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The present study explored how motor cortical activity was influenced by visual perception of complex environments that either afforded or obstructed arm and leg reactions in young, healthy adults. Most importantly, we focused on compensatory balance reactions where the arms were required to regain stability following unexpected postural perturbation. Our first question was if motor cortical activity from the hand area automatically corresponds to the visual environment. Affordance-based priming of the motor system was assessed using single-pulse Transcranial Magnetic Stimulation (TMS) to determine if visual access to a wall-mounted support handle influenced corticospinal excitability. We evaluated if hand actions were automatically facilitated and/or suppressed by viewing an available handle within graspable range. Our second question was if the requirement for rapid movement to recover balance played a role in modulating any affordance effect in the hands. The goal was to disentangle motor demands related to postural threat from the impact of observation alone. For balance trials, a custom-built, lean and release apparatus was used to impose temporally unpredictable postural perturbations. In all balance trials, perturbations were of sufficient magnitude to evoke a compensatory change-in-support response; therefore, any recovery action needed to carefully take into account the affordances and constraints of the perceived environment to prevent a fall. Consistent with our first hypothesis, activity in an intrinsic hand muscle was increased when participants passively viewed a wall-mounted safety handle, in both seated and standing contexts. Contrary to our second hypothesis, this visual priming was absent when perturbations were imposed and the handle was needed to regain balance. Our results reveal that motor set is influenced by simply viewing objects that afford a grasp. We suggest that such preparation may provide an advantage when generating balance recovery actions that require quickly grasping a supportive handle. This priming effect likely competes with other task-dependent influences that regulate cortical motor output. Future studies should expand from limitations inherent with single-pulse TMS alone, to determine if vision of our surrounding world influences motor set in other contexts (e.g., intensified postural threat) and investigate if this priming corresponds to overt behavior.

Background When automatic, yet unwanted action is quickly inhibited, short-lived suppression throughout the motor system ensues. This effect is referred to as global suppression. Although response inhibition is essential for behavioral flexibility, widespread motor suppression may delay action reprogramming. In reactive balance control, even fleeting suppression of the motor system could interfere with our ability to adapt compensatory reactions quickly enough to avoid a fall. Research Question Is muscle activity in the hand suppressed when a prepotent compensatory step becomes suddenly blocked in a balance recovery task? Methods Nineteen young adults were tested using a lean and release apparatus. Participants were occasionally released from a support cable resulting in forward body displacement. At the start of each trial, vision was occluded and a leg block was either placed in front of the legs or removed to allow a forward step. After goggles opened, the cable was released to cause a postural perturbation and participants had to either quickly step forward (STEP) or use a feet-in-place reaction to regain stability (NO-STEP). Step trials were much more frequent to promote stepping. Transcranial magnetic stimulation (TMS) was delivered shortly after receving vision (but before postural perturbation) to assess corticospinal excitability in an intrinsic hand muscle that was irrelevant to the balance recovery task. Results Repeated measures ANOVA compared motor-evoked potentials across two step conditions (STEP, NO-STEP) and two TMS latencies (100 ms, 200 ms). The resultant interaction provided evidence of motor suppression in the hand when a forward step was blocked. Significance Inhibition of a hand muscle uninvolved in a compensatory leg response provided evidence of global suppression in a whole-body, reactive balance context. Such widespread suppression of the motor system has implications for maintaining postural equilibrium, where even a momentary shutdown across body regions could interfere with the ability to adapt corrective balance reactions.

