Musical Sophistication and Multilingualism: Effects on Arcuate Fasciculus Characteristics.

The processing of auditory stimuli which are structured in time is thought to involve the arcuate fasciculus, the white matter tract which connects the temporal cortex and the inferior frontal gyrus. Research has indicated effects of both musical and language experience on the structural characteristics of the arcuate fasciculus. Here, we investigated in a sample of n = 84 young adults whether continuous conceptualizations of musical and multilingual experience related to structural characteristics of the arcuate fasciculus, measured using diffusion tensor imaging. Probabilistic tractography was used to identify the dorsal and ventral parts of the white matter tract. Linear regressions indicated that different aspects of musical sophistication related to the arcuate fasciculus' volume (emotional engagement with music), volumetric asymmetry (musical training and music perceptual abilities), and fractional anisotropy (music perceptual abilities). Our conceptualization of multilingual experience, accounting for participants' proficiency in reading, writing, understanding, and speaking different languages, was not related to the structural characteristics of the arcuate fasciculus. We discuss our results in the context of other research on hemispheric specializations and a dual-stream model of auditory processing.

Gamified Practice Improves Paretic Arm Motor Behavior in Individuals With Stroke.

BACKGROUND: Stroke is a heterogeneous condition, making choice of treatment, and determination of how to structure rehabilitation outcomes difficult. Individualized goal-directed and repetitive physical practice is an important determinant of motor learning. Yet, many investigations of motor learning after stroke deliver task practice without consideration of individual capability of the learner. OBJECTIVE: We developed a gamified arm rehabilitation task for people with stroke that is personalized to individual capacity for paretic arm movement, provides a high dose of practice, progresses through increasingly difficulty levels that are dependent on the performance of the individual, and is practiced in an engaging environment. The objectives of the current study were to determine if 10 days of gamified, object intercept training using the paretic arm would improve arm movement speed and clinical outcome measures of impairment or function. METHODS: Individuals with chronic stroke and age-matched controls engaged in 10 days of gamified, skilled motor practice of a semi-immersive virtual reality-based intercept and release task. The paretic arm was assessed using the Fugl-Meyer Assessment (motor impairment) and Wolf Motor Function Test (motor function) before and after training. RESULTS: Both groups showed faster arm movement speed with practice; individuals with stroke demonstrated reduced paretic arm motor impairment and increased function after the intervention. Age and sex (for both groups), and time post-stroke were not related to changes in movement speed. CONCLUSIONS: Findings indicate that gamified motor training positively affects paretic arm motor behavior in individuals with mild to severe chronic stroke.

Sex differences in patterns of white matter neuroplasticity after balance training in young adults.

Introduction: In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task. Methods: 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training. Results: Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance). Discussion: The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

Data-driven biomarkers better associate with stroke motor outcomes than theory-based biomarkers.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to model chronic motor outcomes after stroke and compares the accuracy of these associations to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients from the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Stroke Recovery Working Group. Using the explained variance metric to measure the strength of the association between chronic motor outcomes and imaging biomarkers, we compared theory-based biomarkers, like lesion load to known motor tracts, to three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had stronger associations with chronic motor outcomes accuracy than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R 2 = 0.210, P < 0.001), performing significantly better than the theory-based biomarkers of lesion load of the corticospinal tract (R 2 = 0.132, P < 0.001) and of multiple descending motor tracts (R 2 = 0.180, P < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R 2 = 0.200, P < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R 2 = 0.167, P < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved the strength of associations for theory-based and data-driven biomarkers. Combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R 2 = 0.241, P < 0.001. Overall, these results demonstrate that out-of-sample associations between chronic motor outcomes and data-driven imaging features, particularly when lesion data is represented in terms of structural disconnection, are stronger than associations between chronic motor outcomes and theory-based biomarkers. However, combining both theory-based and data-driven models provides the most robust associations.

Examining Sex Differences in Relationships Between Subjective and Objective Measures of Upper Extremity Motor Impairment in a Sample of Stroke Survivors.

BACKGROUND AND PURPOSE: Rehabilitation professionals use subjective and objective outcome measures to assess stroke-related impact and impairment. Understanding if subjective and objective findings correlate among stroke survivors, especially if these associations differ between females and males, can inform care decisions. METHODS: A retrospective cross-sectional design was used, with data selected from subacute to chronic stroke survivors on age, time since stroke, the hand domain from the Stroke Impact Scale version 3.0 (SIS-H), and the Fugl-Meyer Upper Extremity (FMUE) Assessment. Group differences were assessed for all outcomes based on sex and time poststroke. Separate correlations for females and males were performed between the subjective (SIS-H) and objective measures (FMUE) of upper limb function and impairment. RESULTS: Data from 148 participants (44 females) were included in this study. SIS-H was significantly correlated with FMUE in both females and males ( P s ≤ 0.001). No significant differences were found between the groups' mean SIS-H or FMUE scores based on sex or time poststroke. DISCUSSION AND CONCLUSIONS: Subjective and objective measures of physical functioning were correlated in both females and males. Although we found no sex differences in our primary outcomes, the sample size of females was disproportionately lower than the males. This is consistent with an ongoing problem in the stroke recovery research field, where females are often underrepresented and understudied, and where females who experience higher levels of impairment are less likely to participate in research.

