Initial contact shapes the perception of friction

Humans efficiently estimate the grip force necessary to lift a variety of objects, including slippery ones. The regulation of grip force starts with the initial contact and takes into account the surface properties, such as friction. This estimation of the frictional strength has been shown to depend critically on cutaneous information. However, the physical and perceptual mechanism that provides such early tactile information remains elusive. In this study, we developed a friction-modulation apparatus to elucidate the effects of the frictional properties of objects during initial contact. We found a correlation between participants’ conscious perception of friction and radial strain patterns of skin deformation. The results provide insights into the tactile cues made available by contact mechanics to the sensorimotor regulation of grip, as well as to the conscious perception of the frictional properties of an object.

We lift glasses of water, regardless of whether they are empty or full and whether they are dry or wet. The sensorimotor mechanisms responsible for this astonishing performance are far from being understood. The grip forces required to lift an object are known to be unconsciously regulated to a value typically 20% above what would cause slippage (1). Remarkably, this regulation starts from the moment our fingers touch the surface. It has been shown that just a hundred milliseconds of contact with a surface are enough to start adjusting fingertip forces to friction. Humans provide larger grasping forces if the surface is made of slippery silk, but smaller if it is made of sandpaper since it provides better grasp (2, 3). It has been further demonstrated that it is friction, and not texture, that determines these adjustments (3). Since 1 mm of indentation of the fingertip is sufficient to reach 80% of the final gross contact area, and fingers often move faster than 10 mm/s toward an object, within this time frame, the sensorimotor system already should be able to extract some estimates of the frictional properties from the initial deformation of the finger pad, before any net load forces start developing.On a physical level, the overall so-called “frictional strength” of the contact is given by the number of asperities in intimate contact and their individual shear strength (4–6). It is the measure of the maximum lateral force on the contact that will lead to slippage. This frictional strength is the main determinant in regulating grip force applied to lift an object of a given weight (3). Failure to properly assess the frictional strength of the surface at initial contact—due to the presence of gloves or anesthesia, for instance—is followed by larger-than-usual grip forces, consequently increasing the real area of contact (7–9).Despite its crucial importance, the mechanical deformation that underpins the encoding of the frictional strength on initial contact remains unclear. It is well known that the timing of the impulses of tactile afferents encodes the information related to force direction (10), local curvature (11), edges (12), and shapes (13) and also contains information about the frictional strength (14, 15). One hypothesis suggests that, at the mechanical level, microslip events at the finger–object interface induce vibrations of the skin (16, 17). Another hypothesis postulates that the sensation of friction is mediated by a radial pattern of skin strain within the contact area. The magnitude of the strain induces internal stresses, which are 21% smaller on a slippery surface than on a high-friction surface (18).Interestingly, roboticists have leveraged these findings to estimate friction on initial contact from the gradient of the lateral traction field. This metric is used to control the force applied by robotic grippers to soft and fragile objects (19–21). In haptic rendering, it is possible to produce tactile sensations by releasing the accumulated stress using ultrasonic friction modulation (22). However, the perception of the frictional strength with a single normal motion is not as salient. Khamis et al. (23) recently showed that participants were unable to differentiate a 73% reduction in friction of a glass plate when it was pressed against their fingertips by a robotic manipulator.Friction is consciously perceived in a passive condition only when the plate starts sliding (24–26). The change in the frictional state from stuck to sliding is perceived after a global lateral displacement of 2.3 mm (27). This transition induces large deformations of the skin, along with a particular strain pattern (25, 28–30). These results suggest that large or rapid deformations can elicit a tactile sensation, but the quasistatic radial strain pattern is too subtle to induce a reliable percept.We hypothesize that the frictional strength can be perceived when actively touching the surface. Active exploration is known to promote acute sensitivity (31–33). We present evidence that during the first instant of contact between the finger and an object, a radial strain pattern exists. Its magnitude is affected by the interfacial friction and correlates with the perception of friction. Combined with the results of the motor-control literature, a picture emerges explaining the mechanical basis upon which friction is encoded.     

Long-term music training tunes how the brain temporally binds signals from multiple senses

Practicing a musical instrument is a rich multisensory experience involving the integration of visual, auditory, and tactile inputs with motor responses. This combined psychophysics-fMRI study used the musician's brain to investigate how sensory-motor experience molds temporal binding of auditory and visual signals. Behaviorally, musicians exhibited a narrower temporal integration window than nonmusicians for music but not for speech. At the neural level, musicians showed increased audiovisual asynchrony responses and effective connectivity selectively for music in a superior temporal sulcus-premotor-cerebellar circuitry. Critically, the premotor asynchrony effects predicted musicians' perceptual sensitivity to audiovisual asynchrony. Our results suggest that piano practicing fine tunes an internal forward model mapping from action plans of piano playing onto visible finger movements and sounds. This internal forward model furnishes more precise estimates of the relative audiovisual timings and hence, stronger prediction error signals specifically for asynchronous music in a premotor-cerebellar circuitry. Our findings show intimate links between action production and audiovisual temporal binding in perception.     

Neural indicators of articulator-specific sensorimotor influences on infant speech perception

While there is increasing acceptance that even young infants detect correspondences between heard and seen speech, the common view is that oral-motor movements related to speech production cannot influence speech perception until infants begin to babble or speak. We investigated the extent of multimodal speech influences on auditory speech perception in prebabbling infants who have limited speech-like oral-motor repertoires. We used event-related potentials (ERPs) to examine how sensorimotor influences to the infant’s own articulatory movements impact auditory speech perception in 3-mo-old infants. In experiment 1, there were ERP discriminative responses to phonetic category changes across two phonetic contrasts (bilabial–dental /ba/-/ɗa/; dental–retroflex /ɗa/-/ɖa/) in a mismatch paradigm, indicating that infants auditorily discriminated both contrasts. In experiment 2, inhibiting infants’ own tongue-tip movements had a disruptive influence on the early ERP discriminative response to the /ɗa/-/ɖa/ contrast only. The same articulatory inhibition had contrasting effects on the perception of the /ba/-/ɗa/ contrast, which requires different articulators (the lips vs. the tongue) during production, and the /ɗa/-/ɖa/ contrast, whereby both phones require tongue-tip movement as a place of articulation. This articulatory distinction between the two contrasts plausibly accounts for the distinct influence of tongue-tip suppression on the neural responses to phonetic category change perception in definitively prebabbling, 3-mo-old, infants. The results showing a specificity in the relation between oral-motor inhibition and phonetic speech discrimination suggest a surprisingly early mapping between auditory and motor speech representation already in prebabbling infants.

