Search

Background Patients with glioblastoma (GBM) and high-grade glioma (HGG, World Health Organization [WHO] grade IV glioma) have a poor prognosis. Consequently, there is an unmet clinical need for accessible and noninvasively acquired predictive biomarkers of overall survival in patients. This study evaluated morphological changes in the brain separated from the tumor invasion site (ie, contralateral hemisphere). Specifically, we examined the prognostic value of widespread alterations of cortical thickness (CT) in GBM/HGG patients. Methods We used FreeSurfer, applied with high-resolution T1-weighted MRI, to examine CT, evaluated prior to standard treatment with surgery and chemoradiation in patients (GBM/HGG, N = 162, mean age 61.3 years) and 127 healthy controls (HC; 61.9 years mean age). We then compared CT in patients to HC and studied patients’ associated changes in CT as a potential biomarker of overall survival. Results Compared to HC cases, patients had thinner gray matter in the contralesional hemisphere at the time of tumor diagnosis. patients had significant cortical thinning in parietal, temporal, and occipital lobes. Fourteen cortical parcels showed reduced CT, whereas in 5, it was thicker in patients’ cases. Notably, CT in the contralesional hemisphere, various lobes, and parcels was predictive of overall survival. A machine learning classification algorithm showed that CT could differentiate short- and long-term survival patients with an accuracy of 83.3%. Conclusions These findings identify previously unnoticed structural changes in the cortex located in the hemisphere contralateral to the primary tumor mass. Observed changes in CT may have prognostic value, which could influence care and treatment planning for individual patients.

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE’s implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question.Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart.Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve’s center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads’ thresholds decreased or remained stable over the 3-week span. The remaining two leads’ thresholds increased by 70–74%, possibly due to scarring or device failure.Significance: This work represents an important first step in establishing the MSE’s viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

Adults with unilateral hearing loss often demonstrate decreased sound localization ability and report that situations requiring spatial hearing are especially challenging. Few studies have evaluated localization abilities combined with training in this population. The present pilot study examined whether localization of two sound types would improve after training, and explored the relation between localization ability or training benefit and demographic factors. Eleven participants with unilateral severe to profound hearing loss attended five training sessions; localization cues gradually decreased across sessions. Localization ability was assessed pre- and post-training. Assessment stimuli were monosyllabic words and spectral and temporal random spectrogram sounds. Root mean square errors for each participant and stimulus type were used in group and correlation analyses; individual data were examined with ordinary least squares regression. Mean pre- to post-training test results were significantly different for all stimulus types. Among the participants, eight significantly improved following training on at least one localization measure, whereas three did not. Participants with the poorest localization ability improved the most and likewise, those with the best pre-training ability showed the least training benefit. Correlation results suggested that test age, age at onset of severe to profound hearing loss and better ear high frequency audibility may contribute to localization ability. Results support the need for continued investigation of localization training efficacy and consideration of localization training within rehabilitation protocols for individuals with unilateral severe to profound hearing loss.

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months’ post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

Determine whether auditory cortex (AC) organization changed following eighth cranial nerve surgery in adults with vestibular-cochlear nerve pathologies. We examined whether hearing thresholds before and after surgery correlated with increased ipsilateral activation of AC from the intact ear.During magnetic resonance imaging sessions before and 3 and 6 months after surgery, subjects listened with the intact ear to noise-like random spectrogram sounds.Departments of Radiology and Otolaryngology of Washington University School of Medicine.Three patients with acoustic neuromas received Gamma Knife radiosurgery (GK); 1 patient with Meniere's disease and 5 with acoustic neuromas had surgical resections (SR); 2 of the latter also had GK. Hearing thresholds in each ear were for pure tone stimuli from 250 to 8000 Hz before and after surgery (3 and 6 months). At the same intervals, we imaged blood oxygen level-dependent responses to auditory stimulation of the intact ear using an interrupted single-event design.Hearing thresholds in 2 of 3 individuals treated with GK did not change. Five of 6 individuals became unilaterally deaf after SRs. Ipsilateral AC activity was present before surgery in 6 of 9 individuals with ipsilateral spatial extents greater than contralateral in 3 of 9. Greater contralateral predominance was significant especially in left compared to right ear affected individuals, including those treated by GK.Lateralization of auditory-evoked responses in AC did not change significantly after surgery possibly due to preexisting sensory loss before surgery, indicating that less than profound loss may prompt cortical reorganization.

To determine changes in cortical neural networks as defined by resting-state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers.Cross-sectional study.Academic medical center.Participants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P.05, uncorrected) entered into a second-stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold-free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface-based reconstruction using Freesurfer.The median age for the 16 subjects was 54 years (range, 27-72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner.The absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors.

We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5years. In an event-related design, we studied blood oxygen level-dependent responses to studied ("old") compared to novel ("new") words. Presentation mode was in Braille or spoken. Responses were larger for identified "new" words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken "new" words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with "old"/"new" recognition. Left dorsolateral prefrontal cortex had larger responses to "old" words only with Braille. Larger occipital cortex responses to "new" Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for "new" words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering "old" words. A larger response when identifying "new" words possibly resulted from exhaustive recollecting the sensory properties of "old" words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a "sensory echo" that aids recollection.

The present fMRI study examined cortical activity to repeated vibrotactile sequences in 11 early blind and 11 sighted participants. All participants performed with >90% accuracy and showed practice induced improvement with faster reaction times in identifying matched and unmatched vibrotactile sequences. In blind only, occipital/temporal and parietal/somatosensory cortices showed practice induced reductions in positive BOLD amplitudes that possibly reflected repetition induced learning effects. The significant findings in occipital cortex of the blind indicated that perceptual processing of tactile inputs in visually deprived cortex is dynamic as response amplitudes changed with practice. Thus, stimulus processing became more efficient. It was hypothesized that the changes in occipital cortex of the blind reflected life-long skill in processing somatosensory inputs. Both groups showed activity reductions with practice in mid/posterior ventrolateral prefrontal cortex. These activity reductions suggested common stimulus-response learning associations for vibrotactile sequences in mid/posterior ventrolateral prefrontal cortex.

