior corona radiata and left PTR. Immediate improvements in AP MOS correlated with increased FA of the right ILF, right SLF, and right corticospinal tract. Immediate step length improvements were associated with increased FA in right and left ATR and right SLF. These findings highlight the importance of white-matter microstructural integrity in motor learning and retention processes in PD and could aid in identifying individuals with PD who would benefit most from balance rehabilitation.

Propulsive Force Modulation Drives Split-Belt Treadmill Adaptation in People with Multiple Sclerosis.

Most people with multiple sclerosis (PwMS) experience significant gait asymmetries between their legs during walking, leading to an increased risk of falls. Split-belt treadmill training, where the speed of each limb is controlled independently, alters each leg's stepping pattern and can improve gait symmetry in PwMS. However, the biomechanical mechanisms of this adaptation in PwMS remain poorly understood. In this study, 32 PwMS underwent a 10 min split-belt treadmill adaptation paradigm with the more affected (MA) leg moving twice as fast as the less affected (LA) leg. The most noteworthy biomechanical adaptation observed was increased peak propulsion asymmetry between the limbs. A kinematic analysis revealed that peak dorsiflexion asymmetry and the onset of plantarflexion in the MA limb were the primary contributors to the observed increases in peak propulsion. In contrast, the joints in the LA limb underwent only immediate reactive adjustments without subsequent adaptation. These findings demonstrate that modulation during gait adaptation in PwMS occurs primarily via propulsive forces and joint motions that contribute to propulsive forces. Understanding these distinct biomechanical changes during adaptation enhances our grasp of the rehabilitative impact of split-belt treadmill training, providing insights for refining therapeutic interventions aimed at improving gait symmetry.

Links between Neuroanatomy and Neurophysiology with Turning Performance in People with Multiple Sclerosis.

Multiple sclerosis is accompanied by decreased mobility and various adaptations affecting neural structure and function. Therefore, the purpose of this project was to understand how motor cortex thickness and corticospinal excitation and inhibition contribute to turning performance in healthy controls and people with multiple sclerosis. In total, 49 participants (23 controls, 26 multiple sclerosis) were included in the final analysis of this study. All participants were instructed to complete a series of turns while wearing wireless inertial sensors. Motor cortex gray matter thickness was measured via magnetic resonance imaging. Corticospinal excitation and inhibition were assessed via transcranial magnetic stimulation and electromyography place on the tibialis anterior muscles bilaterally. People with multiple sclerosis demonstrated reduced turning performance for a variety of turning variables. Further, we observed significant cortical thinning of the motor cortex in the multiple sclerosis group. People with multiple sclerosis demonstrated no significant reductions in excitatory neurotransmission, whereas a reduction in inhibitory activity was observed. Significant correlations were primarily observed in the multiple sclerosis group, demonstrating lateralization to the left hemisphere. The results showed that both cortical thickness and inhibitory activity were associated with turning performance in people with multiple sclerosis and may indicate that people with multiple sclerosis rely on different neural resources to perform dynamic movements typically associated with fall risk.

Split-Belt Treadmill Adaptation Improves Spatial and Temporal Gait Symmetry in People with Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by degradation of the myelin sheath resulting in impaired neural communication throughout the body. As a result, most people with MS (PwMS) experience gait asymmetries between their legs leading to an increased risk of falls. Recent work indicates that split-belt treadmill adaptation, where the speed of each leg is controlled independently, can decrease gait asymmetries for other neurodegenerative impairments. The purpose of this study was to test the efficacy of split-belt treadmill training to improve gait symmetry in PwMS. In this study, 35 PwMS underwent a 10 min split-belt treadmill adaptation paradigm, with the faster paced belt moving under the more affected limb. Step length asymmetry (SLA) and phase coordination index (PCI) were the primary outcome measures used to assess spatial and temporal gait symmetries, respectively. It was predicted that participants with a worse baseline symmetry would have a greater response to split-belt treadmill adaptation. Following this adaptation paradigm, PwMS experienced aftereffects that improved gait symmetry, with a significant difference between predicted responders and nonresponders in both SLA and PCI change (p < 0.001). Additionally, there was no correlation between SLA and PCI change. These findings suggest that PwMS retain the ability for gait adaptation, with those most asymmetrical at baseline demonstrating the greatest improvement, and that there may be separate neural mechanisms for spatial and temporal locomotor adjustments.

Somatosensory Information in Skilled Motor Performance: A Narrative Review.

