Showing papers on "Somatosensory system published in 2003"

Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex

Abstract: The rodent primary somatosensory cortex is spontaneously active in the form of locally synchronous membrane depolarizations (UP states) separated by quiescent hyperpolarized periods (DOWN states) both under anesthesia and during quiet wakefulness. In vivo whole-cell recordings and tetrode unit recordings were combined with voltage-sensitive dye imaging to analyze the relationship of the activity of individual pyramidal neurons in layer 2/3 to the ensemble spatiotemporal dynamics of the spontaneous depolarizations. These were either brief and localized to an area of a barrel column or occurred as propagating waves dependent on local glutamatergic synaptic transmission in layer 2/3. Spontaneous activity inhibited the sensory responses evoked by whisker deflection, accounting almost entirely for the large trial-to-trial variability of sensory-evoked postsynaptic potentials and action potentials. Subthreshold sensory synaptic responses evoked while a cortical area was spontaneously depolarized were smaller, briefer and spatially more confined. Surprisingly, whisker deflections evoked fewer action potentials during the spontaneous depolarizations despite neurons being closer to threshold. The ongoing spontaneous activity thus regulates the amplitude and the time-dependent spread of the sensory response in layer 2/3 barrel cortex.

Clinical usefulness of laser-evoked potentials.

Abstract: In contrast to the function of the visual or auditory pathways which are electrophysiologically accessible by visual or auditory evoked potentials, the somatosensory pathway cannot be investigated as a whole by conventional somatosensory evoked potentials (SEP), because these only reflect function of large fibers, dorsal columns, medial lemniscus and their thalamo-cortical projections mediating sensations like touch and vibration. The other half of the somatosensory system, signaling temperature and pain perception, uses a different set of afferents and different central pathways, the function of which is accessible by laser-evoked potentials (LEPs). LEP can document lesions of the spinothalamic tract and (lateral) brainstem and of thalamo-cortical projections conveying thermo-nociceptive signals. In the peripheral nerve, LEP can help distinguish between large and small fiber neuropathies. The rapid heating of the skin by infrared laser pulses can easily be applied to non-glabrous skin in any dermatome. In recent years, many clinical studies have demonstrated that LEP can supply evidence for establishing clinical diagnoses when deficits of the nociceptive system are present. This review outlines principles and recording techniques for LEP in patients and compiles typical LEP findings in patients with lesions due to different diseases at various levels of the nociceptive pathways. Limitations for the use of LEP are pointed out, too, like the uncertainty of lesion location along these pathways and the fact that LEP can reliably show correlates of reduced nociceptive function but only rarely of enhanced transmission (like in hyperalgesia).

Auditory Cortical Neurons Respond to Somatosensory Stimulation

Abstract: The prevailing hierarchical model of cortical sensory processing holds that early processing is specific to individual modalities and that combination of information from different modalities is deferred until higher-order stages of processing. In this paper, we present physiological evidence of multisensory convergence at an early stage of cortical auditory processing. We used multi-neuron cluster recordings, along with a limited sample of single-unit recordings, to determine whether neurons in the macaque auditory cortex respond to cutaneous stimulation. We found coextensive cutaneous and auditory responses in caudomedial auditory cortex, an area lying adjacent to A1, and at the second stage of the auditory cortical hierarchy. Somatosensory-auditory convergence in auditory cortex may underlie effects observed in human studies. Convergence of inputs from different sensory modalities at very early stages of cortical sensory processing has important implications for both our developing understanding of multisensory processing and established views of unisensory processing.

Dynamic Receptive Fields of Reconstructed Pyramidal Cells in Layers 3 and 2 of Rat Somatosensory Barrel Cortex

