Secondary somatosensory cortex of primates: beyond body maps, toward conscious self-in-the-world maps.

Recent human imaging studies have revealed the involvement of the secondary somatosensory cortex (SII) in processes that require high-level information integration, such as self-consciousness, social relations, whole body representation, and metaphorical extrapolations. These functions are far beyond its known role in the formation of body maps (even in their most complex forms), requiring the integration of different information modalities in addition to somatosensory information. However, no evidence of such complex processing seems to have been detected at the neuronal level in animal experiments, which would constitute a major discrepancy between human and non-human animals. This article scrutinizes this gap, introducing experimental evidence of human and non-human primates' SII functions set in context with their evolutionary significance and mechanisms, functionally situating the human SII as a primate brain. Based on the presented data, a new concept of a somatocentric holistic self is proposed, represented as a more comprehensive body-in-the-world map in the primate SII, taking into account evolutionary aspects that characterize the human SII and its implication in the emergence of self-consciousness. Finally, the idea of projection is introduced from the viewpoint of cognitive science, providing a logical explanation to bridge this gap between observed behavior and neurophysiological data.

Visual Responsiveness of Neurons in the Secondary Somatosensory Area and its Surrounding Parietal Operculum Regions in Awake Macaque Monkeys.

Previous neurophysiological studies performed in macaque monkeys have shown that the secondary somatosensory cortex (SII) is essentially engaged in the processing of somatosensory information and no other sensory input has been reported. In contrast, recent human brain-imaging studies have revealed the effects of visual and auditory stimuli on SII activity, which suggest multisensory integration in the human SII. To determine whether multisensory responses of the SII also exist in nonhuman primates, we recorded single-unit activity in response to visual and auditory stimuli from the SII and surrounding regions in 8 hemispheres from 6 awake monkeys. Among 1157 recorded neurons, 306 neurons responded to visual stimuli. These visual neurons usually responded to rather complex stimuli, such as stimulation of the peripersonal space (40.5%), observation of human action (29.1%), and moving-object stimulation outside the monkey's reach (23.9%). We occasionally applied auditory stimuli to visual neurons and found 10 auditory-responsive neurons that exhibited somatosensory responses. The visual neurons were distributed continuously along the lateral sulcus covering the entire SII, along with other somatosensory neurons. These results highlight the need to investigate novel functional roles-other than somesthetic sensory processing-of the SII.

Periostin, a neurite outgrowth-promoting factor, is expressed at high levels in the primate cerebral cortex.

Periostin (POSTN or osteoblast specific factor) is an extracellular matrix protein originally identified as a protein highly expressed in osteoblasts. Recently, periostin has been reported to function in axon regeneration and neuroprotection. In the present study, we focused on periostin function in cortical evolution. We performed a comparative gene expression analysis of periostin between rodents (mice) and primates (marmosets and macaques). Periostin was expressed at higher levels in the primate cerebral cortex compared to the mouse cerebral cortex. Furthermore, we performed overexpression experiments of periostin in vivo and in vitro. Periostin exhibited neurite outgrowth activity in cortical neurons. These results suggested the possibility that prolonged and increased periostin expression in the primate cerebral cortex enhances the cortical plasticity of the mammalian cerebral cortex.

Identification of tool use acquisition-associated genes in the primate neocortex.

Japanese macaques are able to learn how to use rakes to take food after only a few weeks of training. Since tool-use training induced rapid morphological changes in some restricted brain areas, this system will be a good model for studying the neural basis of plasticity in human brains. To examine the mechanisms of tool-use associated brain expansion on the molecular and cellular level, here, we performed comprehensive analysis of gene expressions with microarray. We identified various transcripts showing differential expression between trained and untrained monkeys in the region around the lateral and intraparietal sulci. Among candidates, we focused on genes related to synapse formation and function. Using quantitative reverse transcription-polymerase chain reaction and histochemical analysis, we confirmed at least three genes (ADAM19, SPON2, and WIF1) with statistically different expression levels in neurons and glial cells. Comparative analysis revealed that tool use-associated genes were more obviously expressed in macaque monkeys than marmosets or mice. Thus, our findings suggest that cognitive tasks induce structural changes in the neocortex via gene expression, and that learning-associated genes innately differ with relation to learning ability.

Neural response to movement of the hand and mouth in the secondary somatosensory cortex of Japanese monkeys during a simple feeding task.

