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Gender identity disorder (GID), or transsexualism as it is more commonly known, is a highly complex clinical entity. Although the exact aetiology of GID is unknown, several environmental, genetic and anatomical theories have been described. The diagnosis of GID can be a difficult process but is established currently using standards of care as defined by the Harry Benjamin International Gender Dysphoria Association. Patients go through extensive psychiatric assessment, including the Real Life Experience, which entails living in the desired gender role 24 h a day for a minimum period of 12 months. The majority of GID patients will eventually go on to have gender realignment surgery, which includes feminising genitoplasty. The clinical features, diagnostic approach and management of male-to-female GID in the UK are reviewed, including the behavioural, psychological and surgical aspects. [ABSTRACT FROM AUTHOR]

Among the various classes of fast-adapting (FA) tactile afferents found in hairy and glabrous skin, FA2 afferents, associated with Pacinian corpuscles (PC), preferentially signal high-frequency sinusoidal events corresponding with vibration percepts, in contrast to other classes associated with lower frequency flutter percepts. The FA2-PC complex is also uniquely sensitive to distant sources of vibration mechanically transmitted through anatomical structures. In the present study, we used a pulsatile waveform to assess the contribution of FA2 afferents to the perception of flutter-range frequency stimuli (~ 20 Hz) in combination with two methods to abolish local FA inputs and force a dependence on FA2 via transmission from adjacent structures. Firstly, we examined frequency discrimination and perception of vibration applied to the hairy skin overlying the ulnar styloid before and during the blockade of intradermal receptors by local anaesthesia. Secondly, we tested frequency discrimination on the digital glabrous skin before and during the blockade of myelinated fibres by ulnar nerve compression. Despite reliance on vibration transmission to activate remote PCs, we found that flutter-range frequency discrimination was unimpeded across both skin types. Comparisons with stimuli applied to the contralateral side also indicated that perceived frequency was unaffected. This confirms that flutter-range frequency perception can be encoded by the FA2-PC system. Our results demonstrate that input from receptors specialised for low-frequency signalling is not mandatory for flutter-range frequency perception. This explains how the constancy of frequency perception might be achieved across different skin regions, irrespective of the afferent type activated for transmitting these signals., Competing Interests: Declarations Competing financial interests Statement The authors declare no competing financial interests., (© 2024. The Author(s).)

In neural prostheses, intensity modulation of a single channel (i.e., through a single stimulating electrode) has been achieved by increasing the magnitude or width of each stimulation pulse, which risks eliciting pain or paraesthesia; and by changing the stimulation rate, which leads to concurrent changes in perceived frequency. In this study, we sought to render a perception of tactile intensity and frequency independently, by means of temporal pulse train patterns of fixed magnitude, delivered non-invasively. Our psychophysical study exploits a previously discovered frequency coding mechanism, where the perceived frequency of stimulus pulses grouped into periodic bursts depends on the duration of the inter-burst interval, rather than the mean pulse rate or periodicity. When electrical stimulus pulses were organised into bursts, perceived intensity was influenced by the number of pulses within a burst, while perceived frequency was determined by the time between the end of one burst envelope and the start of the next. The perceived amplitude was modulated by 1.6× while perceived frequency was varied independently by 2× within the tested range (20-40 Hz). Thus, the sensation of intensity might be controlled independently from frequency through a single stimulation channel without having to vary the injected electrical current. This can form the basis for improving strategies in delivering more complex and natural sensations for prosthetic hand users., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ng, So, Fang, Birznieks and Vickery.)

When manipulating objects, humans begin adjusting their grip force to friction within 100 ms of contact. During motor adaptation, subjects become aware of the slipperiness of touched surfaces. Previously, we have demonstrated that humans cannot perceive frictional differences when surfaces are brought in contact with an immobilised finger, but can do so when there is submillimeter lateral displacement or subjects actively make the contact movement. Similarly, in, we investigated how humans perceive friction in the absence of intentional exploratory sliding or rubbing movements, to mimic object manipulation interactions. We used a two-alternative forced-choice paradigm in which subjects had to reach and touch one surface followed by another, and then indicate which felt more slippery. Subjects correctly identified the more slippery surface in 87 ± 8% of cases (mean ± SD; n = 12). Biomechanical analysis of finger pad skin displacement patterns revealed the presence of tiny (<1 mm) localised slips, known to be sufficient to perceive frictional differences. We tested whether these skin movements arise as a result of natural hand reaching kinematics. The task was repeated with the introduction of a hand support, eliminating the hand reaching movement and minimising fingertip movement deviations from a straight path. As a result, our subjects' performance significantly declined (66 ± 12% correct, mean ± SD; n = 12), suggesting that unrestricted reaching movement kinematics and factors such as physiological tremor, play a crucial role in enhancing or enabling friction perception upon initial contact. KEY POINTS: More slippery objects require a stronger grip to prevent them from slipping out of hands. Grip force adjustments to friction driven by tactile sensory signals are largely automatic and do not necessitate cognitive involvement; nevertheless, some associated awareness of grip surface slipperiness under such sensory conditions is present and helps to select a safe and appropriate movement plan. When gripping an object, tactile receptors provide frictional information without intentional rubbing or sliding fingers over the surface. However, we have discovered that submillimeter range lateral displacement might be required to enhance or enable friction sensing. The present study provides evidence that such small lateral movements causing localised partial slips arise and are an inherent part of natural reaching movement kinematics., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. We investigated how torque information is encoded by human tactile afferents in the fingerpads and compared them to 97 afferents recorded in monkeys ( n = 3; 2 females) in our previous study. Human data included slowly-adapting Type-II (SA-II) afferents, which are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 human subjects (19 females). Torques were superimposed on a 2, 3, or 4 N background normal force. Unitary recordings were made from fast-adapting Type-I (FA-I, n = 39), and slowly-adapting Type-I (SA-I, n = 31) and Type-II (SA-II, n = 13) afferents supplying the fingerpads via microelectrodes inserted into the median nerve. All three afferent types encoded torque magnitude and direction, with torque sensitivity being higher with smaller normal forces. SA-I afferent responses to static torque were inferior to dynamic stimuli in humans, while in monkeys the opposite was true. In humans this might be compensated by the addition of sustained SA-II afferent input, and their capacity to increase or decrease firing rates with direction of rotation. We conclude that the discrimination capacity of individual afferents of each type was inferior in humans than monkeys which could be because of differences in fingertip tissue compliance and skin friction. SIGNIFICANCE STATEMENT We investigated how individual human tactile nerve fibers encode rotational forces (torques) and compared them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialized to encode directional skin strain yet, so far, torque encoding has only been studied in monkeys. We find that human SA-I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by SA-II afferent input. This indicates that variation in afferent types might complement each other signaling different stimulus features possibly providing computational advantage to discriminate stimuli., (Copyright © 2023 the authors.)

