Sensorimotor integration in healthy aging: Baseline differences and response to sensory training.

Sensorimotor integration is the process through which somatosensory information is incorporated to inform motor output. Given its important behavioural implications, understanding the influence of healthy aging on the underlying neurophysiology of sensorimotor integration and whether it is modifiable through intervention is important. The aims of the current work were to: 1) profile aging-related differences in sensorimotor integration, and 2) to determine if sensorimotor integration in older adults can be modulated in response to sensory training. A group of older healthy individuals and younger healthy individuals participated in two experimental sessions. First, baseline neurophysiology of sensorimotor integration was assessed. Short-latency afferent inhibition, afferent facilitation, and long-latency afferent inhibition provided nerve-based assessment of sensorimotor integration. Vibration-based measures of sensorimotor integration combined vibration of abductor pollicis brevis with single and paired-pulse transcranial magnetic stimulation techniques. In the second experimental session, a 15-min block of sensory training designed to modulate sensorimotor integration preceded the same neurophysiological assessment. Results indicate that there are aging-related differences in nerve-based measures of sensorimotor integration, specifically short- and long-latency afferent inhibition. In contrast, there are not aging-related differences when peripheral muscle belly vibration is used to probe sensorimotor integration. Following sensory training there is a reduction in the cortical response to vibration. These results suggest that there is differential aging-related modulation of sensorimotor integration, based on the type of afferent information. Additionally, sensorimotor integration is modifiable with a single session of sensory training, and this ability for neuroplastic change is retained with healthy aging.

Interhemispheric inhibition of corticospinal projections to forearm muscles.

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 15ms. Inhibition was most pronounced for the 10ms 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.

Corticomotor excitability changes seen in the resting forearm during contralateral rhythmical movement and force manipulations: a TMS study.

The aim of this study was to examine changes in corticomotor excitability to a resting wrist extensor muscle during contralateral rhythmical isotonic and static isometric wrist contractions (flexion/extension) at different loads and positions, using transcranial magnetic stimulation (TMS). TMS-induced motor-evoked potentials (MEPs) were recorded from the relaxed right extensor carpi radialis (ECR) and flexor carpi radialis (FCR) respectively, while the left arm underwent unimanual manipulations. Rhythmical isotonic (0.5 Hz) flexion and extension movements of the left wrist under 3 load conditions (no, low and high force) and a frequency matched passive movement condition were collected, along with isometric flexion/extension contractions in each position (low and high force). TMS was delivered at eight positions (4 in the flexion phase and 4 in the extension phase) during the continuous movement conditions and each of these positions was sampled with isometric contraction. The potentials evoked by TMS in right ECR were potentiated when the left ECR was engaged, independent of position within that phase of contraction or contraction type (isotonic and isometric). Motor cortical excitability of the resting right ECR increased as load demands increased to the left wrist. Passive rhythmical movement did not influence excitability to the resting ECR implying that voluntary motor drive is required. Our findings indicated that the increase in corticomotor drive during both rhythmic isotonic and static isometric contractions of the opposite limb is likely mediated by interhemispheric interactions between cortical motor areas. Improving our understanding of these cortical networks can be useful in future methods to enhance neuroplasticity through neurorehabilitation methods.

Human parietal and primary motor cortical interactions are selectively modulated during the transport and grip formation of goal-directed hand actions.

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.

Challenging the brain: Exploring the link between effort and cortical activation.

To better understand the contributions of effort on cortical activation associated with motor tasks, healthy participants with varying capacities for isolating the control of individual finger movements performed tasks consisting of a single concurrent abduction of all digits (Easy) and paired finger abduction with digits 2 and 3 abducted together concurrently with digits 4 and 5 (Hard). Brain activity was inferred from measurement using functional magnetic resonance imaging. Effort was measured physiologically using electrodermal responses (EDR) and subjectively using the Borg scale. On average, the Borg score for the Hard task was significantly higher (p=0.007) than for the Easy task (2.9+/-1.1 vs. 1.4+/-0.7, respectively). Similarly, the average normalized peak-to-peak amplitude of the EDR was significantly higher (p=0.002) for the Hard task than for the Easy task (20.4+/-6.5% vs. 12.1+/-4.9%, respectively). The Hard task produced increases in sensorimotor network activation, including supplementary motor area, premotor, sensorimotor and parietal cortices, cerebellum and thalamus. When the imaging data were subdivided based on Borg score, there was an increase in activation and involvement of additional areas, including extrastriate and prefrontal cortices. Subdividing the data based on EDR amplitude produced greater effects including activation of the premotor and parietal cortices. These results show that the effort required for task performance influences the interpretation of fMRI data. This work establishes understanding and methodology for advancing future studies of the link between effort and motor control, and may be clinically relevant to sensorimotor recovery from neurologic injury.

