Responsiveness and Somatotopic Organization of Anterior Parietal Field 3b and Adjoining Cortex in Newborn and Infant Monkeys

Microelectrodes were used to record from somatosensory areas 3b and adjoining areas 3a and 1 in newborn monkeys. At birth, area 3b was responsive to cutaneous stimuli and had an adult-like somatotopic organization in marmosets and one squirrel monkey, while areas 1 and 3a had only limited responsiveness. In newborn macaque monkeys, cortex was unresponsive to cutaneous stimuli; however, by 1 month, areas 3b and 1 appeared to be adult-like in responsiveness and somatotopic organization.     

Afferent Modulation of Warmth Sensation and Heat Pain in the Human Hand

The hands of 14 normal humans were used to determine the somatotopic organization of the modulation of warmth sensation and heat pain by different forms of cutaneous stimuli. Test stimuli were 5-sec heat pulses ranging from 36° to 51°C, delivered to the fingerpads of digits 1, 2, 4, and 5 with a contact thermode. Conditioning stimuli (15 sec) bracketed the test stimuli and included vibration, noxious and innocuous heat, cold, and electrical pulses delivered to the fingerpads of digits that were adjacent or nonadjacent to the tested digits. Noxious (48° ± 1.3°C), but not innocuous (43°C), heat stimuli increased the perceived magnitude estimation of innocuous test stimuli (36–43°C) by 20–37% when delivered to adjacent, but not to nonadjacent, digits. No other conditioning stimuli had any effect on the intensity of warmth perception. In contrast, both noxious and innocuous heat or electrical conditioning reduced the magnitude estimation of noxious (50–5°C), but not innocuous, test pulses by 12–22% when delivered to adjacent digits. Conditioning of nonadjacent digits was significantly less effective. The analgesic effects of noxious and innocuous conditioning were approximately equal. Vibratory (120 Hz, 3.5 μm) and cold (15°C) conditioning stimuli were ineffective. The results are consistent with a dermatomal somatotopic organization of tactile and heat modulatory influences on warmth sensation and heat pain. The results further suggest that the neural mechanisms subserving warmth mediate a negative feedback influence on heat pain intensity.     

Symmetric sensorimotor somatotopy

Background

Functional imaging has recently been used to investigate detailed somatosensory organization in human cortex. Such studies frequently assume that human cortical areas are only identifiable insofar as they resemble those measured invasively in monkeys. This is true despite the electrophysiological basis of the latter recordings, which are typically extracellular recordings of action potentials from a restricted sample of cells.

Methodology/Principal Findings

Using high-resolution functional magnetic resonance imaging in human subjects, we found a widely distributed cortical response in both primary somatosensory and motor cortex upon pneumatic stimulation of the hairless surface of the thumb, index and ring fingers. Though not organized in a discrete somatotopic fashion, the population activity in response to thumb and index finger stimulation indicated a disproportionate response to fingertip stimulation, and one that was modulated by stimulation direction. Furthermore, the activation was structured with a line of symmetry through the central sulcus reflecting inputs both to primary somatosensory cortex and, precentrally, to primary motor cortex.

Conclusions/Significance

In considering functional activation that is not somatotopically or anatomically restricted as in monkey electrophysiology studies, our methodology reveals finger-related activation that is not organized in a simple somatotopic manner but is nevertheless as structured as it is widespread. Our findings suggest a striking functional mirroring in cortical areas conventionally ascribed either an input or an output somatotopic function.     

Are there ventricle-specific postnatal maturational differences in myocardial beta-adrenoceptors?

