The perception of affective touch in Parkinson's disease and its relation to small fibre neuropathy

Affective touch sensation is conducted by a sub‐class of C‐fibres in hairy skin known as C‐Tactile (CT) afferents. CT afferents respond maximally to gentle skin stroking at velocities between 1 and 10 cm/s. Parkinson's disease (PD) is characterised by markedly reduced cutaneous C‐fibres. It is not known if affective touch perception is influenced by C‐fibre density and if affective touch is impaired in PD compared to healthy controls. We predicted that perceived pleasantness to gentle stroking in PD would correlate with C‐afferent density and that affective touch perception would be impaired in PD compared to healthy controls. Twenty‐four PD patients and 27 control subjects rated the pleasantness of brush stroking at an optimum CT stimulation velocity (3 cm/s) and two sub‐optimal velocities (0.3 and 30 cm/s). PD patients underwent quantification of C‐fibre density using skin biopsies and corneal confocal microscopy. All participants rated a stroking velocity of 3 cm/s as the most pleasant with significantly lower ratings for 0.3 and 30 cm/s. There was a significant positive correlation between C‐fibre density and pleasantness ratings at 3 and 30 cm/s but not 0.3 cm/s. Mean pleasantness ratings were consistently higher in PD patients compared to control subjects across all three velocities. This study shows that perceived pleasantness to gentle touch correlates significantly with C‐fibre density in PD. The higher perceived pleasantness in PD patients compared to controls suggests central sensitisation to peripheral inputs, which may have been enhanced by dopamine therapy.     

Gentle stroking elicits somatosensory ERP that differentiates between hairy and glabrous skin

Here we asked whether, similar to visual and auditory event-related potentials (ERPs), somatosensory ERPs reflect affect. Participants were stroked on hairy or glabrous skin at five stroking velocities (0.5, 1, 3, 10 and 20 cm/s). For stroking of hairy skin, pleasantness ratings related to velocity in an inverted u-shaped manner. ERPs showed a negativity at 400 ms following touch onset over somatosensory cortex contra-lateral to the stimulation site. This negativity, referred to as sN400, was larger for intermediate than for faster and slower velocities and positively predicted pleasantness ratings. For stroking of glabrous skin, pleasantness showed again an inverted u-shaped relation with velocity and, additionally, increased linearly with faster stroking. The sN400 revealed no quadratic effect and instead was larger for faster velocities. Its amplitude failed to significantly predict pleasantness. In sum, as was reported for other senses, a touch’s affective value modulates the somatosensory ERP. Notably, however, this ERP and associated subjective pleasantness dissociate between hairy and glabrous skin underscoring functional differences between the skin with which we typically receive touch and the skin with which we typically reach out to touch.     

Visual perception of the arm manipulates the experienced pleasantness of touch

Touch, such as a caress, can be interpreted as very pleasant. The emotional valence assigned to touch is likely related to certain bottom-up factors, such as optimal activation of C-tactile (CT) afferents. It is however unclear if besides somatosensory input, contextual factors related to the own body also play a role in the perceived pleasantness of touch. To test this, we manipulated visual appearance of the participant’s arm (veridical vision, no vision, pixelated moving statistic projected onto the arm (i.e. crawling skin)). We used slow velocity stroking (CT optimal stroking) with a soft brush to induce pleasant touch, and fast velocity stroking as a control condition. After each visual condition we asked participants (N = 23) to rate the emotional valence of the stroking they felt. After slow velocity stroking ratings on perceived pleasantness (but not on perceived unpleasantness) were modulated by visual condition, with veridical vision of the arm resulting in higher pleasantness ratings than both no vision and pixelated vision. We conclude that contextual processes affect the perceived pleasantness of touch. These findings shed a new light on the underlying mechanisms of how humans experience pleasant touch and show that pleasant touch not solely dependents on bottom up information.     