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned “old” and “new” rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes.

Studies examining the effect of soy protein on cardiovascular disease (CVD) risk factors have not taken advantage of the postprandial state as an adjunct to the fasting lipid profile. The American Heart Association has acknowledged the efficacy of soy protein in reducing CVD risk factors to be limited. We hypothesized that the postprandial state would be more sensitive to any favorable changes associated with consuming soy protein compared with the fasting lipid profile. Furthermore, the presence of isoflavones in soy would enhance this effect. Thirty sedentary males aged 18-30 years were randomly assigned to milk protein (Milk), isoflavone-poor soy (Soy-), or isoflavone-rich soy (Soy+). Usual diets were supplemented with 25 g/day of protein for 28 days. Serum samples were collected before and after supplementation in a fasted state and postprandially at 30, 60, 120, 240, and 360 min after a high-fat, 1,000 kcal shake. Triacylglycerol (TAG), total cholesterol, non-esterified fatty acids, apolipoproteins B-100 and A-I and glucose concentrations were quantified. Fasting concentrations were not different after any protein supplementation. Postprandial TAG and TAG AUC increased after Soy-consumption supporting the postprandial state as a more sensitive indicator of soy ingestion effects on CVD risk factors compared with the fasting lipid profile. Furthermore, the absence of isoflavones in soy protein may have deleterious consequences on purported cardio-protective effects.

Functional connectivity (fcMRI) was analyzed in individuals with spastic diplegia and age-matched controls. Pearson correlations (r-values) were computed between resting state spontaneous activity in selected seed regions (sROI) and each voxel throughout the brain. Seed ROI were centered on foci activated by tactile stimulation of the second fingertip in somatosensory and parietal dorsal attention regions. The group with diplegia showed significantly expanded networks for the somatomotor but not dorsal attention areas. These expanded networks overran nearly all topological representations in somatosensory and motor areas despite a sROI in a fingertip focus. A possible underlying cause for altered fcMRI in the group with dipegia, and generally sensorimotor deficits in spastic diplegia, is that prenatal third trimester white-matter injury leads to localized damage to subplate neurons. We hypothesize that intracortical connections become dominant in spastic diplegia through successful competition with diminished or absent thalamocortical inputs. Similar to the effects of subplate ablations on ocular dominance columns (Kanold and Shatz, Neuron 2006;51:627–638), a spike timing-dependent plasticity model is proposed to explain a shift towards intracortical inputs.

Motor deficits in cerebral palsy (CP) have been well documented; however, associated sensory impairment in CP remains poorly understood. We examined tactile object recognition in the hands using geometric shapes, common objects, and capital letters. Discrimination of tactile roughness was tested using paired horizontal gratings of varied groove widths passively translated across the index finger. We tested 17 individuals with hemiplegia (mean 13y 9mo [SD 5y 2mo]; 6 males, 11 females), 21 with diplegia (mean 14y 10mo [SD 7y]; 10 males, 11 females), and 21 without disabilities (mean 14y 10mo [SD 5y 1mo]; 11 males, 10 females). All participants with CP fell within level I or II of the Gross Motor Function Classification System and level I or II of the Manual Abilities Classification System. Individuals with CP were significantly less accurate compared with those without disabilities on all tactile object-recognition tasks using their non-dominant hand. Both groups of patients also had significantly higher thresholds for groove-width differences with both hands compared with those without disabilities. Within the group with diplegia, only roughness discrimination differed between hands, whereas within the group with hemiplegia, significant between-limb differences were present for all tasks. Despite mild motor deficits compared with the entire population of individuals with CP, this sample demonstrated ubiquitous tactile deficits.

The traditional lipid profile compared with nuclear magnetic resonance (NMR) may underestimate the risk for cardiovascular disease and may explain some of the discrepancies in results between studies analyzing the salubrious effects of soy. Our purpose was to compare the traditional lipid profile with NMR quantification of the number of lipoprotein particles, subclasses, and diameters or sizes in 30 sedentary males, between 18 and 30 years of age, consuming 1 of the following 3 supplements daily for 28 days: milk protein (Milk), isoflavone-poor soy protein (Soy–), or isoflavone-rich soy protein (Soy+). The study used a double-blind, parallel-arm design with random assignment to 1 of the 3 protein supplement groups. Fasting EDTA blood samples were collected at baseline and after 28 days of supplementation and analyzed for the number and size of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particles, respectively. Fasting serum samples were analyzed for concentrations of total cholesterol (TC), LDL cholesterol (LDL-C), total HDL cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides (TGs), free fatty acids (FFAs), and glucose. Fasting heparin blood samples were collected at baseline and after supplementation and analyzed for apolipoproteins A-I, A-II, B, C-II, C-III, and E, as well as hepatic and lipoprotein lipase concentrations. HDL3-C increased by 47.2% after Soy+ supplementation and hepatic lipase decreased 19.2% after Soy– supplementation (p < 0.05). HDL-C and apolipoproteins A-I and A-II were found to increase in all 3 groups (p < 0.05). Results support that NMR analysis of lipoprotein particle number and size are not more sensitive to the effect of soy protein on CVD risk compared with the traditional lipid profile. Furthermore, the lack of isoflavones in soy protein seems to have a deleterious effect on hepatic lipase.

