David A.E. Bolton

Transient inhibition of the dorsolateral prefrontal cortex disrupts attention-based modulation of tactile stimuli at early stages of somatosensory processing

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 (40s; 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.

The impact of light fingertip touch on haptic cortical processing during a standing balance task

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.

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.

Age-related loss in attention-based modulation of tactile stimuli at early stages of somatosensory processing

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.

Contribution of primary motor cortex to compensatory balance reactions.

BackgroundRapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs.ResultsOur results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles.ConclusionsPresent findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.

Transient inhibition of the dorsolateral prefrontal cortex disrupts somatosensory modulation during standing balance as measured by electroencephalography

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 &thgr;-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.

Transient inhibition of primary motor cortex suppresses hand muscle responses during a reactive reach to grasp

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.

Attention-based modulation of tactile stimuli: A comparison between prefrontal lesion patients and healthy age-matched controls

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.

Transcranial magnetic stimulation techniques to study the somatosensory system: Research applications

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.

Theta burst repetitive transcranial magnetic stimulation attenuates somatosensory evoked potentials from the lower limb

BackgroundContinuous 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.ResultsFollowing 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.ConclusionWe 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.