Diminished sensitivity and specificity at recognising facial emotional expressions of varying intensity underlie emotion-specific recognition deficits in autism spectrum disorders

BackgroundA plethora of research on facial emotion recognition in autism spectrum disorders (ASD) exists and reported deficits in ASD compared to controls, particularly for negative basic emotions. However, these studies have largely used static high intensity stimuli. The current study investigated facial emotion recognition across three levels of expression intensity from videos, looking at accuracy rates to investigate impairments in facial emotion recognition and error patterns (’confusions’) to explore potential underlying factors.MethodTwelve individuals with ASD (9 M/3F; M(age) = 17.3) and 12 matched controls (9 M/3F; M(age) = 16.9) completed a facial emotion recognition task including 9 emotion categories (anger, disgust, fear, sadness, surprise, happiness, contempt, embarrassment, pride) and neutral, each expressed by 12 encoders at low, intermediate, and high intensity.ResultsA facial emotion recognition deficit was found overall for the ASD group compared to controls, as well as deficits in recognising individual negative emotions at varying expression intensities. Compared to controls, the ASD group showed significantly more, albeit typical, confusions between emotion categories (at high intensity), and significantly more confusions of emotions as ‘neutral’ (at low intensity).ConclusionsThe facial emotion recognition deficits identified in ASD, particularly for negative emotions, are in line with previous studies using other types of stimuli. Error analysis showed that individuals with ASD had difficulties detecting emotional information in the face (sensitivity) at low intensity, and correctly identifying emotional information (specificity) at high intensity. These results suggest different underlying mechanisms for the facial emotion recognition deficits at low vs high expression intensity.     

Visual afference mediates head and trunk stability in vestibular hypofunction

Humans must maintain head and trunk stability while walking. The purpose of this study was to compare the kinematics of healthy controls and patients with vestibular hypofunction (VH) when walking and making head rotations of different frequencies in both light and dark conditions. We recruited eight individuals with VH and nine healthy control subjects to perform four tasks at their preferred gait speed, being normal walk, walking and making yaw head rotations at 1.5 Hz and 2 Hz, and walking in the dark and making yaw head rotations at 1.5 Hz. Linear kinematics as well as head, trunk, and pelvis angular velocities were captured using the Vicon motion analysis system (Vicon Motion Systems, Oxford, UK). We found no difference in walking velocities for any of the four walking conditions across groups. The lateral displacement of the center of mass was increased in VH patients. In the dark, patients had more head instability in pitch (larger amplitudes and velocities) even though they were walking and making active yaw head rotations. Patients also had a smaller relative phase angle (mean 3.50 ± standard deviation 2.13°) than controls (mean 10.31 ± standard deviation 2.70°) (p < 0.01). Our data suggest that patients with VH have difficulty walking with a straight trajectory when turning their head. Additionally, patients with VH have an abnormal excursion of spontaneous pitch head rotation while walking and making active yaw head turns, which is dependent on vision. Rehabilitation for these patients should consider applying unique head rotation frequencies when training gait with head turns as well as alternating their exposure to light.     

Gentle touch perception: From early childhood to adolescence

Affective touch plays an important role in children’s social interaction and is involved in shaping the development of the social brain. The positive affective component of touch is thought to be conveyed via a group of unmyelinated, low-threshold mechanoreceptive afferents, known as C-tactile fibers that are optimally activated by gentle, slow, stroking touch. Touch targeting these C-tactile fibers has been shown to decrease the heart rate in infants. The current study investigated the relationship between age and psychophysical ratings in response to affective touch. A total of n = 43 participants (early childhood: aged 5–8 years, 9 girls, 12 boys; late childhood: aged 9–12 years, 12 girls, 10 boys) were presented with C-tactile optimal and sub-optimal stroking velocities and rated touch pleasantness on an affective pictorial scale. For both age groups, we found that children preferred C-tactile-targeted stimulation. A comparison with previously published data showed that the children’s preference for C-tactile-targeted stimulation was similar to those obtained in adolescents and adults. We speculate that the effect of C-tactile-targeted touch, which is linked with pleasantness, shapes the children’s preference for C-tactile over non-C-tactile-targeted stimulation, and that C-tactile afferent stimulation is important for social development.     