Abstract: A major aim of sensory physiology is to identify those synaptic connections in cortical representational areas (functional maps) by which sensory stimuli are transformed into a specific pattern of sub- (PSPs) and suprathreshold (APs) electrical activity. In the neocortex such maps consist of functional units, referred to as columns (Mountcastle, 1957; Hubel & Wiesel, 1962). These comprise the cells in different cortical layers that respond to a particular sensory stimulus. To understand sensory maps mechanistically and at a subcellular resolution, firstly the synaptic connections between cells that constitute a column and also those between different columns have to be identified in a layer-specific manner. Secondly the spatial and temporal transformations of PSP and AP patterns along sensory pathways and in the different cortical layers have to be understood. The coarse layout of sensory information flow within a column is comparable across different sensory cortices. Afferent signals arrive in cortical layer 4 (L4) from thalamic nuclei. They are relayed from L4 to supragranular layers 3 (L3) and 2 (L2) as well as to infragranular layers (L5 and L6). Extracellular unit recording and anatomical work have compiled a detailed picture of the columnar cytoarchitecture and AP activity in columns of some sensory cortices. The detailed anatomy and synaptic mechanisms of the connections that generate specific patterns of PSPs and APs are, however, largely unclear. Few studies have determined both the soma location and the dendritic and axonal morphology of cortical cells as well as their sub- and suprathreshold RFs (e.g. Ito, 1992; Brecht & Sakmann, 2002a,b). Such measurements are, however, a prerequisite if one wants to infer how PSPs or APs represent a sensory stimulus in the different layers of the cortex. L4 of the rodent somatosensory cortex contains aggregates of neuronal somata referred to as barrels, which are innervated in a strict topographical order by inputs representing individual facial whiskers (Woolsey & Van der Loos, 1970). Anatomical studies have demonstrated that barrel cells are targeted by thalamic inputs from the ventral posterior medial nucleus (VPM), which are part of the lemniscal pathway (Diamond, 1995), while the septa between barrels are innervated by thalamic afferents projecting from the posterior medial nucleus (POM), which belong to the paralemniscal pathway (Koralek et al. 1988; Lu & Lin, 1993). While most lemniscal afferents innervate the barrels, some VPM inputs also target the L5B/L6 border and paralemniscal POM afferents densely innervate L5A (Koralek et al. 1988; Lu & Lin, 1993). Barrel borders and the morphology of a cortical cell can be visualised simultaneously (Ito, 1992), such that the laminar position of a cell and its position relative to barrel column borders as well as its detailed dendritic and axonal morphology can be measured. Such techniques provided physiological evidence that lemniscal (the VPM/barrel projection) and paralemniscal (the POM/septum projection) pathways are largely segregated in L4 (Brecht & Sakmann, 2002a). Furthermore the RFs of barrel and septum cells are dynamic but are narrow and restricted to a PW and at most the first order SuWs. The homogeneous appearance of L3 and L2 in the horizontal plane may indicate merging of the whisker-specific anatomical pathways, whose strict separation in L4 gives rise to the discontinuous appearance of barrels (Woolsey & Van der Loos, 1970). The projection pattern of L4 spiny neuron axons suggests, however, that selectively connected barrel columns also exist (Petersen & Sakmann, 2000; Petersen et al. 2003; Lubke et al. 2003). The convergence of whisker-evoked responses between columns is also suggested by unit recordings from unidentified cells (Simons, 1978, 1995; Armstrong-James & Fox, 1987; Armstrong-James et al. 1992; Armstrong-James, 1995). They show that suprathreshold RFs in L3 and L2 cells are larger in size than those of L4 cells. The work of Ahissar and colleagues on the representation of temporal frequencies in L2/3 cell spike trains suggests a merging of barrel and septum inputs in supragranular layers (Ahissar et al. 2001). Anatomical data, however, suggest that barrel and septal pathways also remain separate in L3 and L2 (Kim & Ebner, 1999). We report here in vivo whole-cell voltage recordings of whisker-evoked PSPs and APs from cells in L2/3, combined with reconstruction of their dendritic and axonal arbors. We determined the horizontal and vertical position of these cells with reference to the barrel map to establish relationships between individual cell classes in L3 and L2 located above barrel and septa, and their sub- and suprathreshold RFs. The aim is to construct relationships between anatomical cell classes and their functional properties. Comparison with similar data from L4 cells (Brecht & Sakmann, 2002b) and incorporation of in vitro data (Feldmeyer et al. 2002; Lubke et al. 2003) on connectivity should allow a quantitative description of the flow of excitation through and between cortical barrel columns.

Long-term depression induced by sensory deprivation during cortical map plasticity in vivo.