Infants rapidly acquire robust representations of the native phonetic repertoire from the natural multisensory speech input of their environment. Multimodal speech signals are generated by a common underlying source—the vocal tract and the articulatory movements used during production (1, 2). Adult speech perception is influenced by synchronously occurring multimodal speech cues, including auditory, visual, motor, and sensorimotor signals (3). Recent advances reveal that speech production relies on both auditory and sensorimotor signals (4, 5), but also, sensorimotor input can affect the perception of auditory (6) and visual (7) speech. Indeed, neural evidence indicates bidirectional interaction between the speech perception and production systems in the adult brain (8). It has been widely assumed that the interactions between the articulator-specific sensorimotor information and acoustic phonetic perception would appear later in development after infants begin to babble and to produce speech themselves. This assumption is not surprising given that motor coordination is immature early in life and appears to have a protracted development. However, to fully understand how infants acquire their native speech sound repertoire, it is critical to examine whether sensorimotor/motoric dimensions of speech are relevant for auditory speech perception even in infants who are prebabbling. If so, then sensorimotor influences on speech perception may be part of the foundation that sets the stage for language acquisition in general and babbling in particular, rather than production experience driving the eventual auditory-sensorimotor/motor speech interaction.While the speech signal that infants experience and learn from is multimodal, speech perception research during the acquisition period has focused mainly on auditory speech perception, and to a modest extent, on audiovisual speech perception. Infants reliably match heard and seen speech at 2 mo of age by looking longer to the face that is articulating the syllable being played (9, 10). Remarkably, infants are also able to match audio and visual speech even for nonnative consonants and vowels, which they have not encountered in their linguistic environment (11). While some have suggested that audiovisual speech perception abilities in infants reflect a domain-general preference for synchronously occurring stimuli (12), there is neural evidence of multimodal phonetic representation already at 2 mo of age (13). In ref. 13, a phonetic mismatch response (MMR) was observed to the category change of an auditory vowel, both when the preceding stimuli were repetitions of visemes (a face articulating the same or a different vowel) or speech sounds. The consistency of the MMRs to the phonetic category change regardless of modality suggests that infants have access to an integrated intermodal representation (13).There is less experimental work investigating sensorimotor interactions with speech perception; however, several recent behavioral studies have addressed this question by experimentally manipulating infants’ own oral-motor movements. In the first such study, 4-mo-old infants’ labial configuration was manipulated (by gently holding an appropriately shaped object in their mouth) to either resemble the shape made for producing /i/ or /u/ vowels while they were tested in an audiovisual matching task. Results showed that infants’ matching of these same vowels was changed by the manipulation (14). The influence of sensorimotor cues on auditory-only speech perception was more recently tested, this time with infants aged 6 mo, who do not typically produce well-formed consonant–vowel (CV) syllables. Replicating previous work (15), English-learning infants this age discriminated a dental /ɗa/–retroflex /ɖa/ phonetic contrast that is nonnative to English speakers, but native to Hindi speakers’ contrast. These two consonants differ, in adult Hindi production, only on the placement of the tongue tip during articulation: The dental involves placement of the tongue tip behind the back front teeth, whereas retroflex production involves curling the tongue tip back and placing it against the roof of the mouth. However, when an infant’s tongue-tip movement was inhibited by having a caregiver gently hold a teether on the tongue, discrimination of this nonnative /ɗa/-/ɖa/ contrast was disrupted (16, 17). A control experiment showed that discrimination of this contrast was maintained when a different teether that does not interfere with tongue-tip movement was used, indicating that it was not the mere presence of a teething toy but rather the inhibition of the relevant articulator that accounted for the disruption of discrimination (16).These specific sensorimotor influences on auditory and audiovisual speech perception provide evidence that the relation between sensorimotor information and auditory speech perception is present in infants who have not had extensive speech production or babbling experience. Although preverbal infants this young have yet to gain the full articulatory control required to generate speech-like sounds, behavioral studies reviewed above suggest that a sensorimotor mapping of the articulators may be available to infants before babbling begins, possibly through spontaneously generated movement patterns during prenatal development (18). These patterns may be progressively refined through orofacial movements (e.g., sucking movements and nonspeech vocalizations) that help to shape the motor articulatory space that must be aligned with the phonetic perceptual space to ensure correct productions.Anatomically, the core neural pathways for speech including the cortical connections between the frontal (productive) and temporal (receptive) speech areas are in place before term birth (19). While the ventral pathway is more mature at birth, the dorsal pathway (i.e., the arcuate fasciculus) that functionally transforms auditory and motor speech codes rivals in maturity by 10 wk (20, 21). In ref. 21, the authors concluded that the functional connectivity, or cross-talk, between the suprasylvian part of the arcuate fasciculus, the posterior part of the superior temporal sulcus, and area 44 in the left inferior frontal region is established within the first few postnatal months based on a unique correlational pattern in the maturational indices across these regions, which also collectively form key nodes of the adult phonological loop. The early maturation and functional engagement of the arcuate fasciculus, which is a bidirectional tract between the productive and receptive areas, suggest that the necessary connectivity that subserves the sensorimotor influence on auditory perception is in place within several months after birth.     