The perceived intensity of a vibrotactile stimulus is thought to depend on single-neuron firing rates (rate coding) and the number of active afferents (population coding). Unaddressed until now is whether the temporal relation of individual spikes also conveys information about tactile intensity. We used cutaneous electro-tactile stimulation to investigate how the temporal structure of a fixed number of spikes in a 1-s train influenced the perception of intensity. Four mean spike rates spanning the flutter and vibratory hum range (36 Hz, 60 Hz; 120 Hz, 180 Hz) were tested, with spikes grouped into a regular pattern, or bursts of 2-6 spikes spaced 3 ms apart. To link a putative neural code to perception, perceived intensity was assessed in 16 human participants (aged 20-45; 4 females) using the psychophysical paradigm of magnitude estimation. Compound sensory nerve action potentials were recorded to assess any stimulus variation in afferent recruitment. The temporal structuring of a fixed number of spikes into periodic bursts of multiple spikes altered perceived intensity as a function of burst spike count. The largest increase was seen at 36 Hz, where the bursts of six spikes were rated 2.1 times stronger than the regularly spaced spikes [95% confidence interval (CI): 1.9-2.3]. The true increase is likely larger as temporal structuring of spikes into bursts had some negative effect on afferent recruitment. We conclude that the perceived intensity can be modulated by changing temporal features of afferent discharge even when normalized for the number of recruited afferents. NEW & NOTEWORTHY Structuring a fixed number of spikes into temporal burst patterns evoke gradations of perceived intensity with burst spike count, emphasizing the importance of spike timing in primary afferents for shaping perception. This forms the basis for new strategies in communicating a range of intensity information to users of neural interfaces by simply varying the timing of spikes in nonspecific primary afferents using fixed-charge electric pulses, without requiring alterations in stimulation current or mean pulse frequency.

Both hearing and touch are sensitive to the frequency of mechanical oscillations-sound waves and tactile vibrations, respectively. The mounting evidence of parallels in temporal frequency processing between the two sensory systems led us to directly address the question of perceptual frequency equivalence between touch and hearing using stimuli of simple and more complex temporal features. In a cross-modal psychophysical paradigm, subjects compared the perceived frequency of pulsatile mechanical vibrations to that elicited by pulsatile acoustic (click) trains, and vice versa. Non-invasive pulsatile stimulation designed to excite a fixed population of afferents was used to induce desired temporal spike trains at frequencies spanning flutter up to vibratory hum (>50 Hz). The cross-modal perceived frequency for regular test pulse trains of either modality was a close match to the presented stimulus physical frequency up to 100 Hz. We then tested whether the recently discovered "burst gap" temporal code for frequency, that is shared by the two senses, renders an equivalent cross-modal frequency perception. When subjects compared trains comprising pairs of pulses (bursts) in one modality against regular trains in the other, the cross-sensory equivalent perceptual frequency best corresponded to the silent interval between the successive bursts in both auditory and tactile test stimuli. These findings suggest that identical acoustic and vibrotactile pulse trains, regardless of pattern, elicit equivalent frequencies, and imply analogous temporal frequency computation strategies in both modalities. This perceptual correspondence raises the possibility of employing a cross-modal comparison as a robust standard to overcome the prevailing methodological limitations in psychophysical investigations and strongly encourages cross-modal approaches for transmitting sensory information such as translating pitch into a similar pattern of vibration on the skin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharma, Ng, Birznieks and Vickery.)

When tactile afferents were manipulated to fire in periodic bursts of spikes, we discovered that the perceived pitch corresponded to the inter-burst interval (burst gap) in a spike train, rather than the spike rate or burst periodicity as previously thought. Given that tactile frequency mechanisms have many analogies to audition, and indications that temporal frequency channels are linked across the two modalities, we investigated whether there is burst gap temporal encoding in the auditory system. To link this putative neural code to perception, human subjects (n = 13, 6 females) assessed pitch elicited by trains of temporally-structured acoustic pulses in psychophysical experiments. Each pulse was designed to excite a fixed population of cochlear neurons, precluding place of excitation cues, and to elicit desired temporal spike trains in activated afferents. We tested periodicities up to 150 Hz using a variety of burst patterns and found striking deviations from periodicity-predicted pitch. Like the tactile system, the duration of the silent gap between successive bursts of neural activity best predicted perceived pitch, emphasising the role of peripheral temporal coding in shaping pitch. This suggests that temporal patterning of stimulus pulses in cochlear implant users might improve pitch perception., (© 2022. The Author(s).)