Reactive balance, a critical automatic movement pattern in response to a perturbation, is directly linked to fall prevention in older adults. Various exercise interventions have been broadly performed to improve reactive balance and thus prevent falls. Curiously, aquatic exercises have been suggested as an effective balance intervention and a safer alternative to exercises on dry land yet the efficacy of aquatic exercises on reactive balance has not been formally investigated. The present clinical trial aims to identify if skills acquired during aquatic exercise are more effectively transferred to a reactive balance task than land exercise. This study is designed as a double-blinded, randomized controlled clinical trial. Forty-four older adults aged 65 years or above who meet the eligibility criteria will be recruited and randomized into an aquatic exercise group or land exercise group. Each group will participate in the same single bout intervention that includes a ball throwing and catching task. A modified lean-and-release test will be implemented on land immediately before, after, and one week after the single bout intervention. The outcomes will include reaction time, rapid response accuracy, and mini-BESTest scores obtained from stepping and grasping reactions. All statistical analyses will be conducted using an intention-to-treat approach. Our conceptual hypothesis is that participants in the aquatic exercise group will demonstrate more improved outcome scores in the lean-and-release test when compared to those in the land exercise group. The results of the present study are expected to provide evidence to support the benefits of aquatic exercises for improving reactive balance in older adults. Further, participants may find aquatic exercises safer and more motivating, thus encouraging them to participate in further aquatic exercise programs.

Assessment of reactive balance traditionally imposes some type of perturbation to upright stance or gait followed by measurement of the resultant corrective behavior. These measures include muscle responses, limb movements, ground reaction forces, and even direct neurophysiological measures such as electroencephalography. Using this approach, researchers and clinicians can infer some basic principles regarding how the nervous system controls balance to avoid a fall. One limitation with the way in which these assessments are currently used is that they heavily emphasize reflexive actions without any need to revise automatic postural reactions. Such an exclusive focus on these highly stereotypical reactions would fail to adequately address how we can modify these reactions should the need arise (e.g., avoiding an obstacle with a recovery step). This would appear to be a glaring omission when one considers the enormous complexity of the environments we face daily. Overall, the status quo when evaluating the neural control of balance fails to truly expose how higher brain resources contribute to preventing falls in complex settings. The present protocol offers a way to require suppression of automatic, but inappropriate corrective balance reactions, and force a selection among alternative action choices to successfully recover balance following postural perturbation.

Mere observation of objects in our surroundings can potentiate movement, a fact reflected by visually-primed activation of motor cortical networks. This mechanism holds potential value for reactive balance control where recovery actions of the arms or legs must be targeted to a new support base to avoid a fall. The present study was conducted to test if viewing a wall-mounted safety handle – the type of handle commonly used to regain balance – results in activation of motor cortical networks. We hypothesized that the hand area of the primary motor cortex would be facilitated shortly after visual access to a safety handle versus when no handle was visible. Here, we used transcranial magnetic stimulation (TMS) to measure corticospinal excitability in hand muscles directly following access to vision while participants performed a seated reach-grasp task. Vision was controlled using liquid crystal lenses and TMS pulses were time-locked to occur shortly after the goggles opened but prior to any cue for movement. Between trials the response environment was unpredictably altered to present either a handle or no handle (i.e. covered). Our results demonstrated a rapid motor facilitation in muscles of the right hand when participants viewed a handle versus trials where this handle was covered. This effect was selective both in terms of the muscles activated and the timing at which it emerged. The First Dorsal Interosseus and Opponens Pollicus muscles (synergists in closing the hand) were facilitated 120 ms after viewing the handle. Interestingly, this effect was absent at earlier (80 ms) and later (160 ms) points. Conversely, Abductor Digiti Minimi, which moves the little finger out from the rest of the hand, tended to diminish when viewing the handle. These findings suggest a rapid engagement of muscles suitable for grasping a handle based on vision. This is consistent with the concept of affordances where vision automatically translates viewed objects into appropriate motor terms. The fact that this affordance effect was present for a wall-mounted safety handle commonly used to regain balance has implications for automatically priming recovery actions with upper limbs suited to our surroundings, even before postural perturbation is detected.

