Large-Scale Reorganization in the Somatosensory Cortex and Thalamus after Sensory Loss in Macaque Monkeys
TL;DR: A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.
Abstract: Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22-23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.
Citations
More filters
TL;DR: In this article, diffusion tensor imaging and functional magnetic resonance imaging were used as surrogate markers of chronic motor impairment and predictors of functional potential for motor recovery in human ischaemic stroke.
Abstract: Human ischaemic stroke is a multistage disorder with various routes of recovery. Neuroimaging allows researchers to explore the pathophysiology and recovery mechanisms in vivo. Based on these findings, motor recovery and chronic motor impairment after stroke have been linked to structural alterations of grey and white matter as well as functional changes in the perilesional tissue. Parameters derived from diffusion tensor imaging and functional magnetic resonance imaging can be used as surrogate markers of chronic motor impairment and predictors of functional potential for motor recovery. These parameters have the potential to tailor individual rehabilitation and stratify patients for experimental therapy studies such as invasive and non-invasive brain stimulation alone or in combination with other facilitators.
3 citations
TL;DR: Limitations to brain plasticity and to the role of experience in shaping the functional organization of the brain are revealed.
Abstract: What forces direct brain organization and its plasticity? When a brain region is deprived of its input would this region reorganize based on compensation for the disability and experience, or would strong limitations of brain structure limit its plasticity? People born without hands activate their sensorimotor hand region while moving body parts used to compensate for this ability (e.g. their feet). This has been taken to suggest an organization based on functions, such as performing manual-like dexterous actions, rather than on body parts. Here we test the selectivity for functionally-compensatory body parts in the sensorimotor cortex of people born without hands. Despite clear compensatory foot use, the sensorimotor hand area in the dysplasic subjects showed preference for non-compensatory body parts whose cortical territory is close to the hand area. This suggests that function-based organization, originally proposed for full congenital blindness and deafness, does not apply to cases of the primary sensorimotor cortex in dysplasia. This is consistent with the idea that experience-independent functional specialization occurs at relatively high levels of representation. Furthermore, it stresses the roles of neuroanatomical constraints such as topographical proximity and connectivity in determining the functional development of brain regions. These findings reveal limitations to brain plasticity and to the role of experience in shaping the functional organization of the brain.
3 citations
Cites background from "Large-Scale Reorganization in the S..."
...While some connectivity can be modulated to permit innervation from remote body parts in cases of deafferentation (43), our data suggests it is not sufficient, in congenital full upper limb dysplasia, to evoke preferential takeover....
[...]
TL;DR: The expectation that drastic reorganization in the cortical circuits was induced after crossing nerve transfer in mice was confirmed, with tomographic imaging of flavoprotein fluorescence responses confirmed.
Abstract: To understand the neural mechanisms underlying the therapeutic effects of crossing nerve transfer for brachial plexus injuries in human patients, we investigated the cortical responses after crossing nerve transfer in mice using conventional and tomographic optical imaging. The distal cut ends of the left median and ulnar nerves were connected to the central cut ends of the right median and ulnar nerves with a sciatic nerve graft at 8 weeks of age. Eight weeks after the operation, the responses in the primary somatosensory cortex (S1) elicited by vibratory stimulation applied to the left forepaw were visualized based on activity-dependent flavoprotein fluorescence changes. In untreated mice, the cortical responses to left forepaw stimulation were mainly observed in the right S1. In mice with nerve crossing transfer, cortical responses to left forepaw stimulation were observed in the left S1 together with clear cortical responses in the right S1. We expected that the right S1 responses in the untreated mice were produced by thalamic inputs to layer IV, whereas those in the operated mice were mediated by callosal inputs from the left S1 to layer II/III of the right S1. To confirm this hypothesis, we performed tomographic imaging of flavoprotein fluorescence responses by macroconfocal microscopy. Flavoprotein fluorescence responses in layer IV were dominant compared to those in layer II/III in untreated mice. In contrast, responses in layer II/III were dominant compared to those in layer IV in operated mice. The peak latency of the cortical responses in the operated mice was longer than that in the untreated mice. These results confirmed our expectation that drastic reorganization in the cortical circuits was induced after crossing nerve transfer in mice.
3 citations
TL;DR: It is proposed that a topographic scaffolding is present at birth that both directs and constrains experience-driven modifications throughout sensory systems and demonstrates that massive shifts in early sensory experience in an otherwise anatomically intact brain are not sufficient for driving cross-modal plasticity.