Human tactile perception and motor control rely on the frictional estimates that stem from the deformation of the skin and slip events. However, it is not clear how exactly these mechanical events relate to the perception of friction. This study aims to quantify how minor lateral displacement and speed enables subjects to feel frictional differences. In a 2-alternative forced-choice protocol, an ultrasonic friction-reduction device was brought in contact perpendicular to the skin surface of an immobilized index finger; after reaching 1N normal force, the plate was moved laterally. A combination of four displacement magnitudes (0.2, 0.5, 1.2 and 2 mm), two levels of friction (high, low) and three displacement speeds (1, 5 and 10 mm/s) were tested. We found that the perception of frictional difference was enabled by submillimeter range lateral displacement. Friction discrimination thresholds were reached with lateral displacements ranging from 0.2 to 0.5 mm and surprisingly speed had only a marginal effect. These results demonstrate that partial slips are sufficient to cause awareness of surface slipperiness. These quantitative data are crucial for designing haptic devices that render slipperiness. The results also show the importance of subtle lateral finger movements present during dexterous manipulation tasks.

It has been suggested that tactile intensity perception can be explained by a linear function of spike rate weighted by afferent type. Other than relying on mathematical models, verifying this experimentally is difficult due to the frequency tuning of different afferent types and changes in population recruitment patterns with vibrotactile frequency. To overcome these complexities, we used pulsatile mechanical stimuli which activate the same afferent population regardless of the repetition rate (frequency), generating one action potential per pulse. We used trains of different frequencies (20-200 Hz) to investigate perceived intensity. Subjects' magnitude ratings increased with pulse rate up to ∼100 Hz and plateaued beyond this frequency. This was true regardless of pulse amplitude, from small pulses that exclusively activated Pacinian (PC) afferents, to pulses large enough to activate other afferents including slowly adapting. Electrical stimulation, which activates afferents indiscriminately, plateaued at a similar frequency, although not in all subjects. As the plateauing did not depend on indentation magnitude and hence on afferent weights, we propose that the contribution of spike count to intensity perception is weighted by a function of frequency. This may explain why fine textures evoking high frequency vibrations of a small magnitude do not feel disproportionally intense.

Sensory suppression refers to the phenomenon that sensory input generated by our own actions, such as moving a finger to press a button to hear a tone, elicits smaller neural responses than sensory input generated by external agents. This observation is usually explained via the internal forward model in which an efference copy of the motor command is used to compute a corollary discharge, which acts to suppress sensory input. However, because moving a finger to press a button is accompanied by neural processes involved in preparing and performing the action, it is unclear whether sensory suppression is the result of movement planning, movement execution, or both. To investigate this, in two experiments, we compared ERPs to self-generated tones that were produced by voluntary, semivoluntary, or involuntary button-presses, with externally generated tones that were produced by a computer. In Experiment 1, the semivoluntary and involuntary button-presses were initiated by the participant or experimenter, respectively, by electrically stimulating the median nerve in the participant's forearm, and in Experiment 2, by applying manual force to the participant's finger. We found that tones produced by voluntary button-presses elicited a smaller N1 component of the ERP than externally generated tones. This is known as N1-suppression. However, tones produced by semivoluntary and involuntary button-presses did not yield significant N1-suppression. We also found that the magnitude of N1-suppression linearly decreased across the voluntary, semivoluntary, and involuntary conditions. These results suggest that movement planning is a necessary condition for producing sensory suppression. We conclude that the most parsimonious account of sensory suppression is the internal forward model., (© 2021 Massachusetts Institute of Technology.)

When presented with an oscillatory sensory input at a particular frequency, F [Hz], neural systems respond with the corresponding frequency, f [Hz], and its multiples. When the input includes two frequencies (F1 and F2) and they are nonlinearly integrated in the system, responses at intermodulation frequencies (i.e., n1*f1+n2*f2 [Hz], where n1 and n2 are non-zero integers) emerge. Utilizing these properties, the steady state evoked potential (SSEP) paradigm allows us to characterize linear and nonlinear neural computation performed in cortical neurocircuitry. Here, we analyzed the steady state evoked local field potentials (LFPs) recorded from the primary (S1) and secondary (S2) somatosensory cortex of anesthetized cats (maintained with alfaxalone) while we presented slow (F1 = 23Hz) and fast (F2 = 200Hz) somatosensory vibration to the contralateral paw pads and digits. Over 9 experimental sessions, we recorded LFPs from N = 1620 and N = 1008 bipolar-referenced sites in S1 and S2 using electrode arrays. Power spectral analyses revealed strong responses at 1) the fundamental (f1, f2), 2) its harmonic, 3) the intermodulation frequencies, and 4) broadband frequencies (50-150Hz). To compare the computational architecture in S1 and S2, we employed simple computational modeling. Our modeling results necessitate nonlinear computation to explain SSEP in S2 more than S1. Combined with our current analysis of LFPs, our paradigm offers a rare opportunity to constrain the computational architecture of hierarchical organization of S1 and S2 and to reveal how a large-scale SSEP can emerge from local neural population activities., Competing Interests: The authors have declared that no competing interests exist.