Abstract: Cortical map plasticity is thought to involve long-term depression (LTD) of cortical synapses, but direct evidence for LTD during plasticity or learning in vivo is lacking. One putative role for LTD is in the reduction of cortical responsiveness to behaviorally irrelevant or unused sensory stimuli, a common feature of map plasticity. Here we show that whisker deprivation, a manipulation that drives map plasticity in rat somatosensory cortex (S1), induces detectable LTD-like depression at intracortical excitatory synapses between cortical layer 4 (L4) and L2/3 pyramidal neurons. This synaptic depression occluded further LTD, enhanced LTP, was column specific, and was driven in part by competition between active and inactive whiskers. The synaptic locus of LTD and these properties suggest that LTD underlies the reduction of cortical responses to deprived whiskers, a major component of S1 map plasticity.

Altered central somatosensory processing in chronic pain patients with “hysterical” anesthesia

Abstract: Objective: The authors hypothesized that central factors may underlie sensory deficits in patients with nondermatomal somatosensory deficits (NDSD) and that functional brain imaging would reveal altered responses in supraspinal nuclei. Background: Patients with chronic pain frequently present with NDSD, ranging from hypoesthesia to complete anesthesia in the absence of substantial pathology and often in association with motor weakness and occasional paralysis. Patients with pain and such pseudoneurologic symptoms can be classified as having both a pain disorder and a conversion disorder (Diagnostic and Statistical Manual of Mental Disorders–IV classification). Methods: The authors tested their hypothesis with functional MRI (fMRI) of brush and noxious stimulation-evoked brain responses in four patients with chronic pain and NDSD. Results: The fMRI findings revealed altered somatosensory-evoked responses in specific forebrain areas. Unperceived stimuli failed to activate areas that were activated with perceived touch and pain: notably, the thalamus, posterior region of the anterior cingulate cortex (ACC), and Brodmann area 44/45. Furthermore, unperceived stimuli were associated with deactivations in primary and secondary somatosensory cortex (S1, S2), posterior parietal cortex, and prefrontal cortex. Finally, unperceived (but not perceived) stimuli activated the rostral ACC. Conclusions: Diminished perception of innocuous and noxious stimuli is associated with altered activity in many parts of the somatosensory pathway or other supraspinal areas. The cortical findings indicate a neurobiological component for at least part of the symptoms in patients presenting with nondermatomal somatosensory deficits.

Cortical connections of the second somatosensory area and the parietal ventral area in macaque monkeys

Abstract: To gain insight into how cortical fields process somatic inputs and ultimately contribute to complex abilities such as tactile object perception, we examined the pattern of connections of two areas in the lateral sulcus of macaque monkeys: the second somatosensory area (S2), and the parietal ventral area (PV). Neuroanatomical tracers were injected into electrophysiologically and/or architectonically defined locations, and labeled cell bodies were identified in cortex ipsilateral and contralateral to the injection site. Transported tracer was related to architectonically defined boundaries so that the full complement of connections of S2 and PV could be appreciated. Our results indicate that S2 is densely interconnected with the primary somatosensory area (3b), PV, and area 7b of the ipsilateral hemisphere, and with S2, 7b, and 3b in the opposite hemisphere. PV is interconnected with areas 3b and 7b, with the parietal rostroventral area, premotor cortex, posterior parietal cortex, and with the medial auditory belt areas. Contralateral connections were restricted to PV in the opposite hemisphere. These data indicate that S2 and PV have unique and overlapping patterns of connections, and that they comprise part of a network that processes both cutaneous and proprioceptive inputs necessary for tactile discrimination and recognition. Although more data are needed, these patterns of interconnections of cortical fields and thalamic nuclei suggest that the somatosensory system may not be segregated into two separate streams of information processing, as has been hypothesized for the visual system. Rather, some fields may be involved in a variety of functions that require motor and sensory integration.

Role of the somatosensory system in primary dystonia.