Neural activity was recorded in the secondary somatosensory cortex (SII) of macaque monkeys during a simple feeding task. Around the border between the representations of the hand and face in SII, we found neurons that became active during both retrieving with the hand and eating; 59% had receptive fields (RFs) in the hand/face and the remaining 41% had no RFs. Neurons that responded to touching objects were rarely found. This suggests their sensorimotor function rather than tactile object recognition.

Modulation of cortical vestibular processing by somatosensory inputs in the posterior insula.

PRIMARY OBJECTIVE: To study the mechanism of somatosensory-vestibular interactions, this study examined the effects of somatosensory inputs on body sway induced by galvanic vestibular stimulation (GVS) in healthy participants and persons with brain injury in the posterior insula, a region constituting a part of the parietoinsular vestibular cortex. RESEARCH DESIGN: This study adopted an experimental, controlled, repeated measures design. METHODS AND PROCEDURES: Participants were 11 healthy individuals, two persons with unilateral posterior insular injury and two age-matched controls. Bipolar GVS was applied to the mastoid processes while participants were sitting with their eyes closed, either lightly touching a stable surface with their index finger or not touching the surface with their index finger. MAIN OUTCOMES AND RESULTS: In healthy participants, tilting was greater with right hemispheric stimulation than with left hemispheric stimulation. Moreover, with right hemispheric stimulation, tilting was greater with a right finger touch than with no touch. The person with right-brain injury showed tilting induced by GVS; however, finger touch had no modulatory effect. In contrast, finger touch enhanced tilting in the person with left-brain injury. CONCLUSIONS: These preliminary results are discussed in light of a hypothesis of right hemispheric dominance of somatosensory-vestibular interactions in the posterior insula.

Adaptive changes in firing of primary auditory cortical neurons following illumination shift from light to dark in freely moving guinea pigs.

Some animals are forced to rely more on non-visual signals, such as audition or olfaction, than on vision when a bright environment becomes dark. By recording from a primary-like auditory cortex (field A) in freely moving guinea pigs, possible changes in the responsiveness of single units were explored in association with illumination changes. For a subset of units, we found that robust decreases (off-decrease) or increases (off-increase) in baseline discharge (BsD) were initiated soon after room light was silently extinguished. These neuronal changes were accompanied by the initiation of explorative locomotion, possibly reflecting a changed internal brain state. Preferred acoustic stimuli evoked salient excitatory responses against the reduced BsD level in the dark for the off-decrease units, and salient inhibitory responses against the increased BsD level for the off-increase units. Histological verification indicated that the units showing such BsD changes were located predominantly in layer V or its vicinity. These results are discussed in the context of the effects of the brainstem neuromodulatory systems that are activated during behavioral adaptation to new environments.

Neural Evidence of Mirror Self-Recognition in the Secondary Somatosensory Cortex of Macaque: Observations from a Single-Cell Recording Experiment and Implications for Consciousness.

Despite mirror self-recognition being regarded as a classical indication of self-awareness, little is known about its neural underpinnings. An increasing body of evidence pointing to a role of multimodal somatosensory neurons in self-recognition guided our investigation toward the secondary somatosensory cortex (SII), as we observed single-neuron activity from a macaque monkey sitting in front of a mirror. The monkey was previously habituated to the mirror, successfully acquiring the ability of mirror self-recognition. While the monkey underwent visual and somatosensory stimulation, multimodal visual and somatosensory activity was detected in the SII, with neurons found to respond to stimuli seen through the mirror. Responses were also modulated by self-related or non-self-related stimuli. These observations corroborate that vision is an important aspect of SII activity, with electrophysiological evidence of mirror self-recognition at the neuronal level, even when such an ability is not innate. We also show that the SII may be involved in distinguishing self and non-self. Together, these results point to the involvement of the SII in the establishment of bodily self-consciousness.

Fast Electrophysiological Mapping of Rat Cortical Motor Representation on a Time Scale of Minutes during Skin Stimulation.