Background Response inhibition involves suppressing automatic, but unwanted action, which allows for behavioral flexibility. This capacity could theoretically contribute to fall prevention, especially in the cluttered environments we face daily. Although much has been learned from cognitive psychology regarding response inhibition, it is unclear if such findings translate to the intensified challenge of coordinating balance recovery reactions. Research question Is the ability to stop a prepotent response preserved when comparing performance on a standard test of response inhibition versus a reactive balance test where compensatory steps must be occasionally suppressed? Methods Twelve young adults completed a stop signal task and reactive balance test separately. The stop signal task evaluates an individual’s ability to quickly suppress a visually-cued button press upon hearing a ‘stop’ tone, and provides a measure of the speed of response inhibition called the Stop Signal Reaction Time (SSRT). Reactive balance was tested by releasing participants from a supported lean position, in situations where the environment was changed during visual occlusion. Upon receiving vision, participants were required to either step to regain balance following cable release (70% of trials), or suppress a step if an obstacle was present (30% of trials). The early muscle response of the stepping leg was compared between the ‘step blocked’ and ‘step allowed’ trials to quantify step suppression. Results SSRT was correlated with muscle activation of the stepping leg when sufficient time was provided to view the response environment (400 ms). Individuals with faster SSRTs exhibited comparably less leg muscle activity when a step was blocked, signifying a superior ability to inhibit an unwanted step. Significance Performance on a standardized test of response inhibition is related to performance on a reactive balance test where automated stepping responses must occasionally be inhibited. This highlights a generalizable neural mechanism for stopping action across different behavioral contexts.

Many diseases, disabilities, and mental health conditions associated with aging can be delayed or prevented through regular exercise. Several barriers to exercise, many of which are exacerbated in rural communities, prevent mid-life and older adults from accessing its benefits. However, recently, a racquet sport named pickleball has become popular among older adults, and it appears to overcome some of these barriers. We conducted a feasibility study to evaluate the impact of a six-week pickleball intervention on measures of muscle function, cognitive function, perceived pain, and cardio-metabolic risk, as well as several psychosocial factors contributing to adherence in sedentary rural participants. Participants improved their vertical jump, cognitive performance, and reported a decrease in self-reported pain, suggesting improved physical and cognitive health across the sample. Participants also reported high levels of satisfaction and demonstrated good adherence over the duration of the study. Perhaps of greatest value was the overwhelmingly positive response from participants to the intervention and follow-up interviews reporting a desire to continue pickleball play beyond the study period. Overall, pickleball appears to be a promising intervention to, (1) elicit functional- and cognitive-related improvements, and (2) motivate mid-life and older adults to adhere to exercise sufficiently long to benefit their health.

Transfer, in which capability acquired in one situation influences performance in another is considered, along with retention, as demonstrative of effectual learning. In this regard, interlimb transfer of functional capacity has commanded particular attention as a means of gauging the generalisation of acquired capability. Both theoretical treatments and prior empirical studies suggest that the successful accomplishment of a physical training regime is required to bring about generalised changes that extend to the untrained limb. In the present study, we pose the following question: Does interlimb transfer occur if and only if the training movements are executed? We report findings from JG-an individual recruited to a larger scale trial, who presented with (unilateral) deficits of motor control. We examined whether changes in the performance of the untrained right limb arose following practice undertaken by the impaired left limb, wherein the majority of JG's attempts to execute the training task were unsuccessful. Comparison was made with a group of "control" participants drawn from the main trial, who did not practice the task. For JG, substantial gains in the performance of the untrained limb (registered 3 days, 10 days and 1 year following training) indicated that effective learning had occurred. Learning was, however, expressed principally when the unimpaired (i.e. untrained) limb was utilised to perform the task. When the impaired limb was used, marked deficiencies in movement execution remained prominent throughout.

Merely viewing objects within reachable space can activate motor cortical networks and potentiate movement. This holds potential value for smooth interaction with objects in our surroundings, and could offer an advantage for quickly generating targeted hand movements (e.g. grasping a support rail to maintain stability). The present study investigated if viewing a wall-mounted safety handle resulted in automatic activation of motor cortical networks, and if this effect changes with age. Twenty-five young adults (18–30 years) and seventeen older adults (65+ years) were included in this study. Single-pulse, transcranial magnetic stimulation was applied over the motor cortical hand representation of young and older adults shortly after they viewed a safety handle within reaching distance. Between trials, vision was occluded and the environment was unpredictably altered to reveal either a safety handle, or no handle (i.e. covered). Modulation of intrinsic hand muscle activity was evident in young adults when viewing a handle, and this was selective in terms of both the muscles activated and the time at which it emerged. By contrast, older adults failed to show any changes when viewing the safety handle. Specifically, the presence of a handle increased corticospinal activity in hand muscles of young adults when TMS was applied 120 ms after opening the goggles (p = .014), but not in the older adults (p > .954). The fact that the visual priming observed in younger adults was absent in older adults suggests that aging may diminish the ability to quickly put our visual world into automatic motor terms.