Newborn hearts have restricted functional reserve and variable responsiveness to inotropes that could be partly due to differences in myocardial beta-adrenoceptors (beta-AR). To clarify this issue, this study documented ventricle-specific changes in myocardial beta-AR density and affinity during postnatal maturation. In vivo left and right ventricle (LV and RV, respectively) biopsies were obtained from newborn (3-day-old, n = 11), immature (14-day-old, n = 7), and adult (n = 6) pigs. Total beta-AR density (B(max), fmol/g) and dissociation constant (K(d), pmol/L) were determined by radioligand binding with I125 iodocyanopindolol. Overall, beta-AR B(max) in the LV significantly decreased with maturation. Interestingly, newborn animal hearts (LV and RV) subdivided into 2 groups: an adult-like low K(d) group with low B(max) and a fetal-like high K(d) group with high B(max), which were significantly different from one another. The high K(d) newborn group also had significantly higher K(d) and B(max) than both immature and adult hearts. Newborns had similar Bmax but higher Kd in the LV than the RV, whereas immature and adult hearts did not have ventricular differences. During maturation, beta-AR density decreased, whereas LV beta-AR binding affinity increased. Variable beta-AR maturity was also identified immediately post partum, which could potentially explain the newborn heart's variable responsiveness to inotropes. The subset of newborn hearts with lower binding affinity (reduced responsiveness) could also contribute to the newborn heart's overall reduction in functional reserve.     

Imaging the spatio-temporal dynamics of supragranular activity in the rat somatosensory cortex in response to stimulation of the paws

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli.     

The Arbors of Axons Terminating in Middle Cortical Layers of Somatosensory Area 3b in Owl Monkeys

The arbors of single axons terminating predominantly in layer IV of the representation of the hand in area 3b of owl monkeys were reconstructed from serial brain sections after axons beneath the cortex were severed and horseradish peroxidase was injected into the white matter. In addition to dense terminations in layer IV, these labeled axons generally had branches extending into deeper layer III, and a few had very sparse terminations in layer VI. Terminal arbors ranged from 100 to 900 μm in diameter, and fine branches with synaptic boutons were unevenly distributed, typically grouped in a large central cluster and one or more smaller side clusters. The results are consistent with three broad conclusions: (1) Since the arbors are large relative to the details of the somatotopic map in area 3b, all regions within a single arbor may not be equally effective in activating cortical cells. (2) Spatially separate branches of single axons may relate to spatially separate modules of neurons of the same class in a manner that allows them to receive the same inputs. (3) Many of the somatotopic changes that have been reported in the hand representation as a result of nerve manipulations in adults could result from alterations in synaptic effectiveness within the arbors of single axons.     

Optical imaging of nociception in primary somatosensory cortex of non-human primates

While the activation of primary somatosensory (SI) cortex during pain perception is consistently reported in functional imaging studies on normal subjects and chronic pain patients, the specific roles of SI, particularly the subregions within SI, in the processing of sensory aspects of pain are still largely unknown. Using optical imaging of intrinsic signal (OIS) and single unit electrophysiology, we studied cortical activation patterns within SI cortex (among Brodmann areas 3a, 3b and 1) and signal amplitude changes to various intensities of non-nociceptive, thermal nociceptive and mechanical nociceptive stimulation of individual distal finerpads in anesthetized squirrel monkeys. We have demonstrated that areas 3a and 1 are preferentially involved in the processing of nociceptive information while areas 3b and 1 are preferentially activated in the processing of non-nociceptive (touch) information. Nociceptive activations of individual fingerpad were organized topographically suggesting that nociceptive topographic map exits in areas 3a and 1. Signal amplitude was enhanced to increasing intensity of mechanical nociceptive stimuli in areas 3a, 3b and 1. Within area 1, nociceptive response co-localizes with the non-nociceptive response. Therefore, we hypothesize that nocicepitve information is area-specifically represented within SI cortex, in which nociceptive inputs are preferentially represented in areas 3a and 1 while non-nociceptive inputs are preferentially represented in areas 3b and 1.     

外周损伤引起成年大鼠体感皮层的功能重组

为了了解外周神经损伤对体感皮层分域组构的影响,在成年大鼠上观察了切断坐骨神经(SC)前、即刻和切断后数周内后爪皮层代表区的改变。在盐酸氯胺酮麻醉下,用微电极记录后爪皮肤轻触刺激在对侧体感皮层工区诱发的多单位反应,得出后爪的皮层代表区图。在16例中,8例大鼠观察了切断SC的即时效应。结果表明,不但SC代表区丧失皮肤反应性,原隐神经(SA)代表区的皮肤反应性也明显下降或消失,同时神经元自发活动也明显减弱。另8例大鼠在切断后数周内做了1～3次重复测定。在最初几天,原SA代表区范围内多数记录点的皮肤反应性仍未恢复,但在原SC代表区内,一些记录点转而对SA皮肤轻触刺激起反应。在随后数周内SA代表区进行性地扩张,占领了大部分原SC代表区。这一结果说明成年大鼠外周神经损伤可导致体感皮层发生显著的重组改变。     