Abstract: The pathophysiology of dystonia is still not fully understood, but it is widely held that a dysfunction of the corticostriatal-thalamocortical motor circuits plays a major role in the pathophysiology of this syndrome. Although the most dramatic symptoms in dystonia seem to be motor in nature, marked somatosensory perceptual deficits are also present in this disease. In addition, several lines of evidence, including neurophysiological, neuroimaging and experimental findings, suggest that both motor and somatosensory functions may be defective in dystonia. Consequently, abnormal processing of the somatosensory input in the central nervous system may lead to inefficient sensorimotor integration, thus contributing substantially to the generation of dystonic movements. Whether somatosensory abnormalities are capable of triggering dystonia is an issue warranting further study. Although it seems unlikely that abnormal somatosensory input is the only drive to dystonia, it might be more correlated to the development of focal hand than generalized dystonia because local somesthetic factors are more selectively involved in the former than in the latter where, instead it seems to be a widespread deficit in processing sensory stimuli of different modality. Because basal ganglia and motor areas are heavily connected not only with somatosensory areas, but also with visual and acoustic areas, it is possible that abnormalities of other sensory modalities, such as visual and acoustic, may also be implicated in the pathophysiology of more severe forms of primary dystonia. Further studies have to be addressed to the assessment of the role of sensory modalities and their interaction on the pathophysiology of different forms of primary dystonia.

Modulations of early somatosensory ERP components by transient and sustained spatial attention.

Abstract: To investigate when and how spatial attention affects somatosensory processing, event-related brain potentials (ERPs) were recorded in response to mechanical tactile stimuli delivered to the left and right hand while attention was directed to one of these hands. The attended hand either remained constant throughout an experimental block (sustained attention), or was changed across successive trials (transient attention). Attentional modulations of the N140 component and a sustained 'processing negativity' for attended stimuli were observed in both attention conditions. However, attentional effects on earlier somatosensory components differed systematically. Sustained attention resulted in a contralateral negativity overlapping with the N80 component, while transient attention was reflected by a bilateral positivity overlapping with the P100 component. This dissociation indicates that sustained and transient attention affect different somatosensory areas. It is suggested that sustained attention can modulate tactile processing within primary somatosensory cortex (S1), while effects of transient attention are located beyond S1. Overall, results demonstrate that spatial selectivity in touch is mediated by activity modulations in modality-specific somatosensory cortex.

Effective behavioral treatment of focal hand dystonia in musicians alters somatosensory cortical organization.

Abstract: New perspectives in neurorehabilitation suggest that behavioral treatments of movement disorders may modify the functional organization of central somatosensory neural networks. On the basis of the assumption that use-dependent reorganization in these networks contributes to the fundamental abnormalities seen in focal dystonia, we treated 10 affected musicians and measured the concomitant somatosensory changes by using whole-head magnetoencephalography. We found that effective treatment, using the method of sensory motor retuning, leads to alterations in the functional organization of the somatosensory cortex. Specifically, before treatment, somatosensory relationships of the individual fingers differ between the affected and unaffected hands, whereas after treatment, finger representations contralateral to the dystonic side become more similar to the less-affected side. Further, somatosensory finger representations are ordered more according to homuncular principles after treatment. In addition, the observed physiologic changes correlated with behavioral data. These results confirm that plastic changes in parallel with emergent neurological dysfunction may be reversed by context-specific, intensive training-based remediation.

Neural substrates of tactile imagery: a functional MRI study.

Abstract: fMRI investigation on the neural substrates involved in tactile imagery is reported. Healthy subjects performed mental imagery of tactile stimulation on the dorsal aspect of the right hand. The results were compared with the regions of activation during the actual tactile stimulation. During imagery, contralateral primary and secondary somatosensory areas were activated along with activation in the left parietal lobe. Activations in left inferior frontal gyri (Brodmann's area 44), left dorsolateral prefrontal area, left precentral gyrus, left insula, and medial frontal gyrus were also observed. In the basal ganglia, activation in the left thalamus (ventral posteromedial nucleus) and putamen was found. Our results suggest that the primary and secondary somatosensory areas are recruited during tactile imagery, and have partially overlapping neural substrates for the perception of tactile stimulation.

Neurons in the Primate Orbitofrontal Cortex Respond to Fat Texture Independently of Viscosity

Abstract: The primate orbitofrontal cortex (OFC) is a site of convergence from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the O...