The ease with which we avoid falling down belies a highly sophisticated and distributed neural network for controlling reactions to maintain upright balance. Although historically these reactions were considered within the sub cortical domain, mounting evidence reveals a distributed network for postural control including a potentially important role for the cerebral cortex. Support for this cortical role comes from direct measurement associated with moments of induced instability as well as indirect links between cognitive task performance and balance recovery. The cerebral cortex appears to be directly involved in the control of rapid balance reactions but also setting the central nervous system in advance to optimize balance recovery reactions even when a future threat to stability is unexpected. In this review the growing body of evidence that now firmly supports a cortical role in the postural responses to externally induced perturbations is presented. Moreover, an updated framework is advanced to help understand how cortical contributions may influence our resistance to falls and on what timescale. The implications for future studies into the neural control of balance are discussed.

Immersion in chest-deep water may augment explicit memory in healthy adults however, there is limited information on how this environment might affect implicit memory or motor learning. The purpose of this study was to compare the speed and accuracy for learning a motor skill on land and in chest-deep water. Verbal word recall and grip strength were included to gain a more complete understanding of the intervention. Sixty-two younger adults (age = 23.3 ± 3.59 yrs.) were randomly assigned to either a water group immersed to the xiphoid or a land group. Participants in both groups completed the same eight practice trials of a mirror-drawing task on two separate days. Outcome measures for this task included time and error numbers to complete each drawing. The number of words recalled using a 12 word recall test, and peak grip strength using a hand dynamometer were measured each day of testing. The influence of environment and repeated practice on each outcome measure were assessed with an analysis of variance and effect sizes (ES). Time and errors for both groups significantly decreased with practice (p < 0.01, ES = 0.11–0.28), however the drawing time was greater in water than on land for trials 1, 5, and 6 (ES = 0.50–0.55). There was a 7% increase in words recalled (9.24 ± 1.19 vs 8.60 ± 1.19) and a 16% increase in grip strength (405 ± 104 vs 342 ± 83) for water than land groups (ES 0.54–0.64). Healthy adults in chest-deep water and on land display comparable mirror-drawing speed and accuracy after minimal practice. Curiously, water immersion may augment verbal word recall and grip strength abilities.

We explored the brain's ability to quickly prevent a pre-potent but unwanted motor response. To address this, transcranial magnetic stimulation was delivered over the motor cortex (hand representation) to probe excitability changes immediately after somatosensory cues prompted subjects to either move as fast as possible or withhold movement. Our results showed a difference in motor cortical excitability 90ms post-stimulus contingent on cues to either promote or prevent movement. We suggest that our study design emphasizing response speed coupled with well-defined early probes allowed us to extend upon similar past investigations into the timing of response inhibition.

Objectives To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing. Methods Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli. Results Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50). Conclusions The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients. Significance The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age.

Posterior parietal cortex (PPC) constitutes a critical cortical node in the sensorimotor system in which goal-directed actions are computed. This information then must be transferred into commands suitable for hand movements to the primary motor cortex (M1). Complexity arises because reach-to-grasp actions not only require directing the hand towards the object (transport component), but also preshaping the hand according to the features of the object (grip component). Yet, the functional influence that specific PPC regions exert over ipsilateral M1 during the planning of different hand movements remains unclear in humans. Here we manipulated transport and grip components of goal-directed hand movements and exploited paired-pulse transcranial magnetic stimulation ((pp)TMS) to probe the functional interactions between M1 and two different PPC regions, namely superior parieto-occipital cortex (SPOC) and the anterior region of the intraparietal sulcus (aIPS), in the left hemisphere. We show that when the extension of the arm is required to contact a target object, SPOC selectively facilitates motor evoked potentials, suggesting that SPOC-M1 interactions are functionally specific to arm transport. In contrast, a different pathway, linking the aIPS and ipsilateral M1, shows enhanced functional connections during the sensorimotor planning of grip. These results support recent human neuroimaging findings arguing for specialized human parietal regions for the planning of arm transport and hand grip during goal-directed actions. Importantly, they provide new insight into the causal influences these different parietal regions exert over ipsilateral motor cortex for specific types of planned hand movements.