Perceived frequency of vibrotactile stimuli can be divided into two distinctive cutaneous sensations-flutter (<60 Hz) and vibratory hum (>60 Hz), mediated by two different tactile afferent types [fast adapting type I (FA1) and fast adapting type II (FA2), respectively]. We recently demonstrated a novel form of neural coding in the human tactile system, where frequency perception of stimulus pulses grouped into periodic bursts in the flutter range depended on the duration of the silent gap between bursts, rather than the periodicity or mean impulse rate. Here, we investigated whether this interburst interval could also explain the perceived frequency of electrocutaneous pulse patterns delivered at frequencies above the flutter range. At stimulus rates of 50 to 190 pulses/s, the burst gap model correctly predicted the perceived frequency. This shows that the burst gap code represents a general coding strategy that spans the range of frequencies traditionally attributed to two different tactile channels. NEW & NOTEWORTHY We present evidence for a generalized frequency processing strategy on tactile afferent inputs that is shared across a broad range of frequencies extending beyond the flutter range, supporting the notion that spike timing has an important role in shaping tactile perception.

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organized by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organization and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organization, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibers, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organization and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information., (© 2020 Wiley Periodicals, LLC.)

We have previously described a novel temporal encoding mechanism in the somatosensory system, where mechanical pulses grouped into periodic bursts create a perceived tactile frequency based on the duration of the silent gap between bursts, rather than the mean rate or the periodicity. This coding strategy may offer new opportunities for transmitting information to the brain using various sensory neural prostheses and haptic interfaces. However, it was not known whether the same coding mechanisms apply when using electrical stimulation, which recruits a different spectrum of afferents. Here, we demonstrate that the predictions of the burst gap coding model for frequency perception apply to burst stimuli delivered with electrical pulses, re-emphasising the importance of the temporal structure of spike patterns in neural processing and perception of tactile stimuli. Reciprocally, the electrical stimulation data confirm that the results observed with mechanical stimulation do indeed depend on neural processing mechanisms in the central nervous system, and are not due to skin mechanical factors and resulting patterns of afferent activation., Competing Interests: The authors have declared that no competing interests exist.

The temporal pattern of action potentials can convey rich information in a variety of sensory systems. We describe a new non-invasive technique that enables precise, reliable generation of action potential patterns in tactile peripheral afferent neurons by brief taps on the skin. Using this technique, we demonstrate sophisticated coding of temporal information in the somatosensory system, that shows that perceived vibration frequency is not encoded in peripheral afferents as was expected by either their firing rate or the underlying periodicity of the stimulus. Instead, a burst gap or silent gap between trains of action potentials conveys frequency information. This opens the possibility of new encoding strategies that could be deployed to convey sensory information using mechanical or electrical stimulation in neural prostheses and brain-machine interfaces, and may extend to senses beyond artificial encoding of aspects of touch. We argue that a focus on appropriate use of effective temporal coding offers more prospects for rapid improvement in the function of these interfaces than attempts to scale-up existing devices., (Copyright © 2020 Vickery, Ng, Potas, Shivdasani, McIntyre, Nagi and Birznieks.)

The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies < 60 Hz) and vibratory hum (frequencies > 60 Hz), subserved by two distinct receptor types (Meissner's and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types., Competing Interests: IB, SM, HN, SN, VM, DM, RV No competing interests declared, (© 2019, Birznieks et al.)

Concept and knowledge maps have been shown to improve students' learning by emphasising meaningful relationships between phenomena. A user-friendly online tool that enables assessment of students' maps with automated feedback might therefore have significant benefits for learning. For that purpose, we developed an online software platform known as Knowledge Maps. Two pilot studies were performed to evaluate the usability and efficacy of Knowledge Maps. Study A demonstrated significantly improved perceptions of learning after using Knowledge Maps to learn pathology. Study B showed significant improvement between pre-test and post-test scores in an anatomy course. These preliminary studies indicate that this software is readily accepted and may have potential benefits for learning., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2019.)

The brainstem dorsal column nuclei (DCN) are essential to inform the brain of tactile and proprioceptive events experienced by the body. However, little is known about how ascending somatosensory information is represented in the DCN. Our objective was to investigate the usefulness of high-frequency (HF) and low-frequency (LF) DCN signal features (SFs) in predicting the nerve from which signals were evoked. We also aimed to explore the robustness of DCN SFs and map their relative information content across the brainstem surface. DCN surface potentials were recorded from urethane-anesthetized Wistar rats during sural and peroneal nerve electrical stimulation. Five salient SFs were extracted from each recording electrode of a seven-electrode array. We used a machine learning approach to quantify and rank information content contained within DCN surface-potential signals following peripheral nerve activation. Machine-learning of SF and electrode position combinations was quantified to determine a hierarchy of information importance for resolving the peripheral origin of nerve activation. A supervised back-propagation artificial neural network (ANN) could predict the nerve from which a response was evoked with up to 96.8 ± 0.8% accuracy. Guided by feature-learnability , we maintained high prediction accuracy after reducing ANN algorithm inputs from 35 (5 SFs from 7 electrodes) to 6 (4 SFs from one electrode and 2 SFs from a second electrode). When the number of input features were reduced, the best performing input combinations included HF and LF features. Feature-learnability also revealed that signals recorded from the same midline electrode can be accurately classified when evoked from bilateral nerve pairs, suggesting DCN surface activity asymmetry. Here we demonstrate a novel method for mapping the information content of signal patterns across the DCN surface and show that DCN SFs are robust across a population. Finally, we also show that the DCN is functionally asymmetrically organized, which challenges our current understanding of somatotopic symmetry across the midline at sub-cortical levels.

