Methodological Problems With Online Concussion Testing.

Reaction time testing is widely used in online computerized concussion assessments, and most concussion studies utilizing the metric have demonstrated varying degrees of difference between concussed and non-concussed individuals. The problem with most of these online concussion assessments is that they predominantly rely on consumer grade technology. Typical administration of these reaction time tests involves presenting a visual stimulus on a computer monitor and prompting the test subject to respond as quickly as possible via keypad or computer mouse. However, inherent delays and variabilities are introduced to the reaction time measure by both computer and associated operating systems that the concussion assessment tool is installed on. The authors hypothesized systems that are typically used to collect concussion reaction time data would demonstrate significant errors in reaction time measurements. To remove human bias, a series of experiments was conducted robotically to assess timing errors introduced by reaction time tests under four different conditions. In the first condition, a visual reaction time test was conducted by flashing a visual stimulus on a computer monitor. Detection was via photodiode and mechanical response was delivered via computer mouse. The second condition employed a mobile device for the visual stimulus, and the mechanical response was delivered to the mobile device's touchscreen. The third condition simulated a tactile reaction time test, and mechanical response was delivered via computer mouse. The fourth condition also simulated a tactile reaction time test, but response was delivered to a dedicated device designed to store the interval between stimulus delivery and response, thus bypassing any problems hypothesized to be introduced by computer and/or computer software. There were significant differences in the range of responses recorded from the four different conditions with the reaction time collected from visual stimulus on a mobile device being the worst and the device with dedicated hardware designed for the task being the best. The results suggest that some of the commonly used visual tasks on consumer grade computers could be (and have been) introducing significant errors for reaction time testing and that dedicated hardware designed for the reaction time task is needed to minimize testing errors.

Quantification of Mild Traumatic Brain Injury via Cortical Metrics: Analytical Methods.

Mild traumatic brain injuries are difficult to diagnose or assess with commonly used diagnostic methods. However, the functional state of cerebral cortical networks can be rapidly and effectively probed by measuring tactile-based sensory percepts (called cortical metrics), which are designed to exercise various components of cortical machinery. In this study, such cortical metrics were obtained from 52 college students before and after they experienced sports-related concussions by delivering vibrotactile stimuli to the index and middle fingertips. Performance on four of the sensory test protocols is described: reaction time, amplitude discrimination, temporal order judgment, and duration discrimination. The collected test performance data were analyzed using methods of uni- and multivariate statistics, receiver operated characteristic (ROC) curves, and discriminant analysis. While individual cortical metrics vary extensively in their ability to discriminate between control and concussed subjects, their combined discriminative performance greatly exceeds that of any individual metric, achieving cross-validated 93.0% sensitivity, 92.3% specificity, 93.0% positive predictive value, and 92.3% negative predictive value. The cortical metrics vector can be used to track an individual's recovery from concussion. The study thus establishes that cortical metrics can be used effectively as a quantitative indicator of central nervous system health status.

An Undergraduate Laboratory Exercise that Demonstrates the Difference Between Peripherally and Centrally Mediated Measures.

One of the first concepts that students of neuroscience are exposed to is the overall organization of the nervous system and the two principle divisions of it: the Peripheral Nervous System (PNS) and the Central Nervous System (CNS). In sensory systems, this fundamental division plays a particularly prominent role in the information processing stream that integrates and processes information from the external environment to the CNS. To better understand the differences between the roles that the PNS and CNS play in information processing, we developed a relatively simple in-class laboratory exercise. The experimental methods used to determine several aspects of a subject's discriminative capacity (threshold detection, amplitude discrimination, duration discrimination) are described. These methods were used either under control conditions or after the students altered their skin sensitivity (i.e., the PNS) by cold water immersion. At the conclusion of the lab exercise, students will thoroughly understand the principle of the PNS vs. CNS, as well as a fundamental understanding of quantitative sensory testing. This fundamental understanding of sensory testing provides a foundation for students to pursue or investigate other aspects of sensory information processing in either independent studies or subsequent lab exercises.

Neurosensory Assessments of Concussion.