Normal aging has been linked to impairments in gating of irrelevant sensory information and neural markers of diminished cognitive processing. Whilst much of the research in this area has focussed on visual and auditory modalities it is unclear to what degree these findings apply to somatosensation. Therefore we investigated how age impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesised that older adults would demonstrate reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. In accord with previous research we also expected to observe diminished P300 responses to attended targets and behavioural deficits. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) with comparisons between two age groups: (1) Young adults (age range 20-39) and (2) Older adults (age range 62-89). ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at several electrodes (C4, CP4, CP3 and FC4). The P300 in response to attended target stimuli was measured at CPZ. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. In both age groups the P100 and LLP were more positive during trials where the stimuli were attended to, whilst the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the older adults versus the young adults. This effect was due to a loss of suppression of the non-attended stimuli in older subjects. Moreover, the P300 was both slower and reduced in peak amplitude for older subjects in response to attended targets. Finally, older adults demonstrated impaired performance in terms of both reduced target detection accuracy and in reporting more false positives. Overall, present results reveal a deficit in suppressing irrelevant tactile information during an attention-demanding task which possibly relates to reduced markers of performance. Such a loss of inhibitory function is consistent with age-related change associated with a decline in executive control via prefrontal regions.

Availability of fingertip touch onto a stable surface reduces body sway for subjects standing with eyes closed. This is largely associated with sensory feedback from the fingertip when mechanical load is limited. Here, it is possible that the central nervous system facilitates cortical sensory processing to augment feedback to control upright stance. To test this, we compared cortical sensory excitability between tasks with and without light finger touch while standing. Subjects stood in tandem on a force plate with eyes closed while lightly touching a stable surface with the index finger. This was, in two different studies, compared to: (1) no haptic contact or (2) light touch on an object not referenced to balance. Throughout testing, the median nerve was stimulated and electroencephalography was used to measure somatosensory evoked potentials (SEPs). As expected, availability of stable light touch reduced medial-lateral COP sway. Peak amplitudes for SEP components revealed reduced P100 (48%), but increased P50 (31%), N140 (80%), and P200 (20%) during stable touch versus no touch. The modulation of P50 and N140 was no longer present when comparing stable to control (touch), which suggested that attending to touch on either surface, regardless of stability reference, accounted for these changes. Conversely, P200 was increased (19%) when touching the stable surface. Our data show SEP modulation during a standing balance task related to hand contact. Facilitation of P200 in particular may indicate task-specific regulation of the cortical representation of fingertip afferent input when it is relevant to providing stable cues for static balance control.

Objective Interhemispheric inhibition (IHI) is typically examined via responses elicited in intrinsic hand muscles. As the cortical representations of proximal and distal muscles in the upper limb are distinguished in terms of their inter-hemispheric projections, we sought to determine whether the IHI parameters established for the hand apply more generally. Methods We investigated IHI at 5 different conditioning stimulus (CS) intensities and a range of short-latency inter-stimulus intervals (ISIs) in healthy participants. Conditioning and test stimuli were delivered over the M1 representation of the right and left flexor carpi radialis respectively. Results IHI increased as a function of CS intensity, and was present for ISIs between 7 and 15 ms. Inhibition was most pronounced for the 10 ms ISI at all CS intensities. Conclusions The range of parameters for which IHI is elicited in projections to the forearm is similar to that reported for the hand. The specific utility lies in delineation of stimulus parameters that permit both potentiation and attenuation of IHI to be assessed. Significance In light of evidence that there is a greater density of callosal projections between cortical areas that represent proximal muscles than between those corresponding to distal limb muscles, and in view of the assumption that variations in functional connectivity to which such differences give rise may have important implications for motor behavior, it is critical to determine whether processes mediating the expression of IHI depend on the effector that is studied. This issue is of further broad significance given the practical utility of movements generated by muscles proximal to the wrist in the context of upper limb rehabilitation.