Integration of signals from different cortical areas in higher order thalamic neurons

Higher order thalamic neurons receive driving inputs from cortical layer 5 and project back to the cortex, reflecting a transthalamic route for corticocortical communication. To determine whether or not individual neurons integrate signals from different cortical populations, we combined electron microscopy “connectomics” in mice with genetic labeling to disambiguate layer 5 synapses from somatosensory and motor cortices to the higher order thalamic posterior medial nucleus. A significant convergence of these inputs was found on 19 of 33 reconstructed thalamic cells, and as a population, the layer 5 synapses were larger and located more proximally on dendrites than were unlabeled synapses. Thus, many or most of these thalamic neurons do not simply relay afferent information but instead integrate signals as disparate in this case as those emanating from sensory and motor cortices. These findings add further depth and complexity to the role of the higher order thalamus in overall cortical functioning.

Until relatively recently, the view of thalamic neurons is that they simply relay information to the cortex with little or no integrative processing. This view drew heavily on lessons learned from the dominant model of the thalamus: the lateral geniculate nucleus (LGN), where receptive fields of geniculate relay cells closely match those of their retinal inputs. However, recent evidence has dramatically changed this view. There are three main reasons for this.First, there is considerable evidence that modulatory input to the thalamus can strongly affect the response properties of thalamic relay cells (reviewed in ref. 1). Examples include the different tonic and burst firing modes, gain of response to driving inputs, etc.Second, new evidence demonstrates that driver inputs that convey different types of peripheral sensory information converge onto single thalamic relay cells, therefore suggesting the possibility of significant integration of information prior to relaying to the cortex. These studies include evidence of retinal inputs with very different receptive fields converging onto single geniculate relay cells (2, 3), of driving inputs from retina and superior colliculus converging onto single geniculate relay cells (4), and of cortical layer 5 and brainstem driver inputs converging onto single cells of the posterior medial nucleus [POm (5)]. However, these examples are few, and each is limited in scale. There is also recent evidence that some thalamic relays may function without traditional driver input (6).Third, the recent division of thalamic nuclei into two functional types, first order and higher order (reviewed in ref. 1), offers potentially new views on the extent to which thalamic neurons transform received information prior to transmission. Unlike first order thalamic relays, which receive driving input from a subcortical source (e.g., the retina for the LGN) and transmit that to the cortex, higher order relays receive inputs primarily from layer 5 of the cortex and thus serve as a transthalamic route for corticocortical communication. Therefore, the distinct functional organization of higher order thalamic relays offers an interesting substrate for thalamic integration of disparate information (7–9). Specifically, since higher order thalamic nuclei commonly receive overlapping projections from layer 5 neurons of multiple, distinct cortical areas (10), we can ask whether these multiple driving inputs containing different types of information converge to synapse onto single relay cells. Because most of thalamus by volume seems to be higher order (1) and because most or all cortical areas send layer 5 projections to the thalamus as the afferent limb in transthalamic pathways (10), such convergence would have major significance for thalamocortical functioning.To provide morphological evidence for such convergence, we employed modern viral tracing techniques to disambiguate multiple long-distance pathways in large volume serial electron microscope (EM) reconstructions (i.e., “connectomics”) in the mouse; by this approach, we could identify possible convergence of layer 5 inputs from somatosensory and motor cortices onto single relay cells of the POm, which is a higher order somatosensory thalamic nucleus. The viral tracing makes use of orthograde labeling of long pathways with an ascorbate peroxidase (APX) from the pea plant (11) that has allowed us to identify separately synaptic terminals from sensory and motor cortices onto neurons of the POm. Our results indicate significant convergence of presumptive driver inputs onto single thalamic neurons from layer 5 cells of disparate sensory and motor cortices.     

Vocal learning is constrained by the statistics of sensorimotor experience

The brain uses sensory feedback to correct behavioral errors. Larger errors by definition require greater corrections, and many models of learning assume that larger sensory feedback errors drive larger motor changes. However, an alternative perspective is that larger errors drive learning less effectively because such errors fall outside the range of errors normally experienced and are therefore unlikely to reflect accurate feedback. This is especially crucial in vocal control because auditory feedback can be contaminated by environmental noise or sensory processing errors. A successful control strategy must therefore rely on feedback to correct errors while disregarding aberrant auditory signals that would lead to maladaptive vocal corrections. We hypothesized that these constraints result in compensation that is greatest for smaller imposed errors and least for larger errors. To test this hypothesis, we manipulated the pitch of auditory feedback in singing Bengalese finches. We found that learning driven by larger sensory errors was both slower than that resulting from smaller errors and showed less complete compensation for the imposed error. Additionally, we found that a simple principle could account for these data: the amount of compensation was proportional to the overlap between the baseline distribution of pitch production and the distribution experienced during the shift. Correspondingly, the fraction of compensation approached zero when pitch was shifted outside of the song’s baseline pitch distribution. Our data demonstrate that sensory errors drive learning best when they fall within the range of production variability, suggesting that learning is constrained by the statistics of sensorimotor experience.     

Accuracy of perception and touch for detecting fever in adults: a hospital-based study from a rural,tertiary hospital in Central India

OBJECTIVES: To evaluate the diagnostic accuracy of the patient's perception, and of the touch of patient attendants and a doctor for detecting fever. METHODS: We enrolled patients older than 13 years who presented with history of fever to the in- and out-patient departments of a rural teaching hospital. The design was a double-blind, cross-sectional analysis of a hospital-based case series, independently comparing reported history of fever and touch of patient attendant and that of doctor against an established reference standard (axillary temperature > 37.5 degrees C). Diagnostic accuracy was measured by computing sensitivity, specificity, and likelihood ratio values. The agreement between the patient, his attendant and the doctor was assessed by kappa statistic. RESULTS: We studied 462 patients of whom 274 (59.3%) were men. A total of 206 patients (44.58%) had fever. The patient's perception of fever (LR+ 1.77; 95% CI 1.52, 2.06), patient attendant's touch (LR+ 2.03; 95% CI 1.74, 2.36) and the doctor's touch (LR+ 3.08; 95% CI 2.51, 3.71) did not accurately distinguish those with and without fever. Doctors (LR- 0.20; 95% CI 0.17, 0.34) and patient attendants (LR- 0.24; 95% CI 0.14, 0.28) were more accurate in ruling out fever. The patient's perception agreed moderately with patient attendant's touch (kappa = 0.44; 95% CI 0.36, 0.53), and the doctor's assessment (kappa = 0.47; 95% CI 0.39, 0.55). There was moderate agreement between patients' attendants and the study doctor (kappa = 0.48; 95% CI 0.40, 0.56). CONCLUSIONS: Our findings suggest that patients, their attendants or doctors cannot accurately detect the presence of a fever without using a thermometer. Doctors should confirm a history of fever by recording temperature.     