Skin vibrations sensed by tactile receptors contribute significantly to the perception of object properties during tactile exploration [1-4] and to sensorimotor control during object manipulation [5]. Sustained low-frequency skin vibration (<60 Hz) evokes a distinct tactile sensation referred to as flutter whose frequency can be clearly perceived [6]. How afferent spiking activity translates into the perception of frequency is still unknown. Measures based on mean spike rates of neurons in the primary somatosensory cortex are sufficient to explain performance in some frequency discrimination tasks [7-11]; however, there is emerging evidence that stimuli can be distinguished based also on temporal features of neural activity [12, 13]. Our study's advance is to demonstrate that temporal features are fundamental for vibrotactile frequency perception. Pulsatile mechanical stimuli were used to elicit specified temporal spike train patterns in tactile afferents, and subsequently psychophysical methods were employed to characterize human frequency perception. Remarkably, the most salient temporal feature determining vibrotactile frequency was not the underlying periodicity but, rather, the duration of the silent gap between successive bursts of neural activity. This burst gap code for frequency represents a previously unknown form of neural coding in the tactile sensory system, which parallels auditory pitch perception mechanisms based on purely temporal information where longer inter-pulse intervals receive higher perceptual weights than short intervals [14]. Our study also demonstrates that human perception of stimuli can be determined exclusively by temporal features of spike trains independent of the mean spike rate and without contribution from population response factors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Neurophysiological studies in primates have found that direction-sensitive neurons in the primary somatosensory cortex (SI) generally increase their response rate with increasing speed of object motion across the skin and show little evidence of speed tuning. We employed psychophysics to determine whether human perception of motion direction could be explained by features of such neurons and whether evidence can be found for a speed-tuned process. After adaptation to motion across the skin, a subsequently presented dynamic test stimulus yields an impression of motion in the opposite direction. We measured the strength of this tactile motion aftereffect (tMAE) induced with different combinations of adapting and test speeds. Distal-to-proximal or proximal-to-distal adapting motion was applied to participants' index fingers using a tactile array, after which participants reported the perceived direction of a bidirectional test stimulus. An intensive code for speed, like that observed in SI neurons, predicts greater adaptation (and a stronger tMAE) the faster the adapting speed, regardless of the test speed. In contrast, speed tuning of direction-sensitive neurons predicts the greatest tMAE when the adapting and test stimuli have matching speeds. We found that the strength of the tMAE increased monotonically with adapting speed, regardless of the test speed, showing no evidence of speed tuning. Our data are consistent with neurophysiological findings that suggest an intensive code for speed along the motion processing pathways comprising neurons sensitive both to speed and direction of motion., (Copyright © 2016 the American Physiological Society.)

Background: A myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors. However, the functional significance of their slow-conducting counterparts, termed C-low threshold mechanoreceptors (C-LTMRs), remains largely unexplored. We recently showed the emergence of brush- and vibration-evoked allodynia in human hairy and glabrous skin during background muscle pain. The allodynia persisted following the preferential blockade of myelinated fibres but was abolished by the preferential blockade of cutaneous C fibres, thereby suggesting a pathway involving hairy skin C-LTMRs and their functional counterparts in glabrous skin in this phenomenon. In the present study, we tested the effects of preferential A- and C-fibre conduction blocks and pharmacological blockade of T-type calcium channel Cav3.2 (expressed selectively on small-fibre LTMRs) on monofilament detection thresholds in healthy participants by compression, low-dose intradermal anaesthesia (xylocaine 0.25 %) and selective T-channel antagonist, TTA-A2., Results: We found that all participants could detect monofilament contacts (as low as 1.6 mN) within the innocuous tactile range regardless of the preferential blockade of myelinated fibres. Furthermore, during the compression block no subject reported a switch in modality from touch to pain. That is, the low-force monofilament contacts were always perceived as non-painful. However, there was a small but significant elevation of monofilament thresholds (~2 mN) in the glabrous skin following the compression block. Importantly, no differences were found in the thresholds across hairy and glabrous regions while the myelinated fibres were conducting or not. The preferential blockade of C fibres in the glabrous skin (with myelinated fibres intact) also resulted in a small but significant elevation of tactile thresholds. Furthermore, the use of T-channel blocker in the glabrous skin during compression block of myelinated fibres resulted in complete abolition of monofilament sensibility within the innocuous tactile range (tested up to ~20 mN)., Conclusions: These observations suggest that C-LTMRs need not be regarded as a redundant tactile system, but appear to complement normal large-myelinated-fibre tactile function. Convergent findings in glabrous and hairy skin lend support for an underlying system of innocuous mechanoreception with Cav3.2-expressing unmyelinated fibres.