In this study, data from the World Mental Health Survey's Northern Ireland (NI) Study of Health and Stress (NISHS) was used to assess the associations between conflict- and non-conflict-related traumatic events and suicidal behaviour, controlling for age and gender and the effects of mental disorders in NI. DSM mental disorders and suicidal ideation, plans and attempts were assessed using the Composite International Diagnostic Interview (CIDI) in a multi-stage, clustered area probability household sample (N = 4,340, response rate 68.4%). The traumatic event categories were based on event types listed in the PTSD section of the CIDI. Suicidal ideation and attempts were more common in women than men, however, rates of suicide plans were similar for both genders. People with mood, anxiety and substance disorders were significantly more likely than those without to endorse suicidal ideation, plan or attempt. The highest odds ratios for all suicidal behaviors were for people with any mental disorder. However, the odds of seriously considering suicide were significantly higher for people with conflict and non-conflict-related traumatic events compared with people who had not experienced a traumatic event. The odds of having a suicide plan remain significantly higher for people with conflict-related traumatic events compared to those with only non-conflict-related events and no traumatic events. Finally, the odds of suicide attempt were significantly higher for people who have only non-conflict-related traumatic events compared with the other two categories. The results suggest that traumatic events associated with the NI conflict may be associated with suicidal ideation and plans, and this effect appears to be in addition to that explained by the presence of mental disorders. The reduced rates of suicide attempts among people who have had a conflict-related traumatic event may reflect a higher rate of single, fatal suicide attempts in this population.

‘Temporally urgent’ reactions are extremely rapid, spatially precise movements that are evoked following discrete stimuli. The involvement of primary motor cortex (M1) and its relationship to stimulus intensity in such reactions is not well understood. Continuous theta burst stimulation (cTBS) suppresses focal regions of the cortex and can assess the involvement of motor cortex in speed of processing. The primary objective of this study was to explore the involvement of M1 in speed of processing with respect to stimulus intensity. Thirteen healthy young adults participated in this experiment. Behavioral testing consisted of a simple button press using the index finger following median nerve stimulation of the opposite limb, at either high or low stimulus intensity. Reaction time was measured by the onset of electromyographic activity from the first dorsal interosseous (FDI) muscle of each limb. Participants completed a 30 min bout of behavioral testing prior to, and 15 min following, the delivery of cTBS to the motor cortical representation of the right FDI. The effect of cTBS on motor cortex was measured by recording the average of 30 motor evoked potentials (MEPs) just prior to, and 5 min following, cTBS. Paired t-tests revealed that, of thirteen participants, five demonstrated a significant attenuation, three demonstrated a significant facilitation and five demonstrated no significant change in MEP amplitude following cTBS. Of the group that demonstrated attenuated MEPs, there was a biologically significant interaction between stimulus intensity and effect of cTBS on reaction time and amplitude of muscle activation. This study demonstrates the variability of potential outcomes associated with the use of cTBS and further study on the mechanisms that underscore the methodology is required. Importantly, changes in motor cortical excitability may be an important determinant of speed of processing following high intensity stimulation.

The introduction of brain stimulation research techniques such as transcranial magnetic stimulation (TMS) has greatly advanced the understanding of the somatosensory system in humans. Over the last several years, several studies have focused on applying TMS in a variety of contexts to alter transiently the excitability of the somatosensory cortex or regions that project to it and exert some control over its activity in specific behavioral contexts. Specific foci that are discussed in this chapter are methods of repetitive TMS, including theta-burst protocols, delivered to the primary somatosensory cortex that have been shown to affect behavioral indices of somatic sensation such as tactile perception. Similar stimulation techniques can also be applied to distant areas that interact with and modulate activity in somatosensory cortex (i.e., attentional or motor networks). For example, suppression of the dorsolateral prefrontal cortex modifies the attention-modulation of somatosensory information in modality-specific cortices. Overall this chapter is focused on understanding the interaction of activity in systems that function with the somatosensory system in behavioral contexts. These include systems such as those that control attention, whether sustained or selective between sensory modalities, or those that control movement based on targets present in other sensory systems.