The purpose of this research was to determine if cortical metrics-a unique set of sensory-based assessment tools-could be used to characterize and differentiate concussed individuals from nonconcussed individuals. Cortical metrics take advantage of the somatotopic relationship between skin and cortex, and the protocols are designed to evoke interactions between adjacent cortical regions to investigate fundamental mechanisms that mediate cortical-cortical interactions. Student athletes, aged 18 to 22 years, were recruited into the study through an athletic training center that made determinations of postconcussion return-to-play status. Sensory-based performance tasks utilizing vibrotactile stimuli applied to tips of the index and middle fingers were administered to test an individual's amplitude discrimination, temporal order judgment, and duration discrimination capacity in the presence and absence of illusion-inducing conditioning stimuli. Comparison of the performances in the presence and absence of conditioning stimuli demonstrated differences between concussed and nonconcussed individuals. Additionally, mathematically combining results from the measures yields a unique central nervous system (CNS) profile that describes an individual's information processing capacity. A comparison was made of CNS profiles of concussed vs. nonconcussed individuals and demonstrated with 99% confidence that the two populations are statistically distinct. The study established solid proof-of-concept that cortical metrics have significant potential as a quantitative biomarker of CNS status.

Altered tactile processing in children with autism spectrum disorder.

Although tactile reactivity issues are commonly reported in children with autism spectrum disorder (ASD), the underlying mechanisms are poorly understood. Less feed-forward inhibition has been proposed as a potential mechanism for some symptoms of ASD. We tested static and dynamic tactile thresholds as a behavioral proxy of feed-forward inhibition in 42 children (21 children with ASD and 21 typically developing [TD] children). Subthreshold conditioning typically raises the dynamic detection threshold, thus comparison of the dynamic to the static threshold generates a metric that predicts gamma-aminobutyric acid (GABA) mediated feed-forward inhibition. Children with ASD had marginally higher static thresholds and a significantly lower ratio between thresholds as compared with TD children. The lower ratio, only seen in children with ASD, might be indicative of less inhibition. Static thresholds were correlated with autism spectrum quotient scores, indicating the higher the tactile threshold, the more ASD traits. The amount of feed-forward inhibition (ratio between dynamic/static) was negatively correlated with autism diagnostic observation schedule repetitive behavior scores, meaning the less inhibition the more ASD symptoms. In summary, children with ASD showed altered tactile processing compared with TD children; thus measuring static and dynamic thresholds could be a potential biomarker for ASD and might be useful for prediction of treatment response with therapeutics, including those that target the GABAergic system. Autism Res 2016, 9: 616-620. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Percept of the duration of a vibrotactile stimulus is altered by changing its amplitude.

There have been numerous studies conducted on time perception. However, very few of these have involved tactile stimuli to assess a subject's capacity for duration discrimination. Previous optical imaging studies in non-human primates demonstrated that increasing the duration of a vibrotactile stimulus resulted in a consistently longer and more well defined evoked SI cortical response. Additionally, and perhaps more interestingly, increasing the amplitude of a vibrotactile stimulus not only evoked a larger magnitude optical intrinsic signal (OIS), but the return to baseline of the evoked response was much longer in duration for larger amplitude stimuli. This led the authors to hypothesize that the magnitude of a vibrotactile stimulus could influence the perception of its duration. In order to test this hypothesis, subjects were asked to compare two sets of vibrotactile stimuli. When vibrotactile stimuli differed only in duration, subjects typically had a difference limen (DL) of approximately 13%, and this followed Weber's Law for standards between 500 and 1500 ms, as increasing the value of the standard yielded a proportional increase in DL. However, the percept of duration was impacted by variations in amplitude of the vibrotactile stimuli. Specifically, increasing the amplitude of the standard stimulus had the effect of increasing the DL, while increasing the amplitude of the test stimulus had the effect of decreasing the DL. A pilot study, conducted on individuals who were concussed, found that increasing the amplitude of the standard did not have an impact on the DL of this group of individuals. Since this effect did not parallel what was predicted from the optical imaging findings in somatosensory cortex of non-human primates, the authors suggest that this particular measure or observation could be sensitive to neuroinflammation and that neuron-glial interactions, impacted by concussion, could have the effect of ignoring, or not integrating, the increased amplitude.