We used fMRI to identify brain areas activated during tactile attention tasks. Participants detected the interval containing target stimulation of higher vibrotactile frequency or longer duration. Attributes were selectively or neutrally cued. A control backwards-counting task included concurrent, but irrelevant corresponding vibrotactile stimulation. Group analyses of average F-statistic maps, participant conjunction maps, and estimated time courses utilized data mapped to a standard average surface atlas (PALS B12). Repeated-measures, random-effects MANOVA examined blood oxygenation level-dependent (BOLD) signal modulation differences amongst tasks in defined regions, where significant responses occurred in at least 50% of the group. Greater than 0.1% increase in BOLD responses were found during at least one of the tactile attention tasks in contralateral parietal opercular OP1, BA 4 finger region, frontal eye field, dorsal premotor, anterior and posterior BA 7, and bilaterally in superior temporal sulcal cortex (BA 22), ventral premotor, supplementary motor area, and frontal operculum/insula. The same tasks suppressed activity in ipsilateral OP4. The BA 22 ROI showed larger responses during neutral cuing. The control task suppressed BOLD in ipsilateral OP1 and OP4 and bilaterally in BA 40, but significantly enhanced responses in dorsal parietal-frontal regions compared with tactile attention tasks. No regional differences were found between selectively cued frequency and duration tasks. Tactile attention effects were most prominent in OP1. Posterior parietal responses possibly reflected the visual attention required for backwards-counting, whereas the frontal regions potentially related to goal-directed behavior when identifying target stimulation.

We focused the present analysis on blood-oxygen-level-dependent responses evoked in four architectonic subdivisions of human posterior parietal operculum (PO) during two groups of tasks involving either vibrotactile stimulation or rubbing different surfaces against the right index finger pad. Activity localized in previously defined parietal opercular subdivisions, OP 1-4, was co-registered to a standard cortical surface-based atlas. Four vibrotactile stimulation tasks involved attention to the parameters of paired vibrations: (1) detect rare target trials when vibration frequencies matched; (2) select the presentation order of the vibration with a higher frequency or (3) longer duration; and (4) divide attention between frequency and duration before selecting stimulus order. Surface stimulation tasks involved various discriminations of different surfaces: (1) smooth surfaces required no discrimination; (2) paired horizontal gratings required determination of the direction of roughness change; (3) paired shapes entailed identifying matched and unmatched shapes; (4) raised letters involved letter recognition. The results showed activity in multiple somatosensory subdivisions bilaterally in human PO that are plausibly homologues of somatosensory areas previously described in animals. All tasks activated OP 1, but in vibrotactile tasks foci were more restricted compared to moving surface tasks. Greater spatial extents of activity especially in OP 1 and 4 when surfaces rubbed the finger pad did not support previously reported somatotopy of the second finger representation in "S2". The varied activity distributions across OP subdivisions may reflect low-level perceptual and/or cognitive processing differences between tasks.

Visual cortex activity in the blind has been shown in Braille literate people, which raise the question of whether Braille literacy influences cross-modal reorganization. We used fMRI to examine visual cortex activation during semantic and phonological tasks with auditory presentation of words in two late-onset blind individuals who lacked Braille literacy. Multiple visual cortical regions were activated in the Braille naive individuals. Positive BOLD responses were noted in lower tier visuotopic (e.g., V1, V2, VP, and V3) and several higher tier visual areas (e.g., V4v, V8, and BA 37). Activity was more extensive and cross-correlation magnitudes were greater during the semantic compared to the phonological task. These results with Braille naive individuals plausibly suggest that visual deprivation alone induces visual cortex reorganization. Cross-modal reorganization of lower tier visual areas may be recruited by developing skills in attending to selected non-visual inputs (e.g., Braille literacy, enhanced auditory skills). Such learning might strengthen remote connections with multisensory cortical areas. Of necessity, the Braille naive participants must attend to auditory stimulation for language. We hypothesize that learning to attend to non-visual inputs probably strengthens the remaining active synapses following visual deprivation, and thereby, increases cross-modal activation of lower tier visual areas when performing highly demanding non-visual tasks of which reading Braille is just one example.

Selective dorsal rhizotomy (SDR) is an effective treatment for lower extremity spasticity in cerebral palsy. Cortical organization in sensory cortex may be abnormal in cerebral palsy, and deafferentation is known to lead to cortical reorganization in many situations. We used functional magnetic resonance imaging (fMRI) of hand sensory stimulation to determine if the partial deafferentation of the lower extremity sensory system, associated with SDR, led to any alterations in the cortical somatosensory representation for the upper limbs. Three patients with spastic diplegia were studied with blood oxygen level-dependent (BOLD)-fMRI before and after SDR. fMRI during tactile stimulation of the digits of the right hand was used to map hand somatosensory cortex. Comparison of the cortical maps devoted to the hand before and after SDR assessed for cortical reorganization following partial deafferentation of the lower extremity. In the one patient with upper extremity involvement, the hand sensory representation was markedly enhanced following SDR. In the other two patients, a normal pattern, but with diminished activity, was seen compared with preoperative findings. SDR for lower limb spastic diplegia does not lead to extensive reorganization of cortex dedicated to the representation of the upper limb. An essentially normal pattern of activation was seen both before and after SDR. The relief of attention demands associated with spasticity may explain the modulation in intensity seen after SDR in the patients who exhibited no upper extremity involvement despite lower limb spasticity.