Historically, research aimed at improving motor performance has largely focused on the neural processes involved in motor execution due to their role in muscle activation. However, accompanying somatosensory and proprioceptive sensory information is also vitally involved in performing motor skills. Here we review research from interdisciplinary fields to provide a description for how somatosensation informs the successful performance of motor skills as well as emphasize the need for careful selection of study methods to isolate the neural processes involved in somatosensory perception. We also discuss upcoming strategies of intervention that have been used to improve performance via somatosensory targets. We believe that a greater appreciation for somatosensation's role in motor learning and control will enable researchers and practitioners to develop and apply methods for the enhancement of human performance that will benefit clinical, healthy, and elite populations alike.

Using the Instrumented Sway System (ISway) to Identify and Compare Balance Domain Deficits in People With Multiple Sclerosis.

OBJECTIVE: To develop a multiple sclerosis (MS)-specific model of balance and examine differences between (1) MS and neurotypical controls and (2) people with MS (PwMS) with (MS-F) and without a fall history (MS-NF). DESIGN AND SETTING: A cross-sectional study was conducted at the Gait and Balance Laboratory at the University of Kansas Medical Center. Balance was measured from the instrumented sway system (ISway) assessment. PARTICIPANTS: In total, 118 people with relapsing-remitting MS (MS-F=39; MS-NF=79) and 46 age-matched neurotypical controls. INTERVENTION: Not applicable. OUTCOME MEASURES: A total of 22 sway measures obtained from the ISway were entered into an exploratory factor analysis to identify underlying balance domains. The model-derived balance domains were compared between (1) PwMS and age-matched, neurotypical controls and (2) MS-F and MS-NF. RESULTS: Three distinct balance domains were identified: (1) sway amplitude and velocity, (2) sway frequency and jerk mediolateral, and (3) sway frequency and jerk anteroposterior, explaining 81.66% of balance variance. PwMS exhibited worse performance (ie, greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (P=.003). MS-F also exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (P=.046). The anteroposterior and mediolateral sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. CONCLUSIONS: This study identified a 3-factor, MS-specific balance model, demonstrating that PwMS, particularly those with a fall history, exhibit disproportionate impairments in sway amplitude and velocity. Identifying postural stability outcomes and domains that are altered in PwMS and clinically relevant (eg, related to falls) would help isolate potential treatment targets.

An Exploration of Yoga in Occupational Therapy Practice for Multiple Sclerosis.

The purpose of this exploratory qualitative study was to provide insight on the use of yoga in occupational therapy (OT) for people with multiple sclerosis (PwMS). This study aimed to answer how and why OT practitioners (OTPs) integrate yoga into clinical practice for PwMS. Eight OTPs, half of whom have also completed yoga teacher training, participated in a semi-structured telephone interview. Interviews were transcribed verbatim, inductively open-coded, and analyzed using thematic data analysis. Themes that emerged were: (a) OT and yoga are a natural fit; (b) improved performance and participation; (c) leveraging personal ties to yoga; and (d) influenced by client factors and clinical environment. The qualitative data provide valuable information about OTPs' justification for, and unique application of, yoga in clinical practice for PwMS. Future researchers should further explore the use of yoga for OT-related outcomes and the experience of PwMS.

I Can Step Clearly Now, the TENS Is On: Transcutaneous Electric Nerve Stimulation Decreases Sensorimotor Uncertainty during Stepping Movements.

Transcutaneous electric nerve stimulation (TENS) is a method of electrical stimulation that elicits activity in sensory nerves and leads to improvements in the clinical metrics of mobility. However, the underlying perceptual mechanisms leading to this improvement are unknown. The aim of this study was to apply a Bayesian inference model to understand how TENS impacts sensorimotor uncertainty during full body stepping movements. Thirty healthy adults visited the lab on two occasions and completed a motor learning protocol in virtual reality (VR) on both visits. Participants were randomly assigned to one of three groups: TENS on first visit only (TN), TENS on second visit only (NT), or a control group where TENS was not applied on either visit (NN). Using methods of Bayesian inference, we calculated the amount of uncertainty in the participants' center of mass (CoM) position estimates on each visit. We found that groups TN and NT decreased the amount of uncertainty in the CoM position estimates in their second visit while group NN showed no difference. The least amount of uncertainty was seen in the TN group. These results suggest that TENS reduces the amount of uncertainty in sensory information, which may be a cause for the observed benefits with TENS.

Novel applications of Bayesian inference clarify sensorimotor uncertainty during stepping movements.