Paired-pulse transcranial magnetic stimulation of primary somatosensory cortex differentially modulates perception and sensorimotor transformations.

Intermodal selective attention is generally associated with facilitation of relevant information. However, recent studies demonstrate reduced activation of primary somatosensory cortex (S1) with continuous vibrotactile tracking during bimodal stimulation. Reduced activation has been hypothesized to reflect an interaction between the sensorimotor and intermodal requirements of the tracking task. Recently, it has been shown that transcranial magnetic stimulation (TMS) involving a supra-threshold test stimulus (TS) preceded by a sub-threshold conditioning stimulus (CS) adversely affects tactile perception by altering excitability of local intracortical circuits. The purpose of the current paper was to use TMS to assess the effects of differential sensorimotor requirements in the right sensorimotor cortex upon local intracortical networks and sensory processing in the left primary somatosensory cortex during constant multimodal stimulation. Single and paired-pulse TMS was used to probe intracortical networks in S1 and sensory processing during a sensorimotor task where a vibrotactile stimulus to the right index finder guided either continuous or discrete sensorimotor responses of the left hand. It was hypothesized that paired-pulse TMS would alter local intracortical networks and reduce performance during the discrete sensorimotor task, but that these effects would be mitigated during the continuous sensorimotor task, possibly a reflection of reduced S1 activation observed previously during a similar continuous sensorimotor task. Regardless of sensorimotor requirements, single-pulse TMS delivered over S1 decreased sensorimotor performance. Paired-pulse TMS further decreased sensorimotor performance only when the vibrotactile stimulus guided a discrete motor response but not when it was required to continuously guide the motor response. This effect disappeared when the TS was replaced by a sub-threshold stimulus. These results suggest that the CS facilitates sensory output neurons during perceptual detection but that differential responsiveness of local cortical networks in S1 suppresses the CS effects during continuous sensory-guided movement. This study highlights the importance of sensorimotor requirements in determining the net result of task-related sensory processing in S1.

Assessing linear time-invariance in human primary somatosensory cortex with BOLD fMRI using vibrotactile stimuli.

The assumption of linear time-invariance (LTI) in the human primary somatosensory cortex (SI) is assessed for fMRI signals generated by variable-duration vibrotactile stimuli. Predictions based on time-shifted summation (TSS) of responses to 2 s stimuli overestimate observed BOLD signal amplitudes in response to longer-duration stimuli, in agreement with previous findings in other primary sensory cortices. To interpret these results, we undertook an alternative approach for LTI assessment by characterizing BOLD signals using two biophysical models. The first model assumes that the input stimulus envelope is proportional to neural activity. The second assumes that neural activity exhibits both transient and steady-state components, consistent with extensive electrophysiological data, and fits the experimental data better. Although nonlinearity remains evident for short stimulus durations, the latter model shows that the TSS procedure to assess LTI overestimates the BOLD signal because the temporal characteristics of neural activity have not been considered adequately. Further research to investigate the BOLD response to time-varying neural activity is required.

Cortical activation following a balance disturbance.