We studied whether default functionality of the human brain, as revealed by task-independent decreases in activity occurring during goal-directed behaviors, is functionally reorganized by blindness. Three groups of otherwise normal adults were studied: early blind, adventitiously blind, and normally sighted. They were imaged by using functional MRI during performance of a word association task (verb generation to nouns) administered by using auditory stimuli in all groups and Braille reading in blind participants. In sighted people, this task normally produces robust task-independent decreases relative to a baseline of quiet wakefulness with eyes closed. Our functional MRI results indicate that task-independent decreases are qualitatively similar across all participant groups in medial and dorsal prefrontal, lateral parietal, anterior precuneus, and posterior cingulate cortices. Similarities in task-independent decreases are consistent with the hypothesis that functional reorganization resulting from the absence of a particular sensory modality does not qualitatively affect default functionality as revealed by task-independent decreases. More generally, these results support the notion that the brain largely operates intrinsically, with sensory information modulating rather than determining system operations.

Brain imaging studies describe visual cortex activity in blind people during nonvisual tasks such as Braille reading, hearing words, or sensory discriminations of tactile or auditory stimuli [for literature citations see Burton et al. ([2002a][1],[b][2]) and Sadato et al. ([2002][3])]. Simply stated

The functional organization of somatosensory and motor cortex was investigated in an individual with a high cervical spinal cord injury, a 5-year absence of nearly all sensory/motor function at and below the shoulders, and rare recovery of some function in years 6–8 after intense and sustained rehabilitation therapies. We used functional magnetic resonance imaging to study brain activity to vibratory stimulation and voluntary movements of body parts above and below the lesion. No response to vibratory stimulation of the hand was observed in the primary somatosensory cortex (SI) hand area, which was conversely recruited during tongue movements that normally evoke responses only in the more lateral face area. This result suggests SI reorganization analogous to previously reported neuroplasticity changes after peripheral lesions in animals and humans. In striking contradistinction, vibratory stimulation of the foot evoked topographically appropriate responses in SI and second somatosensory cortex (SII). Motor cortex responses, tied to a visuomotor tracking task, displayed a near-typical topography, although they were more widespread in premotor regions. These findings suggest possible preservation of motor and some somatosensory cortical representations in the absence of overt movements or conscious sensations for several years after spinal cord injury and have implications for future rehabilitation and neural-repair therapies.

The purpose of this study was to determine whether initial muscle length influenced the extent of isometric force deficit following 20 in vitro lengthening contractions of the soleus muscle from Fischer 344 rats. Force deficit was evaluated following one of five protocols: (1) lengthening contractions from optimal muscle length (Lo) to 120% Lo; (2) lengthening contractions from 80% Lo to Lo; (3) lengthening contractions from Lo to 120% Lo but with a stimulation frequency that elicited the same force as protocol 2; (4) 20 isometric contractions at Lo; (5) 20 stretches +/- 20% Lo in inactive muscle. Following lengthening contractions, extent of force deficit significantly differed between protocols 1, 2, and 3 (P < 0.05). Maximal isometric force (Po) was decreased by approximately 32%, approximately 8%, and approximately 15% in protocols 1, 2, and 3, respectively. In contrast, neither isometric contractions nor passive stretching (protocols 4 and 5) resulted in any reduction in Po. Irrespective of muscle length, the extent of force deficit was highly correlated (R = -0.774, P < 0.001) with peak force during active lengthening. Thus, the magnitude of isometric force deficit following lengthening contractions is influenced by both initial muscle length and peak force development. These findings have important practical implications for both exercise conditioning and rehabilitation, which are discussed.

Karnes JL, Burton HW. Continuous therapeutic ultrasound accelerates repair of contraction-induced skeletal muscle damage in rats. Arch Phys Med Rehabil 2002;83:1-4. Objective: To examine the effect of ultrasonography on the repair of muscle injured through repeated eccentric contractions. Design: Randomized, case-control study. Setting: Laboratory animal facility. Animals: Thirty-three Sprague-Dawley rats. Interventions: Specimens were anesthetized and each foot strapped, in turn, onto a motorized foot pedal, which moved the ankle repeatedly through a range of 110°. Extensor digitorum longus muscles were injured by stimulating the peroneal nerve during foot plantarflexion. Continuous 1.0MHz ultrasound treatments at 0.5W/cm 2 were applied through water submersion technique to 1 limb daily for 3, 5, or 7 days postinjury. The contralateral limb served as an injured control. Main Outcome Measures: Extensor digitorum longus maximum isometric tetanic force (P o ) was measured in vitro from all extensor digitorum longus muscles and used as a functional index of muscle injury. Results: Analysis of variance and Tukey post hoc analysis showed no significant differences in P o between treated and untreated limbs at 3 and 5 days, but at 7 days postinjury, P o of ultrasound-treated muscle was significantly higher than was untreated muscle. Conclusion: Seven days of continuous therapeutic ultrasound improved force production after contraction-induced muscle injury. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity.

Monaural hearing induces auditory system reorganization. Imbalanced input also degrades time-intensity cues for sound localization and signal segregation for listening in noise. While there have been studies of bilateral auditory deprivation and later hearing restoration (e.g. cochlear implants), less is known about unilateral auditory deprivation and subsequent hearing improvement. We investigated effects of long-term congenital unilateral hearing loss on localization, speech understanding, and cortical organization following hearing recovery. Hearing in the congenitally affected ear of a 41 year old female improved significantly after stapedotomy and reconstruction. Pre-operative hearing threshold levels showed unilateral, mixed, moderately-severe to profound hearing loss. The contralateral ear had hearing threshold levels within normal limits. Testing was completed prior to, and three and nine months after surgery. Measurements were of sound localization with intensity-roved stimuli and speech recognition in various noise conditions. We also evoked magnetic resonance signals with monaural stimulation to the unaffected ear. Activation magnitudes were determined in core, belt, and parabelt auditory cortex regions via an interrupted single event design. Hearing improvement following 40 years of congenital unilateral hearing loss resulted in substantially improved sound localization and speech recognition in noise. Auditory cortex also reorganized. Contralateral auditory cortex responses were increased after hearing recovery and the extent of activated cortex was bilateral, including a greater portion of the posterior superior temporal plane. Thus, prolonged predominant monaural stimulation did not prevent auditory system changes consequent to restored binaural hearing. Results support future research of unilateral auditory deprivation effects and plasticity, with consideration for length of deprivation, age at hearing correction, degree and type of hearing loss.

