Atypical spatiotemporal activation of cerebellar lobules during emotional face processing in adolescents with autism.

Autism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.

Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

The human amygdala and pain: evidence from neuroimaging.

The amygdala, a small deep brain structure involved in behavioral processing through interactions with other brain regions, has garnered increased attention in recent years in relation to pain processing. As pain is a multidimensional experience that encompasses physical sensation, affect, and cognition, the amygdala is well suited to play a part in this process. Multiple neuroimaging studies of pain in humans have reported activation in the amygdala. Here, we summarize these studies by performing a coordinate-based meta-analysis within experimentally induced and clinical pain studies using an activation likelihood estimate analysis. The results are presented in relation to locations of peak activation within and outside of amygdala subregions. The majority of studies identified coordinates consistent with human amygdala cytoarchitecture indicating reproducibility in neuroanatomical labeling across labs, analysis methods, and imaging modalities. Differences were noted between healthy and clinical pain studies: in clinical pain studies, peak activation was located in the laterobasal region, suggestive of the cognitive-affective overlay present among individuals suffering from chronic pain; while the less understood superficial region of the amygdala was prominent among experimental pain studies. Taken together, these findings suggest several important directions for further research exploring the amygdala's role in pain processing.

The cerebellum and addiction: insights gained from neuroimaging research.

Although cerebellar alterations have been consistently noted in the addiction literature, the pathophysiology of this link remains unclear. The cerebellum is commonly classified as a motor structure, but human functional neuroimaging along with clinical observations in cerebellar stroke patients and anatomical tract tracing in non-human primates suggests its involvement in cognitive and affective processing. A comprehensive literature search on the role of the cerebellum in addiction was performed. This review article (1) considers the potential role of the cerebellum in addiction; (2) summarizes the cerebellar structural alterations linked to addiction; (3) presents the functional neuroimaging evidence linking the cerebellum with addiction; and (4) proposes a model for addiction that underscores the role of the cerebellum. The data implicate the cerebellum as an intermediary between motor and reward, motivation and cognitive control systems, as all are relevant etiologic factors in addiction. Furthermore, consideration of these findings could contribute to deeper and more sophisticated insights into normal reward and motivational function. The goal of this review is to spread awareness of cerebellar involvement in addictive processes, and to suggest a preliminary model for its potential role.

Refractive errors in patients with Bardet Biedl syndrome.

PURPOSE: Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy. Within corneal development, primary cilia serve a critical role. We sought to investigate the association of BBS with corneal astigmatism among a cohort of patients with BBS. METHODS: This was a cross-sectional, retrospective study performed at a pediatric ophthalmology department of a tertiary hospital. The study enrolled 45 patients with genetically confirmed Bardet-Biedl syndrome, encompassing a total of 90 eyes observed from February 2011 to August 2021. Spherical and cylindrical refractive errors and keratometry outcome measures, including diopter (D) values at the flattest and steepest axes, were recorded. Corneal astigmatism of greater than 3D is considered extreme corneal astigmatism based on previously published data. RESULTS: Among 45 patients (M:26; F:19), the mean age was 16.4 ± 8.2 years, and the mean best-corrected visual acuity was 20/60. The most common molecular diagnosis was BBS1, seen in 24 of 45 (53.3%). Among all the patients, the mean spherical refractive error was -2.9 ± 3.8D. The mean cylindrical refractive error was 2.6 ± 1.5D. The mean keratometry values at the flattest axis was 43.5 ± 5.3D (39.4-75.0) and at the steepest axis was 47.2 ± 7.3D(41.5-84.0). Among all the patients with BBS, the mean corneal astigmatism was 3.7 ± 1.0D(0.5-7.1), which is considered extreme. CONCLUSION: A cohort of individuals with BBS demonstrated high corneal astigmatism. These results suggest an association between corneal astigmatism and primary ciliary dysfunction and may assist in clinical management and future therapeutic targets among BBS and other corneal disorders.

The long-term impact of cerebellar tumor resection on executive functioning, anxiety, and fear of pain: A mixed methodology pilot study.