Vibrotactile discriminative capacity is impacted in a digit-specific manner with concurrent unattended hand stimulation.

A number of perceptual and neurophysiological studies have investigated the effects of delivering unilateral versus bilateral tactile sensory stimulation. While a number of studies indicate that perceptual discrimination degrades with opposite-hand stimulation, there have been no reports that examined the digit specificity of cross-hemispheric interactions to discriminative capabilities. The purpose of this study was to determine whether unattended hand (UH) stimulation significantly degraded or improved amplitude discriminative capacity on the attended hand (AH) in a digit-specific manner. The methods are based on a sensory perceptual task (vibrotactile amplitude discriminative capacity on the tips of the fingers D2 and D3 of the left hand) in the absence and presence of conditioning stimuli delivered to D2 and D3 of the right hand. Non-specific equal-amplitude stimulation to D2 and D3 of the UH significantly worsened amplitude discrimination (AD) performance, while delivering unequal-amplitude stimuli to D2 and D3 of the UH worsened task performance only under the condition in which the unattended stimuli failed to appropriately match the stimulus parameters on the AH. Additionally, delivering single-site stimuli to D2 or D3 of the UH resulted in degraded performance on the AD task when the stimulus amplitude did not match the amplitude of the stimulus applied to homologous digits of the AH. The findings demonstrate that there is a reduction in performance under conditions where UH stimulation least matched stimulation applied to the AH, while there was little or no change in performance when stimulus conditions on the homologous digit(s) of the contralateral sites were similar. Results suggest that bilateral interactions influence perception in a context-dependent manner that is digit specific.

Functional deficits in carpal tunnel syndrome reflect reorganization of primary somatosensory cortex.

Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20-60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit's contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release cycles (r = -0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients.

An undergraduate laboratory exercise to study sensory inhibition.

Sensory inhibition was first described by von Békésy as a process in which excitation of a field of sensory neurons leads to the reduction of activity of surrounding neurons and thus promotes contrast enhancement of the excited field. In the context of somatosensory cortex, the cortical neurons excited by touch or vibration will suppress excitation of neurons from surrounding receptive fields. USING TACTILE STIMULATORS BOTH DESIGNED AND FABRICATED AT THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, WE CONDUCTED TWO SIMPLE EXPERIMENTS IN WHICH SENSORY INHIBITION PLAYS A ROLE IN INFORMATION PROCESSING: a unilateral study in which stimuli are delivered to the digits of one hand, and a bilateral study in which stimuli are delivered to the digits of both hands. In the unilateral study, we demonstrated that threshold detection on the third digit (D3) is impacted by conditioning stimuli delivered to adjacent digits 2 (D2) and digits 4 (D4). In the bilateral study, we delivered different conditions of bilateral stimulation in order to investigate the impact that conditioning stimulation of the right hand had on amplitude discriminative capacity of the left hand. The results demonstrated that conditioning stimulation on the right hand had a significant impact on the discriminative capacity of the left hand, and this alteration in discriminative capacity was consistent with previous animal studies in which somatosensory cortical responses evoked by stimulus conditions of unilateral vs. bilateral stimulation were compared. At the conclusion of this exercise, students will appreciate the fundamentals of sensory inhibition as well as the logistics of obtaining and analyzing data from human subjects. This study is designed to help students prepare for studying other facets of sensory processing by providing a firm foundation in the experimental methods and procedures.

Centrally-mediated sensory information processing is impacted with increased alcohol consumption in college-aged individuals.