Hyper-responsiveness to touch mediates social dysfunction in adults with autism spectrum disorders

This study investigated whether hyper-responsiveness to touch serves as a mediating variable that predicts social dysfunction in adults with autism spectrum disorders (ASD). Data were obtained from all adults with administratively defined intellectual disability in a region in Sweden (n = 915, where 143 had ASD). A multiple mediation modeling analysis revealed a well-fitted model (Satorra–Bentler scaled chi-square = 10.91, df = 7, p = 0.14, CFI = 0.99, RMSEA = 0.025), demonstrating that social dysfunction among adults with ASD was completely mediated by hyper-responsiveness to touch followed by impairment of speech and aggressive/destructive behavior. The results demonstrated that in adulthood, the tactile sensory system is foundational for social functioning in people with ASD, with diagnosis and intervention implications.     

Impact of tactile function on upper limb motor function in children with Developmental Coordination Disorder

This study investigated the presence of, and relationship between tactile dysfunction and upper limb motor function in children with Developmental Coordination Disorder (DCD) compared to typical developing (TD) children. Participants were 36 children aged 6–12 years. Presence of DCD (n = 20) or TD (n = 16) was confirmed using the Movement Assessment Battery for Children, second edition. All children participated in a comprehensive assessment of tactile registration (Semmes Weinstein Monofilaments); tactile spatial perception (Single Point Localisation (SPL) and two-point discrimination (2PD)); haptic perception (Stereognosis); speed of simple everyday manual tasks (Jebsen–Taylor Test of Hand Function (JTTHF)); and handwriting speed and accuracy (Evaluation Tool of Children's Handwriting (ETCH)). Compared to TD children, children with DCD demonstrated poorer localisation of touch in the non-dominant hand (p = 0.04), slower speed of alphabet writing (p < 0.05) and less legible handwriting (p < 0.01), but no difference in speed of simple everyday manual tasks (JTTHF: p > 0.05). Regression analysis showed that spatial tactile perception (SPL) predicted handwriting legibility (ETCH: r = 0.11) and speed of functional tasks (JTTHF: r = 0.33). These results suggest that tactile function, specifically single point localisation, should be a primary tactile assessment employed to determine reasons for upper limb motor difficulties experienced by children with DCD.     

Symptoms from masked acrolein exposure suggest altered trigeminal reactivity in chemical intolerance

BackgroundChemical intolerance (CI) is a widespread occupational and public health problem characterized by symptoms that reportedly result from low-levels of chemical exposure. The mechanisms behind CI are unknown, however modifications of the chemical senses (rather than toxic processes) have been suggested as key components. The aim of this study was to investigate whether individuals with self-reported CI report more sensory irritation during masked acrolein exposure compared to controls without CI.MethodsIndividuals with CI (n = 18) and controls without CI (n = 19) were exposed in an exposure chamber. Each participant took part in two exposure conditions – one with heptane (the masking compound), and one with heptane and acrolein at a dose below previously reported sensory irritation thresholds. The exposures lasted for 60 min. Symptoms and confidence ratings were measured continuously throughout the exposure as were measurements of electrodermal activity and self-reported tear-film break-up time. Participants were blind to exposure condition.ResultsIndividuals with CI, compared with controls reported greater sensory irritation in the eyes, nose and throat when exposed to acrolein masked with heptane. There was no difference during exposure to heptane.ConclusionsMasked exposure to acrolein at a concentration below the previously reported detection threshold is perceived as more irritating by individuals with CI compared with controls. The results indicate that there is altered trigeminal reactivity in those with CI compared to controls.     