Neuronal responses in somatosensory cortical areas 3b and 1-2 (S1) were recorded during an attention task involving cue directed selection of one of three simultaneous stimuli: dual sinewave shaped vibrotactile stimuli applied to mirror sites on both hands or a similarly timed auditory tone. The cued stimulus occurred with one of two equally probable patterns: a constant amplitude vibration or the latter with a superimposed brief sinewave amplitude pulse midway during stimulation. Uncued stimuli always contained amplitude pulses. Two monkeys signaled the absence or presence of an amplitude pulse by appropriately moving a foot pedal up or down. Cues initiated trials by marking the location where the monkey had to discriminate the stimulus pattern. Cue location and stimulus pattern varied randomly per trial. Approximately 50% of cells (44/77 in 3b and 39/77 in 1-2) had significantly different firing rates to stimulation cued to the contralateral hand relative to spatially cuing the ipsilateral hand or cross-modally the auditory stimulus. Relatively suppressed firing rates during times prior to the epoch containing amplitude pulses improved signal-to-noise ratios for responses to amplitude pulses. Instances of significant enhanced activity during and after intervals with amplitude pulses were rare and relative to suppressed activity when cues directed attention to the ipsilateral hand or auditory stimulus. The present findings suggest that attention influences even the earliest stage somatosensory cortical processing. Findings were more modest in S1 than those previously seen in S2 (Burton et al., Somatosens Mot Res 14: 237-267, 1997), which supports the concept of multistage attention processes for touch.

We used positron emission tomography to study cortical regions mediating tactile attention. Cues selectively directed subjects to attend to the roughness or duration of contact with embossed gratings that rubbed against a single fingertip with controlled speed and force. The task required discriminating between paired gratings that differed in tactile features of roughness and/or length. For different blocks of trials, cues directed attention to one tactile feature or indicated a divided attention strategy to a change in either feature. All attention conditions unambiguously activated several somatosensory foci in the parietal cortex, including somatotopically appropriate portions of the primary somatosensory cortex in the postcentral gyrus (S1) and the secondary somatosensory region (S2) within parietal opercular regions. There was no evidence for separate processing foci for selective and divided attention strategies, or for selectively attending to roughness versus stimulus duration. We observed a greater magnitude blood flow change in S2 versus S1 during attention tasks, which suggests that S2 might actually influence S1 activity. Despite these differences, modulation of S1 and S2 supports concepts of early selection in tactile attention. There were also examples of non-sensory foci in frontal cortex, anterior cingulate gyrus and bilateral superior parietal regions at the fundus of the postcentral sulcus. Posterior parietal regions observed in this study did not overlap foci seen in studies of visual attention. Thus, the posterior parietal region may be subdivided into modality-specific subregions, each of which processes information needed to attend to a specific modality. These non-sensory areas may constitute a network that provides a source of modulating influences on the earlier stage, sensory areas.

This study examined the architectonic organization of the macaque's primary somatosensory cortex near the tip of the intraparietal sulcus (IPS), using myelin and Nissl stains plus immunohistochemical labeling with the SMI-32 antibody. The surface cortex between the IPS and central sulcus (overlapping area 2) was distinguished from surrounding cortex (areas 1 post-central dimple and cortex immediately anterior to the tip of the IPS. Physiological mappings verified that the and 5) by relatively light SMI-32 immunoreactivity. This distinguishing architectonic feature was most evident between the architectonic transition correlated with a change in receptive field properties, consistent with their marking the boundary between areas 2 and 5. These results suggest that area 2 occupies surface cortex anterior to the IPS, but not within the IPS.

This study examined cortical connections of areas 3b and 1 in 17 macaque monkeys in reference to regional somatotopography. The fluorescent retrograde tracers Fast Blue and Diamidino Yellow and the anterograde tracer Rhodamine Dextran were injected into closely related cutaneously responsive sites in primary somatosensory cortex, e. g., adjacent digits. Supra- and infragranular layers in nearly all studied areas contained labeled pyramidal cells. Labeled infragranular cells predominated at the fringes of a distribution where cells labeled from different tracer injections in the same brain intermixed more. All topographical regions across area 1 have reciprocal connections with areas 4, 3a, 3b, 1, 2, and 5. Intrinsic connections within area 1 and between it and area 2 are greatest; those with area 3b are less. Intrinsic connections within area 3b exceed all other nearby projections from this area which reciprocally connects with areas 3a, 1 and 2. Connections appear topographically organized, including those with poorly mapped regions, like area 5. These connections link representations of neighboring skin and skip map regions that include disjoint dermatomal areas. Connections from adjacent digit representations overlap; however, double-labeled cells were not found. Distal and proximal digit zones mostly interconnect within an area. Intrinsic connections spread further in area 1 than in area 3b, thereby joining more disparate topographical zones than interareal connections, which project more homotopically. The domain over which the map in somatosensory cortical area I (SI) dynamically changes following in tracortical microstimulation (Recanzone, Merzenich and Dinse, Cerebral Cortex 2:181-196, 1992) may depend on the range of intrinsic connections observed in this study. The extent of connections between cortical areas was less than expected and this challenges the hypothesis that these connections directly create receptive field enlargements.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