Cyclin-dependent kinase-5 (Cdk5) is over-expressed in both neurons and microvessels in hypoxic regions of stroke tissue and has a significant pathological role following hyper-phosphorylation leading to calpain-induced cell death. Here, we have identified a critical role of Cdk5 in cytoskeleton/focal dynamics, wherein its activator, p35, redistributes along actin microfilaments of spreading cells co-localising with p(Tyr15)Cdk5, talin/integrin beta-1 at the lamellipodia in polarising cells. Cdk5 inhibition (roscovitine) resulted in actin-cytoskeleton disorganisation, prevention of protein co-localization and inhibition of movement. Cells expressing Cdk5 (D144N) kinase mutant, were unable to spread, migrate and form tube-like structures or sprouts, while Cdk5 wild-type over-expression showed enhanced motility and angiogenesis in vitro, which was maintained during hypoxia. Gene microarray studies demonstrated myocyte enhancer factor (MEF2C) as a substrate for Cdk5-mediated angiogenesis in vitro. MEF2C showed nuclear co-immunoprecipitation with Cdk5 and almost complete inhibition of differentiation and sprout formation following siRNA knock-down. In hypoxia, insertion of Cdk5/p25-inhibitory peptide (CIP) vector preserved and enhanced in vitro angiogenesis. These results demonstrate the existence of critical and complementary signalling pathways through Cdk5 and p35, and through which coordination is a required factor for successful angiogenesis in sustained hypoxic condition. © 2013 Bosutti et al.

Background Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation which has been shown to alter cortical excitability in the upper limb representation of primary somatosensory cortex (SI). However, it is unknown whether cTBS modulates cortical excitability within the lower limb representation in SI. The present study investigates the effects of cTBS over the SI lower limb representation on cortical somatosensory evoked potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve stimulation at the knee. SEPs and H-reflex were recorded before and in four time blocks up to 30 minutes following cTBS targeting the lower limb representation within SI. Results Following cTBS, the P1-N1 first cortical potential was significantly decreased at 12–16 minutes. CTBS also suppressed the P2-N2 second cortical potential for up to 30 minutes following stimulation. The H-reflex remained statistically unchanged following cTBS although there was a modest suppression observed. Conclusion We conclude that cTBS decreases cortical excitability of the lower limb representation of SI as evidenced by suppressed SEP amplitude. The duration and magnitude of the cTBS after effects are similar to those observed in upper limb studies.

Several studies have shown that a light fingertip touch on a stable surface reduces body sway for individuals standing with their eyes closed even when touch forces are too low to offer mechanical support. It has been proposed that this is due to the availability of sway-relevant sensory feedback from the hand compensating for lost vision. Recently, we revealed modulation of cortical sensory transmission of information from the hand depending on the task (e.g. relevant or not relevant to balance control). Of interest in the present study is the potential origin of task-specific modulation of cortically evoked sensory potentials linked to balance control. We aimed to investigate the role of the prefrontal cortex by temporarily suppressing this region and observing differences in cortical events. Continuous θ-burst stimulation was applied to either the prefrontal cortex or a control stimulation site before balance testing. During balance testing, individuals stood in tandem on a force plate with their eyes closed while lightly touching a stable surface or a sway-referenced surface with the index finger. Throughout testing, the median nerve was stimulated and electroencephalography was used to measure somatosensory-evoked potentials. As expected, the availability of stable light touch reduced the medial-lateral centre of pressure sway. Importantly, in the present study, there was a loss of task-related P200 modulation at FCZ following stimulation of the prefrontal cortex. The present findings support the hypothesis that the prefrontal cortex may serve to regulate task-related sensory reweighting of haptic information that may be used during the control of standing balance.