From the Cover: Neurophysiological coordination of duet singing

Coordination of behavior for cooperative performances often relies on linkages mediated by sensory cues exchanged between participants. How neurophysiological responses to sensory information affect motor programs to coordinate behavior between individuals is not known. We investigated how plain-tailed wrens (Pheugopedius euophrys) use acoustic feedback to coordinate extraordinary duet performances in which females and males rapidly take turns singing. We made simultaneous neurophysiological recordings in a song control area “HVC” in pairs of singing wrens at a field site in Ecuador. HVC is a premotor area that integrates auditory feedback and is necessary for song production. We found that spiking activity of HVC neurons in each sex increased for production of its own syllables. In contrast, hearing sensory feedback produced by the bird’s partner decreased HVC activity during duet singing, potentially coordinating HVC premotor activity in each bird through inhibition. When birds sang alone, HVC neurons in females but not males were inhibited by hearing the partner bird. When birds were anesthetized with urethane, which antagonizes GABAergic (γ-aminobutyric acid) transmission, HVC neurons were excited rather than inhibited, suggesting a role for GABA in the coordination of duet singing. These data suggest that HVC integrates information across partners during duets and that rapid turn taking may be mediated, in part, by inhibition.

Animals routinely rely on sensory feedback for the control of their own behavior. In cooperative performances, such sensory feedback can include cues produced by other participants (1–8). For example, in interactive vocal communication, including human speech, individuals take turns vocalizing. This “turn taking” is a consequence of each participant responding to auditory cues from a partner (4–6, 9, 10). The role of such “heterogenous” (other-generated) feedback in the control of vocal turn taking and other cooperative performances is largely unknown.Plain-tailed wrens (Pheugopedius euophrys) are neotropical songbirds that cooperate to produce extraordinary duet performances but also sing by themselves (Fig. 1A) (4, 10, 11). Singing in plain-tailed wrens is performed by both females and males and used for territorial defense and other functions, including mate guarding and attraction (1, 11–16). During duets, female and male plain-tailed wrens take turns, alternating syllables at a rate of between 2 and 5 Hz (Fig. 1A) (4, 11).Open in a separate windowFig. 1.Neural control of solo and duet singing in plain-tailed wrens. (A) Spectrogram of a singing bout that included male solo syllables (blue line, top) followed by a duet. Solo syllables for both sexes (only male solo syllables are shown here) are sung at lower amplitudes than syllables produced in duets. Note that the smeared appearance of wren syllables in spectrograms reflects the acoustic structure of plain-tailed wren singing. (B and C) Each bird has a motor system that is used to produce song and sensory systems that mediate feedback. (B) During solo singing, the bird hears its own song, which is known as autogenous feedback (orange). (C) During duet singing, each bird hears both its own singing and the singing of its partner, known as heterogenous feedback (green). The key difference between solo and duet singing is heterogenous feedback that couples the neural systems of the two birds. This coupling results in changes in syllable amplitude and timing in both birds.There is a categorical difference between solo and duet singing. In solo singing, the singing bird receives only autogenous (hearing its own vocalization) feedback (Fig. 1B). The partner may hear the solo song if it is nearby, a heterogenous (other-generated) cue. In duet singing, birds receive both heterogenous and autogenous feedback as they alternate syllable production (Fig. 1C). Participants use heterogenous feedback during duet singing for precise timing of syllable production (4, 11). For example, when a male temporarily stops participating in a duet, the duration of intersyllable intervals between female syllables increases (4), showing an effect of heterogenous feedback on the timing of syllable production.How does the brain of each wren integrate heterogenous acoustic cues to coordinate the precise timing of syllable production between individuals during duet performances? To address this question, we examined neurophysiological activity in HVC, a nucleus in the nidopallium [an analogue of mammalian cortex (17, 18)]. HVC is necessary for song learning, production, and timing in species of songbirds that do not perform duets (19–24). Neurons in HVC are active during singing and respond to playback of the bird’s own learned song (25–27). In addition, recent work has shown that HVC is also involved in vocal turn taking (19).To examine the role of heterogenous feedback in the control of duet performances, we compared neurophysiological activity in HVC when female or male wrens sang solo syllables with syllables sung during duets. Neurophysiological recordings were made in awake and anesthetized pairs of wrens at the Yanayacu Biological Station and Center for Creative Studies on the slopes of the Antisana volcano in Ecuador. We found that heterogenous cues inhibited HVC activity during duet performances in both females and males, but inhibition was only observed in females during solo singing.     

Sensory computations in the cuneate nucleus of macaques

Tactile nerve fibers fall into a few classes that can be readily distinguished based on their spatiotemporal response properties. Because nerve fibers reflect local skin deformations, they individually carry ambiguous signals about object features. In contrast, cortical neurons exhibit heterogeneous response properties that reflect computations applied to convergent input from multiple classes of afferents, which confer to them a selectivity for behaviorally relevant features of objects. The conventional view is that these complex response properties arise within the cortex itself, implying that sensory signals are not processed to any significant extent in the two intervening structures—the cuneate nucleus (CN) and the thalamus. To test this hypothesis, we recorded the responses evoked in the CN to a battery of stimuli that have been extensively used to characterize tactile coding in both the periphery and cortex, including skin indentations, vibrations, random dot patterns, and scanned edges. We found that CN responses are more similar to their cortical counterparts than they are to their inputs: CN neurons receive input from multiple classes of nerve fibers, they have spatially complex receptive fields, and they exhibit selectivity for object features. Contrary to consensus, then, the CN plays a key role in processing tactile information.