To assess functional connectivity in cortical networks in patients with nonbothersome tinnitus compared with a normal healthy nontinnitus control group by measuring low-frequency (0.1 Hz) spontaneous blood oxygenation level-dependent (BOLD) signals at rest.Case-control.Academic medical center.Nonbothersome, idiopathic subjective tinnitus for at least 6 months (n = 18) and a normal healthy nontinnitus control group (n = 23).Functional connectivity differences in 58 a priori selected seed regions of interest encompassing cortical loci in the default mode, attention, auditory, visual, somatosensory, and cognitive networks.The median age of the 18 subjects was 54 years (interquartile range [IQR], 52-57), 66% were male, 90% were white, median Tinnitus Handicap Inventory (THI) score was 8 (IQR, 4-14), and a median Beck Depression Index score was 1 (IQR, 0-5). The median age for the control group was 46 years (IQR, 39-54), and 52% were male. Of the 58 seeds analyzed, no regions had significantly different functional connectivity among the nonbothersome tinnitus group when compared with the control group.Among nonbothersome tinnitus patients, the tinnitus percept does not appear to alter the functional connectivity of the auditory cortex or other key cortical regions. Trial Registration ClinicalTrials.gov Identifier: NCT01049828.

We studied activation magnitudes in core, belt, and parabelt auditory cortex in adults with normal hearing (NH) and unilateral hearing loss (UHL) using an interrupted, single-event design and monaural stimulation with random spectrographic sounds. NH patients had one ear blocked and received stimulation on the side matching the intact ear in UHL. The objective was to determine whether the side of deafness affected lateralization and magnitude of evoked blood oxygen level-dependent responses across different auditory cortical fields (ACFs). Regardless of ear of stimulation, NH showed larger contralateral responses in several ACFs. With right ear stimulation in UHL, ipsilateral responses were larger compared to NH in core and belt ACFs, indicating neuroplasticity in the right hemisphere. With left ear stimulation in UHL, only posterior core ACFs showed larger ipsilateral responses, suggesting that most ACFs in the left hemisphere had greater resilience against reduced crossed inputs from a deafferented right ear. Parabelt regions located posterolateral to core and belt auditory cortex showed reduced activation in UHL compared to NH irrespective of RE/LE stimulation and lateralization of inputs. Thus, the effect in UHL compared to NH differed by ACF and ear of deafness.

Background The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm3 brain volumes in 17 patients with moderate-severe bothersome tinnitus (Tinnitus Handicap Index: average 53.5 ± 3.6 (range 38-76)) and 17 age-matched controls. Results In bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex. Conclusions These results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.

Neurocognitive tests compared abilities in people with bothersome tinnitus against an age-, gender-, and education-matched normative population. Participants between 18 and 60 years had subjective, unilateral or bilateral, nonpulsatile tinnitus for >6 months and a Tinnitus Handicap Inventory score of ≥ 38. Results from a first testing session showed deficits in learning, learning rates, immediate recall of heard words, and use of a serial order encoding strategy. Initial reliance on serial order encoding and, later, increased intrusion of incorrect words towards normal levels might indicate a less demanding strategy to compensate for weakness in associative memory for semantic categories.

Positron emission tomographic measurements were used to study the distribution of focal changes in cerebral blood flow (CBF) induced by vibrotactile stimulation of the hands and feet in 22 normal humans. Subjects received bolus intravenous saline injections containing approximately 60 mCi 15O-labeled water. Active regions during stimulation were defined relative to resting, nonstimulated states. Scan data from different subjects were averaged after stereotactic standardization. The results identified previously described foci of increased CBF in postrolandic sensory cortex (primary somatosensory cortex) and supplementary motor cortex. New statistical testing procedures provided independent demonstrations of two additional increases in regional CBF, bilaterally, within the sylvian fissure. One site along the parietal operculum corresponded to previous conjectures about a second somatosensory cortical area (SII) in humans. Another site also was found on the insula. No topographic organization was found in either location. The discussion considers these responsive areas to innocuous tactile stimuli in reference to suggestions about a role for SII in the perception of pain.

Somatosensory deficits have been identified in cerebral palsy (CP), but associated cortical brain activity in CP remains poorly understood. Functional MRI was used to measure blood oxygenation level-dependent (BOLD) responses during three tactile tasks in 10 participants with spastic diplegia (mean age: 18.70 years, SD: 7.99 years; 5 females) and 10 age-matched controls (mean age: 18.60 years, SD: 3.86 years; 5 females). Tactile stimulation involved servo-controlled translation of smooth or embossed surfaces across the right index finger pad; the discrimination tasks with embossed surfaces involved judging whether (1) paired shapes were similar or different, and (2) a rougher set of horizontal gratings preceded or followed a smoother one. Velocity and duration of surface translation was identical across all trials. In addition, an event-related design revealed response dynamics per trial in both groups. Compared to controls, individuals with spastic diplegia had significantly reduced spatial extents in activated cortical areas and smaller BOLD response magnitudes in cortical areas for somatosensation, motor, and goal-directed/attention behaviors. These results provide mechanisms for the widespread somatosensory deficits in CP. The reduced activation noted across multiple cortical areas might contribute to motor deficits in CP.

This paper describes the use of an action research model to effect curricular change--specifically, to develop a core curriculum that prepares public health and health professions students to meet emerging needs in today's health care environment. The action research process is based on a series of steps wherein the problem is identified, data are collected and interpreted, action is taken, and action is reflected upon. These steps are then repeated. Consensus building proceeds as participants engage in continual analysis and implementation of changes, followed by more analysis. This process led to the emergence of three core content focus areas: Population, Wellness and Disability; Evidence-Based Practice; and Communication and Professionalism. "Focus Area Working Groups" were established to further delineate each content area. These groups initially developed 62 learning objectives across the three focus areas. Those objectives were subsequently distilled and refined, resulting in 25 "Core Essentials" that now define the core curriculum and serve as content guides rather than prescriptive learning objectives. The action research model proved to be beneficial in helping faculty from diverse health disciplines build consensus as they identified common professional and interprofessional learning needs.