Although recent work suggests that cortical processing can be involved in the control of balance responses, the central mechanisms involved in these reactions remain unclear. We presently investigated the characteristics of scalp-recorded perturbation-evoked responses (PERs) following a balance disturbance. Eight young adults stabilized an inverted pendulum using their ankle musculature while seated. When perturbations were applied to the pendulum, subjects were instructed to return (active condition) or not return (passive condition) the pendulum to its original stable position. Primary measures included peak latency and amplitude of early PERs (the first negative peak between 100 and 150 ms, N1), amplitude of late PERs (between 200 and 400 ms) and onset and initial amplitude of ankle muscle responses. Based on the timing of PERs, we hypothesized that N1 would represent sensory processing of the balance disturbance and that late PERs would be linked to the sensorimotor processing of balance corrections. Our results revealed that N1 was maximal over frontal-central electrode sites (FCz and Cz). Average N1 measures at FCz, Cz, and CPz were comparable between active and passive tasks ( p>0.05). In contrast, the amplitude of late PERs at Cz was less positive for the active condition than for the passive ( p<0.05). The similarity in N1 between tasks suggests a sensory representation of early PERs. Differences in late PERs may represent sensorimotor processing related to the execution of balance responses.

Tactile stimulus predictability modulates activity in a tactile-motor cortical network.

Manipulating objects in the hand requires the continuous transformation of sensory input into appropriate motor behaviour. Using a novel vibrotactile device combined with fMRI, the cortical network associated with tactile sensorimotor transformations was investigated. Continuous tactile stimuli were delivered in a random or predictable pattern to the second digit on the right hand of all subjects. To better distinguish sensory and motor processes, subjects were instructed to make proportionate motor gripping responses with their left hand. A consistent cortical network of activation was revealed that included the supplementary motor, dorsal and ventral premotor, posterior parietal, primary and secondary somatosensory and primary motor cortex. Tracking the unpredictable versus predictable tactile stimulus led to greater delays in motor responses and to increased performance errors. Cortical effects due to stimulus predictability were observed in several components of the network, though it was most evident as increased cortical activation in frontal motor regions during tracking of unpredictable tactile stimuli. In contrast to the proposed hypotheses, primary and secondary somatosensory cortices contralateral to tactile input did not reveal enhanced responses during unpredictable tracking. Facilitation during unpredictable tracking was also observed in primary somatosensory cortex contralateral to motor responses, the receptive site for movement-related afference. The present study provides a novel and controlled approach to investigate the loci associated with tactile-motor processing and to measure the task-specific effect of stimulus predictability on network components.

Adaptation in the motor cortex following cervical spinal cord injury.

BACKGROUND: The nature of the adaptive changes that occur in the cerebral cortex following injury to the cervical spinal cord are largely unknown. OBJECTIVE: To investigate these adaptive changes by examining the relationship between the motor cortical representation of the paretic right upper extremity compared with that of the tongue. The tongue was selected because the spinal cord injury (SCI) does not affect its movement and the cortical representation of the tongue is adjacent to that of the paretic upper extremity. METHODS: FMRI was used to map cortical representations associated with simple motor tasks of the right upper extremity and tongue in 14 control subjects and 9 patients with remote (>5.5 months) cervical SCI. RESULTS: The mean value for the site of maximum cortical activation during upper limb movement was identical between the two groups. The site of maximum left hemispheric cortical activation during tongue movement was 12.8 mm (p < 0.01) medial and superior to that of control subjects, indicating the presence of a shift in cortical activation. CONCLUSION: The findings indicate that the adult motor cortex does indeed adapt following cervical SCI. The nature of the adaptation and the underlying biological mechanisms responsible for this change require further investigation.

New devices to deliver somatosensory stimuli during functional MRI.

A new class of devices are described for improving investigation of somatosensory neuronal activation using fMRI. Dubbed magnetomechanical vibrotactile devices (MVDs), the principle of operation involves driving wire coils with small oscillatory currents in the large static magnetic field inherent to MRI scanners. The resulting Lorentz forces can be oriented to generate large vibrations that are easily converted to translational motions as large as several centimeters. Representative data demonstrate the flexibility of MVDs to generate different well-controlled vibratory and tactile stimuli to activate special proprioceptive and cutaneous somatosensory afferent pathways. The implications of these data are discussed with respect to the literature on existing devices for producing sensorimotor activation, as well as expanding the scope of current fMRI investigations.

Quantifying head motion associated with motor tasks used in fMRI.