This pilot study investigated the long-term impact of a surgery-only treatment (no exposure to other treatments, such as chemotherapy and radiation) for pediatric cerebellar low-grade gliomas on executive function, anxiety, and fear of pain (FOP) beliefs. Twelve patients who underwent surgical glioma resection during childhood (surgery age was 4-16 years, study visit age was 10-28 years), and 12 pain-free controls matched for age, sex, race, and handedness were tested. The spatial extent of resection was precisely mapped using magnetic resonance imaging (MRI). Executive function, anxiety, and FOP were assessed using validated self-report age-appropriate questionnaires for children and adults. Structured clinical interviews at a post-surgery follow-up visit were completed (average: 89 months, range: 20-99). No significant differences in FOP (FOPQ-C t[14 = 1.81, p = 0.09; FOPQ-III t[4] = 0.29, p = 0.79), executive function scores (BRIEF t[20] = 0.30, p = 0.28), or anxiety scores (MASC t[16] = 0.19, p = 0.85; MAQ t[4] = 1.80, p = 0.15) were found in pediatric or adult patients compared to pain-free controls. Clinical interviews mainly categorized pediatric patients as not anxious. One participant reported mild/subclinical anxiety, and one had moderate clinical anxiety. Neither psychologists nor patients endorsed impairments to executive functioning, anxiety, or FOP. Our pilot results suggest that pediatric cerebellar tumor survivors treated with surgery-only have favorable long-term functioning related to these themes. While these results are promising, they will need to be replicated in a larger patient sample.

FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain.

PURPOSE: To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. DESIGN: Prospective case series. METHODS: 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. RESULTS: With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. CONCLUSION: FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.

BOLD responses in somatosensory cortices better reflect heat sensation than pain.

The discovery of cortical networks that participate in pain processing has led to the common generalization that blood oxygen level-dependent (BOLD) responses in these areas indicate the processing of pain. Physical stimuli have fundamental properties that elicit sensations distinguishable from pain, such as heat. We hypothesized that pain intensity coding may reflect the intensity coding of heat sensation during the presentation of thermal stimuli during fMRI. Six 3T fMRI heat scans were collected for 16 healthy subjects, corresponding to perceptual levels of "low innocuous heat," "moderate innocuous heat," "high innocuous heat," "low painful heat," "moderate painful heat," and "high painful heat" delivered by a contact thermode to the face. Subjects rated pain and heat intensity separately after each scan. A general linear model analysis detected different patterns of brain activation for the different phases of the biphasic response to heat. During high painful heat, the early phase was associated with significant anterior insula and anterior cingulate cortex activation. Persistent responses were detected in the right dorsolateral prefrontal cortex and inferior parietal lobule. Only the late phase showed significant correlations with perceptual ratings. Significant heat intensity correlated activation was identified in contralateral primary and secondary somatosensory cortices, motor cortex, and superior temporal lobe. These areas were significantly more related to heat ratings than pain. These results indicate that heat intensity is encoded by the somatosensory cortices, and that pain evaluation may either arise from multimodal evaluative processes, or is a distributed process.

Clinical Neuroimaging of Photophobia in Individuals With Chronic Ocular Surface Pain.

PURPOSE: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain by using functional magnetic resonance imaging (fMRI). DESIGN: Cross-sectional case/control analysis. METHODS: A total of 16 individuals from the Miami Veterans Affairs eye clinic underwent comprehensive ocular surface evaluations and were surveyed for ocular surface symptoms. Case patients included patients who reported chronic ocular surface pain symptoms and light sensitivity at least most of the time over 1 week. Controls included persons without chronic ocular surface pain who reported no or minimal light sensitivity. All patients viewed light stimuli during 2 fMRI scans, one before and one after topical anesthetic instillation, and rated their level of pain intensity to the stimulus at the end of each scan. Areas of brain activation in response to light stimuli presentation were correlated with pain responses and examined post- vs pre-anesthesia. RESULTS: Case patients (n = 8) reported higher pain intensity ratings than controls (n = 8) in response to light stimuli during fMRI. Case patient ratings correlated more with light-evoked activation in pain-related areas within the trigeminal brainstem, primary somatosensory cortex (S1), anterior mid-cingulate cortex (aMCC), and insula than in controls. Topical anesthesia led to varying responses in pain ratings among case patients as well as decreased light-evoked activation in S1 and aMCC. CONCLUSIONS: The trigeminal nociceptive system may contribute to photophobia in individuals with chronic ocular surface pain. We demonstrate modulation of cortical structures in this pathway with topically applied anesthetic to the eyes. Further understanding of modulatory interactions that govern ocular surface pain and photophobia is critical for developing effective, precision-based therapies.

Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.

Introduction: To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain. Methods: Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed. Results: At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not. Discussion: BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.

Placebos in pediatrics: A cross-sectional survey investigating physicians' perspectives.

OBJECTIVE: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians' current practice, opinions, knowledge, and likelihood of recommending placebos in the future. METHODS: A cross-sectional web-based survey administered by REDCap was conducted at Boston Children's Hospital between October 2021 and March 2022. Physicians (n = 1157) were invited to participate through an email containing a link to a 23-item survey designed to assess physicians' attitudes and perceptions towards the clinical use of placebo in pediatrics. RESULTS: From 207 (18%) returned surveys, 109 (9%) were fully completed. Most respondents (79%) believed that enhancing the therapeutic components that contribute to the placebo response may be a way of improving pediatric care. However, whereas most (62%) found placebo treatments permissible, only one-third reported recommending them. In pediatrics, placebos are typically introduced as a medicine that "might help" (43%). The most common treatments recommended to enhance placebo effects are physical therapy, vitamins, and over-the-counter analgesics. Physicians most frequently recommend placebos for occasional pain, headaches, and anxiety disorders. Finally, the great majority of physicians (87%) stated they would be more likely to recommend placebo treatments if there were safety and ethical guidelines for open-label placebos. CONCLUSIONS: Placebo treatments seem permissible to physicians in pediatric care, but the development of safety and ethical guidelines may be necessary before physicians systematically incorporate the benefits of the placebo effect in pediatrics.

Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes.

Introduction: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. Methods: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. Results: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. Discussion: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.

Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images.

The cerebellum is reliably activated during both acute and chronic pain conditions, but it is unclear whether the response to aversive painful stimuli can be generalized to other aversive stimuli. We hypothesized that cerebellar activation during pain reflects higher-level encoding of aversive stimuli. We used functional magnetic resonance imaging (fMRI) to compare cerebellar responses in 11 healthy volunteers to noxious heat (46 °C) applied to the hand and to the passive viewing of images selected from the International Affective Picture System. Aversive stimuli in the form of noxious heat and unpleasant pictures (unpleasant vs neutral) activated overlapping areas in the posterior cerebellum, specifically in hemispheric lobule VI, Crus I, and VIIb. Pleasant pictures (pleasant vs neutral) did not share the same pattern of activation as observed with the aversive stimuli. Cerebellar areas that showed functional overlap with both heat pain and unpleasant picture viewing were significantly inversely correlated with fMRI signals measured in limbic system structures, including the anterior hypothalamus, subgenual anterior cingulate cortex, and the parahippocampal gyrus. Heat-specific functional connectivity was detected in many regions including primary motor cortex, secondary somatosensory cortex, anterior insula, and the periaqueductal gray. The overlap between cerebellar lobuli reactive to noxious heat and passive viewing of unpleasant images suggest that the cerebellum may contain specific regions involved in encoding generalized aversive processing. The separate cortical networks suggest that noxious heat-evoked responses in the cerebellum can be divided into sensorimotor and emotional networks.

Neuroimaging of the periaqueductal gray: state of the field.

This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region.

Supraspinal Mechanisms Underlying Ocular Pain.

Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.

A lateralized model of the pain-depression dyad.