The human nervous system relies on sensory information from the feet and legs to control the way we balance and walk. However, even in healthy individuals this sensory information is inherently variable and clouded with uncertainty. Researchers have found that the central nervous system (CNS) estimates body position amid the uncertainty of sensory signals in a way consistent with Bayesian inference. Bayesian inference posits that the brain accounts for variability in sensory data by combining it with learned expectations built from previous movement attempts. While initial findings on this topic are promising, they have neglected to study full-body movements such as gait and balance. The purpose of this research was to determine if the CNS controls balance-related stepping tasks in a way that fits a Bayesian framework. To address this purpose, we created a virtual reality protocol where participants moved their center of mass (CoM) to various targets while relying on uncertain visual cues and compensating for an alternating shift to the cursor position. We showed that as incoming sensory information became less certain, participants relied more on their learned expectation of body position and demonstrated more uncertainty in their responses. Accordingly, as participants learned to control and estimate their CoM position during our mobility task, they relied both on the sensory information they were receiving as well as learned expectations for its location. These results provide further evidence that the CNS is aware of the variability in sensory information and is proficient at compensating for the resultant uncertainty. We aim to apply these findings as a method for measuring the efficacy of interventions targeting sensory function.

Inhibitory signaling as a predictor of leg force control in young and older adults.

As the populations of the United States and developed nations age, motor control performance is adversely impacted, resulting in functional impairments that can diminish quality of life. Generally, force control in the lower limb worsens with age, with older adults (OA) displaying more variable and less accurate submaximal forces. Corticospinal inhibitory signaling may influence force control, with those OA who maintain corticospinal inhibitory signaling capacity achieving steadier forces. This study aimed to assess the relationships between lower limb force control and transcranial magnetic stimulation (TMS) measures of corticospinal inhibition (i.e., cortical silent period (cSP) duration and depth). 15 OA and 14 young adults (YA) were recruited for this study. All subjects underwent a TMS protocol to elicit the cSP while maintaining 15% of their maximal force in their knee extensor muscles. OA and YA did not display differences in force control metrics or corticospinal inhibitory measures. However, in OA, maximal cSP depth (%dSP max) was associated with lower force variability. No other significant relationships existed in the YA or OA groups. Future studies will benefit from evaluating a range of target forces and target muscles to assess potential relationships between sensorimotor inhibitory capacity and control of muscle force output.

Bridging the callosal gap in gait: corpus callosum white matter integrity's role in lower limb coordination.

Bilateral coordination of the lower extremities is an essential component of mobility. The corpus callosum bridges the two hemispheres of the brain and is integral for the coordination of such complex movements. The aim of this project was to assess structural integrity of the transcallosal sensorimotor fiber tracts and identify their associations with gait coordination using novel methods of ecologically valid mobility assessments in persons with multiple sclerosis and age-/gender-matched neurotypical adults. Neurotypical adults (n = 29) and persons with multiple sclerosis (n = 27) underwent gait and diffusion tensor imaging assessments; the lower limb coordination via Phase Coordination Index, and radial diffusivity, an indirect marker of myelination, were applied as the primary outcome measures. Persons with multiple sclerosis possessed poorer transcallosal white matter microstructural integrity of sensorimotor fiber tracts compared to the neurotypical adults. Further, persons with multiple sclerosis demonstrated significantly poorer bilateral coordination of the lower limbs during over-ground walking in comparison to an age and gender-matched neurotypical cohort. Finally, bilateral coordination of the lower limbs was significantly associated with white matter microstructural integrity of the dorsal premotor and primary motor fiber bundles in persons with multiple sclerosis, but not in neurotypical adults. This analysis revealed that persons with multiple sclerosis exhibit poorer transcallosal microstructural integrity than neurotypical peers. Furthermore, these structural deficits were correlated to poorer consistency and accuracy of gait in those with multiple sclerosis. Together, these results, emphasize the importance of transcallosal communication for gait coordination in those with multiple sclerosis.

Discriminative Mobility Characteristics between Neurotypical Young, Middle-Aged, and Older Adults Using Wireless Inertial Sensors.