Alcohol consumption can have an impact on a variety of centrally-mediated functions of the nervous system, and some aspects of sensory perception can be altered as a result of long-term alcohol use. In order to assess the potential impact of alcohol intake on sensory information processing, metrics of sensory perception (simple and choice reaction time; static and dynamic threshold detection; amplitude discrimination with and without pre-exposure to conditioning stimulation) were tested in college-aged subjects (18 to 26 years of age) across a broad range of levels of alcohol consumption. The analysis indicated no detectable associations between reaction time and threshold measures with alcohol consumption. However, measures of adaptation to short duration (0.5s) conditioning stimuli were significantly associated with alcohol consumption: the impact of a confounding conditioning stimulus on amplitude discriminative capacity was comparable to values reported in previous studies on healthy controls (28.9±8.6) for light drinkers while the same adaptation metric for heavy drinkers (consuming greater than 60 drinks per month) was significantly reduced (8.9±7.1). The results suggest that while some of the sensory perceptual metrics which are normally impacted in chronic alcoholism (e.g., reaction time and threshold detection) were relatively insensitive to change with increased alcohol consumption in young non-alcoholic individuals, other metrics, which are influenced predominantly by centrally-mediated mechanisms, demonstrate a deviation from normative values with increased consumption. Results of this study suggest that higher levels of alcohol consumption may be associated with alterations in centrally-mediated neural mechanisms in this age group.

A novel device for the study of somatosensory information processing.

Current methods for applying multi-site vibratory stimuli to the skin typically involve the use of multiple, individual vibrotactile stimulators. Limitations of such an arrangement include difficulty with both positioning the stimuli as well as ensuring that stimuli are delivered in a synchronized and deliberate manner. Previously, we reported a two-site tactile stimulator that was developed in order to solve these problems (Tannan et al., 2007a). Due to both the success of that novel stimulator and the limitations that were inherent in that device, we designed and fabricated a four-site stimulator that provides a number of advantages over the previous version. First, the device can stimulate four independent skin sites and is primarily designed for stimulating the digit tips. Second, the positioning of the probe tips has been re-designed to provide better ergonomic hand placement. Third, the device is much more portable than the previously reported stimulator. Fourth, the stimulator head has a much smaller footprint on the table or surface where it resides. To demonstrate the capacity of the device for delivering tactile stimulation at four independent sites, a finger agnosia protocol, in the presence and absence of conditioning stimuli, was conducted on seventeen healthy control subjects. The study demonstrated that with increasing amplitudes of vibrotactile conditioning stimuli concurrent with the agnosia test, inaccuracies of digit identification increased, particularly at digits D3 and D4. The results are consistent with prior studies that implicated synchronization of adjacent and near-adjacent cortical ensembles with conditioning stimuli in impacting TOJ performance (Tommerdahl et al., 2007a,b).

Somatosensory information processing in the aging population.

While it is well known that skin physiology - and consequently sensitivity to peripheral stimuli - degrades with age, what is less appreciated is that centrally mediated mechanisms allow for maintenance of the same degree of functionality in processing these peripheral inputs and interacting with the external environment. In order to demonstrate this concept, we obtained observations of processing speed, sensitivity (thresholds), discriminative capacity, and adaptation metrics on subjects ranging in age from 18 to 70. The results indicate that although reaction speed and sensory thresholds change with age, discriminative capacity, and adaptation metrics do not. The significance of these findings is that similar metrics of adaptation have been demonstrated to change significantly when the central nervous system (CNS) is compromised. Such compromise has been demonstrated in subject populations with autism, chronic pain, acute NMDA receptor block, concussion, and with tactile-thermal interactions. If the metric of adaptation parallels cortical plasticity, the results of the current study suggest that the CNS in the aging population is still capable of plastic changes, and this cortical plasticity could be the mechanism that compensates for the degradations that are known to naturally occur with age. Thus, these quantitative measures - since they can be obtained efficiently and objectively, and appear to deviate from normative values significantly with systemic cortical alterations - could be useful indicators of cerebral cortical health.

Altered central sensitization in subgroups of women with vulvodynia.