The topographic map of motor cortical representation, called the motor map, is not invariant, but can be altered by motor learning, neurological injury, and functional recovery from injury. Although much attention has been paid to short-term changes of the motor map, robust measures have not been established. The existing mapping methods are time-consuming, and the obtained maps are confounded by time preference. The purpose of this study was to examine the dynamics of the motor map on a timescale of minutes during transient somatosensory input by a fast motor mapping technique. We applied 32-channel micro-electrocorticographic electrode arrays to the rat sensorimotor cortex for cortical stimulation, and the topographic profile of motor thresholds in forelimb muscle was identified by fast motor mapping. Sequential motor maps were obtained every few minutes before, during, and just after skin stimulation to the dorsal forearm using a wool buff. During skin stimulation, the motor map expanded and the center of gravity of the map was shifted caudally. The expansion of the map persisted for at least a few minutes after the end of skin stimulation. Although the motor threshold of the hotspot was not changed, the area in which it was decreased appeared caudally to the hotspot, which may be in the somatosensory cortex. The present study demonstrated rapid enlargement of the forelimb motor map in the order of a few minutes induced by skin stimulation. This helps to understand the spatial dynamism of motor cortical representation that is modulated rapidly by somatosensory input.

Rapid Identification of Cortical Motor Areas in Rodents by High-Frequency Automatic Cortical Stimulation and Novel Motor Threshold Algorithm.

Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity) and clinical practice (e.g., before resecting brain tumors involving the motor cortex). However, compilation of motor maps based on the motor threshold (MT) requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs) through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12) the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS) significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8), while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help to study the functional significance of short-term plasticity in motor learning and recovery from brain injuries. Besides this advantage, particularly in the case of human patients or experimental animals that are less trained to remain at rest, shorter mapping time is physically and mentally less demanding and might allow the evaluation of motor maps in awake individuals as well.

Integration of the upper and lower lips in the postcentral area 2 of conscious macaque monkeys (Macaca fuscata).

The representation of the lip in area 2 of the postcentral somatosensory cortex was studied in conscious macaque monkeys by recording single-neurone activities. Seventy penetrations were made in the oral region of six hemispheres of four animals and 1157 neurones were isolated. The receptive field characteristics of 839 neurones were identified. Among them, 363 neurones along 47 penetrations responded to mechanical lip stimulation (lip neurones). A substantial number of lip neurones (17%, 62/363) had composite receptive fields that included not only the lip but also other oral structures. Although, the majority of lip neurones had receptive fields on either the upper or the lower lip (unilabial neurones), about 20% had receptive fields including both the upper and lower lips (bilabial neurones). Receptive field features of bilabial neurones were summarized as follows: (1) the receptive fields always included the corresponding sites of the upper and lower lips that would come into contact when the jaw closed; (2) the submodality preferences of the upper and lower portions of the receptive fields were identical in all cases; (3) if a light stroking stimulus in a specific direction was adequate, portions of the receptive field on the upper and lower lips responded with a common directional preference. Furthermore, bilabial receptive fields were unlikely to be the simple 'dimer' of unilabial receptive fields: the relative incidence of neurones with bilateral or composite receptive fields was much higher in bilabial than in unilabial neurones. That is, bilabial integration was accompanied by the integration of both sides of the lips, and of the lip and other adjacent oral structures. These features of bilabial neurones appear to be suitable for the form discrimination of objects held in the anterior part of the mouth. These neurones may be the prerequisite neural basis for the oral stereognosis that would take place in the neighbouring association cortices.

Hand before foot? Cortical somatotopy suggests manual dexterity is primitive and evolved independently of bipedalism.

People have long speculated whether the evolution of bipedalism in early hominins triggered tool use (by freeing their hands) or whether the necessity of making and using tools encouraged the shift to upright gait. Either way, it is commonly thought that one led to the other. In this study, we sought to shed new light on the origins of manual dexterity and bipedalism by mapping the neural representations in the brain of the fingers and toes of living people and monkeys. Contrary to the 'hand-in-glove' notion outlined above, our results suggest that adaptations underlying tool use evolved independently of those required for human bipedality. In both humans and monkeys, we found that each finger was represented separately in the primary sensorimotor cortex just as they are physically separated in the hand. This reflects the ability to use each digit independently, as required for the complex manipulation involved in tool use. The neural mapping of the subjects' toes differed, however. In the monkeys, the somatotopic representation of the toes was fused, showing that the digits function predominantly as a unit in general grasping. Humans, by contrast, had an independent neurological representation of the big toe (hallux), suggesting association with bipedal locomotion. These observations suggest that the brain circuits for the hand had advanced beyond simple grasping, whereas our primate ancestors were still general arboreal quadrupeds. This early adaptation laid the foundation for the evolution of manual dexterity, which was preserved and enhanced in hominins. In hominins, a separate adaptation, involving the neural separation of the big toe, apparently occurred with bipedality. This accords with the known fossil evidence, including the recently reported hominin fossils which have been dated to 4.4 million years ago.

