Tactile Detection in Fibromyalgia: A Systematic Review and a Meta-Analysis

Fibromyalgia is a chronic pain syndrome characterized by sensorimotor deficits and distortions of body representation, that could both be caused by alterations in sensory processing. Several studies suggest a hypersensitivity to various sensory stimulations in fibromyalgia but results on detection of both noxious and non-noxious tactile stimulation, which are particularly relevant for body representation and motor control, remain conflicting. Therefore, the aim of this study is to systematically review and quantify the detection thresholds to noxious and non-noxious tactile stimuli in individuals with fibromyalgia compared to pain-free controls. A systematic review and a meta-analysis were performed in the MEDLINE, EMBASE, CINAHL, Cochrane, PsycInfo and Web of Science databases using keywords related to fibromyalgia, tactile pain detection threshold, tactile detection threshold and quantitative sensory testing. Nineteen studies were included in the review, with 12 in the meta-analysis. Despite the heterogeneity of the results, the data from both the review and from the meta-analysis suggest a trend toward hyperalgesia and no difference of sensitivity to non-noxious tactile stimuli in participants with fibromyalgia compared to healthy controls. This contradicts the hypothesis of a general increase in responsiveness of the central nervous system to noxious and non-noxious stimulations in fibromyalgia. This study shows no alteration of the sensitivity to non-noxious tactile stimulation in fibromyalgia, suggesting that an altered unimodal processing is not sufficient to explain symptoms such as sensorimotor impairments and body representation distortions. Future research should investigate whether alterations in multisensory integration could contribute to these symptoms.

Thalamocortical mechanisms regulating the relationship between transient beta events and human tactile perception

Transient neocortical events with high spectral power in the 15-29Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, non-lemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300ms time scale to suppress sensory information. Further analysis showed that the same beta generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event faciliatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

Respiration, heartbeat, and conscious tactile perception

Cardiac activity has been shown to interact with conscious tactile perception: Detecting near-threshold tactile stimuli is more likely during diastole than systole and heart slowing is more pronounced for detected compared to undetected stimuli. Here, we investigated how cardiac cycle effects on conscious tactile perception relate to respiration given the natural coupling of these two dominant body rhythms. Forty-one healthy participants had to report conscious perception of weak electrical pulses applied to the left index finger (yes/no) and confidence about their yes/no-decision (unconfident/confident) while electrocardiography (ECG), respiratory activity (chest circumference), and finger pulse oximetry were recorded. We confirmed the previous findings of higher tactile detection rate during diastole and unimodal distribution of hits in diastole, more specifically, we found this only when participants were confident about their detection decision. Lowest tactile detection rate occurred 250-300 ms after the R-peak corresponding to pulse-wave onsets in the finger. Inspiration was locked to tactile stimulation, and this was more consistent in hits than misses. Respiratory cycles accompanying misses were longer as compared to hits and correct rejections. Cardiac cycle effects on conscious tactile perception interact with decision confidence and coincide with pulse-wave arrival, which suggests the involvement of higher cognitive processing in this phenomenon possibly related to predictive coding. The more consistent phase-locking of inspiration with stimulus onsets for hits than misses is in line with previous reports of phase-locked inspiration to cognitive task onsets which were interpreted as tuning the sensory system for incoming information.

Locus coeruleus spiking differently correlates with S1 cortex activity and pupil diameter in a tactile detection task

We examined the relationships between activity in the locus coeruleus (LC), activity in the primary somatosensory cortex (S1), and pupil diameter in mice performing a tactile detection task. While LC spiking consistently preceded S1 membrane potential depolarization and pupil dilation, the correlation between S1 and pupil was more heterogeneous. Furthermore, the relationships between LC, S1, and pupil varied on timescales of sub-seconds to seconds within trials. Our data suggest that pupil diameter can be dissociated from LC spiking and cannot be used as a stationary index of LC activity.

Disorder-specific alterations of tactile sensitivity in neurodevelopmental disorders

Alterations of tactile processing have long been identified in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the extent to which these alterations are disorder-specific, rather than disorder-general, and how they relate to the core symptoms of each disorder, remains unclear. We measured and compared tactile detection, discrimination, and order judgment thresholds between a large sample of children with ASD, ADHD, ASD + ADHD combined and typically developing controls. The pattern of results suggested that while difficulties with tactile detection and order judgement were more common in children with ADHD, difficulties with tactile discrimination were more common in children with ASD. Interestingly, in our subsequent correlation analyses between tactile perception and disorder-specific clinical symptoms, tactile detection and order judgment correlated exclusively with the core symptoms of ADHD, while tactile discrimination correlated exclusively with the symptoms of ASD. When taken together, these results suggest that disorder-specific alterations of lower-level sensory processes exist and are specifically related to higher-level clinical symptoms of each disorder.

Layer 6 ensembles can selectively regulate the behavioral impact and layer-specific representation of sensory deviants

Predictive models can enhance the salience of unanticipated input. Here, we tested a key potential node in neocortical model formation in this process, layer (L) 6, using behavioral, electrophysiological and imaging methods in mouse primary somatosensory neocortex. We found that deviant stimuli enhanced tactile detection and were encoded in L2/3 neural tuning. To test the contribution of L6, we applied weak optogenetic drive that changed which L6 neurons were sensory responsive, without affecting overall firing rates in L6 or L2/3. This stimulation selectively suppressed behavioral sensitivity to deviant stimuli, without impacting baseline performance. This stimulation also eliminated deviance encoding in L2/3 but did not impair basic stimulus responses across layers. In contrast, stronger L6 drive inhibited firing and suppressed overall sensory function. These findings indicate that, despite their sparse activity, specific ensembles of stimulus driven L6 neurons are required to form neocortical predictions, and to realize their behavioral benefit.