Age-related mobility research often highlights significant mobility differences comparing neurotypical young and older adults, while neglecting to report mobility outcomes for middle-aged adults. Moreover, these analyses regularly do not determine which measures of mobility can discriminate groups into their age brackets. Thus, the current study aimed to provide a comprehensive analysis for commonly performed aspects of mobility (walking, turning, sit-to-stand, and balance) to determine which variables were significantly different and furthermore, able to discriminate between neurotypical young adults (YAs), middle-aged adults (MAAs), and older adults (OAs). This study recruited 20 YAs, 20 MAAs, and 20 OAs. Participants came into the laboratory and completed mobility testing while wearing wireless inertial sensors. Mobility tests assessed included three distinct two-minute walks, 360° turns, five times sit-to-stands, and a clinical balance test, capturing 99 distinct mobility metrics. Of the various mobility tests assessed, only 360° turning measures demonstrated significance between YAs and MAAs, although the capacity to discriminate between groups was achieved for gait and turning measures. A variety of mobility measures demonstrated significance between MAAs and OAs, and furthermore discrimination was achieved for each mobility test. These results indicate greater mobility differences between MAAs and OAs, although discrimination is achievable for both group comparisons.

The effect of shoe cushioning on gait and balance in females with multiple sclerosis.

Gait and balance deficits are significant concerns for people with multiple sclerosis (MS). Shoe cushioning can influence mobility and balance, but its effect on walking and balance remains unknown in MS. This study aimed to determine how shoe cushioning affects gait and balance in females with MS (FwMS). We hypothesized that extra cushioning would improve gait but reduce balance performance. FwMS performed gait (n = 18) and balance (n = 17) assessments instrumented using inertial sensors in two different shoe conditions: a standard-cushioned and an extra-cushioned shoe. Care was taken to ensure minimal differences between shoe types other than midsole cushioning, but shoe construction was not identical between conditions. Spatiotemporal gait parameters were assessed during a 2-min walk test, while postural sway measures were evaluated using the modified Clinical Test of Sensory Interaction and Balance. In the extra-cushioned shoe, FwMS spent less time in the double support and stance phase with more time in the single support and swing phase. No differences in stride length, gait speed, or elevation at midswing were observed between shoe conditions. Decreased path length, RMS sway, and sway velocity were observed in the extra-cushioned shoe. No differences were observed in the gait cycle's spatial composition between shoe conditions, but FwMS demonstrated improvements in the gait cycle's temporal parameters and postural sway in the extra-cushioned shoe. This may suggest a less cautious walking strategy and improved balance when wearing a shoe with extra cushioning.

The assessment of center of mass and center of pressure during quiet stance: Current applications and future directions.

This perspective article provides a brief review of our understanding of how center of pressure (CoP) and center of mass (CoM) are traditionally utilized to measure quiet standing and how technological advancements are allowing for measurements to be derived outside the confines of a laboratory setting. Furthermore, this viewpoint provides descriptions of what CoP and CoM outcomes may reflect, a discussion of recent developments in selected balance outcomes, the importance of measuring instantaneous balance outcomes, and directions for future questions/research. Considering the enormous number and cost of falls annually, conclusions drawn from this perspective underscore the need for more cohesive efforts to advance our understanding of balance performance. As we refine the technology and algorithms used to portably assess postural stability, the question of which measurement (i.e. CoP or CoM) to utilize seems to be highly dependent on the question being asked. Further, the complexity of the question appears to span multiple disciplines and cultivate exploration of the intrinsic mechanisms of stability. Recently developed multi-dimensional methods for assessing balance performance may provide additional insight into balance, improving our ability to predict balance impairments and falls outside the laboratory and in the clinic. However, additional work will be necessary to understand the clinical significance and predictive capacity of these outcomes in various fall-prone populations.

Middle-age people with multiple sclerosis demonstrate similar mobility characteristics to neurotypical older adults.

BACKGROUND: Clinical trials often report significant mobility differences between neurotypical and atypical groups, however, these analyses often do not determine which measures are capable of discriminating between groups. Additionally, indirect evidence supports the notion that some mobility impaired populations demonstrate similar mobility deficits. Thus, the current study aimed to provide a comprehensive analysis of three distinct aspects of mobility (walking, turning, and balance) to determine which variables were significantly different and were also able to discriminate between neurotypical older adults (OA) and middle-aged people with multiple sclerosis (PwMS), and between middle-aged neurotypical adults and PwMS. METHODS: This study recruited 21 neurotypical OA, 19 middle-aged neurotypical adults, and 30 people with relapsing remitting MS. Participants came into the laboratory on two separate occasions to complete mobility testing while wearing wireless inertial sensors. Testing included a self-selected pace two-minute walk, a series of 180˚ and 360˚ turns, and a clinical balance test capturing a total of 99 distinct mobility characteristics. We determined significant differences for gait and turning measures through univariate analyses and a series of repeated measures analysis of variance in determining significance for balance conditions and measures. In determining discrimination between groups, the Area Under the Curve (AUC) was calculated for all individual mobility measures with a threshold of 0.80, denoting excellent discrimination. Additionally, a stepwise regression of the top five AUC producing variables was performed to determine whether a combination of variables could enhance discrimination while accounting for multicollinearity. RESULTS: The results between neurotypical OA and middle-aged PwMS demonstrated significant differences for three gait and one turning variable, with no variable or combination of variables able to provide excellent discrimination between groups. Between middle-age neurotypical adults and PwMS a variety of mean and variability gait measures demonstrated significant differences between groups; however, no variable or combination of variables met discriminatory threshold. For turning, five 360˚ turn variables demonstrated significant differences and furthermore, the combination of 360˚ mean turn duration and variability of peak turn velocity were able to discriminate between groups. Finally, the majority of postural sway measures demonstrated significant group differences and the ability to discriminate between groups, particularly during more challenging balance conditions where participants stood on a compliant surface. CONCLUSION: These results offer a comprehensive analysis of mobility differences and measures capable of discriminating between middle-age neurotypical adults and PwMS. Additionally, these results provide evidence that OA and middle-age PwMS display similar movement characteristics and thus a potential indicator of advanced aging from a mobility perspective.

