Distinct Cortical Correlates of Perception and Motor Function in Balance Control.

Fluctuations in brain activity alter how we perceive our body and generate movements but have not been investigated in functional whole-body behaviors. During reactive balance, we recently showed that evoked brain activity is associated with the balance ability in young individuals. Furthermore, in PD, impaired whole-body motion perception in reactive balance is associated with impaired balance. Here, we investigated the brain activity during the whole-body motion perception in reactive balance in young adults (9 female, 10 male). We hypothesized that both ongoing and evoked cortical activity influences the efficiency of information processing for successful perception and movement during whole-body behaviors. We characterized two cortical signals using electroencephalography localized to the SMA: (1) the "N1," a perturbation-evoked potential that decreases in amplitude with expectancy and is larger in individuals with lower balance function, and (2) preperturbation ß power, a transient rhythm that favors maintenance of the current sensorimotor state and is inversely associated with tactile perception. In a two-alternative forced choice task, participants judged whether pairs of backward support surface perturbations during standing were in the "same" or "different" direction. As expected, lower whole-body perception was associated with lower balance ability. Within a perturbation pair, N1 attenuation was larger on correctly perceived trials and associated with better balance, but not perception. In contrast, preperturbation ß power was higher on incorrectly perceived trials and associated with poorer perception, but not balance. Together, ongoing and evoked cortical activity have unique roles in information processing that give rise to distinct associations with perceptual and balance ability.

Precise cortical contributions to sensorimotor feedback 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 Parkinson's disease.

Somatotopic Specificity of Perceptual and Neurophysiological Changes Associated with Visuo-proprioceptive Realignment.

When visual and proprioceptive estimates of hand position disagree (e.g., viewing the hand underwater), the brain realigns them to reduce mismatch. This perceptual change is reflected in primary motor cortex (M1) excitability, suggesting potential relevance for hand movement. Here, we asked whether fingertip visuo-proprioceptive misalignment affects only the brain's representation of that finger (somatotopically focal), or extends to other parts of the limb that would be needed to move the misaligned finger (somatotopically broad). In Experiments 1 and 2, before and after misaligned or veridical visuo-proprioceptive training at the index finger, we used transcranial magnetic stimulation to assess M1 representation of five hand and arm muscles. The index finger representation showed an association between M1 excitability and visuo-proprioceptive realignment, as did the pinkie finger representation to a lesser extent. Forearm flexors, forearm extensors, and biceps did not show any such relationship. In Experiment 3, participants indicated their proprioceptive estimate of the fingertip, knuckle, wrist, and elbow, before and after misalignment at the fingertip. Proprioceptive realignment at the knuckle, but not the wrist or elbow, was correlated with realignment at the fingertip. These results suggest the effects of visuo-proprioceptive mismatch are somatotopically focal in both sensory and motor domains.

Somatosensory changes associated with motor skill learning.

Trial-and-error motor adaptation has been linked to somatosensory plasticity and shifts in proprioception (limb position sense). The role of sensory processing in motor skill learning is less understood. Unlike adaptation, skill learning involves the acquisition of new movement patterns in the absence of perturbation, with performance limited by the speed-accuracy trade-off. We investigated somatosensory changes during motor skill learning at the behavioral and neurophysiological levels. Twenty-eight healthy young adults practiced a maze-tracing task, guiding a robotic manipulandum through an irregular two-dimensional track featuring several abrupt turns. Practice occurred on days 1 and 2. Skill was assessed before practice on day 1 and again on day 3, with learning indicated by a shift in the speed-accuracy function between these assessments. Proprioceptive function was quantified with a passive two-alternative forced-choice task. In a subset of 15 participants, we measured short-latency afferent inhibition (SAI) to index somatosensory projections to motor cortex. We found that motor practice enhanced the speed-accuracy skill function (F4,108 = 32.15, P < 0.001) and was associated with improved proprioceptive sensitivity at retention (t22 = 24.75, P = 0.0031). Furthermore, SAI increased after training (F1,14 = 5.41, P = 0.036). Interestingly, individuals with larger increases in SAI, reflecting enhanced somatosensory afference to motor cortex, demonstrated larger improvements in motor skill learning. These findings suggest that SAI may be an important functional mechanism for some aspect of motor skill learning. Further research is needed to test what parameters (task complexity, practice time, etc.) are specifically linked to somatosensory function.NEW & NOTEWORTHY Somatosensory processing has been implicated in motor adaptation, where performance recovers from a perturbation such as a force field. We investigated somatosensory function during motor skill learning, where a new motor pattern is acquired in the absence of perturbation. After skill practice, we found changes in proprioception and short-latency afferent inhibition (SAI), signifying somatosensory change at both the behavioral and neurophysiological levels. SAI may be an important functional mechanism by which individuals learn motor skills.