Tactile-spatial and cross-modal attention effects in the primary somatosensory cortical areas 3b and 1-2 of rhesus monkeys

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

Ablations of areas 3b (SI proper) and 3a of somatosensory cortex in marmosets deactivate the second and parietal ventral somatosensory areas

Partial ablations of specific parts of cortical areas 3b (SI proper) and 3a in marmosets were found to render somatotopically equivalent parts of two other cortical somatosensory fields, the second somatosensory area (SII) and the parietal ventral area (PV), unresponsive to peripheral stimulation. Microelectrode recordings in anesthetized marmosets first established the responsiveness and locations of the representations of body parts, including the hand in areas 3a and 3b, SII, and in some cases PV. The hand representations in areas 3a and 3b were then removed by aspiration. Immediately afterwards, additional recordings established that regions of SII and PV that formerly represented the hand were no longer responsive to cutaneous stimulation of the hand (or any other skin surface). Other parts of these fields, representing parts of the body other than the hand, remained responsive to stimulation of the previously effective receptive fields. We conclude that SII and PV depend on inputs (either direct or indirect) from areas 3a and 3b for their activation.     

Disorders in learning and memory processes in the monkey model of Alzheimer's disease: the role of the cerebral cortex associative areas

Processes of novelty learning and keeping the results in Alzheimer's disease in two groups of rhesus-monkeys (three monkeys in each group), were studied: following neurotoxins administrati- on (I group) and saline administration (II group). In two months after the injections (the C1 stage), considerable differences between the groups were revealed in the task of differentiation among contour shapes. For the I group monkeys the learning was difficult: the correct decision making did not reach 85 %, and the probability of refusing to make a decision increased. For the II group monkeys the learning characteristics were not disturbed. In six months after the injections (the C3 stage) the differences between the groups in the task of differentiation among new stimuli (heads of two monkeys) remained at the same level. When studying characteristics of the operative memory associated with keeping the learning results achieved at the C1 stage, a considerable worsening of these characteristics was revealed: diminishing of the correct decision making probability at the C1 stage (actually to the level of 0.5), increase in the probability of refusing to make a decision. The structural-functional organization of interaction between sensory and cognitive processes in learning and keeping the information in the operative memory, is discussed in association with the control of motivation and attention system and the role of the cortex associative areas.     

Chronological observations of primary somatosensory cortical maps in kittens following low thoracic (T12) spinal cord transection at 2 weeks of age.

The present study investigated the reorganization of the somatosensory cortex in kittens following T12 spinal cord transection at 2 weeks of age. Multiunit electrophysiological methods were used to map the somatosensory cortex of kittens at 3, 6, and 9 weeks after the transection. The entire reorganized cortical region was driven by substitute cutaneous inputs, primarily from the trunk, at 3 weeks after spinal cord transection. Although the level of cortical responsiveness remained the same throughout the 9 weeks studied, internal trunk representation changed, and there was an increase in shoulder girdle representation and emergence of forelimb representation. Poor somatotopic and topographic order was observed in the reorganized cortex, regardless of time posttransection. Finally, trunk receptive fields displayed a wide variety of shapes, sizes, and orientations not seen in the normal cortex.     

Do newborn vocalizations affect the behavioral and hormonal responses of nonreproductive male common marmosets (Callithrix jacchus)?