Abnormal cortical sensory activation in dystonia: An fMRI study

Abstract: Despite the obvious motor manifestations of focal dystonia, it is recognised that the sensory system plays an important role in this condition. This functional magnetic resonance imaging study examines the sensory representations of individual digits both within the subregions of the primary sensory cortex (SI) and in other nonprimary sensory areas. Patients with focal dystonia and controls were scanned during vibrotactile stimulation of both the index (digit 2) and little (digit 5) fingers of their dominant hand (which was the affected hand in all the dystonic subjects). The activation maps obtained were analysed for location, size, and magnitude of activation and three-dimensional (3-D) orientation of digit representations. Data from both groups were compared. There were significant differences in the average 3-D separation between the two digit representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends for reversed ordering of the representation of the two digits in both the secondary sensory cortex and posterior parietal area between the two groups. In addition, in dystonic subjects, there was significant under activation in the secondary somatosensory cortex (SII/area 40) for both digits and in the posterior parietal area for digit 5. These results indicate the presence of widespread activation abnormalities in the cortical sensory system in dystonia.

Focal Lysolecithin-Induced Demyelination of Peripheral Afferents Results in Neuropathic Pain Behavior That Is Attenuated by Cannabinoids

Abstract: Demyelinating diseases can be associated with painful sensory phenomena such as tactile allodynia and hyperalgesia. To study the mechanisms underlying demyelination-induced pain, we have characterized a novel model of demyelination of the sciatic or saphenous nerve. Topical lysolecithin application causes focal demyelination of afferent nerve A-fibers without axonal loss, as assessed either by electron and light microscopy or by immunohistochemical analysis of dorsal root ganglia (DRG) for a neuronal injury marker, activating transcription factor 3. Focal demyelination is accompanied by spontaneous action potentials in afferents and increased expression of neuropeptide Y and Na v 1.3 sodium channels specifically in DRG neurons that coexpress a specific marker of myelinated afferents. In contrast, expression of tetrodotoxin-resistant, Na v 1.8 sodium channels is specifically decreased in the same subgroup of DRG cells. Central sensitization of somatosensory processing is also induced, with increased behavioral reflex responsiveness to thermal and mechanical stimuli. These changes are reversed by intrathecal administration of an NMDA receptor antagonist or cannabinoid (CB) receptor agonist, but not by a μ-opioid receptor agonist. Recovery of behavioral reflexes occurred ∼3 weeks after lysolecithin treatment. This is the first time that demyelination of afferent A-fibers has been shown to specifically induce neuropathic pain and indicates that axonal damage is not a prerequisite for development of the pain state. The profile of phenotypic changes in DRG is distinct from other pain models and displays a sensitivity to NMDA and CB receptor agents that may be exploitable therapeutically.

Single-cell study of motor cortex projections to the barrel field in rats

Abstract: In freely moving rats, whisking is associated with a slow modulation of neuronal excitability in the primary somatosensory cortex. Because it persists after the blockade of vibrissa input, it was suggested that the slow modulation might be mediated by motor-sensory corticocortical connections and perhaps result from the corollary discharges of corticofugal cells. In the present study, we identified motor cortical cells that project to the barrel field and reconstructed their axonal projections after juxtacellularly staining single cells with a biotinylated tracer. On the basis of the final destination of main axons, two groups of neurons contribute to motor-sensory projections: callosal cells (87.5%) and corticofugal cells (12.5%). Axon collaterals of callosal cells arborize in layers five to six of the granular and dysgranular zones and give off several branches that ascend between the barrels to ramify in the molecular layer. In contrast, the axon collaterals of corticofugal cells do not ramify in the infragranular layers but in layer 1. The origin of the majority of motor sensory projections from callosally projecting cells does not support the notion that the slow modulation results from the corollary discharges of corticofugal axons. It would rather originate from a separate population of cells, which could output the slow signal to the barrel field in parallel with the corticofugal commands to a brainstem pattern generator. As free whisking is characterized by bilateral concerted movements of the vibrissae, the transcallosal contribution of motor-sensory axons represents a substrate for synchronizing the slow modulation across both hemispheres.