Cross-generational effects of parental low dose BPA exposure on the Gonadotropin-Releasing Hormone3 system and larval behavior in medaka (Oryzias latipes)

Growing evidence indicates that chronic exposure to Bisphenol A (BPA) may disrupt normal brain function and behavior mediated by gonadotropin-releasing hormone (GnRH) pathways. Previous studies have shown that low dose BPA (200 ng/ml) exposure during embryogenesis altered development of extra-hypothalamic GnRH3 systems and non-reproductive locomotor behavior in medaka. Effects of parental low-dose BPA exposure on the development of GnRH3 systems and locomotor behavior of offspring are not well known. This study examines whether the neurophysiological and behavioral effects of BPA in parents (F0 generation) are carried over to their offspring (F1 generation) using stable transgenic medaka embryos/larvae with GnRH3 neurons tagged with green fluorescent protein (GFP). Parental fish were exposed to BPA (200 ng/ml) for either life-long or different developmental time windows. Fertilized F1 eggs were collected and raised in egg/fish water with no environmental exposure to BPA. All experiments were performed on F1 embryos/larvae, which were grouped based on the following parental (F0) BPA exposure conditions – (i) Group 1 (G1): through life; (ii) G2: during embryogenesis and early larval development [1–14 days post fertilization (dpf)]; (iii) G3: during neurogenesis (1–5 dpf); and (iv) G4: during sex differentiation (5–14 dpf). Embryos from unexposed vehicle treated parents served as controls (G0). G1 embryos showed significantly reduced survival rates and delayed hatching time compared to other groups, while G4 embryos hatched significantly earlier than all other groups. At 3 dpf, the GnRH3-GFP intensity was increased by 47% in G3 embryos and decreased in G4 embryos by 59% compared to controls. At 4 dpf, G1 fish showed 42% increased intensity, while GFP intensity was reduced by 44% in G3 subjects. In addition, the mean brain size of G1, G3 and G4 embryos were smaller than that of control at 4 dpf. At 20 dpf, all larvae from BPA-treated parents showed significantly decreased total movement (distance covered) compared with controls, with G2 and G3 fish showing reduced velocity of movement. While at 20 dpf no group differences were seen in the soma diameter of GnRH3-GFP neurons, a 34% decrease in SV2 expression, a marker for synaptic transmission, in G1 larvae was observed. These data suggest that parental BPA exposure during critical windows of embryonic development or chronic treatment affects next-generation offspring both in embryonic and larval brain development as well as larval behavior.     

Intensity changes in a continuous tone: Auditory cortical potentials comparison with frequency changes

ObjectivesTo examine auditory cortical potentials in normal-hearing subjects to intensity increments in a continuous pure tone at low, mid, and high frequency.MethodsElectrical scalp potentials were recorded in response to randomly occurring 100 ms intensity increments of continuous 250, 1000, and 4000 Hz tones every 1.4 s. The magnitude of intensity change varied between 0, 2, 4, 6, and 8 dB above the 80 dB SPL continuous tone.ResultsPotentials included N100, P200, and a slow negative (SN) wave. N100 latencies were delayed whereas amplitudes were not affected for 250 Hz compared to 1000 and 4000 Hz. Functions relating the magnitude of the intensity change and N100 latency/amplitude did not differ in their slope among the three frequencies. No consistent relationship between intensity increment and SN was observed. Cortical dipole sources for N100 did not differ in location or orientation between the three frequencies.ConclusionsThe relationship between intensity increments and N100 latency/amplitude did not differ between tonal frequencies. A cortical tonotopic arrangement was not observed for intensity increments. Our results are in contrast to prior studies of brain activities to brief frequency changes showing cortical tonotopic organization.SignificanceThese results suggest that intensity and frequency discrimination employ distinct central processes.     

Developmental changes in somatosensory processing in cerebral palsy and healthy individuals