The coding of tactile information has been extensively studied in the peripheral nerves and in the primary somatosensory cortex (S1, Brodmann’s area 3b) of nonhuman primates, leading to the conclusion that sensory representations in S1 differ from those at the periphery in at least two important ways. First, while cutaneous nerve fibers can be divided into a small number of classes each responding to a different aspect of skin deformation (1–3), individual S1 neurons integrate sensory signals from multiple classes of nerve fibers (4–7). Indeed, while each class of nerve fibers exhibits stereotyped responses to certain stimulus classes, for example, skin indentations or sinusoidal vibrations, cortical responses to these same stimuli include features of the responses from multiple tactile classes or submodalities. Second, the responses of cortical neurons reflect computations on these inputs. For example, the spatial receptive fields (RFs) of S1 neurons comprise excitatory and inhibitory subfields, implying a spatial computation (8, 9). Similarly, S1 neurons act as temporal filters, as evidenced by the fact that their responses to vibrations reflect both integration and differentiation of their inputs in time (10). These computations give rise to increasingly explicit rate-based representations of object features, such as the orientation of an edge indented into the skin or the texture of a surface scanned across the skin (5, 8).In contrast to the well-studied peripheral and cortical representations of touch, comparatively less is known about the contribution of the cuneate nucleus (CN) to the processing of tactile information. The textbook view is that the CN acts as a simple relay station despite the fact that the response properties of neurons in the CN or equivalent brain structures (e.g., nucleus principalis) exhibit responses that are not identical to those of nerve fibers (11–15), implying some processing. However, CN responses have not been investigated using stimuli whose representation in the nerve and cortex has been quantitatively characterized (12, 13, 16, 17). This precludes a quantitative analysis of how tactile signals are transformed in this structure.To fill this gap, we recorded the responses evoked in individual CN neurons to a battery of tactile stimuli that have been extensively used to characterize the response properties of tactile nerve fibers and of neurons in S1, including skin indentations, vibrations, embossed dot patterns, and scanned edges. We then compared CN responses to their upstream (nerve fibers) and downstream counterparts [Brodmann’s area 3b or S1, the first stage of processing in the cortex (18, 19)] to assess the degree to which tactile signals are processed in the CN. The picture that emerges is one in which the CN plays an integral part in the transformation of tactile information as it ascends the neuraxis.     

Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission

Na⁺-activated K⁺ (K_Na) channels are expressed in neurons and are activated by Na⁺ influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that K_Na channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of K_Na channels by Na⁺ transients via AMPA receptors shapes the decay of AMPA-mediated current as well as the amplitude of the synaptic potential. Thus, the coupling between K_Na channels and AMPA receptors by synaptically induced Na⁺ transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.     

Direct observation of stepping rotation of V-ATPase reveals rigid component in coupling between Vo and V1 motors

V-ATPases are rotary motor proteins that convert the chemical energy of ATP into the electrochemical potential of ions across cell membranes. V-ATPases consist of two rotary motors, V_o and V₁, and Enterococcus hirae V-ATPase (EhV_oV₁) actively transports Na⁺ in V_o (EhV_o) by using torque generated by ATP hydrolysis in V₁ (EhV₁). Here, we observed ATP-driven stepping rotation of detergent-solubilized EhV_oV₁ wild-type, aE634A, and BR350K mutants under various Na⁺ and ATP concentrations ([Na⁺] and [ATP], respectively) by using a 40-nm gold nanoparticle as a low-load probe. When [Na⁺] was low and [ATP] was high, under the condition that only Na⁺ binding to EhV_o is rate limiting, wild-type and aE634A exhibited 10 pausing positions reflecting 10-fold symmetry of the EhV_o rotor and almost no backward steps. Duration time before the forward steps was inversely proportional to [Na⁺], confirming that Na⁺ binding triggers the steps. When both [ATP] and [Na⁺] were low, under the condition that both Na⁺ and ATP bindings are rate limiting, aE634A exhibited 13 pausing positions reflecting 10- and 3-fold symmetries of EhV_o and EhV₁, respectively. The distribution of duration time before the forward step was fitted well by the sum of two exponential decay functions with distinct time constants. Furthermore, occasional backward steps smaller than 36° were observed. Small backward steps were also observed during three long ATP cleavage pauses of BR350K. These results indicate that EhV_o and EhV₁ do not share pausing positions, Na⁺ and ATP bindings occur at different angles, and the coupling between EhV_o and EhV₁ has a rigid component.