Abstract: Topographic sensory maps are a prominent feature of the adult primate brain. Here, we asked whether topographic representations of the environment are fundamental to early development. Using fMRI, we find that the newborn somato-motor system, spanning frontoparietal cortex and subcortex, comprises multiple topographic body representations. The organization of these large-scale body maps was indistinguishable from those in adults and already exhibited features stereotypical of adult maps. Finer-scale differentiation of individual fingers increased over the first two years, suggesting that topographic representations are refined during early development. Last, we found that somato-motor representations were unchanged in two visually impaired monkeys who relied entirely on touch for interacting with their environment, demonstrating that massive shifts in early sensory experience in an otherwise anatomically intact brain are not sufficient for driving cross-modal plasticity. We propose that a topographic scaffolding is present at birth that both directs and constrains experience-driven modifications throughout sensory systems.
3 citations
TL;DR: The traditional experimental challenges of measuring serotonin, how voltammetry overcomes some of these difficulties, and future plans to better understand the function of serotonin in behavior are discussed.
Abstract: Serotonin's involvement in many physiological processes including anxiety, stress, aggression, and mood has been known for decades; however, a more in-depth characterization of serotonin function in the brain is still missing. Insufficient progress in our understanding of serotonin function is in part due to the lack of effective tools to selectively measure this neurotransmitter on a relevant time scale in vivo. An analytical technique for serotonin measurements, fast-scan cyclic voltammetry was recently pioneered in anesthetized rodents and is beginning to shed light on the complexity of serotonergic activity on a subsecond time scale. Complementary, due to even more recent technological developments, ambient serotonin levels can now also be assessed with high temporal resolution using a method called fast-scan controlled-adsorption voltammetry. Here, we discuss the traditional experimental challenges of measuring serotonin, how voltammetry overcomes some of these difficulties, and future plans to better understand the function of serotonin in behavior.
2 citations
References
More filters
TL;DR: The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae of kittens, leading to a significant decreases in the level of oxidative enzyme activity one to several synapses away.
1,862 citations
TL;DR: A very strong direct relationship is reported between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation, indicating that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
Abstract: Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
1,692 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...A small expansion of the face inputs into the hand region of the cortex was seen long after hand or arm amputations (Flor et al., 1995; Florence and Kaas, 1995; Grüsser et al., 2004), or immediately after median and radial nerve injury or block (Silva et al....
[...]
TL;DR: The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2–8 months after surgical amputation of digit 3, or of both digits 2 and 3.
Abstract: The cortical representations ofthe hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2-8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Suc cessive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and pal mar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et aI., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representa tions (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically main tained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500-700 JIm on either side of the initial boundaries of the representation of the amputated digits. More dis tant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every
1,327 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...…the cortical maps has been demonstrated in a variety of mammalian species after different kinds of deprivations including digit or limb amputations (Merzenich et al., 1984; Wall and Cusick, 1984; Calford and Tweedale, 1988; Turnbull and Rasmusson, 1991; Florence et al., 1998), nerve transections…...
[...]
...Since then, reorganization of the cortical maps has been demonstrated in a variety of mammalian species after different kinds of deprivations including digit or limb amputations (Merzenich et al., 1984; Wall and Cusick, 1984; Calford and Tweedale, 1988; Turnbull and Rasmusson, 1991; Florence et al., 1998), nerve transections (Wall and Kaas, 1985; Garraghty and Kaas, 1991b), dorsal root transections (Pons et al....
[...]
TL;DR: The results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it.
Abstract: After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2 millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it.
1,051 citations
"Large-Scale Reorganization in the S..." refers background or methods in this paper
...It is possible that this has not been reported before because the foot region of the cortex was not mapped previously (Pons et al., 1991; Jain et al., 1997)....
[...]
...in macaque monkeys (Pons et al., 1991) and a comparable 5 mm...
[...]
...After an extensive recovery period the boundaries of the face representation shift medially into the hand region by as much as 10 –14 mm in macaque monkeys (Pons et al., 1991) and a comparable 5 mm in smaller owl monkeys (Jain et al., 1997)....
[...]
...Limits of plasticity in area 3b The maximal extent of shift in representational boundaries reported before this study is in the range of 10 –14 mm for macaque monkeys (Pons et al., 1991) and 5 mm for smaller brained owl monkeys (Jain et al....
[...]
...In contrast, after transection of the dorsal roots of the spinal cord from C2 to T4, the deprived hand, arm, and occiput regions of area 3b come to respond to the inputs from the chin (Pons et al., 1991)....
[...]
TL;DR: This paper found that after the median nerve was transected and ligated in adult owl and squirrel monkeys, the cortical sectors representing it within skin surface representations in Areas 3b and 1 were completely occupied by 'new' and expanded representations of surrounding skin fields.
948 citations