ObjectiveCerebral palsy (CP) is a motor disorder that causes physical disability in human development. Recent work has shown that somatosensory deficits are a serious problem for people with CP. There is however no information about the influence of age on brain correlates of tactile sensitivity.MethodsProprioception, touch and pain pressure thresholds, as well as somatosensory evoked potentials (SEP) elicited by tactile stimulation in lips and thumbs were examined in 15 children with CP (range 5–14 y), 14 adults with CP (range 22–55 y), 15 healthy children (range 5–14 y), and 15 healthy adults (range 22–42 y).ResultsChildren with CP as compared to healthy controls showed more reduced sensitivity for non-painful stimuli, but enhanced sensitivity for painful stimuli. Early SEP amplitudes (P50 and P100) were more enhanced in children and adults with CP than in healthy participants. A functional hemispheric asymmetry was observed in CP when left- and right-side body parts were stimulated.ConclusionsData suggest the possibility that altered somatosensory brain processing in CP might be reflecting an enhanced excitability of the somatosensory cortex.SignificanceAssessment of somatosensory functions may have implications for future neuromodulatory treatment of pain complaints and motor rehabilitation programs in children and adults with cerebral palsy.     

Developmental PCB exposure increases susceptibility to audiogenic seizures in adulthood

Developmental exposure to polychlorinated biphenyls (PCBs) causes auditory deficits. Thus, we recently conducted a study to investigate if developmental PCB exposure would exacerbate noise-induced hearing loss in adulthood. Unexpectedly, some PCB-exposed rats exhibited seizure-like behaviors when exposed to loud noise. Therefore, we conducted the current experiment to determine if adult rats perinatally exposed to PCBs are more susceptible to audiogenic seizures when tested in a standard audiogenic seizure paradigm. Adult male and female rats exposed to PCBs during gestation and lactation (0, 1, 3 or 6 mg/kg/day) and previously tested in the noise-induced hearing loss study were presented with a 100 dB noise stimulus. If they did not exhibit clonus in response to the 100 dB noise, they were exposed to a 105 dB stimulus 24–48 h later. This was followed by an 110 dB stimulus 24–48 h later if they did not exhibit clonus at 105 dB. Female and male rats exposed to either 3 or 6 mg/kg PCBs exhibited a significantly higher incidence of audiogenic seizures, shorter latency to onset of seizures, and greater severity of seizures compared to controls. Thyroxine measured in littermates at weaning was significantly lower in all PCB groups compared to controls, suggesting a potential mechanism for the increased incidence of audiogenic seizures. This is the first study to show that developmental PCB exposure increases the susceptibility to audiogenic seizures in adulthood.     

Low dose exposure to Bisphenol A alters development of gonadotropin-releasing hormone 3 neurons and larval locomotor behavior in Japanese Medaka

Accumulating evidence indicates that chronic low dose exposure to Bisphenol A (BPA), an endocrine disruptor, may disrupt normal brain development and behavior mediated by the gonadotropin-releasing hormone (GnRH) pathways. While it is known that GnRH neurons in the hypothalamus regulate reproductive physiology and behavior, functional roles of extra-hypothalamic GnRH neurons remain unclear. Furthermore, little is known whether BPA interacts with extra-hypothalamic GnRH3 neural systems in vulnerable developing brains. Here we examined the impact of low dose BPA exposure on the developing GnRH3 neural system, eye and brain growth, and locomotor activity in transgenic medaka embryos and larvae with GnRH3 neurons tagged with GFP. Fertilized eggs were collected daily and embryos/larvae were chronically exposed to 200 ng/ml of BPA, starting at 1 day post fertilization (dpf). BPA significantly increased fluorescence intensity of the GnRH3-GFP neural population in the terminal nerve (TN) of the forebrain at 3 dpf, but decreased the intensity at 5 dpf, compared with controls. BPA advanced eye pigmentation without affecting eye and brain size development, and accelerated times to hatch. Following chronic BPA exposure, 20 dpf larvae showed suppression of locomotion, both in distance covered and speed of movement (47% and 43% reduction, respectively). BPA-induced hypoactivity was accompanied by decreased cell body sizes of individual TN-GnRH3 neurons (14% smaller than those of controls), but not of non-GnRH3 neurons. These novel data demonstrate complex neurobehavioral effects of BPA on the development of extra-hypothalamic GnRH3 neurons in teleost fish.     

