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.
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TL;DR: It is proposed that the traditional concept of the body schema should be divided into three components: primary somatosensory representations, which are representations of the skin surface that are typically somatotopically organized, and have been shown to change dynamically due to peripheral or central modifications.
185 citations
01 Jan 2012
TL;DR: The unique anatomy of the pathway for facial sensations, involving the trigeminal ganglion and its associated nuclei within the brainstem, and the opportunities that this offers for training and rehabilitation are addressed.
Abstract: This chapter addresses the unique anatomy of the pathway for facial sensations, involving the trigeminal ganglion and its associated nuclei within the brainstem. The innervation of specialized cranial structures such as the teeth, tongue, oral and nasal mucosa, cornea, meninges, and conjunctiva are considered. This chapter will also address trigeminal mechanisms in clinically relevant conditions such as toothache, headache and trigeminal neuralgia including using advances in imaging techniques and resolution. Thus it is now possible to obtain functional MR images (fMRI) of the trigeminal pathway from ganglion to cortex. Magnetoencephalography (MEG) and fMRI techniques have provided more details on cortical organization in facial regions of both S1 and S2, while diffusion tensor imaging has been useful for visualizing trigeminothalamic pathways. Plasticity of the system after injury, its association with pain conditions, and the opportunities that this offers for training and rehabilitation, are further areas of current research that are discussed.
179 citations
TL;DR: The brain’s ability to reorganise itself is key to the authors' recovery from injuries, but the subsequent mismatch between old and new organisation may lead to pain, so a ‘maladaptive plasticity’ theory is argued against by showing that phantom pain in upper limb amputees is independent of cortical remapping.
Abstract: The role of cortical activity in generating and abolishing chronic pain is increasingly emphasized in the clinical community. Perhaps the most striking example of this is the maladaptive plasticity theory, according to which phantom pain arises from remapping of cortically neighbouring representations (lower face) into the territory of the missing hand following amputation. This theory has been extended to a wide range of chronic pain conditions, such as complex regional pain syndrome. Yet, despite its growing popularity, the evidence to support the maladaptive plasticity theory is largely based on correlations between pain ratings and oftentimes crude measurements of cortical reorganization, with little consideration of potential contributions of other clinical factors, such as adaptive behaviour, in driving the identified brain plasticity. Here, we used a physiologically meaningful measurement of cortical reorganization to reassess its relationship to phantom pain in upper limb amputees. We identified small yet consistent shifts in lip representation contralateral to the missing hand towards, but not invading, the hand area. However, we were unable to identify any statistical relationship between cortical reorganization and phantom sensations or pain either with this measurement or with the traditional Euclidian distance measurement. Instead, we demonstrate that other factors may contribute to the observed remapping. Further research that reassesses more broadly the relationship between cortical reorganization and chronic pain is warranted.
148 citations
Cites background from "Large-Scale Reorganization in the S..."
...…in the primary somatosensory cortex (SI), where the lower face representation takes over the cortical territory of the missing hand (Pons et al., 1991; Jain et al., 2008) (see Devor and Wall, 1978; Florence and Kaas, 1995; Kambi et al., 2014 for reorganization in subcortical structures)....
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TL;DR: It is suggested that acute stroke activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere within 30–50 min of stroke onset, and not merely loss of activity.
Abstract: Most processing of sensation involves the cortical hemisphere opposite (contralateral) to the stimulated limb. Stroke patients can exhibit changes in the interhemispheric balance of sensory signal processing. It is unclear whether these changes are the result of poststroke rewiring and experience, or whether they could result from the immediate effect of circuit loss. We evaluated the effect of mini-strokes over short timescales (<2 h) where cortical rewiring is unlikely by monitoring sensory-evoked activity throughout much of both cortical hemispheres using voltage-sensitive dye imaging. Blockade of a single pial arteriole within the C57BL6J mouse forelimb somatosensory cortex reduced the response evoked by stimulation of the limb contralateral to the stroke. However, after stroke, the ipsilateral (uncrossed) forelimb response within the unaffected hemisphere was spared and became independent of the contralateral forelimb cortex. Within the unaffected hemisphere, mini-strokes in the opposite hemisphere significantly enhanced sensory responses produced by stimulation of either contralateral or ipsilateral pathways within 30-50 min of stroke onset. Stroke-induced enhancement of responses within the spared hemisphere was not reproduced by inhibition of either cortex or thalamus using pharmacological agents in nonischemic animals. I/LnJ acallosal mice showed similar rapid interhemispheric redistribution of sensory processing after stroke, suggesting that subcortical connections and not transcallosal projections were mediating the novel activation patterns. Thalamic inactivation before stroke prevented the bilateral rearrangement of sensory responses. These findings suggest that acute stroke, and not merely loss of activity, activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere.