In blind, occipital cortex showed robust activation to non-visual stimuli in many prior functional neuroimaging studies. The cognitive processes represented by these activations are not fully determined, although a verbal recognition memory role has been demonstrated. In congenitally blind and sighted (10 per group) we contrasted responses to a vibrotactile one-back frequency retention task with 5s delays and a vibrotactile amplitude-change (A–C) task; both tasks involved the same vibration parameters. The one-back paradigm required continuous updating for working memory (WM). Findings in both groups confirmed roles in WM for right hemisphere dorsolateral prefrontal (DLPFC) and dorsal/ventral attention components of posterior parietal cortex (PPC). Negative findings in bilateral ventrolateral prefrontal cortex suggested task performance without sub-vocalization. In bilateral occipital cortex, blind showed comparable positive responses to both tasks whereas WM evoked large negative responses in sighted. Greater utilization of attention resources in blind were suggested as causing larger responses in dorsal and ventral attention systems, right DLPFC, and persistent responses across delays between trials in somatosensory and premotor cortex. In sighted, responses in somatosensory and premotor areas showed iterated peaks matched to stimulation trial intervals. The findings in occipital cortex of blind suggest that tactile activations do not represent cognitive operations for non-verbal WM task. However, these data suggest a role in sensory processing for tactile information in blind that parallels a similar contribution for visual stimuli in occipital cortex of sighted.

Wingert JR, Burton H, Sinclair RJ, Brunstrom JE, Damiano DL. Joint-position sense and kinesthesia in cerebral palsy. Objectives To examine joint-position sense and kinesthesia in all extremities in participants with diplegic or hemiplegic cerebral palsy (CP). Design Survey of joint-position sense and kinesthesia differences between aged-matched controls and 2 groups with CP. Setting University movement assessment laboratory. Participants Population-based sample of participants with CP, diplegia (n=21), hemiplegia (n=17), and age-matched volunteers (n=21) without neurologic disease. Interventions Not applicable. Main Outcome Measures Joint-position sense and kinesthesia were measured in the transverse plane (forearm pronation/supination and hip internal/external rotation) using a custom-built device. For joint-position sense, participants actively rotated the tested limb to align the distal end with 10 target positions first with the limb and targets visible to assess their ability to perform the task motorically. The task was then repeated with vision of the limb occluded, with targets remaining visible. Joint-position sense error was determined by the magnitude and direction of the rotation errors for each limb in the vision and no vision conditions. Kinesthesia was evaluated by the ability to detect passive limb rotation without vision. Results No group differences were detected in the vision condition. Indicative of joint-position sense deficits, a significant increase in errors was found in the no vision condition in all limbs except the dominant upper limb for both groups with CP. Joint-position sense errors were systematically biased toward the direction of internal rotation. Kinesthesia deficits were evident on the nondominant upper limb in diplegia and hemiplegia, and bilaterally in the lower limbs in hemiplegia. In hemiplegia, joint-position sense and kinesthesia deficits were noted on the dominant limbs, but were significantly worse on the nondominant limbs. Conclusions These results indicate that people with CP have proprioception deficits in all limbs.

The organization of ipsilateral cortical connections of the rat primary somatic sensory area (SI) was analyzed following small injections of multiple fluorescent tracers in the same case, into two or three SI body representations identified electrophysiologically. Labeling patterns were studied in tangential cortical sections and in flattened reconstructions from coronal sections. The cytochrome oxidase staining in tangential sections served as a control for injection location and to position labeling patterns found within granular portion of SI. The results show that most connections made with SI are reciprocal. Their topographical organization show different degrees of precision in the different areas. Homotypical and heterotypical connections were defined, the latter being more evident within the granular portion of SI. The findings: (1) were consistent with subdividing rat SI into four distinct areas with each having its own pattern of connections, (2) revealed two topographically organized regions in parietal cortex lateral to SI called second somatosensory (SII) and parietal ventral (PV) areas, (3) confirmed a topographical pattern in motor cortex and suggested an organization for connections between SI and an agranular medial field, and (4) demonstrated three more regions in parietal cortex connected to SI: posterior to SI called parietal medial; lateral to PV called parietal rhinal; posterior to SII called parietal lateral. Differences were noted in the distinctions between and within the maps when label distributions were plotted separately from supra- and infragranular layers. These findings agree with previous parcellations of the rat SI (Chapin et al., '87: J. Comp Neurol 263:326-346), squirrel PV and SII (Krubitzer et al., '86: J. Comp Neurol 250:403-430), and the organization of rat corticospinal neurons in many of the same areas (Li et al., '90: Somat Motor Res 7:315-335).

During manual sensing of object attributes like surface texture, the tactile receptor sheet is conjointly activated at numerous loci. What is the role of spatially selective attention in perception under these conditions? We show that the requirement for spatial focus of attention is minimal in the detection of an abrupt change in texture. In contrast, spatial attention may help in a variety of other tasks of comparable difficulty. These include detecting the absence of a texture change at one of many loci, distinguishing its direction, and discriminating between different textures. Attentional demand appears to vary along a continuum in these tasks, rather than being all-or-none.