Rotary ATPases are ubiquitously expressed in living organisms and play important roles in biological energy conversions (1–6). These rotary ATPases are classified into F-, V-, and A-ATPases based on their amino acid sequences and physiological functions (6). Eukaryotic and bacterial F-ATPases (F_oF₁) and archaeal A-ATPases (A_oA₁) mainly function as ATP synthases driven by the electrochemical potential of ions across the cell membrane, although they can also act as active ion pumps driven by ATP hydrolysis depending on the cellular environment. In contrast, V-ATPases (V_oV₁) in eukaryotes primarily function as active ion pumps. V-ATPases are also found in bacteria, and some of them are termed V/A-ATPases based on their origin and physiological function in ATP synthesis (6–8).To date, numerous studies have been conducted to understand how the two motor proteins (i.e., F₁/A₁/V₁ and F_o/A_o/V_o) of the rotary ATPases couple their rotational motions and functions. Single-molecule studies using fluorescent probes (9–12), gold nanoparticle (AuNP) or nanorod probes (13–21), and Förster resonance energy transfer (16, 22, 23) have revealed the rotational dynamics of rotary ATPases for both ATP hydrolysis/synthesis directions. Furthermore, recent cryo–electron microscopic (cryo-EM) single-particle analyses have revealed entire architectures of the rotary ATPases with different structural states at atomic resolutions (24–35). In particular, several studies have demonstrated elastic coupling of F_oF₁ due to large deformations of the peripheral stalk connecting F_o and F₁ (25, 29, 35). However, few studies on other types of rotary ATPases with different functions and subunit compositions have been performed, and a comprehensive understanding of the energy transduction mechanism remains elusive.Enterococcus hirae V-ATPase (EhV_oV₁) works as an ATP-driven sodium ion (Na⁺) pump to maintain Na⁺ concentrations ([Na⁺]) inside the cell (Fig. 1A) (37–41). Note that we use the term V-ATPase or V_oV₁ because its physiological function is not ATP synthesis but active ion transport. EhV_oV₁ is a multisubunit complex composed of nine different subunits, namely, ac₁₀dE₂G₂ and A₃B₃DF complexes in EhV_o and EhV₁, respectively. In the EhV₁ A₃B₃DF complex, three pairs of the A and B subunits form a heterohexameric A₃B₃ stator ring, and the central rotor DF subcomplex is inserted into the A₃B₃ ring (Fig. 1B, Bottom) (42, 43). The EhV_o ac₁₀dE₂G₂ complex transports Na⁺ across the cell membrane. The membrane-embedded rotor ring is formed by a decamer of the tetrahelical transmembrane c subunit (c₁₀ ring; Fig. 1B, Top) connected with the central DF stalk via the d subunit (26, 44). The stator a subunit works as an ion channel, and two EG peripheral stalks interact with the a subunit and A₃B₃ ring to assure rotary coupling between EhV_o and EhV₁.Open in a separate windowFig. 1.(A) Overall architecture of EhV_oV₁. The dotted circular arcs represent the rotation direction driven by ATP hydrolysis. (B) (Top) Top view of the a subunit (cyan) and c₁₀ ring (brown) of EhV_o and (Bottom) A (yellow), B (orange), D (green), and F subunits (pink) of EhV₁. The black arrow in Top indicates the path of Na⁺ movement during ATP-driven rotation. The arcs in Bottom represent the catalytic AB pairs. (C) Side view of the a subunit viewed from the c subunit. This structure was constructed by the SWISS-MODEL server (36) using a structure of the a subunit of V-ATPase from T. thermophilus. The black arrows represent the path of Na⁺ movement during ATP-driven rotation. The mutated residue, aGlu634, is located on the surface of the entry half-channel of the a subunit as highlighted in red letters and a circle.In EhV₁, the ATP hydrolysis reaction is catalyzed at the interfaces of three A and B subunits. It drives a counterclockwise rotation of the DF rotor subunits as viewed from the EhV_o side (Fig. 1B, Bottom). Like other F₁/A₁/V₁ (11, 45), EhV₁ is a stepping motor that rotates 120° per one ATP hydrolysis (46). We previously revealed that the 120° step of isolated EhV₁ is further divided into 40 and 80° substeps by using high-speed and high-precision single-molecule imaging analysis with AuNP as a low-load probe (47). A main pause before the 40° substep involves ATP cleavage, phosphate release, and ATP binding events. The ATP binding triggers the 40° substep because the duration time is inversely proportional to [ATP]. The 80° substep is triggered by ADP release after a subpause with [ATP]-independent duration time. While the chemomechanical coupling scheme in EhV₁ has been revealed, because our previous single-molecule observation of EhV_oV₁ did not clearly resolve the pauses and steps (17), the elementary steps in the rotation of EhV_oV₁ have not been revealed.Although the mechanism of ion transport in F_o/A_o/V_o is not fully understood, the so-called “two-channel” model has been widely accepted (48–54). In this model, the a-subunit has two half-channels for ion entry/exit into/from the ion-binding sites of the rotor c ring. In the case of EhV_o, Na⁺ enters the half-channel from the cytoplasmic side and binds to the negatively charged Na⁺-binding sites of the c subunit (44, 55). Then, the charge-neutralized c subunit can move into the hydrophobic lipid membrane (53, 56). The rotational torque generated by ATP hydrolysis in EhV₁ is transmitted to EhV_o via the rotor d subunit, allowing the c₁₀ ring to rotate unidirectionally in the lipid membrane. Na⁺ translocated by a nearly single turn of the c₁₀ ring reaches another half-channel of the a subunit, which connects the Na⁺-binding site of the c subunit to the extracellular side. Then, Na⁺ is pumped out of the cell by a hydrated microenvironment (57) and/or electrostatic repulsion with the positively charged residues in the a subunit, aArg573 and aArg629, located at the interface between the two half-channels (Fig. 1C and SI Appendix, Fig. S1) (26). Because EhV_oV₁ has the c₁₀ ring, 10 Na⁺ are transported per single turn. Therefore, the step size of EhV_o is expected to be 36° (360°/10), similar to Escherichia coli and yeast F_oF₁, which also have c₁₀ rings (13, 14, 22, 35).The ion-to-ATP ratio is a central issue in the coupling mechanism of rotary ATPases. All known F₁/A₁/V₁ have three catalytic sites and threefold structural symmetry and hydrolyze or synthesize three ATP molecules per single turn. In contrast, the number of protomers forming the rotor c ring of F_o/A_o/V_o varies from 8 to 17 depending on the species, suggesting wide variations in the ion-to-ATP ratio of rotary ATPases (58, 59). In EhV_oV₁, because the rotor c ring of EhV_o has a 10-fold structural symmetry (Fig. 1B, Top), this enzyme has a structural symmetry mismatch and a noninteger ratio between transported Na⁺ and hydrolyzed ATP (10/3 = 3.3). If the rotational coupling between EhV_o and EhV₁ is elastic, as reported for E. coli and yeast F_oF₁, the symmetry mismatch is relieved by large deformations of the peripheral stalk and/or the central rotor (25, 29, 35, 60). On the other hand, if the coupling is rather rigid due to the multiple peripheral stalks of EhV_oV₁, the pausing positions of both EhV_o and EhV₁ would be observed independently in a single-molecule observation. To address this issue, it is required to directly visualize the rotational pauses and steps of EhV_oV₁ under conditions where the elementary steps of the rotation such as the bindings of Na⁺ and ATP to EhV_o and EhV₁, respectively, are both rate-limiting.Here we carried out high-speed and high-precision single-molecule imaging of the rotation of detergent-solubilized EhV_oV₁ by using 40-nm AuNP as a low-load probe. To resolve the rotational pauses and steps of EhV_o, a glutamate residue in the stator a subunit (aGlu634) was replaced with alanine. Since the mutated aGlu634 is located on the surface of the Na⁺ entry half-channel (Fig. 1C and SI Appendix, Fig. S2), Na⁺ binding to the c subunit in the EhV_oV₁(aE634A) mutant (hereinafter referred to as aE634A) is expected to become slower than in the wild type. The rotation rate of aE634A decreased about 10 times compared with that of the wild type, allowing us to clearly resolve the rotational pauses and steps in EhV_o. Under the condition that only Na⁺ binding is rate-limiting, aE634A showed 10 pausing positions per single turn and a step size of about 36°, consistent with 10 protomers in the c₁₀ ring of EhV_o. The duration time before the forward step was inversely proportional to [Na⁺], indicating that the dwell corresponds to the waiting time for Na⁺ binding. On the other hand, under the condition that both Na⁺ and ATP bindings are rate-limiting, 13 pausing positions per single turn were observed. Furthermore, backward steps smaller than 36° were occasionally observed only when ATP binding is also rate-limiting, indicating that EhV_oV₁ undergoes Brownian motion between adjacent pausing positions of EhV_o and EhV₁ when no torque is applied from EhV₁. Backward steps of 36° or larger than 36° were rarely observed, suggesting the suppression of reverse Na⁺ transport. Small backward steps were also frequently observed during three long ATP cleavage pauses of another mutant, EhV_oV₁(BR350K), in which ATP hydrolysis is rate-limiting for the rotation (47). From these results, we conclude that EhV_o and EhV₁ do not share their pausing positions, Na⁺ and ATP bindings occur at different angles, and their coupling has a rigid component.     

