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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.

Those with profound sensorineural hearing loss from single sided deafness (SSD) generally experience greater cognitive effort and fatigue in adverse sound environments. We studied cases with right ear, SSD compared to normal hearing (NH) individuals. SSD cases were significantly less correct in naming last words in spectrally degraded 8- and 16-band vocoded sentences, despite high semantic predictability. Group differences were not significant for less intelligible 4-band sentences, irrespective of predictability. SSD also had diminished BOLD percent signal changes to these same sentences in left hemisphere (LH) cortical regions of early auditory, association auditory, inferior frontal, premotor, inferior parietal, dorsolateral prefrontal, posterior cingulate, temporal-parietal-occipital junction, and posterior opercular. Cortical regions with lower amplitude responses in SSD than NH were mostly components of a LH language network, previously noted as concerned with speech recognition. Recorded BOLD signal magnitudes were averages from all vertices within predefined parcels from these cortex regions. Parcels from different regions in SSD showed significantly larger signal magnitudes to sentences of greater intelligibility (e.g., 8- or 16- vs. 4-band) in all except early auditory and posterior cingulate cortex. Significantly lower response magnitudes occurred in SSD than NH in regions prior studies found responsible for phonetics and phonology of speech, cognitive extraction of meaning, controlled retrieval of word meaning, and semantics. The findings suggested reduced activation of a LH fronto-temporo-parietal network in SSD contributed to difficulty processing speech for word meaning and sentence semantics. Effortful listening experienced by SSD might reflect diminished activation to degraded speech in the affected LH language network parcels. SSD showed no compensatory activity in matched right hemisphere parcels.

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.

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.

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.

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).

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.

Previous neuroimaging studies of language processing in blind individuals described cortical activation of primary (V1) and higher tier visual areas, irrespective of the age of blindness onset. Specifically, participants were given nouns and asked to generate an associated verb. These results confirmed the presence of adaptations in the visual cortex of blind people and suggested that these responses represented linguistic operations. The present functional magnetic resonance imaging study attempted to further characterize these responses as being preferential for semantic or phonological processing. Three groups of participants (sighted, earlyonset, and late-onset blind) heard lists of related words and attended to either a common meaning (semantic task) or common rhyme (phonological task) that linked the words. In all three groups, the semantic task elicited stronger activity in the left anterior inferior frontal gyrus and the phonological task evoked stronger activity bilaterally in the inferior parietal cortex and posterior aspects of the left inferior frontal gyrus. Only blind individuals showed activity in occipital, temporal, and parietal components of visual cortex. The spatial extent of visual cortex activity was greatest in early blind, who exhibited activation in all ventral and dorsal visual cortex subdivisions (V1 through MT) for both tasks. Preferential activation appeared for the semantic task. Late blind individuals exhibited responses in ventral and dorsal V1, ventral V2, VP and V8, but only for the semantic task. Our findings support prior evidence of visual cortex activity in blind people engaged in auditory language processing and suggest that this activity may be related to semantic processing.

Literacy for blind people requires learning Braille. Along with others, we have shown that reading Braille activates visual cortex. This includes striate cortex (V1), i.e., banks of calcarine sulcus, and several higher visual areas in lingual, fusiform, cuneus, lateral occipital, inferior temporal, and middle temporal gyri. The spatial extent and magnitude of magnetic resonance (MR) signals in visual cortex is greatest for those who became blind early in life. Individuals who lost sight as adults, and subsequently learned Braille, still exhibited activity in some of the same visual cortex regions, especially V1. These findings suggest these visual cortex regions become adapted to processing tactile information and that this cross-modal neural change might support Braille literacy. Here we tested the alternative hypothesis that these regions directly respond to linguistic aspects of a task. Accordingly, language task performance by blind persons should activate the same visual cortex regions regardless of input modality. Specifically, visual cortex activity in blind people ought to arise during a language task involving heard words. Eight early blind, six late blind, and eight sighted subjects were studied using functional magnetic resonance imaging (fMRI) during covert generation of verbs to heard nouns. The control task was passive listening to indecipherable sounds (reverse words) matched to the nouns in sound intensity, duration, and spectral content. Functional responses were analyzed at the level of individual subjects using methods based on the general linear model and at the group level, using voxel based ANOVA and t-test analyses. Blind and sighted subjects showed comparable activation of language areas in left inferior frontal, dorsolateral prefrontal, and left posterior superior temporal gyri. The main distinction was bilateral, left dominant activation of the same visual cortex regions previously noted with Braille reading in all blind subjects. The spatial extent and magnitude of responses was greatest on the left in early blind individuals. Responses in the late blind group mostly were confined to V1 and nearby portions of the lingual and fusiform gyri. These results confirm the presence of adaptations in visual cortex of blind people but argue against the notion that this activity during Braille reading represents somatosensory (haptic) processing. Rather, we suggest that these responses can be most parsimoniously explained in terms of linguistic operations. It remains possible that these responses represent adaptations which initially are for processing either sound or touch, but which are later generalized to the other modality during acquisition of Braille reading skills.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109–110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