Pain and Analgesia

Abstract: The accepted definition of pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Analgesia is the alleviation or the absence of pain. Damaging or threatening physiological changes activate sensory neurons that support homeostasis, which drive autonomic, motoric, immune, behavioural, emotional and mnemonic responses. In humans, nociceptive neurons directly activate limbic sensory (insula) and limbic motor (cingulate) cortices as well as somatosensory cortices; they also produce glial and other immune (inflammatory) and stress-related (sympathetic) responses, which can lead to chronic pathological pain, considered by many to be a disease state. The pharmacologies of these overlapping systems involve numerous common agents, such as glutamate, adenosine, substance P, catecholamines, opioids, cannabinoids, prostanoids and so on, but accelerating advances in technology and in our knowledge of these systems suggest that selectively analgesic pathways and agents may be found that could underpin clinically useful therapies for chronic pain. Key Concepts: Small-diameter primary afferent fibres that innervate all tissues of the body (except the brain itself) and signal damaging or threatening physiological changes (as the sensory component of homeostasis) underlie pain sensation. In humans, pain is associated with activation of limbic sensory (insula) and limbic motor (cingulate) cortices, as well as the somatosensory cortices; the first two regions may represent the feeling and the motivation (unpleasantness) of pain, respectively. Primary afferent neurotransmitters are most commonly glutamate and adenosine. A host of peptides, growth factors and other neuromodulatory agents may also be co-released. These agents work together to effects changes on other neurons and on glia. Activation of primary afferents contributes to (neurogenic) inflammation via release of neurotransmitters/neuromodulators from peripheral terminals that activate other nociceptors as well as cause increased permeability and vasodilation of local blood vessels. Hyperalgesia, that is, pain caused by normally nonpainful events as well as increased responses to painful events, is produced by activation of local immune (glial) elements, sensitisation of peripheral and central neurons, and responsiveness to low-threshold (tactile) A-beta and C fibres. Endogenous anti-nociceptive inhibitory systems underlie the effects of vibration, cooling and cardiorespiratory events on pain and are supported by aminergic, opiatergic and cannabinoid agents. Chronic, pathological pain (lasting longer than 3–6 months) can result if injury or disease alters the balance of the homeostatic and immune systems to produce a persistent ‘pain memory’. Conversely, intense, unremitting pain can produce homeostatic, emotional, nutritional and sleep imbalances that can be fatal. Opiates including morphine and the endogenous peptides inhibit nociceptive activity in the periphery and at all levels of the neuraxis. They are more effective for inflammatory pain than for pain resulting from injury to the nervous system. Opiate effects can be heightened by local anesthetics and adrenergic agonists. Keywords: nociception; injury; inflammation; hyperalgesia; spinothalamic

Corticothalamic projections from the rat primary somatosensory cortex.

Abstract: To study the cells of origin of corticothalamic inputs to the ventral posterior and posterior medial nuclei of the somatosensory thalamus in rats, we injected small aliquots of tracer into each nucleus and analyzed the pattern of retrograde labeling in the posteromedial barrel subfield of primary somatosensory cortex, which can be divided into barrel and nonbarrel zones. The ventral posterior nucleus is innervated by neurons in layer VIa of both zones, whereas the posterior medial nucleus is innervated by neurons in layers Vb and VIb of both zones with additional innervation from layer VIa of nonbarrel cortex. Thus, only the posterior medial nucleus receives a layer Vb input. Because the layer Vb input is interpreted as the initiation of a feedforward cortico-thalamocortical pathway, this implies that the target of the posterior medial nucleus, which includes the nonbarrel cortex, is a higher-order cortical area. We thus suggest that this cortical zone, which is classically considered part of the primary somatosensory cortex, should be reclassified as higher-order cortex.

Augmentation of Plasticity of the Central Auditory System by the Basal Forebrain and/or Somatosensory Cortex

Abstract: Auditory conditioning (associative learning) or focal electric stimulation of the primary auditory cortex (AC) evokes reorganization (plasticity) of the cochleotopic (frequency) map of the inferior...

Imperceptible stimuli and sensory processing impediment.

Abstract: Weak sensory stimuli can fully escape conscious perception and yet evoke minute electroencephalography (EEG) responses ([1][1]), indicating at least partial cortical processing of such “subliminal” input. We used functional magnetic resonance imaging (fMRI) during imperceptible electrical finger