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions.

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language--the site of such integration seems to be the parietal and extending opercular cortices.

Postcentral neurons with covert receptive fields in conscious macaque monkeys: their selective responsiveness to simultaneous two-point stimuli applied to discrete oral portions.

The representation of the oral structures in the postcentral somatosensory cortex was studied in conscious macaque monkeys by recording the activity of single neurons. A total of 2,807 neurons were isolated in the oral regions of three hemispheres in two animals. Of these, 375 neurons (area 3a, 3; area 3b, 123; area 1, 99; area 2, 150) lacked an apparent receptive field (RF), and their relative frequency was significantly higher in area 2 (19%) than in more rostral areas (area 3a, 8%; area 3b, 10%; area 1, 12%). We tested the responsiveness of these neurons to stimuli applied simultaneously to two discrete, but functionally related, oral structures (interstructural two-point stimuli: iTPS). Neurons in areas 3a, 3b, and 1 that lacked an apparent RF were not responsive to iTPS. However, 35 neurons in area 2 responded stably to iTPS applied to either of the following sets of oral structures: the tongue and incisors (n=18), incisors and lip (n=9), lip and tongue (n=12), or upper and lower lips (n=8). Of them, 19 neurons were activated during self-movements such as tongue protrusion, lip licking, and food manipulation. The neurons selectively responsive to iTPS might detect converging inputs from different oral structures and play a pivotal role in detecting objects straddling different oral structures and the mutual contact of oral structures.

Converging patterns of inputs from oral structures in the postcentral somatosensory cortex of conscious macaque monkeys.

Single neuronal activities were recorded in the oral region of the postcentral gyrus in conscious Japanese monkeys. Among 5,756 neurons isolated, receptive fields (RFs) and submodalities were identified in 1,502 neurons in area 3b, 970 in area 1, and 1,461 in area 2. The relative incidence of neurons that had bilateral RFs increased gradually upon moving caudally from area 3b to area 2 (bilateral integration). A total of 276 neurons had bimaxillary RFs covering both the maxillary and mandibular divisions of the trigeminal nerve, such as the upper and lower lips, upper and lower teeth, palate and tongue, or combinations thereof. There was also a tendency for the relative incidence of neurons with bimaxillary RFs to increase across the postcentral gyrus but with an abrupt change in area 2 (bimaxillary integration). A total of 382 neurons had composite RFs covering more than one of five oral structures: lip, cheek mucosa, teeth/gingiva, tongue, and palate. The relative incidence of neurons with composite RFs was significantly higher in area 2 than in areas 3b and 1 (interstructural integration). These results indicate that the convergence of inputs from oral structures proceeds in a hierarchical manner across the postcentral gyrus, but chiefly in area 2 for the bimaxillary and interstructural integrations. The relative incidence of neurons with composite RFs was higher among neurons associated with the teeth/gingiva or palate than among neurons associated with the tongue or lip in all three areas. We interpret this to mean that anatomical or functional differences between oral structures might be reflected in the converging patterns in the oral representation.

Hierarchical somesthetic processing of tongue inputs in the postcentral somatosensory cortex of conscious macaque monkeys.

The representation of the oral structures in the lateralmost part of the postcentral somatosensory cortex in conscious macaque monkeys was studied by recording the activities of single neurons. A total of 104 penetrations were made in the oral regions of six hemispheres in four animals and 2,292 neurons were isolated. The characteristics of the receptive fields (RF) of 1,598 neurons were identified. Of them, 513 neurons (area 3b, 196; area 1, 104; area 2, 213) along 44 penetrations responded to mechanical stimulation of the tongue (tongue neurons). The relative incidence of tongue neurons that had bilateral RFs increased gradually (bilateral integration) on moving caudally from area 3b to area 2. There was also a tendency for the RFs on the tongue to expand in the anteroposterior axis of the tongue (anteroposterior integration). Furthermore, the relative incidence of tongue neurons with composite RFs covering both the tongue and other surrounding oral structures was significantly higher in area 2 than in areas 3b and 1 (interstructural integration). As a result of the bilateral, anteroposterior and interstructural integration, the extent of the RFs of tongue neurons increased progressively from area 3b to area 2. We therefore concluded that hierarchical somatosensory processing, which has been established in the postcentral somatosensory cortex representing other body parts, is also present in the oral representation. We speculate that the hierarchical scheme in the oral representation might be a prerequisite neural process for the oral stereognosis that eventually takes place in the association cortices.