Rapid balance reactions such as compensatory reach to grasp represent important response strategies following unexpected loss of balance. While it has been assumed that early corrective actions arise from subcortical networks, recent research has prompted speculation about the potential role of cortical involvement. With reach to grasp reactions there is evidence of parallels in the control of perturbation-evoked reaching versus rapid voluntary reaching. However, the potential role of cortical involvement in such rapid balance reactions remains speculative. To test if cortical motor regions are involved we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants involved in two reaching conditions: (1) rapid compensatory perturbation-evoked reach to grasp and (2) voluntary reach to grasp in response to an auditory cue. We hypothesized that following cTBS to the left M1 hand area we would find diminished EMG responses in the reaching (right) hand for both compensatory and voluntary movements. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair with a stable handle positioned in front of their right shoulder. The chair was held vertical by a magnet and triggered to fall backward randomly. To regain balance, participants were instructed to reach for the handle as quickly as possible with the right hand upon chair release. Intermixed with perturbation trials, participants were also required to reach for the same handle but in response to an auditory tone. Muscle activity was recorded from several muscles of the right arm/hand using electromyography. As expected, movement time and muscle onsets were much faster following perturbation versus auditory-cued reaching. The novel finding from our study was the reduced amplitude of hand muscle activity post-cTBS for both perturbation-cued and auditory-cued reaches. Moreover, this reduction was specific to the cTBS-targeted hand with no effect on remaining arm muscles. These findings support the idea that cortical networks contribute to both volitional and perturbation-evoked reaches and provide evidence for M1involvement in driving early arm responses toward a target following sudden loss of balance.

Previous work suggests that balance perturbations to the body opposing the direction of progression during walking lead to larger amplitude corrective reactions than perturbations concurrent with walking direction. To test this hypothesis, subjects received forward and backward perturbations applied to the pelvis through a padded harness, while walking forwards or backwards on a treadmill. Contrary to our hypothesis, the greatest responses were associated with backward perturbations regardless of the direction of walking.

Damage to the dorsolateral prefrontal cortex (DLPFC) impairs gating of irrelevant sensory information at early cortical processing stages. We investigated how transient inhibition of DLPFC impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesized that suppression of DLPFC using continuous theta burst stimulation (cTBS) would result in reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) in one of three groups following: (1) cTBS over DLPFC (40 s; 600 pulses of 3 stimuli at 50 Hz repeated at 5 Hz using 80% of resting motor threshold for abductor pollicis brevis), (2) sham stimulation, or (3) no stimulation. ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at C4, CP4, and CP3 electrodes. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. The P100 and LLP were significantly more positive during trials where the stimuli were attended to, while the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the cTBS group versus sham and no-stimulation groups. While the P100 was clearly reduced for non-attended stimuli relative to attended stimuli in the sham and no-stimulation groups, this effect was attenuated following cTBS. The reduction in attentional modulation of the P100 following cTBS suggests that the DLPFC contributes to filtering irrelevant somatosensory information at early cortical processing stages. Notably the influence of the DLPFC in attention-based modulation was evident even within digits of the same hand. The present results support the use of cTBS as an effective means of transiently suppressing DLPFC excitability.

Debate persists about the effectiveness of poststroke behavioral interventions for progress toward motor recovery. The current meta-analysis assessed the effect of electromyogram (EMG)-triggered neuromuscular stimulation on arm and hand functions. Computer searches of PubMed and Cochran databases, as well as hand searches of reference lists identified seven EMG-triggered neuromuscular stimulation studies. Outcome measures focused on arm and hand motor capability functions. In addition, the quality of each study was rated on three guidelines: randomization, double blind, and dropouts. After adjusting data for consistency in the arm/hand outcome measures and to avoid bias, five active stimulation studies were included in the analysis. Rehabilitation treatment in each study focused on wrist extension. The total number of individuals in the treatment groups was 47 whereas the control groups had 39 subjects. The meta-analysis revealed a significant overall mean effect size (delta=0.82, S.D.=0.59). A homogeneity test indicated that the pooled standardized effect sizes estimated the same treatment effect. A fail-safe test for null effect findings revealed that 15 studies were required to reduce the large effect (0.82) to a small effect (0.20). These improved wrist extension motor capabilities findings support EMG-triggered neuromuscular stimulation as an effective poststroke protocol.