Non-invasive brain stimulation to assess neurophysiologic underpinnings of lower limb motor impairment in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory disease resulting in axonal demyelination and an amalgamation of symptoms which commonly result in decreased quality of life due to mobility dysfunction and limited participation in meaningful activities. NEW METHOD: The use of non-invasive brain stimulation (NIBS) techniques, specifically transcranial magnetic and transcranial direct current stimulation, have been essential in understanding the pathophysiological decrements related to disease progression, particularly with regard to motor impairments. Although the research in this area has primarily focused on the upper extremities, new interest has arisen in understanding the neurophysiological underpinnings of lower limb impairment. Therefore, the purpose of this review is to: first, provide an overview of common NIBS techniques used to explore sensorimotor neurophysiology; second, summarize lower limb neuromuscular and mobility impairments typically observed in PwMS; third, review the current knowledge regarding interactions between TMS-assessed neurophysiology and lower limb impairments in PwMS; and fourth, provide recommendations for future NIBS studies based on current gaps in the literature. RESULTS: PwMS exhibit reduced excitability and increased inhibitory neurophysiologic function which has been related to disease severity and lower limb motor impairments. Comparison with existing methods: Moreover, promising results indicate that the use of repetitive stimulation and transcranial direct current stimulation may prime neural adaptability and prove useful as a therapeutic tool in ameliorating lower limb impairments. CONCLUSIONS: While these studies are both informative and promising, additional studies are necessary to be conclusive. As such, studies assessing objective measures of lower limb impairments associated with neurophysiological adaptations need further evaluation.

Relating Response Inhibition, Brain Connectivity, and Freezing of Gait in People with Parkinson's Disease.

OBJECTIVE: Freezing of gait (FoG) in Parkinson's disease (PD) has been associated with response inhibition. However, the relationship between response inhibition, neural dysfunction, and PD remains unclear. We assessed response inhibition and microstructural integrity of brain regions involved in response inhibition [right hemisphere inferior frontal cortex (IFC), bilateral pre-supplementary motor areas (preSMA), and subthalamic nuclei (STN)] in PD subjects with and without FoG and elderly controls. METHOD: Twenty-one people with PD and FoG (PD-FoG), 18 without FoG (PD-noFoG), and 19 age-matched controls (HC) completed a Stop-Signal Task (SST) and MRI scan. Probabilistic fiber tractography assessed structural integrity (fractional anisotropy, FA) among IFC, preSMA, and STN regions. RESULTS: Stop-signal performance did not differ between PD and HC, nor between PD-FoG and PD-noFoG. Differences in white matter integrity were observed across groups (.001 < p < .064), but were restricted to PD versus HC groups; no differences in FA were observed between PD-FoG and PD-noFoG (p > .096). Interestingly, worse FoG was associated with higher (better) mean FA in the r-preSMA, (ß = .547, p = .015). Microstructural integrity of the r-IFC, r-preSMA, and r-STN tracts correlated with stop-signal performance in HC (p ≤ .019), but not people with PD. CONCLUSION: These results do not support inefficient response inhibition in PD-FoG. Those with PD exhibited white matter loss in the response inhibition network, but this was not associated with FoG, nor with response inhibition deficits, suggesting FoG-specific neural changes may occur outside the response inhibition network. As shown previously, white matter loss was associated with response inhibition in elderly controls, suggesting PD may disturb this relationship.