Integration of information by convergence of inputs onto sensory cortical neurons is a requisite for processing higher-order stimulus features. Convergence across defined peripheral input classes has generally been thought to occur at levels beyond the primary sensory cortex, however recent work has shown that this does not hold for the convergence of slowly-adapting and rapidly-adapting inputs in primary somatosensory cortex. We have used a new analysis method for multi-unit recordings, to show convergence of inputs deriving from the rapidly-adapting and Pacinian channels in a proportion of neurons in both primary and secondary somatosensory cortex in the anaesthetised cat. We have validated this method using single-unit recordings. The secondary somatosensory cortex has a greater proportion of sites that show convergence of this type than primary somatosensory cortex. These findings support the hypothesis that the more complex features processed in higher cortical areas require a greater degree of convergence across input classes, but also shows that this convergence is apparent in the primary somatosensory cortex.

Current prosthetic limbs are limited by a lack of tactile feedback. Slip feedback is particularly important to inform grip. Object slip is marked by both a change in the normal grip force applied and a change in force tangential to the fingertips. In this study, we demonstrate that a new multi-axial tactile sensor composed of gold nanoparticle strain gauges is able to record slip and reconstruct the X, Y, and Z forces incident on the sensor's surface due to a slipping object. We entered the X, Y, and Z force components generated by the slip event into a noisy leaky integrate and fire model to simulate the firing responses of SA1 and FA1 afferents. We also recorded a uniaxial normal force input representative of tactile contact. A single set of SA1 model and FA1 model parameters generated realistic firing patterns for both the slip and normal force recordings. These results suggest that canonical SA1 and FA1 afferent models could be used to generate biomimetic electrical stimulation patterns for both slip and touch stimuli. When used to activate the tactile afferents of an amputee, these electrical stimulation patterns could create natural and distinguishable slip and touch percepts for closed loop control of an upper limb neural prosthesis.

Using a multi-channel platinum surface electrode array, recordings from cat primary visual cortex were obtained in response to visual stimuli, and electrical stimuli delivered using the elements of the array itself. Neural responses to electrical stimuli were consistent, regardless of stimulus polarity or leading phase (biphasic), although thresholds were lower for monophasic than biphasic pulses. Both visual and electrical stimuli reliably evoked responses with characteristic components, which interacted with each other in a nonlinear summation showing first facilitation then suppression during the window of interaction. The chronaxie for eliciting threshold cortical responses was about 100 mus, and the charge density with a pulse width of 50-100 mus was around 55 muC cm(-2). These data form the basis of understanding the types of cortical responses to stimuli delivered by devices suitable for chronic implantation.

Objective: To examine the early and late surgical outcomes of feminizing genitoplasty (FG) in adult transsexuals in a UK single surgeon practice over a 10-year period., Patients and Methods: Computerized and manual databases were searched over the period 1994-2004 to identify patients who had undergone male to female FG. Case-notes were retrieved and analysed to identify epidemiological data, the number and type of perioperative problems, early results at outpatient review, late occurring problems and patient satisfaction. A telephone questionnaire was then conducted targeting all FG patients in our series. The questions were directed at identifying surgical complications, outcome and patient satisfaction., Results: In all, 233 case-notes were identified and 222 (95%) were retrieved. All patients had penectomy, urethroplasty and labiaplasty, 207 (93%) had formation of a neoclitoris, and 202 (91%) had a skin-lined neovagina. The median (range) age was 41 (19-76) years. The median hospital stay was 10 (6-21) days. A record of the first outpatient visit was available in 197 (84.5%) cases. The median time to follow up was 56 (8-351) days. Over all, 82.2% had an adequate vaginal depth, with a median depth of 13 (5-15) cm and 6.1% had developed vaginal stenosis. Three (1.7%) patients had had a vaginal prolapse, two (1.1%) had a degree of vaginal skin flap necrosis and one (0.6%) was troubled with vaginal hair growth. In 86.3% of the patients the neoclitorizes were sensitive. There was urethral stenosis in 18.3% of the patients and 5.6% complained of spraying of urine. Minor corrective urethral surgery was undertaken in 36 patients including 42 urethral dilatations, and eight meatotomies were performed. At the first clinic visit 174 (88.3%) patients were 'happy', 13 (6.6%) were 'unhappy' and 10 (5.1%) made no comment. Of the 233 patients, we successfully contacted 70 (30%). All had had penectomy and labioplasty, 64 (91%) had a clitoroplasty and 62 (89%) a neovagina. The median age was 43 (19-76) years and the median follow up was 36 (9-96) months. Overall, 63 (98%) had a sensate neoclitoris, with 31 (48%) able to achieve orgasm; nine (14%) were hypersensitive. Vaginal depth was considered adequate by 38 (61%) and 14 (23%) had or were having regular intercourse. Vaginal hair growth troubled 18 (29%), four (6%) had a vaginal prolapse and two (3%) had vaginal necrosis. Urinary problems were reported by 19 (27%) patients, of these 18 (26%) required revision surgery, 14 (20%) complained of urinary spraying, 18 (26%) had an upward directed stream and 16 (23%) had urethral stenosis. The patients deemed the cosmetic result acceptable in 53 (76%) cases and 56 (80%) said the surgery met with their expectations., Conclusion: This is largest series of early results after male to female FG. Complications are common after this complex surgery and long-term follow-up is difficult, as patients tend to re-locate at the start of their 'new life' after FG. There were good overall cosmetic and functional results, with a sustained high patient satisfaction.