Processing of affective and emotionally neutral tactile stimuli in the insular cortex

The insula is important for the processing of pleasant aspects of touch whereas its role in the processing of emotionally neutral touch has been less explored. Here, we used a network approach to investigate the insular processing of pleasant stroking touch and emotionally neutral vibratory touch, analysing functional magnetic resonance imaging data from 23 healthy adult participants. Vibration and skin stroking activated areas in the posterior, middle and anterior insula. Psychophysiological interaction analyses suggested that skin stroking increased functional connectivity between the posterior and ventral anterior insula. Vibration instead increased functional connectivity between the posterior and dorsal anterior insula, and induced a stronger decrease of the default mode network activity compared to stroking. These results confirmed findings from previous studies showing that the posterior insula processes affective touch information. We suggest that this is accomplished by relaying tactile information from the posterior insula to ventral anterior insula, an area tightly connected to the emotional parts of the brain. However, our results also suggested that the insula processes tactile information with less emotional valence. A central hub in this processing seemed to be the right dorsal anterior insula.     

Low intensity microwave radiation induced oxidative stress,inflammatory response and DNA damage in rat brain

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n = 6 in each group): group I consisted of sham exposed (control) rats, group II–IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2 h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration.Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p < 0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p < 0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p < 0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p < 0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure.     

Association of neurobehavioral performance with R2* in the caudate nucleus of asymptomatic welders

ObjectivesWelding fumes contain several metals including manganese (Mn) and iron (Fe) that may affect the nervous system. Previous studies of potential welding-related neurotoxicity have focused primarily on Mn exposure. The current study examined neurobehavioral and brain imaging changes in asymptomatic welders and their associations with both Mn and Fe exposure measurements.MethodsData were obtained from subjects with (n = 46) and without (controls; n = 31) a history of welding exposure. Occupational questionnaires estimated recent (HrsW; welding hours and E₉₀; cumulative exposure, past 90 days) and lifetime (YrsW; total welding years and ELT; cumulative exposure, lifetime) exposure. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe concentrations in the basal ganglia [caudate nucleus (CN), putamen, and globus pallidus], amygdala, and hippocampus. Comprehensive neuropsychological tests were conducted to examine behavioral differences between welders and controls. Correlation analyses were conducted between neuropsychological tests and those exposure measurements that showed significant group differences.ResultsCompared to controls, welders had significantly higher R2* in the CN and lower performance on the Phonemic Fluency test. Correlation analyses revealed that welders’ Phonemic Fluency scores were inversely associated with R2* in the CN, but not with the PI or R1 in any brain region of interest studied.DiscussionThe results showed that neurobehavioral performance for the asymptomatic welders in our study was worse than individuals who had not welded, and suggest the differences may be associated with higher Fe accumulation in the CN.     

Quantitative sensory testing of temperature,pain, and touch in adults with Down syndrome

The spinothalamic pathway mediates sensations of temperature, pain, and touch. These functions seem impaired in children with Down syndrome (DS), but have not been extensively examined in adults. The objective of the present study was to compare the spinothalamic-mediated sensory functions between adults with DS and adults from the general population and to examine in the DS group the relationship between the sensory functions and level of intellectual functioning. Quantitative sensory testing (QST) was performed in 188 adults with DS (mean age 37.5 years) and 142 age-matched control participants (median age 40.5 years). Temperature, pain, and touch were evaluated with tests for cold–warm discrimination, sharp–dull discrimination (pinprick), and tactile threshold, respectively. Level of intellectual functioning was estimated with the Social Functioning Scale for Intellectual Disability (intellectual disability level) and the Wechsler Preschool and Primary Scale of Intelligence – Revised (intelligence level). Overall, the difference in spinothalamic-mediated sensory functions between the DS and control groups was not statistically significant. However, DS participants with a lower intelligence level had a statistically significant lower performance on the sharp–dull discrimination test than DS participants with higher intelligence level (adjusted p = .006) and control participants (adjusted p = .017). It was concluded that intellectual functioning level is an important factor to take into account for the assessment of spinothalamic-mediated sensory functioning in adults with DS: a lower level could coincide with impaired sensory functioning, but could also hamper QST assessment.