Evaluation of microglia activation related markers following a clinical course of TBS: A non-human primate study.

While the applicability and popularity of theta burst stimulation (TBS) paradigms remain, current knowledge of their neurobiological effects is still limited, especially with respect to their impact on glial cells and neuroinflammatory processes. We used a multimodal imaging approach to assess the effects of a clinical course of TBS on markers for microglia activation and tissue injury as an indirect assessment of neuroinflammatory processes. Healthy non-human primates received continuous TBS (cTBS), intermittent TBS (iTBS), or sham stimulation over the motor cortex at 90% of resting motor threshold. Stimulation was delivered to the awake subjects 5 times a week for 3-4 weeks. Translocator protein (TSPO) expression was evaluated using Positron Emission Tomography and [11C]PBR28, and myo-inositol (mI) and N-acetyl-aspartate (NAA) concentrations were assessed with Magnetic Resonance Spectroscopy. Animals were then euthanized, and immunofluorescence staining was performed using antibodies against TSPO. Paired t-tests showed no significant changes in [11C]PBR28 measurements after stimulation. Similarly, no significant changes in mI and NAA concentrations were found. Post-mortem TSPO evaluation showed comparable mean immunofluorescence intensity after active TBS and sham delivery. The current study suggests that in healthy brains a clinical course of TBS, as evaluated with in-vivo imaging techniques (PET and MRS), did not measurably modulate the expression of glia related markers and metabolite associated with neural viability.

Opera trainees' cognitive functioning is associated with physiological stress during performance.

In an opera performance, singers must perform difficult musical repertoire at a high level while dealing with the stress of standing before a large audience. Previous literature suggests that individuals with better cognitive functions experience less stress. During a music performance such functions, especially attention, memory, and executive function, are in high demand, suggesting that cognitive functions may play a role in music performance. This study used physiological and cognitive measures to examine this phenomenon in opera performance. Cardiac activity data were collected from 24 opera trainees during a resting-state period before and during a real-life performance. Heart-rate variability (HRV) was used as an indicator of physiological stress, such that higher HRV indicates lower stress. Standardized neuropsychological tests were used to measure attention (IVA-2), memory (CVLT-3, WMS-IV), and executive function (Trail Making Test). Results showed cognitive function- and state-specific relationships between HRV and cognitive function: HRV during the resting state had a positive correlation with attention, while HRV during a performance had a positive correlation with executive function. These results suggest that greater cognitive function is related to lower stress during opera performance. The findings of this study provide initial evidence for a relationship between cognitive functions and music performance stress in opera trainees.

Investigating female versus male differences in white matter neuroplasticity associated with complex visuo-motor learning.

Magnetic resonance imaging (MRI) has increasingly been used to characterize structure-function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38-51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18-29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation.

Frontoparietal function and underlying structure reflect capacity for motor skill acquisition during healthy aging.

While capacity for motor skill acquisition changes with healthy aging, there has been little consideration of how age-related changes in brain function or baseline brain structure support motor skill acquisition. We examined: (1) age-dependent changes in functional reorganization related to frontoparietal regions during motor skill acquisition, and (2) whether capacity for motor skill acquisition relates to baseline white matter microstructure in frontoparietal tracts. Healthy older and younger adults engaged in 4 weeks of skilled motor practice. Resting-state functional connectivity (rsFC) assessed functional reorganization before and after practice. Diffusion tensor imaging indexed microstructure of a frontoparietal tract at baseline, generated by rsFC seeds. Motor skill acquisition was associated with decreases in rsFC in healthy older adults and increases in rsFC in healthy younger adults. Frontoparietal tract microstructure was lower in healthy older versus younger adults, yet it was negatively associated with rate of skill acquisition regardless of group. Findings indicate that age-dependent alterations in frontoparietal function and baseline structure of a frontoparietal tract reflect capacity for motor skill acquisition.

Interhemispheric inhibition between dorsal premotor and primary motor cortices is released during preparation of unimanual but not bimanual movements.