Somatosensory representations occupy parietal postcentral gyral (S1) and lateral sulcal-opercular cortex (S2). To address the issue of possible multiple activation foci in these regions and possible differences due to stimulating skin directly or through an imposed tool, we studied changes in cerebral blood flow with positron emission tomography during passive tactile stimulation of one or two fingertips. Restrained fingers were rubbed with embossed gratings using a rotating drum stimulator in 11 subjects. For different scans, gratings touched the skin directly for optimal stimulation of cutaneous receptors (called skin mode stimulation) or indirectly through an imposed guitar plectrum snugly fitted to the same fingers (called tool mode stimulation). The latter was expected to stimulate deep receptors better. Subjects estimated roughness after each scan. Direct skin contact activated statistically validated foci in both hemispheres. On the contralateral side these foci occurred in the anterior and posterior limbs of the postcentral gyrus and on the ipsilateral side only in the posterior limb. Tool mode stimulation activated one contralateral focus that was in the posterior limb of the postcentral gyrus. These results suggest at least two maps for distal fingertips in S1 with the anterior and posterior foci corresponding, respectively, to activations in area 3b and the junction between areas 1 and 2. In contralateral S2, skin mode stimulation activated a peak that was anterior and medial to a focus associated with tool mode stimulation. The magnitude of PET counts contralateral to stimulation was greater in the anterior S1 and the S2 regions during initial scans but reversed to more activation in the posterior S1 during later scans. These short-term practice effects suggest changes in neural activity with stimulus novelty.

MRI revealed activation foci in human somatosensory cortex during protocols involving stimulation of the fingertips with a textured surface. A 2D T2*-weighted gradient echo sequence was used to acquire images. The imaging protocol included acquiring images while subjects performed specific tactile stimulation paradigms (activation scans) or rested. Three different paradigms were used to produce functional activation using a textured surface to rub the fingertips of one hand. First, motor sensory activation was produced by rubbing the textured surface held in one hand against the fingertips of the opposite hand only during the activation scans. Second, the hand holding the textured surface moved throughout the experiment but touched the fingertips of the opposite hand only during the activation scans. Third, subjects remained still in the magnet throughout the entire study while an investigator rubbed the textured surface against the subjects' fingertips during the activation scans. Images were postprocessed using a cross-correlation scheme. The results revealed multiple foci of motor sensory activation near the central sulcus, postcentral sulcus, and prefrontal cortex.

Publisher Summary This chapter considers the cerebral cortical areas responsible for low-threshold touch perception in primates. It emphasizes on cognitive factors in tactile perception, discusses receptive field organization in the cortex, and highlights the issues that may benefit from future study. On the basis of anatomical and physiological criteria, approximately ten parietal cortical areas involve somatosensory processing. These areas display separable cytoarchitecture and form a connected somatosensory network because they share thalamic and cortical connections. All ten areas respond in some way to cutaneous or deep receptor stimulation and most contain somatotopically-organized maps. The physiological perspective primarily focuses on the isolated elements responsible for perceptions of well-controlled tactile stimuli.

Responses of 66 neurons in primary somatosensory cortex (SI) of three anesthetized monkeys (Macaca mulatta) were characterized with grating patterns of 550- to 2900-mm groove width (Gw) and 250-mm ridge width, and/or pairs of 3-mm-wide ridges (bars) spaced 1-20 mm apart. Surfaces were stroked across single fingertips at parametrically varied levels of force (25-150 g) and velocity (25-100 mm/sec). The average firing rates (AFRs) of many cells varied with Gw, but force and velocity altered response functions (e.g., from linear to plateau or inverted). Slowly adapting (SA) cells were more sensitive to force, rapidly adapting (RA) cells to velocity. Force and velocity affected all cells sensitive to Gw, which suggests that response independence (e.g., AFR correlated with Gw but not force or velocity) may require active touch. Discharge intervals of many cells replicated stimulus temporal period. This temporal fidelity in SAs far exceeded examples reported for active touch. However, discharge burst duration and AFR increased with Gw, supporting a neural rate rather than temporal code for roughness. Force and velocity altered the Gw at which some cells fired once in phase to stimulus cycle ("tuning point"). Responses to bar edges suggest cortical replication of peripheral mechanoreceptor sensitivity to skin curvature, leading to this temporal fidelity in some cortical cells. Graded RA responses to Gw without obvious stimulus temporal replication may reflect early stages of integrative processing in supra- and infragranular layers that blur obvious temporal patterning and lead to a rate code correlated with spatial variation and proportional to perceived roughness.

Cortical connections between various body representations in areas 3b and 1 and lateral parietal cortex were examined in 18 macaque monkeys. We injected tracers (Fast Blue, Diamidino Yellow, Horseradish Peroxidase, and Rhodamine Dextran), alone or in combination, into closely related cutaneous responsive sites, e. g., adjacent digits. Separated patches of labeling were found across the parietal operculum and insula for all injected locations. On the basis of cytoarchitectural criteria, the labeled regions include the second somatosensory area (SH), retroinsular area (Ri) and granular insula (Ig). Assuming the connections are homotopical from physiologically identified body representations in primary somatosensory cortex, the labeling patterns in SII include complete anterior and posterior body maps. The orientation of the body is erect in the posterior and supine in the anterior SII region. Area 3b has greater density of connections with anterior SIL The maps are mirror images aligned along the distal extremities. The anterior-posterior (A-P) length of the “SII region” exceeds 7 mm; it extends in the coronal plane from the fundus of the lateral sulcus to surface cortex near the anterior tip of the intraparietal sulcus. Two additional topographically organized maps are likely in Ri. These are “worm-like” body maps oriented along the A-P axis and joined at the head representation. Connections with the center of Ig are not somatotopically organized. The diversity of somatosensory areas in lateral parietal cortex revealed by the labeled connections was discussed in reference to prior mapping of SII in monkeys and was compared to reports of multiple areas in this region of cortex in other species.