Parental care in mammals is influenced by sensory stimuli from infants, such as sight and sound, and by changes in the hormone levels of caretakers. To determine the responsiveness of common marmoset (Callithrix jacchus) adult males with and without previous experience in caretaking to newborn sensory cues, we exposed twelve males to infant vocalization recordings and assessed their hormonal and behavioral responses. Males were placed in the testing cage for 10 min under two conditions: (a) control condition (exposure to adult conspecific vocalization recordings), and (b) experimental condition (exposure to infant vocalization recordings). We recorded the frequency of approach towards the sound source, the time spent near it and locomotion frequency of males in the cage under both conditions. Blood samples were collected after each test for cortisol, measured by the enzyme immunoassay method. Infant vocalization affects the behavioral and hormonal responses of non-reproductive male common marmosets. All males approached and spent more time near the sound source and showed an increase in locomotion during infant vocalization exposure compared to the control condition. Successive exposure to infant vocalization increased the responsiveness in inexperienced males. Cortisol levels were significantly higher following infant vocalization exposure compared to the control condition. These findings support the assumption that sound stimuli from the newborn are critical in initiating and maintaining caretaker responsiveness and that cortisol seems to be important for alertness to sensory stimuli, modulating their motivation to interact with infants.     

Chronological Observations of Primary Somatosensory Cortical Maps in Kittens following Low Thoracic (T12) Spinal Cord Transection at 2 Weeks of Age

The present study investigated the reorganization of the somatosensory cortex in kittens following T₁₂ spinal cord transection at 2 weeks of age. Multiunit electrophysiological methods were used to map the somatosensory cortex of kittens at 3, 6, and 9 weeks after the transection. The entire reorganized cortical region was driven by substitute cutaneous inputs, primarily from the trunk, at 3 weeks after spinal cord transection. Although the level of cortical responsiveness remained the same throughout the 9 weeks studied, internal trunk representation changed, and there was an increase in shoulder girdle representation and emergence of forelimb representation. Poor somatotopic and topographic order was observed in the reorganized cortex, regardless of time posttransection. Finally, trunk receptive fields displayed a wide variety of shapes, sizes, and orientations not seen in the normal cortex.     

Neuroprotective effects on somatotopic maps resulting from piracetam treatment and environmental enrichment after focal cortical injury

Acute and chronic postlesion reorganization of the cortical maps was examined in adult rats using electrophysiological mapping of the forepaw area in the primary somatosensory cortex. Recordings were made before and after (first 12 hr and 3 wk) induction of a focal thermal-ischemic lesion to a restricted part of the forepaw area. The influence of an anti-ischemic substance (piracetam) and housing in an enriched environment (EE) or impoverished environment (IE) on the organization of the spared regions of the cortical maps adjacent to the lesion was investigated. The results revealed (1) a gradual expansion of the injured zone and a cellular loss that were smaller in the piracetam-treated (PT) rats than in the placebo (PL) rats; (2) a better preservation of the somatotopic organization and the neuronal responsiveness in the maps of the PT rats during the first 12 hr after the lesion; (3) a gradual compression and fragmentation of the remaining forepaw map over the first 3 postlesion wk. These changes were found in all PL rats, with the most detrimental effects in the animals exposed to an IE. In the PT-EE animals, a contrasting substantial preservation of the map was observed. (4) Cortical responsiveness was diminished in the PL rats, whatever the environment, and in the PT-IE rats; but it was not significantly affected in the PT-EE animals. The findings demonstrate the protective function of acute piracetam treatment on electrophysiological properties of cortical neurons within the peri-infarct tissue and highlight the neuroprotective effects of an environmental therapy combined with the piracetam treatment during the weeks after ischemic damage.     

Attention-related,cross-modality modulation of somatosensory neurons in primate ventrobasal (VB) thalamus

Attention-related modulation (AM) of the somatosensory responses of single neurons has been demonstrated in the cerebral cortex and medullary dorsal horn, but not in the ventrobasal thalamus. The somatically evoked activity was recorded of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys while they detected the termination of task-relevant somatic or visual stimuli. Eighteen of 56 somatically responsive VPL neurons are reported that were recorded for enough time for a complete analysis of their responses during both the visual and somatic attention tasks. All neurons were spontaneously active and responded either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%) showed AM only during the visual task, two others (2/7, 28.6%) only during the somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All five cells showing AM during the somatosensory task had enhanced responses to the task-relevant somatic stimulus. In contrast, the somatosensory responses of all five cells showing AM during the visual task were reduced. It is concluded that selective attention is associated with a modality specific modulation of the somatosensory responses of a sub-population of neurons within the primate VPL nucleus.     