A Tablet-Based Tool for Accurate Measurement of Hand Proprioception After Stroke.

BACKGROUND AND PURPOSE: Proprioceptive deficits in the hand are common following stroke, but current clinical measurement techniques are too imprecise to detect subtle impairments or small changes. We developed a tablet-based tool to measure static hand proprioception using an adaptive staircase procedure. METHODS: In 16 individuals with chronic stroke and age-matched controls, we quantified proprioception at the metacarpophalangeal joint of the index finger using 3 methods: the tablet task, a custom passive movement direction discrimination test (PMDD), and a manual assessment similar to the Fugl-Meyer (F-M) proprioception subsection. RESULTS: The tablet-based measure and the PMDD both identified impaired proprioception in the affected hand relative to the unaffected hand (P = 0.024 and 0.028), and relative to the control group (P = 0.040 and 0.032), while manual assessment did not. The PMDD had a ceiling effect as movement excursions greater than 15 were not biomechanically feasible. The tablet-based measure and the PMDD detected impaired proprioception in 56% to 75%, and the F-M in only 29%, of patients. PMDD and tablet-based measures were both correlated with primary tactile sensation, but not manual dexterity. DISCUSSION AND CONCLUSIONS: Both the tablet-based tool and the custom PMDD performed better than manual assessment. The PMDD may be useful when the deficit is mild or assessment of dynamic proprioception is desired. As the tablet-based measure does not have the ceiling effect that is associated with the PMDD, it may be useful with any level of proprioceptive impairment, and may be preferable if testing or clinician training time needs to be minimized, or pain or spasticity is present.Video Abstract available for more insights from the authors (see the Video, Supplementary Digital Content 1, available at: http://links.lww.com/JNPT/A256).

Modality-specific Changes in Motor Cortex Excitability After Visuo-proprioceptive Realignment.

Spatial realignment of visual and proprioceptive estimates of hand position is necessary both to keep the estimates in register over time and to compensate for sensory perturbations. Such realignment affects perceived hand position, which the brain must use to plan hand movements. We would therefore expect visuo-proprioceptive realignment to affect the motor system at some level, but the physiological basis of this interaction is unknown. Here, we asked whether activity in primary motor cortex (M1), a well-known substrate of motor control, shows evidence of change after visuo-proprioceptive realignment. In two sessions each, 32 healthy adults experienced spatially misaligned or veridical visual and proprioceptive information about their static left index finger. Participants indicated perceived finger position with no performance feedback or knowledge of results. Using TMS over the M1 representation of the misaligned finger, we found no average difference between sessions. However, regression analysis indicated that, in the misaligned session only, proprioceptive realignment was linked with a decrease in M1 activity and visual realignment was linked with an increase in M1 activity. Proprioceptive and visual realignment were inversely related to each other. These results suggest that visuo-proprioceptive realignment does indeed have a physiological impact on the motor system. The lack of a between-session mean difference in M1 activity suggests that the basis of the effect is not the multisensory realignment computation itself, independent of modality. Rather, the changes in M1 are consistent with a modality-specific neural mechanism, such as modulation of somatosensory cortex or dorsal stream visual areas that impact M1.

Cerebellar role in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder associated with motor and cognitive impairments. The mechanisms underlying the pathophysiology and treatments have traditionally focused on basal ganglia-thalamo-cortical pathways due to striatal dopamine loss, but more recent evidence has highlighted the role of the cerebellum. In this Neuro Forum article, I review evidence from neuroimaging and noninvasive brain stimulation that demonstrates altered cerebellar activity in PD may be both a pathophysiological and compensatory mechanism depending on dopaminergic medication and symptoms.

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory.

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants' confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function.

Distinct cortical correlates of perception and motor function in balance control.