Selective spatial attention has a greater effect on detection of the absence of an amplitude change than it has on detection of the presence of such a change. Attention to one of four fingertips was manipulated by an 80% valid tactile cue in two-interval forced-choice tasks. In one task, the target was a vibrotactile amplitude change appearing among constant-amplitude distractors; in the other task, targets of constant amplitude had to be detected amid amplitude changes at the other fingertips. Cuing had a greater effect on the latter task than it did on the former. This asymmetry is consistent with the presence-absence asymmetry found in visual search and does not depend on the difficulty of the two tasks. A statistical model shows that a pooled activity mechanism could account for these experimental results.

Single neuron responses from the second somatosensory cortical area (SII) of macaque monkeys were studied using computer-controlled vibratory stimuli ranging in frequency from 10 to 300 Hz. Results were obtained using chronic recording techniques in awake or lightly tranquilized animals. Most neurons were unable to follow the temporal order of vibrations in excess of 10 Hz. A smaller sample of cells provided faithful reproduction of frequencies up to 50–75 Hz and another responded to low amplitude, high frequency stimulation in excess of 100 Hz. Cells that displayed temporally cohesive responses to lower frequencies demonstrated predictable, time-locked discharges to successive stimulus cycles. Cells activated by higher frequencies showed a lower probability of following successive stimulus cycles. These findings are discussed in reference to the hypothesis that SII may provide a parallel channel for processing high frequency vibrotactile inputs from Pacinian receptors.

Thalamocortical connections between ipsilateral thalamus and the first somatic sensory area were traced with simultaneous injections of different fluorescent tracers. Labeled neuronal elements in the antero-medial part (POm) of the posterior nucleus (PO) were topographically organized as an up-right body representation that mirrored a map in the ventroposterior nuclei (VP). No topography was observed in the posterior part of PO. These findings suggest POm in rodents provides precisely organized projections, parallel with those from VP.

Adrenergic neurons from the superior cervical ganglion of the neonatal rat, when studied under certain culture conditions, develop cholinergic properties including hexamethonium-sensitive synaptic interactions, choline acetyltransferase activity and synaptic endings containing clear vesicles. Evidence from correlative biochemical, physiological and morphological studies on populations of neurons indicates that cholinergic function is acquired by the majority of neurons and not by subpopulation. The factors that influence the development of cholinergic function in culture include the presence of non-neuronal cells, the addition of human placental serum and chick embryo extract to the culture medium as well as the stage of development at which the neurons are placed in culture. Neurons from mature rats, maintained as explants in culture, develop low choline acetyltransferase activity and the synaptic endings containing dense-cored vesicles. In contrast, if dissociated, these adult neurons develop several cholinergic characteristics. Studies to determine which adrenergic properties are retained in neurons expressing cholinergic characteristics have shown an increase in the activities of tyrosine hydroxylase and dopamine beta-hydroxylase in both explanted and dissociated perinatal neurons. In addition, tyrosine hydroxylase has been localized immunocytochemically in neurons identified as cholinergic by electrophysiological methods.

Reading Braille activates visual cortex in blind people [Burton et al., J Neurophysiol 2002;87: 589-611; Sadato et al., Nature 1996;380:526-528; Sadato et al., Brain 1998;121:1213-1229]. Because learning Braille requires extensive training, we had sighted and blind people read raised block capital letters to determine whether all groups engage visual cortex similarly when reading by touch. Letters were passively rubbed across the right index finger at 30 mm/s using an MR-compatible drum stimulator. Age-matched sighted, early blind (lost sight 0–5 years), and late blind (lost sight >5.5 years) volunteers performed three tasks: stating an identified letter, stating a verb containing an identified letter, and feeling a moving smooth surface. Responses were voiced immediately after the drum stopped moving across the fingertip. All groups showed increased activity in visual areas V1 and V2 during both letter identification tasks. Blind compared to sighted participants showed greater activation increases predominantly in the parafoveal-peripheral portions of visuotopic areas and posterior parts of BA 20 and 37. Sighted participants showed suppressed activity in most of the same areas except for small positive responses bilaterally in V1, left V5/MT+, and bilaterally in BA 37/20. Blind individuals showed suppression of the language areas in the frontal cortex, while sighted individuals showed slight positive responses. Early blind showed a more extensive distribution of activity in superior temporal sulcal multisensory areas. These results show cross-modal reorganization of visual cortex and altered response dynamics in nonvisual areas that plausibly reflect mechanisms for adaptive plasticity in blindness.

Blind individuals show visual cortex activity during Braille reading. We examined whether such cross-modal activations reflect processing somatosensory stimuli independent of language by identifying cortical activity during a one-back vibrotactile matching task. Three groups (sighted, early-onset, and late-onset [>12 years] blind) detected whether paired vibrations (25 and 100 Hz), delivered to the right index finger, differed in frequency. Three successive paired vibrations, followed by a no-stimulation interval, were presented in a long event-related design. A fixed effects average z-score analysis showed increased activity throughout the visuotopic visual cortex, where it was mostly restricted to foveal and parafoveal eccentricities. Early blind showed the most extensive distribution of activity. Late blind exhibited activity mostly in similar regions but with declining response magnitudes with age of blindness onset. Three sighted individuals had suprathreshold activity in V1 but negative responses elsewhere in visual cortex. Mixed effects ANOVA confirmed group distinctions in defined regions (V1, V3, V4v, V7, LOC, and MT). These results suggest cross-modal adaptation to tactile stimulation in visual cortex independent of language processes. All groups showed increased activity in left primary (S1) and bilateral second somatosensory areas, but without response magnitude differences between groups throughout sensorimotor cortex. Early blind showed the greatest spatial extent of S1 activity. Blind participants had more extensive bilateral activity in anterior intraparietal sulcus and supramarginal gyrus. Extensive usage of touch in Braille reading may underlie observed S1 expansions in the reading finger representation. In addition, learned attentiveness to touch may explain similar expansion of parietal tactile attention regions.