Topography of social touching depends on emotional bonds between humans

Nonhuman primates use social touch for maintenance and reinforcement of social structures, yet the role of social touch in human bonding in different reproductive, affiliative, and kinship-based relationships remains unresolved. Here we reveal quantified, relationship-specific maps of bodily regions where social touch is allowed in a large cross-cultural dataset (N = 1,368 from Finland, France, Italy, Russia, and the United Kingdom). Participants were shown front and back silhouettes of human bodies with a word denoting one member of their social network. They were asked to color, on separate trials, the bodily regions where each individual in their social network would be allowed to touch them. Across all tested cultures, the total bodily area where touching was allowed was linearly dependent (mean r² = 0.54) on the emotional bond with the toucher, but independent of when that person was last encountered. Close acquaintances and family members were touched for more reasons than less familiar individuals. The bodily area others are allowed to touch thus represented, in a parametric fashion, the strength of the relationship-specific emotional bond. We propose that the spatial patterns of human social touch reflect an important mechanism supporting the maintenance of social bonds.The time primates devote to grooming each other far exceeds the requirements of hygiene. Kinship and the power dynamics of the group determine the amount of grooming devoted to different individuals (1), and grooming relationships are fairly stable over time, predicting aid in times of stress (2). Because such allogrooming follows relationship-specific patterns, it likely serves social functions, such as establishment and maintenance of complex social structures (2) and reduction of tension between individuals (3, 4).Human social bonds are characterized by mutual positive emotions, such as trust and affection between the dyad, that maintain the individuals’ proximity to significant others and modulate interpersonal behavior (5, 6). It is possible that social touch could help maintain the multitude of emotional bonds humans have in all areas of life, ranging from intimate romantic bonds to kinship and friendships. Postnatal skin-to-skin contact indeed promotes mother–infant bonding, and the quantity and quality of social touch are positively associated with relationship satisfaction in adult romantic couples (7). Touching also facilitates confiding via speech (8), and even a brief touch can lead to more positive evaluations of the toucher (9, 10), increased compliance (11), and prosocial behavior, such as more generous tipping in restaurants (12). Behavioral evidence further suggests that human social touch is particularly dependent on the emotional bond between the parties (13): The bodily regions where one may touch different individuals in their social network are relationship-specific (14), with hands and arms being routinely touched by even emotionally distant acquaintances, whereas touching the head, neck, and buttocks is typically restricted to emotionally closer relationships (13, 14).Altogether, the human and monkey data thus suggest that relationship-specific spatial patterns of social touch are intimately related to the establishment and maintenance of social structures and affective relationships among human adults. As the degree of social touching varies across cultures (15, 16), it however remains unclear whether the relationship between social touch and interpersonal emotional bonds mainly reflects biologically driven bonding or culture-based normative behavior. Here we reveal relationship-specific social touching patterns in humans in a large multicultural sample of 1,368 individuals. We focused on the association between social touching and interpersonal emotional bonds, because such bonds are the best predictors for engaging in social contact with someone and consequently tell the positions of different individuals in one’s social network (17).We first explored the reasons for social touching across different social relationships (experiment 1). We then (in experiments 2 and 3) used a high-resolution self-reporting tool [emBODY (18); SI Appendix, Fig. S1] to quantify relationship-specific maps of bodily regions where social touch is allowed. Participants also evaluated how pleasant they would find the touch by different social network members, and they reported when they had last seen each network member. We show that the total bodily area allowed for touching is linearly dependent on the emotional bond with the toucher across a wide range of European cultures (Finland, France, Italy, Russia, and the United Kingdom), with the strength of two individuals’ social bond predicting, on average, 54% of the variance in spatial touching patterns.     

Direct role of structural dynamics in electron-lattice coupling of superconducting cuprates

The mechanism of electron pairing in high-temperature superconductors is still the subject of intense debate. Here, we provide direct evidence of the role of structural dynamics, with selective atomic motions (buckling of copper–oxygen planes), in the anisotropic electron-lattice coupling. The transient structures were determined using time-resolved electron diffraction, following carrier excitation with polarized femtosecond heating pulses, and examined for different dopings and temperatures. The deformation amplitude reaches 0.5% of the c axis value of 30 Å when the light polarization is in the direction of the copper–oxygen bond, but its decay slows down at 45°. These findings suggest a selective dynamical lattice involvement with the anisotropic electron–phonon coupling being on a time scale (1–3.5 ps depending on direction) of the same order of magnitude as that of the spin exchange of electron pairing in the high-temperature superconducting phase.     