Chronic pain and depression are two frequently co-occurring and debilitating conditions. Even though the former is treated as a physical affliction, and the latter as a mental illness, both disorders closely share neural substrates. Here, we review the association of pain with depression, especially when symptoms are lateralized on either side of the body. We also explore the overlapping regions in the forebrain implicated in these conditions. Finally, we synthesize these findings into a model, which addresses gaps in our understanding of comorbid pain and depression. Our lateralized pain-depression dyad model suggests that individuals diagnosed with depression should be closely monitored for pain symptoms in the left hemibody. Conversely, for patients in pain, with the exception of acute pain with a known source, referrals in today's pain centers for psychological evaluation should be part of standard practice, within the framework of an interdisciplinary approach to pain treatment.

Pain mechanisms and management in corneal cross-linking: a review.

Though corneal collagen cross-linking (CXL) is an increasingly available and effective treatment for keratoconus, few reports have considered its impact on pain-related physiology in depth. This comprehensive narrative review summarises mechanisms underlying pain in CXL and clinical care possibilities, with the goal of future improvement in management of CXL-related pain. Postoperative pain associated with CXL is largely due to primary afferent nerve injury and, to a smaller extent, inflammation. Chronification of pain after CXL has not been reported, even as long-term nerve damage without regeneration following standard CXL treatment is frequently observed. The lack of pain chronification may be due to the minimally invasive nature of the procedure, with its rapidly recovering superficial corneal wound, and to the positive anti-inflammatory changes of the tear film that have been described after CXL. Different CXL approaches have been developed, with the transepithelial epithelial-on technique (epi-on) associated with less postsurgical pain than the gold standard, epithelial-off technique (epi-off). After the first few days, however, the difference in pain scores and need for analgesics between epi-on and epi-off disappear. Patients experience relatively high-intensity pain the first few days post-CXL, and many strategies for acute pain control following CXL have been studied. Currently, no method of pain management is considered superior or universally accepted. Acute pain following CXL is a recognised and clinically significant side effect, but few CXL studies have systematically investigated postoperative pain and its management. This review aims to improve patient pain outcomes following this increasingly common procedure.

A fMRI evaluation of lamotrigine for the treatment of trigeminal neuropathic pain: pilot study.

Using functional magnetic resonance imaging (fMRI) methods, we evaluated the effects of lamotrigine vs placebo in a double-blind 1:1 randomized trial. Six patients with neuropathic pain were recruited for the study. All subjects had baseline pain >4/10 on a visual analog scale (VAS) and allodynia to brush as inclusion criteria for the study. Patients underwent two fMRI sessions, with half of the subjects receiving placebo first and half receiving drug first (based on the blinding protocol). Lamotrigine decreased their average pain intensity level from 5.6 to 3.5 on a VAS. All subjects had brush, cold, and heat applied to the affected and mirror-unaffected sides of their face. The results show: 1) in a small cohort, lamotrigine had a significant effect on heat VAS but not on the other stimuli; and 2) contrast analysis of fMRI results for heat stimuli applied to the affected face for lamotrigine vs placebo produced an overall decrease in blood oxygen dependent level signal, suggesting a potential inhibitory effect of the drug on predominantly cortical regions (frontal, parietal, and temporal).

Segmentally arranged somatotopy within the face representation of human primary somatosensory cortex.

Though somatotypic representation within the face in human primary somatosensory cortex (S1) to innocuous stimuli is controversial; previous work suggests that painful heat is represented based on an "onion-skin" or segmental pattern on the face. The aim of this study was to determine if face somatotopy for brush stimuli in S1 also follows this segmental representation model. Twelve healthy subjects (nine men: three women) underwent functional magnetic resonance imaging to measure blood oxygen level dependent signals during brush (1 Hz, 15 s) applied to their faces. Separate functional scans were collected for brush stimuli repetitively applied to each of five separate stimulation sites on the right side of the face. These sites were arranged in a vertical, horizontal, and circular manner encompassing the three divisions of the trigeminal nerve. To minimize inter-individual morphological differences in the post-central gyrus across subjects, cortical surface-based registration was implemented before group statistical image analysis. Based on activation foci, somatotopic activation in the post-central gyrus was detected for brush, consistent with the segmental face representation model.

C-Fiber Assays in the Cornea vs. Skin.

C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.