OBJECTIVE: To investigate the clinical correlates of central nervous system alterations among women with vulvodynia. Altered central sensitization has been linked to dysfunction in central nervous system-inhibitory pathways (e.g., γ-aminobutyric acidergic), and metrics of sensory adaptation, a centrally mediated process that is sensitive to this dysfunction, could potentially be used to identify women at risk of treatment failure using conventional approaches. METHODS: Twelve women with vulvodynia and 20 age-matched controls participated in this study, which was conducted by sensory testing of the right hand's index and middle fingers. The following sensory precepts were assessed: (1) vibrotactile detection threshold; (2) amplitude discrimination capacity (defined as the ability to detect differences in intensity of simultaneously delivered stimuli to 2 fingers); and (3) a metric of adaptation (determined by the impact that applying conditioning stimuli have on amplitude discriminative capacity). RESULTS: Participants did not differ on key demographic variables, vibrotactile detection threshold, and amplitude discrimination capacity. However, we found significant differences from controls in adaptation metrics in 1 subgroup of vulvodynia patients. Compared with healthy controls and women with a shorter history of pain [n=5; duration (y) = 3.4 ± 1.3], those with a longer history [n=7; duration (y) = 9.3 ± 1.4)] were found to be less likely to have adaptation metrics similar to control values. DISCUSSION: Chronic pain is thought to lead to altered central sensitization, and adaptation is a centrally mediated process that is sensitive to this condition. This report suggests that similar alterations exist in a subgroup of vulvodynia patients.

An Undergraduate Laboratory Exercise to Study Weber's Law.

Weber's Law describes the relationship between actual and perceived differences in stimulus intensity. To observe the relationship described in this law, we developed an exercise for undergraduate students, as experiential learning is an integral part of scientific education. We describe the experimental methods used for determining the subject's discriminative capacity at multiple vibrotactile amplitudes. A novel four-point stimulator (designed and fabricated at the University of North Carolina) was used for the study. Features of the device, such as automated skin detection, make it feasible to perform this laboratory exercise in a reasonable lab period. At the conclusion of the lab exercise, students will thoroughly understand the principle of Weber's Law as well as fundamental quantitative sensory testing concepts. This introduction to sensory testing will provide a suitable foundation for the undergraduate neuroscience student to investigate other aspects of sensory information processing in subsequent lab exercises.

The impact of non-noxious heat on tactile information processing.

A significant number of studies that evaluated tactile-pain interactions employed heat to evoke nociceptive responses. However, relatively few studies have examined the effects of non-noxious thermal stimulation on tactile discriminative capacity. In this study, the impact that non-noxious heat had on three features of tactile information processing capacity was evaluated: vibrotactile threshold, amplitude discriminative capacity, and adaptation. It was found that warming the skin made a significant improvement on a subject's ability to detect a vibrotactile stimulus, and although the subjects' capacities for discriminating between two amplitudes of vibrotactile stimulation did not change with skin heating, the impact that adapting or conditioning stimulation normally had on amplitude discrimination capacity was significantly attenuated by the change in temperature. These results suggested that although the improvements in tactile sensitivity that were observed could have been a result of enhanced peripheral activity, the changes in measures that reflect a decrease in the sensitization to repetitive stimulation are most likely centrally mediated. The authors speculate that these centrally mediated changes could be a reflection of a change in the balance of cortical excitation and inhibition.

Effects of the N-methyl-D-Aspartate receptor antagonist dextromethorphan on vibrotactile adaptation.

BACKGROUND: Previous reports have demonstrated that short durations of vibrotactile stimuli (less than or equal to 2 sec) effectively and consistently modify both the perceptual response in humans as well as the neurophysiological response in somatosensory cortex. The change in cortical response with adaptation has been well established by a number of studies, and other reports have extended those findings in determining that both GABA- and NMDAR-mediated neurotransmission play a significant role in the dynamic response of somatosensory cortical neurons. In this study, we evaluated the impact that dextromethorphan (DXM), an NMDAR antagonist, had on two distinct vibrotactile adaptation tasks. RESULTS: All subjects, both those that ingested 60 mg DXM and those that ingested placebo, were evaluated for their amplitude discriminative capacity between two simultaneously delivered vibrotactile stimuli both with and without 3 conditions of pre-exposure to adapting stimulation. The results demonstrated that the perceptual metrics of subjects who ingested 60 mg DXM were significantly altered from that of controls when the amplitude discrimination task followed one of the conditions of adapting stimulation. Without the condition of pre-exposure to an adapting stimulus (or stimuli), there was little difference between the observations obtained from the subjects that ingested DXM and controls. Peak impact on subject response occurred at 60 min post-ingestion, whereas the scores of controls who ingested placebo were not impacted. CONCLUSION: The results - that DXM blocks vibrotactile adaptation - is consistent with the suggestion that NMDAR-mediated neurotransmission plays a significant role in the perceptual adaptive response. This finding is also consistent with neurophysiological findings that report observations of the effects of NMDAR block on the SI cortical response to repetitive vibrotactile stimulation.