In functional magnetic resonance imaging (fMRI) studies, long experiment times and small intensity changes associated with brain activation frequently lead to image artifacts due to head motion. Methods to minimize and correct for head motion by restraint, fast imaging, and retrospective image registration are typically combined but do not completely solve the problem, particularly for specific patient populations. As an initial step toward optimizing future designs of head restraints and improving motion correction techniques, the head motion characteristics of groups of stroke subjects, age-matched controls, and young adults were investigated with the aid of an MR simulator and a highly accurate position tracking system. Position measurements were recorded during motor tasks involving either the hand or the foot. Head motion was strongly dependent on the subject group and less upon the task conditions based on ANOVA calculations (P < 0.05). The stroke subjects exhibited approximately twice the head motion compared to that of age-matched controls, and the latter's head motion was about twice that of young adults. Moreover, the range of head motion in stroke subjects over all tasks was approximately 2 +/- 1 mm, with the motion occurring predominantly as translation in the superior-inferior direction and pitch rotation (nodding). These results lead to several recommendations on the design of fMRI motor experiments and suggest that improved motion correction strategies are required to examine such patient populations comprehensively.

Cortical representation of whole-body movement is modulated by proprioceptive discharge in humans.

Previous studies have revealed the influence of ongoing sensory discharge on modulating the central representation of muscle afferents from individual limbs. In the present study, we explored the potential for such modulatory influence on the afferent discharge arising from induced whole-body movement. Vestibular and somato-sensory inputs arise from such whole-body movement. The convergence of these two modalities is important in motor control, especially for the maintenance of postural stability. We hypothesised that transmission of proprioceptive and vestibular information to the cortex would be reduced as a result of muscle-spindle discharge in knee extensor muscles. Perturbation-evoked responses (PERs), recorded from central scalp electrodes (C3, CZ, C4), were evoked through rapid translations of subjects who were seated in a chair on a movable platform. PERs were recorded during passive linear translations alone and preceded by vibration of the patellar tendon. The PER was characterised by a slow, negative potential peaking at approximately 150 ms (N150) following displacement of the chair. The amplitude of the PER was reduced following vibration to 56% of the control. Such reduction of PERs was comparable to the attenuation of somatosensory evoked potentials and soleus H-reflex magnitudes from tibial-nerve stimulation. We conclude that muscle-spindle discharge in knee extensor muscles leads to gating of both of these afferent pathways. These results have potential implications to the understanding of the CNS control of stability during ongoing movement.

Bilateral movement enhances ipsilesional cortical activity in acute stroke: a pilot functional MRI study.

Functional MRI was performed in two acute stroke patients and six control subjects performing unilateral and bilateral repetitive gripping tasks. Patients were tested at three time points during recovery. Initially, bilateral movement enhanced activation in the primary motor cortex (M1) of the affected hemisphere compared with unilateral paretic hand movement. With recovery, activation of M1 in the affected hemisphere did not differ between unilateral paretic hand and bilateral movement. These preliminary data may have potential implications for acute stroke motor rehabilitation.

Task-relevant selective modulation of somatosensory afferent paths from the lower limb.

Leg movement attenuates initial somatosensory evoked potentials (SEPS) from both cutaneous and muscle afferent origin. To date, as different sensory inputs become relevant for task performance, selective facilitation from such movement-related gating influences has not been shown. We hypothesized that initial SEP amplitudes from cutaneous (sural nerve, SN) and muscle afferent (tibial nerve, TN) sources are dependent on the relevance of the specific afferent information to task performance. SEPs were obtained at rest and during three movement conditions. In each movement condition, the left foot was passively moved episodically and additional cutaneous 'codes' of sensory information were applied to the dorsum of the left foot. Subjects were instructed to: simply relax (passive), or to make a response following the cessation of movement, dependent either on the cutaneous code (cutaneous task), or the passive movement trajectory of the left foot (position task). Passive movement, with no required subsequent response, attenuated initial TN and SN SEPs to approximately 40% of that at rest (p < 0.05). Versus passive movement, when cutaneous inputs provided the relevant cue for the task, mean SN SEPs significantly increased (p < 0.05), and when the proprioceptive inputs provided the relevant cue for the task, mean TN SEPs significantly increased (p < 0.05). We conclude that specific relevancy of sensory information selectively facilitates somatosensory paths from movement-related attenuation.

Upper limb H reflexes and somatosensory evoked potentials modulated by movement.