A number of human and animal studies have reported a differential representation of the frequency of vibrotactile stimuli in the somatosensory cortices: neurons in the primary somatosensory cortex (SI) are predominantly responsive to lower frequencies of tactile vibration, and those in the secondary somatosensory cortex (SII) are predominantly responsive to higher frequencies. We employed transcranial magnetic stimulation (TMS) over SI in human subjects to investigate the extent to which the inactivation of SI disrupted the discrimination of vibrotactile stimulation at frequencies that give rise to the tactile sensations of flutter (30 Hz) and vibration (200 Hz). Frequency discrimination around the 30-Hz standard following application of TMS to SI was reduced in seven of the eight subjects, and around the 200-Hz standard was reduced in all eight subjects. The average change in discrimination following TMS was about 20% for both low and high frequencies of vibrotactile stimulation. These data suggest that disruption of SI: (1) has a direct effect on the discrimination of both low and high frequencies of vibrotactile stimuli, consistent with a serial model of processing, or (2) has a direct effect on low-frequency vibrotactile stimuli and an indirect effect on the processing of high-frequency vibrotactile stimuli by SII via cortico-cortical connections between the two regions.

Introduction: Determining the history and development of feminizing genitoplasty is fascinating and instructive but fraught with difficulty. Earliest examples relate to practices carried out in ancient cultures. Gender reassignment surgery (GRS) developed from reconstructive procedures for congenital abnormalities. Some surgery was disguised, techniques were not recorded, and operations were carried out in secret., Aim: The aim of this article is to review the historical development of male-to-female GRS., Methods: Information was gleaned from Medline and general Internet searches. Further evidence was found by reviewing the references of early articles. A fascinating insight was also found in the autobiographies of GRS patients., Results: The first recorded case was by Abrahams in 1931. Techniques evolved from the early vaginal absence work of Beck and Graves. Pioneers of GRS were Sir Harold Gillies in England and Georges Burou of Casablanca. In the 1950s, they both used invagination of the penile skin sheath to form a vagina. Howard Jones, of Johns Hopkins, published the second classic technique using penile and scrotal skin flaps. These two methods form the basis of male-to-female GRS today. The history of GRS reveals a struggle to improve functionality as well as cosmesis. In particular, the neovagina but also a functioning neoclitoris, which has developed from a cosmetic swelling into an innovated organ, derived from the glans penis and harvested penile neurovascular bundle., Conclusions: Improved function and cosmesis continue to be the aim of the gender dysphoria surgeon. However, this review suggests the future management of transwomen should address not only refinements of surgical techniques but also prospective collection of posttreatment quality-of-life issues.

Objective: To present the argument that the only secure foundation for a theory of behaviour, and ultimately of mind, rests at the level of single neurons, and to assess progress at this level of explanation., Methods: Relevant data were obtained by a search of PubMed, last updated in January 2007, focused on implemented models from single-neuron studies., Results: Technical limitations on recording neural activity produce trade-offs between temporal and spatial resolution and the ability to track the massively parallel activity of the nervous system. The properties of the single neuron that would need to be measured and the techniques available to obtain the data are described. The concept of a fixed neuronal identity may be impeding progress and should be replaced with the concept of dynamically assigned neuron identity., Conclusion: Modern data collection techniques make it possible to obtain data at the single-neuron level on the complete nervous systems of simple organisms. Present models based on this data do not provide an integrated explanation of behaviour. However, there do not appear to be insurmountable theoretical or practical obstacles to building such models in the future or of scaling the data collection up to more complex organisms.

We characterised membrane currents in undifferentiated RGC-5 cells, a cell line used in in vitro models of apoptosis and glaucoma. The cells were inexcitable, with no voltage-dependent Na(+) currents or action potentials. Some novel currents were observed including basal Cl(-) currents, inwardly rectifiying K(+) currents and Gd(3+) insensitive stretch-activated currents. Our results highlight the differences between the electrophysiological properties of undifferentiated RGC-5 cells and retinal ganglion cells.

We have used information theory to analyse the responses of neurons in area 21a of the cat to disparity stimuli. Visual stimuli consisted of drifting sinusoidal gratings presented simultaneously to each eye. The relative spatial phase of the gratings varied between stimulus periods in a pseudo-random sequence of 45 degrees increments that covered the full 360 degrees. The mean information content of the responses of all neurons across all phases was 0.72 bits (+/-0.10, SE, n=29). The information conveyed by each neuron was well correlated with the extent to which the interocular phase difference modulated the response of the cell. However, information content was not simply related to firing rate, as there was usually significant information content in the neuronal responses to phase differences that elicited the minimum firing rate. In general, burst responses (impulse intervals <4 ms) did not convey more information than that conveyed by the total response. The contribution to the cumulative information of the response in successive 100-ms segments decreased over the course of the 1-s stimulus. The ratio of information transmitted at 200 ms to that transmitted over the full second had a median of 0.30 while the ratio of 500 ms to 1 s was 0.68.

We investigated binocular suppression in area 21a cells of the anaesthetized cat using drifting sinusoidal gratings presented simultaneously to each eye. The grating presented to the dominant eye was always oriented optimally and the grating presented to the non-dominant eye was either at the same orientation, but at the least effective relative spatial phase, or orthogonal. The binocular response of approximately 80% of cells was less than the monocular dominant eye response when there was a mismatch in orientation or spatial location between stimuli. Response suppression in the two binocular stimulus conditions had a correlation coefficient (r) of 0.55. We propose a parsimonious model to account for the response facilitation and suppression by binocular stimulation of area 21a neurons.