Meeting report

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

Attention-related, cross-modality modulation of somatosensory neurons in primate ventrobasal (VB) thalamus

Attention-related modulation (AM) of the somatosensory responses of single neurons has been demonstrated in the cerebral cortex and medullary dorsal horn, but not in the ventrobasal thalamus. The somatically evoked activity was recorded of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys while they detected the termination of task-relevant somatic or visual stimuli. Eighteen of 56 somatically responsive VPL neurons are reported that were recorded for enough time for a complete analysis of their responses during both the visual and somatic attention tasks. All neurons were spontaneously active and responded either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%) showed AM only during the visual task, two others (2/7, 28.6%) only during the somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All five cells showing AM during the somatosensory task had enhanced responses to the task-relevant somatic stimulus. In contrast, the somatosensory responses of all five cells showing AM during the visual task were reduced. It is concluded that selective attention is associated with a modality specific modulation of the somatosensory responses of a sub-population of neurons within the primate VPL nucleus.     

Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation

We describe methods of localizing functional regions of the mesial wall, based on 47 patients studied intraoperatively or following chronic implantation of subdural electrodes. Somatosensory evoked potentials were recorded to stimulation of posterior tibial, dorsal pudendal, median, and trigeminal nerves. Bipolar cortical stimulation was performed, and in 4 cases movement-related potentials were recorded.The cingulate and marginal sulci formed the inferior and posterior borders of the sensorimotor areas and the supplementary motor area (SMA). The foot sensory area occupied the posterior paracentral lobule, while the genitalia were represented anterior to the foot sensory area, near the cingulate sulcus. The foot motor area was anterior and superior to the sensory areas, but there was overlap in these representations. There was a rough somatotopic organization within the SMA, with the face represented anterior to the hand. However, there was little evidence of the “pre-SMA” region described in monkeys. Complex movements involving more than one extremity were elicited by stimulation of much of the SMA. The region comprising the supplementary sensory area was not clearly identified, but may involve much of the precuneus. Movement-related potentials did not provide additional localizing information, although in some recordings readiness potentials were recorded from the SMA that appeared to be locally generated.     

Impact of Chronodisruption during Primate Pregnancy on the Maternal and Newborn Temperature Rhythms

Disruption of the maternal environment during pregnancy is a key contributor to offspring diseases that develop in adult life. To explore the impact of chronodisruption during pregnancy in primates, we exposed pregnant capuchin monkeys to constant light (eliminating the maternal melatonin rhythm) from the last third of gestation to term. Maternal temperature and activity circadian rhythms were assessed as well as the newborn temperature rhythm. Additionally we studied the effect of daily maternal melatonin replacement during pregnancy on these rhythms. Ten pregnant capuchin monkeys were exposed to constant light from 60% of gestation to term. Five received a daily oral dose of melatonin (250 µg kg/body weight) at 1800 h (LL+Mel) and the other five a placebo (LL). Six additional pregnant females were maintained in a 14∶10 light:dark cycles and their newborns were used as controls (LD). Rhythms were recorded 96 h before delivery in the mother and at 4–6 days of age in the newborn. Exposure to constant light had no effect on the maternal body temperature rhythm however it delayed the acrophase of the activity rhythm. Neither rhythm was affected by melatonin replacement. In contrast, maternal exposure to constant light affected the newborn body temperature rhythm. This rhythm was entrained in control newborns whereas LL newborns showed a random distribution of the acrophases over 24-h. In addition, mean temperature was decreased (34.0±0.6 vs 36.1±0.2°C, in LL and control, respectively P<0.05). Maternal melatonin replacement during pregnancy re-synchronized the acrophases and restored mean temperature to the values in control newborns. Our findings demonstrate that prenatal melatonin is a Zeitgeber for the newborn temperature rhythm and supports normal body temperature maintenance. Altogether these prenatal melatonin effects highlight the physiological importance of the maternal melatonin rhythm during pregnancy for the newborn primate.