In the human lower limb, the magnitudes of both Hoffmann (H) reflexes and primary somatosensory evoked potentials (SEPs) from scalp electrodes, are reduced by active and/or passive movement. We surmised that similar effects occur for the upper limb and specifically hypothesised that amplitudes of median nerve induced flexor carpii radialis H reflexes and cortical SEPs are reduced with passive movement about the wrist or elbow. The results showed (P<0. 05) that either movement significantly attenuated mean magnitudes of SEPs elicited from stimulation at elbow or wrist and that reflex magnitudes attenuated with wrist movement. Thus, the upper limb shows similar movement-induced modulation to the lower limb. These attenuations of fast conducting sensory paths consequent to movement per se, may be a basic level of motor control, initiated from muscle mechanoreceptor discharge. Upon this basic level, more complex modulations then may be laid as appropriate for the particular characteristics of active motor tasks.

The afferent origin of the secondary somatosensory evoked potential from the lower limb in humans.

The afferent origin of the secondary somatosensory evoked potential elicited from stimulation of the sural and tibial nerves was investigated as the limb was cooled. It was hypothesized that the peak of this potential is initiated from primary afferents in the A alpha group. We conclude that the peak of the secondary SEP arises from an afferent source whose diameter is of similar size to that of large diameter A alpha afferents.

Cutaneous reflexes of the human leg during passive movement.

1. Four experiments tested the hypothesis that movement-induced discharge of somatosensory receptors attenuates cutaneous reflexes in the human lower limb. In the first experiment, cutaneous reflexes were evoked in the isometrically contracting tibialis anterior muscle (TA) by a train of stimuli to the tibial nerve at the ankle. The constancy of stimulus amplitudes was indirectly verified by monitoring M waves elicited in the abductor hallucis muscle. There was a small increase in the reflex excitation (early latency, EL) during passive cycling movement of the leg compared with when the leg was stationary, a result opposite to that hypothesized. There was no significant effect on the magnitude of the subsequent inhibitory reflex component (middle latency, ML), even with increased rate of movement, or on the latency of any of the reflex components. 2. In the second experiment, the two reflex components (EL and ML) elicited in TA at four positions in the movement cycle were compared with corresponding reflexes elicited with the limb stationary at those positions. Despite the markedly different degree of stretch of the leg muscles, movement phase exerted no statistically significant effect on EL or ML reflex magnitudes. 3. In the third experiment, taps to the quadriceps tendon, to elicit muscle spindle discharge, had no effect on the magnitude of ML in TA muscle. The conditioning attenuated EL magnitude for the first 110 ms. Tendon tap to the skin over the tibia revealed similar attenuation of EL. 4. The sural nerve was stimulated at the ankle in the fourth experiment. TA EMG reflex excitatory and inhibitory responses still showed no significant attenuation with passive movement. Initial somatosensory evoked potentials (SEPs), measured from scalp electrodes, were attenuated by movement. 5. The results indicate that there is separate control of transmission in Ia and cutaneous pathways during leg movement. This suggests that modulation of the cutaneous reflex during locomotion is not the result of inhibition arising from motion-related sensory receptor discharge.

Prefrontal cortex regulates inhibition and excitation in distributed neural networks.

Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.

Generalisability of sensory gating during passive movement of the legs.

Movement-related gating of somatosensory evoked potentials in the upper limb is restricted mainly to nerve stimulation supplying the moved limb segment. In the lower limb, this principle may not be followed. Tibial nerve (stimulation at the knee) somatosensory evoked potentials (SEPs) and soleus H reflexes exhibit quite similar patterns of modulation during movement. We hypothesised that movement-related gating of initial SEPs in the leg would be generalised from ipsilateral to contralateral leg movement and that such sensory gating would not be generalised to modalities with no functional relevance to the movement. Somatosensory, visual, and auditory evoked potentials (SEPs, VEPs, and AEPs) were recorded from scalp electrodes during unilateral passive movement. Short-latency tibial nerve SEPs, representing the first cortical components, and soleus H reflexes in both the moved leg and the stationary leg were attenuated compared to non-movement controls (p<0.05). Neither VEPs nor middle latency AEPs were modulated (p>0.05). We conclude that sensory gating occurs during contralateral movement. This gating is absent in other sensory modalities with no apparent functional relationship to the imposed movement.