Previous research applying transcranial magnetic stimulation during unimanual reaction time tasks indicates a transient change in the inhibitory influence of the dorsal premotor cortex over the contralateral primary motor cortex shortly after the presentation of an imperative stimulus. The degree of interhemispheric inhibition from the dorsal premotor cortex to the contralateral primary motor cortex shifts depending on whether the targeted effector representation in the primary motor cortex is selected for movement. Further, the timing of changes in inhibition covaries with the selection demands of the reaction time task. Less is known about modulation of dorsal premotor to primary motor cortex interhemispheric inhibition during the preparation of bimanual movements. In this study, we used a dual coil transcranial magnetic stimulation to measure dorsal premotor to primary motor cortex interhemispheric inhibition between both hemispheres during unimanual and bimanual simple reaction time trials. Interhemispheric inhibition was measured early and late in the 'pre-movement period' (defined as the period immediately after the onset of the imperative stimulus and before the beginning of voluntary muscle activity). We discovered that interhemispheric inhibition was more facilitatory early in the pre-movement period compared with late in the pre-movement period during unimanual reaction time trials. In contrast, interhemispheric inhibition was unchanged throughout the pre-movement period during symmetrical bimanual reaction time trials. These results suggest that there is greater interaction between the dorsal premotor cortex and contralateral primary motor cortex during the preparation of unimanual actions compared to bimanual actions.

White matter hyperintensities modify relationships between corticospinal tract damage and motor outcomes after stroke.

Motor outcomes after stroke relate to corticospinal tract (CST) damage. Concurrent damage from white matter hyperintensities (WMHs) might impact neurological capacity for recovery after CST injury. Here, we evaluated if WMHs modulate the relationship between CST damage and post-stroke motor impairment outcome. We included 223 individuals from the ENIGMA Stroke Recovery Working Group. CST damage was indexed with weighted CST lesion load (CST-LL). Mixed effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment. WMH volume related to motor impairment above and beyond CST-LL (ß = 0.178, p = 0.022). We tested if relationships varied by WMH severity (mild vs. moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (ß = 0.888, p < 0.001) with a CST-LL x WMH interaction (ß = -0.211, 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (ß = 0.299, p = 0.044), but did not significantly relate to CST-LL or a CST-LL x WMH interaction. WMH-related damage may be under-recognised in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.

Resting-state brain connectivity correlates of musical sophistication.

Introduction: A growing body of research has investigated how performing arts training, and more specifically, music training, impacts the brain. Recent meta-analytic work has identified multiple brain areas where activity varies as a function of levels of musical expertise gained through music training. However, research has also shown that musical sophistication may be high even without music training. Thus, we aim to extend previous work by investigating whether the functional connectivity of these areas relates to interindividual differences in musical sophistication, and to characterize differences in connectivity attributed to performing arts training. Methods: We analyzed resting-state functional magnetic resonance imaging from n = 74 participants, of whom 37 received performing arts training, that is, including a musical instrument, singing, and/or acting, at university level. We used a validated, continuous measure of musical sophistication to further characterize our sample. Following standard pre-processing, fifteen brain areas were identified a priori based on meta-analytic work and used as seeds in separate seed-to-voxel analyses to examine the effect of musical sophistication across the sample, and between-group analyses to examine the effects of performing arts training. Results: Connectivity of bilateral superior temporal gyrus, bilateral precentral gyrus and cerebellum, and bilateral putamen, left insula, and left thalamus varied with different aspects of musical sophistication. By including these measures of these aspects as covariates in post hoc analyses, we found that connectivity of the right superior temporal gyrus and left precentral gyrus relate to effects of performing arts training beyond effects of individual musical sophistication. Discussion: Our results highlight the potential role of sensory areas in active engagement with music, the potential role of motor areas in emotion processing, and the potential role of connectivity between putamen and lingual gyrus in general musical sophistication.

Females exhibit smaller volumes of brain activation and lower inter-subject variability during motor tasks.

Past work has shown that brain structure and function differ between females and males. Males have larger cortical and sub-cortical volume and surface area (both total and subregional), while females have greater cortical thickness in most brain regions. Functional differences are also reported in the literature, yet to date little work has systematically considered whether patterns of brain activity indexed with functional magnetic resonance imaging (fMRI) differ between females and males. The current study sought to remediate this issue by employing task-based whole brain motor mapping analyses using an openly available dataset. We tested differences in patterns of functional brain activity associated with 12 voluntary movement patterns in females versus males. Results suggest that females exhibited smaller volumes of brain activation across all 12 movement tasks, and lower patterns of variability in 10 of the 12 movements. We also observed that females had greater cortical thickness, which is in alignment with previous analyses of structural differences. Overall, these findings provide a basis for considering biological sex in future fMRI research and provide a foundation of understanding differences in how neurological pathologies present in females vs males.

Premotor and Posterior Parietal Cortex Activity is Increased for Slow, as well as Fast Walking Poststroke: An fNIRS Study.