Absence of stimulus-driven synchronization effects on sensory perception in autism: Evidence for local underconnectivity?

BACKGROUND: A number of neurophysiological characteristics demonstrated in autism share the common theme of under-connectivity in the cerebral cortex. One of the prominent theories of the cause of the dysfunctional connectivity in autism is based on distinct anatomical structures that differ between the autistic and the neurotypical cortex. The functional minicolumn has been identified as occupying a much smaller space in the cortex of people with autism as compared to neurotypical controls, and this aberration in architecture has been proposed to lead to under-connectivity at the local or within-macrocolumn level, which in turn leads to dysfunctional connectivity globally across cortical areas in persons with autism. Numerous reports have indicated reduced synchronization of activity on a large scale in the brains of people with autism. We hypothesized that if the larger-scale aberrant dynamics in autism were due - at least in part - to a widespread propagation of the errors introduced at the level of local connectivity between minicolumns, then aberrations in local functional connectivity should also be detectable in autism. METHODS: Recently, we reported a method for measuring the perceptual changes that are impacted by the presence of synchronized conditioning stimuli on the skin. In this study, the temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 10 adult autism subjects were assessed both in the absence and presence of synchronized conditioning vibrotactile stimuli. RESULTS: Our previous report demonstrated that delivering simultaneous and synchronized vibrotactile stimuli to near-adjacent skin sites decreases a subject's ability to determine temporal order by 3 to 4-fold. However, results presented in this report show that subjects with autism do not demonstrate such decreased capacity in temporal order judgment (TOJ) in the presence of synchronized conditioning stimuli, although these same subjects do have TOJ thresholds well above that of controls. CONCLUSION: It is speculated that the differences in sensory perceptual capacities in the presence of synchronized conditioning stimuli in autism are due to local under-connectivity in cortex at the minicolumnar organizational level, and that the above-average TOJ thresholds in autism could be attributed to structural differences that have been observed in the frontostrial system of this population.

A quantitative method for determining spatial discriminative capacity.

BACKGROUND: The traditional two-point discrimination (TPD) test, a widely used tactile spatial acuity measure, has been criticized as being imprecise because it is based on subjective criteria and involves a number of non-spatial cues. The results of a recent study showed that as two stimuli were delivered simultaneously, vibrotactile amplitude discrimination became worse when the two stimuli were positioned relatively close together and was significantly degraded when the probes were within a subject's two-point limen. The impairment of amplitude discrimination with decreasing inter-probe distance suggested that the metric of amplitude discrimination could possibly provide a means of objective and quantitative measurement of spatial discrimination capacity. METHODS: A two alternative forced-choice (2AFC) tracking procedure was used to assess a subject's ability to discriminate the amplitude difference between two stimuli positioned at near-adjacent skin sites. Two 25 Hz flutter stimuli, identical except for a constant difference in amplitude, were delivered simultaneously to the hand dorsum. The stimuli were initially spaced 30 mm apart, and the inter-stimulus distance was modified on a trial-by-trial basis based on the subject's performance of discriminating the stimulus with higher intensity. The experiment was repeated via sequential, rather than simultaneous, delivery of the same vibrotactile stimuli. RESULTS: Results obtained from this study showed that the performance of the amplitude discrimination task was significantly degraded when the stimuli were delivered simultaneously and were near a subject's two-point limen. In contrast, subjects were able to correctly discriminate between the amplitudes of the two stimuli when they were sequentially delivered at all inter-probe distances (including those within the two-point limen), and improved when an adapting stimulus was delivered prior to simultaneously delivered stimuli. CONCLUSION: Subjects' capacity to discriminate the amplitude difference between two vibrotactile stimulations was degraded as the inter-stimulus distance approached the limit of their two-point spatial discriminative capacity. This degradation of spatial discriminative capacity lessened when an adapting stimulus was used. Performance of the task, as well as improvement on the task with adaptation, would most likely be impaired if the cortical information processing capacity of a subject or subject population were systemically altered, and thus, the methods described could be effective measures for use in clinical or clinical research applications.