An 8-year prospective study of the relationship between cognitive performance and falling in very old adults

OBJECTIVES: To determine whether cognitive performance, as distinct from cognitive impairment, predicts falling during an 8-year follow-up in a community-based sample of very old adults and to evaluate how cognitive change is associated with falling. DESIGN: Prospective cohort study including three waves of data collected in 1992, 1994, and 2000. SETTING: Population based, with the baseline sample drawn from the electoral roll. PARTICIPANTS: Inclusion criteria were completion of at least three cognitive tests at baseline and completion of the falls questionnaire at Wave 6 (N=539). MEASUREMENTS: Assessments of health and medical conditions, visual acuity, cognitive function, functional reach, semitandem stand, and grip strength were conducted in 1992 (baseline), 1994, and 2000. Self-report information on falls in the previous 12 months was obtained on each of these occasions. Marginal models using generalized estimating equations were used to assess the association between baseline cognitive performance and falling over 8 years, adjusting for sociodemographic, health, and sensorimotor variables. Random effects models were used to assess the relationship between change in cognitive performance and change in fall rate and fall risk over 8 years. RESULTS: Mini-Mental State Examination and verbal reasoning at baseline predicted rate of falling over an 8-year period. Within individuals, declines in verbal ability, processing speed, and immediate memory were associated with increases in rates of falling and fall risk. CONCLUSION: Cognitive performance is associated with falling over 8 years in very old adults and should be assessed in clinical practice when evaluating short- and long-term fall risk.     

Fusion of visual cues is not mandatory in children

Human adults can go beyond the limits of individual sensory systems’ resolutions by integrating multiple estimates (e.g., vision and touch) to reduce uncertainty. Little is known about how this ability develops. Although some multisensory abilities are present from early infancy, it is not until age ≥8 y that children use multiple modalities to reduce sensory uncertainty. Here we show that uncertainty reduction by sensory integration does not emerge until 12 y even within the single modality of vision, in judgments of surface slant based on stereoscopic and texture information. However, adults’ integration of sensory information comes at a cost of losing access to the individual estimates that feed into the integrated percept (“sensory fusion”). By contrast, 6-y-olds do not experience fusion, but are able to keep stereo and texture information separate. This ability enables them to outperform adults when discriminating stimuli in which these information sources conflict. Further, unlike adults, 6-y-olds show speed gains consistent with following the fastest-available single cue. Therefore, whereas the mature visual system is optimized for reducing sensory uncertainty, the developing visual system may be optimized for speed and for detecting sensory conflicts. Such conflicts could provide the error signals needed to learn the relationships between sensory information sources and to recalibrate them while the body is growing.     

Neural representations of kinematic laws of motion: evidence for action-perception coupling

Behavioral and modeling studies have established that curved and drawing human hand movements obey the 2/3 power law, which dictates a strong coupling between movement curvature and velocity. Human motion perception seems to reflect this constraint. The functional MRI study reported here demonstrates that the brain's response to this law of motion is much stronger and more widespread than to other types of motion. Compliance with this law is reflected in the activation of a large network of brain areas subserving motor production, visual motion processing, and action observation functions. Hence, these results strongly support the notion of similar neural coding for motion perception and production. These findings suggest that cortical motion representations are optimally tuned to the kinematic and geometrical invariants characterizing biological actions.     

Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals.

We have shown previously the existence of small, activity-dependent changes in intrinsic optical properties of cortex that are useful for optical imaging of cortical functional architecture. In this study we introduce a higher resolution optical imaging system that offers spatial and temporal resolution exceeding that achieved by most alternative imaging techniques for imaging cortical functional architecture or for monitoring local changes in cerebral blood volume or oxygen saturation. In addition, we investigated the mechanisms responsible for the activity-dependent intrinsic signals evoked by sensory stimuli, and studied their origins and wavelength dependence. These studies enabled high-resolution visualization of cortical functional architecture at wavelengths ranging from 480 to 940 nm. With the use of near-infrared illumination it was possible to image cortical functional architecture through the intact dura or even through a thinned skull. In addition, the same imaging technique proved useful for imaging and discriminating sensory-evoked, activity-dependent changes in local blood volume and oxygen saturation (oxygen delivery). Illumination at 570 nm allowed imaging of activity-dependent blood volume increases, whereas at 600-630 nm, the predominant signal probably originated from activity-dependent oxygen delivery from capillaries. The onset of oxygen delivery started prior to the blood volume increase. Thus, optical imaging based on intrinsic signals is a minimally invasive procedure for monitoring short- and long-term changes in cerebral activity.     

Investigation of Low-Pressure Sn-Passivated Cu-to-Cu Direct Bonding in 3D-Integration

Cu-to-Cu direct bonding plays an important role in three-dimensional integrated circuits (3D IC). However, the bonding process always requires high temperature, high pressure, and a high degree of consistency in height. In this study, Sn is passivated over electroplated copper. Because Sn is a soft material and has a low melting point, a successful bond can be achieved under low temperature and low pressure (1 MPa) without any planarization process. In this experiment, Sn thickness, bonding temperature, and bonding pressure are variables. Three values of thicknesses of Sn, i.e., 1 μm, 800 nm, and 600 nm were used to calculate the minimum value of Sn thickness required to compensate for the height difference. Additionally, the bonding process was conducted at two temperatures, 220 °C and 250 °C, and their optimized parameters with required pressure were found. Moreover, the optimized parameters after the Cu planarization were also investigated, and it was observed that the bonding can succeed under severe conditions as well. Finally, transmission electron microscopy (TEM) was used to observe the adhesion property between different metals and intermetallic compounds (IMCs).