Methods: Twenty individuals in the chronic stage of stroke walked: (1) at their normal pace, (2) slower than normal, and (3) as fast as possible. Functional near-infrared spectroscopy was used to assess bilateral prefrontal, premotor, sensorimotor, and posterior parietal cortices during walking. Results: No significant differences in laterality were observed between walking speeds. The ipsilesional prefrontal cortex was overall more active than the contralesional prefrontal cortex. Premotor and posterior parietal cortex activity were larger during slow and fast walking compared to normal-paced walking with no differences between slow and fast walking. Greater increases in brain activation in the ipsilesional prefrontal cortex during fast compared to normal-paced walking related to greater gait speed modulation. Conclusions: Brain activation is not linearly related to gait speed. Ipsilesional prefrontal cortex, bilateral premotor, and bilateral posterior parietal cortices are important areas for gait speed modulation and could be an area of interest for neurostimulation.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Improved processing speed and decreased functional connectivity in individuals with chronic stroke after paired exercise and motor training.

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in neurologically intact populations and may be effective in altering cognitive function post-stroke. We sought to determine if high-intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 ± 11 years; 4 females), or control (n = 11; 68 ± 8 years; 2 females) groups. Both groups performed 5-days of paretic upper limb motor training after either high-intensity aerobic exercise (3 intervals of 3 min each, total exercise duration of 23-min) or watching a documentary (control). Resting-state fMRI, and trail making test part A (TMT-A) and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < 0.001); there was no added benefit of exercise for implicit motor sequence learning (p = 0.738). The exercise group experienced greater overall cognitive-motor improvements measured with the TMT-A. Regardless of group, the changes in task score, and dwell time during TMT-A were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (task score: p = 0.025; dwell time: p = 0.043), which is thought to reflect a reduction in the cognitive demand and increased automaticity. Aerobic exercise may improve cognitive-motor processing speed post-stroke.

Optimizing automated white matter hyperintensity segmentation in individuals with stroke.

White matter hyperintensities (WMHs) are a risk factor for stroke. Consequently, many individuals who suffer a stroke have comorbid WMHs. The impact of WMHs on stroke recovery is an active area of research. Automated WMH segmentation methods are often employed as they require minimal user input and reduce risk of rater bias; however, these automated methods have not been specifically validated for use in individuals with stroke. Here, we present methodological validation of automated WMH segmentation methods in individuals with stroke. We first optimized parameters for FSL's publicly available WMH segmentation software BIANCA in two independent (multi-site) datasets. Our optimized BIANCA protocol achieved good performance within each independent dataset, when the BIANCA model was trained and tested in the same dataset or trained on mixed-sample data. BIANCA segmentation failed when generalizing a trained model to a new testing dataset. We therefore contrasted BIANCA's performance with SAMSEG, an unsupervised WMH segmentation tool available through FreeSurfer. SAMSEG does not require prior WMH masks for model training and was more robust to handling multi-site data. However, SAMSEG performance was slightly lower than BIANCA when data from a single site were tested. This manuscript will serve as a guide for the development and utilization of WMH analysis pipelines for individuals with stroke.

White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Real world evidence of improved attention and cognition during physical therapy paired with neuromodulation: a brain vital signs study.

Background: Non-invasive neuromodulation using translingual neurostimulation (TLNS) has been shown to advance rehabilitation outcomes, particularly when paired with physical therapy (PT). Together with motor gains, patient-reported observations of incidental improvements in cognitive function have been noted. Both studies in healthy individuals and case reports in clinical populations have linked TLNS to improvements in attention-related cognitive processes. We investigated if the use of combined TLNS/PT would translate to changes in objective neurophysiological cognitive measures in a real-world clinical sample of patients from two separate rehabilitation clinics. Methods: Brain vital signs were derived from event-related potentials (ERPs), specifically auditory sensation (N100), basic attention (P300), and cognitive processing (N400). Additional analyses explored the attention-related N200 response given prior evidence of attention effects from TLNS/PT. The real-world patient sample included a diverse clinical group spanning from mild-to-moderate traumatic brain injury (TBI), stroke, Multiple Sclerosis (MS), Parkinson's Disease (PD), and other neurological conditions. Patient data were also acquired from a standard clinical measure of cognition for comparison. Results: Results showed significant N100 variation between baseline and endpoint following TLNS/PT treatment, with further examination showing condition-specific significant improvements in attention processing (i.e., N100 and N200). Additionally, CogBAT composite scores increased significantly from baseline to endpoint. Discussion: The current study highlighted real-world neuromodulation improvements in neurophysiological correlates of attention. Overall, the real-world findings support the concept of neuromodulation-related improvements extending beyond physical therapy to include potential attention benefits for cognitive rehabilitation.