135 citations
TL;DR: It is shown that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.
Abstract: Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.
132 citations
Cites background from "Large-Scale Reorganization in the S..."
...…can lead to major long-term reorganization of cortical topographic maps, reflecting remarkable plasticity in the adult brain (Wall and Egger, 1971; Jain et al., 1997, 2008; Bruehlmeier et al., 1998; Green et al., 1998; Curt et al., 2002; Endo et al., 2007; Ghosh et al., 2009, 2010; Tandon et al.,…...
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TL;DR: Data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory 'neuroprotective' strategies should be directed at preventing early neutrophil influx and modifying microglial activation.
Abstract: Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were ‘dead at the scene’ or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1–3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil α-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1–3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1–3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8+ lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative enzymes myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate oxidase (gp91phox), and of the pro-inflammatory matrix metalloproteinase (MMP)-9, was analysed to determine their potential to cause oxidative and proteolytic damage. Oxidative activity, inferred from MPO and gp91phox immunoreactivity, was primarily associated with neutrophils and activated microglia. Phagocytic macrophages had weak or no expression of MPO or gp91phox. Only neutrophils expressed MMP-9. These data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory ‘neuroprotective’ strategies should be directed at preventing early neutrophil influx and modifying microglial activation.
753 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...However, in this case the lesion extended to the ipsilateral ventral horn and part of the white matter at the junction of the ventral and lateral funiculi as evidenced by the presence of translucent scar tissue, which is likely because of secondary damage after the lesion (Fleming et al., 2006)....
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TL;DR: The results of studies directed toward determining the time course and likely mechanisms underlying this remarkable plasticity of the cortex representing the skin of the median nerve within parietal somatosensory fields 3b and 1 are described.
725 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...…of restricted expansions, after median nerve cut only radial nerve inputs expand into the deprived region of area 3b although the deprived median nerve region lies immediately adjacent to the normally innervated face region (Merzenich et al., 1983a; Wall et al., 1983; Garraghty and Kaas, 1991b)....
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...One of the earliest definitive studies on adult brain plasticity in primates showed that after transection of the median nerve to the hand in monkeys, remaining inputs to the hand expand into the deprived hand region of somatosensory area 3b of cortex (Merzenich et al., 1983a,b)....
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...The organization of the cortex after median nerve or median and ulnar nerve cuts has been explored after as much as five (Merzenich et al., 1983b; Garraghty and Kaas, 1991b) or 11 months (Garraghty et al., 1994)....
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TL;DR: While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain.
704 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...Adult brains retain a remarkable ability to change in response to injuries that interrupt transmission of peripheral inputs resulting from damage to the peripheral or central pathways (Jones, 2000; Chen et al., 2002; Jain, 2002; Kaas et al., 2008)....
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TL;DR: The data suggest that chronic pain is accompanied by cortical reorganization and may serve an important function in the persistence of the pain experience.
669 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...A lesion at this level is expected to remove most of the inputs from digits 3, 4, and 5, while preserving those from most of the palm, digits 1 and 2 and the anterior arm (Sherrington, 1939; Florence et al., 1988; Flor et al., 1997; Darian-Smith and Ciferri, 2005)....
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TL;DR: The growth of intracortical but not thalamocortical connections could account for much of the reorganization of the sensory maps in cortex in macaque monkeys with long-standing, accidental trauma to a forelimb.
Abstract: Distributions of thalamic and cortical connections were investigated in four macaque monkeys with long-standing, accidental trauma to a forelimb, to determine whether the growth of new connections plays a role in the reorganization of somatosensory cortex that occurs after major alterations in peripheral somatosensory inputs. In each monkey, microelectrode recordings of cortical areas 3b and 1 demonstrated massive reorganizations of the cortex related to the affected limb. Injections of tracers in area 1 of these monkeys revealed normal patterns of thalamocortical connections, but markedly expanded lateral connections in areas 3b and 1. Thus, the growth of intracortical but not thalamocortical connections could account for much of the reorganization of the sensory maps in cortex.
427 citations
"Large-Scale Reorganization in the S..." refers background in this paper
...…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., 1991;…...
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...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....
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..., 1997), perhaps in combination with limited neuronal growth (Florence et al., 1998)....
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