Fluctuations in brain state alter how we perceive our body and generate movements but have not been investigated in functional whole-body behaviors. During reactive balance control, we recently showed that evoked brain activity is associated with balance ability in healthy young individuals. Further, in individuals with Parkinson's disease, impairments in whole-body motion perception in reactive balance are associated with clinical balance impairment. Here we investigated brain activity during whole-body motion perception in reactive balance in healthy young adults. We hypothesized that flexibility in brain states underlies successful perception and movement during whole-body movement. We characterized two cortical sensorimotor signals using electroencephalography localized to the supplementary motor area: 1) the "N1 response", a perturbation-evoked potential that decreases in amplitude with expectancy and is larger in individuals with lower balance function; and 2) pre-perturbation beta oscillatory activity, a rhythm that favors maintenance of the current sensorimotor state and is inversely associated with perception in seated somatosensory perceptual tasks. In a two-alternative forced choice task, participants judged whether pairs of backward support-surface perturbations during standing were in the "same" or "different" direction. As expected, lower whole-body perception was associated with lower balance ability. Within a perturbation pair, N1 attenuation was larger on correctly perceived trials and associated with better balance, but not perception. In contrast, pre-perturbation beta power was higher on incorrectly perceived trials and associated with poorer perception, but not balance. Taken together, flexibility in different cortical processes influences perceptual accuracy but have distinct associations with balance and perceptual ability.

State-dependent interhemispheric inhibition reveals individual differences in motor behavior in chronic stroke.

OBJECTIVE: To investigate state-dependent interhemispheric inhibition (IHI) in chronic stroke survivors compared to neurotypical older adult controls, and test whether abnormal IHI modulation was associated with upper extremity motor behavior. METHODS: Dual-coil transcranial magnetic stimulation (TMS) measured IHI bi-directionally, between non-lesioned and lesioned motor cortex (M1) in two activity states: (1) at rest and (2) during contralateral isometric hand muscle contraction. IHI was tested by delivering a conditioning stimulus 8-msec or 50-msec prior to a test stimulus over contralateral M1. Paretic motor behavior was assessed by clinical measures of impairment, strength, and dexterity, and mirroring activity in the non-paretic hand. RESULTS: Stroke survivors demonstrated reduced IHI at rest, and less IHI modulation (active - rest) compared to controls. Individual differences in IHI modulation were related to motor behavior differences where greater IHI modulation was associated with greater motor impairment and more mirroring. In contrast, there were no relationships between IHI at rest and motor behavior. CONCLUSIONS: Abnormal state-dependent interhemispheric circuit activity may be more sensitive to post-stroke motor deficits than when assessed in a single motor state. SIGNIFICANCE: Characterizing state-dependent changes in neural circuitry may enhance models of stroke recovery and inform rehabilitation interventions.

Delayed cortical engagement associated with balance dysfunction after stroke.

Cortical resources are typically engaged for balance and mobility in older adults, but these resources are impaired post-stroke. Although slowed balance and mobility after stroke have been well-characterized, the effects of unilateral cortical lesions due to stroke on neuromechanical control of balance is poorly understood. Our central hypothesis is that stroke impairs the ability to rapidly and effectively engage the cerebral cortex during balance and mobility behaviors, resulting in asymmetrical contributions of each limb to balance control. Using electroencephalography (EEG), we assessed cortical N1 responses evoked over fronto-midline regions (Cz) during balance recovery in response to backward support-surface perturbations loading both legs, as well as posterior-lateral directions that preferentially load the paretic or nonparetic leg. Cortical N1 responses were smaller and delayed in the stroke group. While older adults exhibited weak or absent relationships between cortical responses and clinical function, stroke survivors exhibited strong associations between slower N1 latencies and slower walking, lower clinical mobility, and lower balance function. We further assessed kinetics of balance recovery during perturbations using center of pressure rate of rise. During backward support-surface perturbations that loaded the legs bilaterally, balance recovery kinetics were not different between stroke and control groups and were not associated with cortical response latency. However, lateralized perturbations revealed slower kinetic reactions during paretic loading compared to controls, and to non-paretic loading within stroke participants. Individuals post stroke had similar nonparetic-loaded kinetic reactions to controls implicating that they effectively compensate for impaired paretic leg kinetics when relying on the non-paretic leg. In contrast, paretic-loaded balance recovery revealed time-synchronized associations between slower cortical responses and slower kinetic reactions only in the stroke group, potentially reflecting the limits of cortical engagement for balance recovery revealed within the behavioral context of paretic motor capacity. Overall, our results implicate individuals after stroke may be uniquely limited in their balance ability by the slowed speed of their cortical engagement, particularly under challenging balance conditions that rely on the paretic leg. We expect this neuromechanical insight will enable progress toward an individualized framework for the assessment and treatment of balance impairments based on the interaction between neuropathology and behavioral context.

