Eric M. Francisco

Altered Central Sensitization in Subgroups of Women With Vulvodynia

ObjectiveTo 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 (eg, &ggr;-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. MethodsTwelve women with vulvodynia and 20 age-matched controls participated in this study, which was conducted by sensory testing of the right hands 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). ResultsParticipants 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. DiscussionChronic 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.

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.

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).

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.

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

Abstract 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.

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.

The Role of Cortical Modularity in Tactile Information Processing: An Approach to Measuring Information Processing Deficits in Autism

Autism is a pervasive developmental disorder that is manifested in a number of neurological alterations. Although there is a large spectrum of behavioral excesses that includes a diverse number of traits, such as repetitive behaviors and/or sensory hyper-responsiveness, many of the neurological problems could be attributed to underlying anatomical and physiological fundamentals that demonstrate significant diversity within this spectrum and make the phenotypic description of the disorder distinctly different from that exhibited by normal physiology. Characterization of neurological features – such as cortical modularity – could lead to a better understanding of the neurophysiological fundamentals of autism. Recently, we have been developing sensory-based diagnostic protocols based on neurophysiological principles that have been elucidated in animal studies conducted both in our laboratories and those of others. One question that we have pursued in our animal studies has been the fundamental role(s) of the cortical minicolumn and macrocolumn in tactile information processing. We have developed experimental models for determining cortical correlates of perception that relate cortical activity patterns in somatosensory cortex (at high resolution in squirrel monkey studies) to measures of human perception. The minicolumnar and macroco‐ lumnar organization of the cerebral cortex is dynamic and interactive, and the patterns of activity that are generated with stimulus-driven activity in SI cortex have been shown to be modular in nature. This determination of modularity is derived from a self-organizing process that takes place via dynamic interactions between minicolumns and columns in the cortex both during and after development. If developmental processes malfunction, then cortical organi‐ zation suffers at a number of scales. Findings by Casanova and colleagues have elegantly demonstrated in post-mortem histological experiments that minicolumn organization in

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 individuals 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 individuals 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.