Perceptual metrics of individuals with autism provide evidence for disinhibition.

Adults with autism exhibit inhibitory deficits that are often manifested in behavioral modifications, such as repetitive behaviors, and/or sensory hyper-responsiveness. If such behaviors are the result of a generalized deficiency in inhibitory neurotransmission, then it stands to reason that deficits involving localized cortical-cortical interactions--such as in sensory discrimination tasks--could be detected and quantified. This study exemplifies a newly developed method for quantifying sensory testing metrics. Our novel sensory discrimination tests may provide (a) an effective means for biobehavioral assessment of deficits specific to autism and (b) an efficient and sensitive measure of change following treatment. The sensory discriminative capacity of ten subjects with autism and ten controls was compared both before and after short duration adapting stimuli. Specifically, vibrotactile amplitude discriminative capacity was obtained both in the presence and absence of 1 sec adapting stimuli that were delivered 1 sec prior to the comparison stimuli. Although adaptation had a pronounced effect on the amplitude discriminative capacity of the control subjects, little or no impact was observed on the sensory discriminative capacity of the subjects with autism. This lack of impact of the adapting stimuli on the responses of the subjects with autism was interpreted to be consistent with the reduced GABAergic-mediated inhibition described in previous reports. One significant aspect of this study is that the methods could prove to be a useful and efficient way to detect specific neural deficits and monitor the efficacy of pharmacological or behavioral treatments in autism.

Effects of stimulus-driven synchronization on sensory perception.

BACKGROUND: A subject's ability to differentiate the loci of two points on the skin depends on the stimulus-evoked pericolumnar lateral inhibitory interactions which increase the spatial contrast between regions of SI cortex that are activated by stimulus-evoked afferent drive. Nevertheless, there is very little known about the impact that neuronal interactions - such as those evoked by mechanical skin stimuli that project to and coordinate synchronized activity in adjacent and/or near-adjacent cortical columns - could have on sensory information processing. METHODS: The temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 20 healthy adult subjects were assessed both in the absence and presence of concurrent conditions of tactile stimulation. These measures were obtained across a number of paired sites - two unilateral and one bilateral - and several conditions of adapting stimuli were delivered both prior to and concurrently with the TOJ and TDT tasks. The pairs of conditioning stimuli were synchronized and periodic, synchronized and non-periodic, or asynchronous and non-periodic. RESULTS: In the absence of any additional stimuli, TOJ and TDT results obtained from the study were comparable across a number of pairs of stimulus sites - unilateral as well as bilateral. In the presence of a 25 Hz conditioning sinusoidal stimulus which was delivered both before, concurrently and after the TOJ task, there was a significant change in the TOJ measured when the two stimuli were located unilaterally on digits 2 and 3. However, in the presence of the same 25 Hz conditioning stimulus, the TOJ obtained when the two stimuli were delivered bilaterally was not impacted. TDT measures were not impacted to the same degree by the concurrent stimuli that were delivered to the unilateral or bilateral stimulus sites. This led to the speculation that the impact that the conditioning stimuli - which were sinusoidal, periodic and synchronous - had on TOJ measures was due to the synchronization of adjacent cortical ensembles in somatosensory cortex, and that the synchronization of these cortical ensembles could have been responsible for the degradation in temporal order judgment. In order to more directly test this hypothesis, the synchronized 25 Hz conditioning stimuli that were delivered during the initial TOJ test were replaced with asynchronous non-periodic 25 Hz conditioning stimuli, and these asynchronous conditioning stimuli did not impact the TOJ measures. CONCLUSION: The results give support to the theory that synchronization of cortical ensembles in SI could significantly impact the topography of temporal perception, and these findings are speculated to be linked mechanistically to previously reported co-activation plasticity studies. Additionally, the impact that such synchronizing conditioning stimuli have on TOJ - which can be measured relatively quickly - could provide an effective means to assess the functional connectivity of neurologically compromised subject populations.