Specific sensorimotor interneuron circuits are sensitive to cerebellar-attention interactions.

Background: Short latency afferent inhibition (SAI) provides a method to investigate mechanisms of sensorimotor integration. Cholinergic involvement in the SAI phenomena suggests that SAI may provide a marker of cognitive influence over implicit sensorimotor processes. Consistent with this hypothesis, we previously demonstrated that visual attention load suppresses SAI circuits preferentially recruited by anterior-to-posterior (AP)-, but not posterior-to-anterior (PA)-current induced by transcranial magnetic stimulation. However, cerebellar modulation can also modulate these same AP-sensitive SAI circuits. Yet, the consequences of concurrent cognitive and implicit cerebellar influences over these AP circuits are unknown. Objective: We used cerebellar intermittent theta-burst stimulation (iTBS) to determine whether the cerebellar modulation of sensory to motor projections interacts with the attentional modulation of sensory to motor circuits probed by SAI. Methods: We assessed AP-SAI and PA-SAI during a concurrent visual detection task of varying attention load before and after cerebellar iTBS. Results: Before cerebellar iTBS, a higher visual attention load suppressed AP-SAI, but not PA-SAI, compared to a lower visual attention load. Post-cerebellar iTBS, the pattern of AP-SAI in response to visual attention load, was reversed; a higher visual attention load enhanced AP-SAI compared to a lower visual attention load. Cerebellar iTBS did not affect PA-SAI regardless of visual attention load. Conclusion: These findings suggest that attention and cerebellar networks converge on overlapping AP-sensitive circuitry to influence motor output by controlling the strength of the afferent projections to the motor cortex. This interaction has important implications for understanding the mechanisms of motor performance and learning.

Somatosensory versus cerebellar contributions to proprioceptive changes associated with motor skill learning: A theta burst stimulation study.

BACKGROUND: It is well established that proprioception (position sense) is important for motor control, yet its role in motor learning and associated plasticity is not well understood. We previously demonstrated that motor skill learning is associated with enhanced proprioception and changes in sensorimotor neurophysiology. However, the neural substrates mediating these effects are unclear. OBJECTIVE: To determine whether suppressing activity in the cerebellum and somatosensory cortex (S1) affects proprioceptive changes associated with motor skill learning. METHODS: 54 healthy young adults practiced a skill involving visually-guided 2D reaching movements through an irregular-shaped track using a robotic manipulandum with their right hand. Proprioception was measured using a passive two-alternative choice task before and after motor practice. Continuous theta burst stimulation (cTBS) was delivered over S1 or the cerebellum (CB) at the end of training for two consecutive days. We compared group differences (S1, CB, Sham) in proprioception and motor skill, quantified by a speed-accuracy function, measured on a third consecutive day (retention). RESULTS: As shown previously, the Sham group demonstrated enhanced proprioceptive sensitivity after training and at retention. The S1 group had impaired proprioceptive function at retention through online changes during practice, whereas the CB group demonstrated offline decrements in proprioceptive function. All groups demonstrated motor skill learning. However, the magnitude of learning differed between the CB and Sham groups, consistent with a role for the cerebellum in motor learning. CONCLUSION: Overall, these findings suggest that the cerebellum and S1 are important for distinct aspects of proprioceptive changes during skill learning.

Changes in Cortical Plasticity in Relation to a History of Concussion during Adolescence.

Adolescence and early adulthood is a critical period for neurophysiological development potentially characterized by an increased susceptibility to the long-term effects of traumatic brain injury. The current study investigated differences in motor cortical physiology and neuroplastic potential across a cohort of young adults with adolescent concussion history and those without. Transcranial magnetic stimulation (TMS) was used to assess motor evoked potential (MEP) amplitude, short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) before and after intermittent theta burst stimulation (iTBS). Pre-iTBS, MEP amplitude, but not SICI or ICF, was greater in the concussion history group. Post-iTBS, the expected increase in MEP amplitude and ICF was tempered in the concussion history group. Change in SICI was variable within the concussion history group. Post hoc assessment revealed that SICI was significantly lower in individuals whose concussion was not diagnosed at the time of injury compared to both those without a concussion history or whose concussion was medically diagnosed. Concussive impacts during adolescence appear to result in a persistent reduction of the ability to modulate facilitatory motor networks. Failure to report/identify concussive impacts close to injury during adolescence also appears to produce persistent change in inhibitory networks. These findings highlight the potential long-term impact of adolescent concussion upon motor cortical physiology.