1. Binocular interactions related to retinal disparity were investigated in single neurons in area 21a of extrastriate cortex in the anaesthetized cat using sinusoidal luminance gratings. 2. The responses of approximately two-thirds of neurons were profoundly modulated by a relative phase difference between identical drifting gratings presented to each eye. This modulation included both facilitatory and inhibitory interocular interactions. The selectivity for binocular disparity was about twice as sharp as the selectivity for monocular spatial position. 3. Significant phase modulation was retained in many neurons at interocular orientation differences exceeding 45 deg. The response suppression associated with stimulation at a phase shift 180 deg from the optimum was stronger than the response suppression to an interocular orientation difference of 90 deg. 4. The proportion of phase modulated neurons and the potency of modulation in area 21a neurons exceed that reported for phase-selective complex cells in area 17. Neurons in area 21a show sharp disparity tuning that is relatively insensitive to changes in orientation and monocular position, which suggests that this extrastriate region has a role in stereoscopic depth perception.

The prelimbic region of medial frontal cortex in the rat receives a direct input from the hippocampus and this functional connection is essential for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated slices of frontal cortex. Repetitive bursts of stimulation at theta frequencies (TBS) were applied to layer II, and monosynaptic EPSPs were monitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimulation at 100 Hz in the presence of the N-methyl--aspartate (NMDA)-antagonist 2-amino-5-phosphonopentanoate (AP5) was reported to be a reliable method of inducing LTD in prelimbic cortex (). However we found that this protocol did not facilitate the induction of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R, S)-alpha-methyl-4- carboxyphenylglycine (MCPG). This drug significantly reduced the incidence of LTP after TBS to only 1 of 14 neurons (P < 0.02, chi2 test). The pooled responses to TBS in MCPG showed significantly reduced potentiation [(P < 0.02, analysis of variance (ANOVA)]. The broad-spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylglycine(S-3HPG) both produced membrane depolarization, an increase in number of spikes evoked by depolarizing current pulses, and a reduction in the afterhyperpolarization. Similar effects were produced by these agonists even when synaptic transmission was blocked by use of the gamma-aminobutyric acid-B (GABAB) receptor agonist, 200 microM baclofen, which suggests that group I mGluRs are present on layer V neurons. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and that this excitatory effect could be mediated by the postsynaptic group I mGluRs.

We investigated binocular interactions in area 21a cells of the anaesthetized cat. Visual stimuli were drifting sinusoidal gratings presented at the same optimal orientation in each eye (iso-oriented condition) or at the optimal orientation in the dominant eye and the orthogonal orientation in the other eye (orthogonal condition). In 68% of cells the response in the binocular iso-oriented condition was greater than the dominant eye monocular response, while in 88% of cells the response in the binocular orthogonal condition was less than the dominant eye monocular response. Our results suggest a possible role for this extrastriate region of cortex in binocular contour rivalry.

1. The spatial and temporal response properties of single cells in area 21a of the anaesthetized cat were assessed using drifting sinusoidal gratings presented at the optimum orientation for each cell. 2. Responses to sinusoidal gratings were dominated by an elevation of the mean discharge, with a relatively small modulated component at the temporal frequency of grating drift. The relative modulation ratio for the majority of cells was less than 1, similar to complex cells in the striate cortex. 3. Of those cells responsive to stimulation with sinusoidal gratings, 94% displayed spatial bandpass characteristics. Values derived from spatial frequency tuning curves were: mean optimum spatial frequency, 0.26 cycles deg-1; mean spatial resolution, 0.86 cycles deg-1; mean spatial bandwidth, 1.8 octaves; and mean normalized bandwidth, 1.3. Two cells (6%) displayed spatial low-pass characteristics. 4. Approximately half our sample of cells (44%) displayed temporal low-pass tuning, while 35% displayed temporal bandpass characteristics. The mean optimum temporal frequency of bandpass cells was 3.3 Hz and the mean temporal bandwidth 1.9 octaves. The remaining cells were classified as temporal broadband (17%) and temporal high-pass (4%). 5. We conclude that the dominant functional input to cells with relatively high spatial frequency selectivity and/or temporal low-pass response properties most probably arises from area 17. The responses of the remaining cells may be explained by input from area 17 or 18.

We investigated the corticocortical connections between area 21a and ipsilateral areas 17 and 18 in the cat. The anterograde/retrograde fluorescent tracer tetramethyl-rhodamine conjugated to dextran (Fluoro-Ruby) was injected into area 21a of the anaesthetized cat. Cell bodies labelled retrogradely from area 21a were consistently observed in both areas 17 and 18, primarily located in the supragranular layers of cortex where they formed discrete patches of cells. Similar numbers of cell bodies were labelled retrogradely in areas 17 and 18 of each animal. Our data are also consistent with previous reports of a reciprocal projection from area 21a back to areas 17 and 18 terminating principally in infragranular cortical layers.

Direct postsynaptic depolarization and firing of single CA1 neurons caused decreased responses to iontophoresed alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). Since there was no associated change in the excitatory postsynaptic potential (EPSP) evoked by electrical stimulation in the same band of stratum radiatum, we infer that the decreased AMPA response was mediated predominantly by extrasynaptic receptors. The decreased AMPA response developed within 10-30 min after conditioning, a time course similar to the delayed increase in AMPA responses associated with long-term potentiation (LTP) [Davies et al. (1989), Nature, 338:500-503; Sergueeva et al. (1993), Neuropharmacology, 32:933-935]. Our observations suggest the existence of mirror-image processes that may regulate AMPA receptors and possibly synaptic efficacy.