RESUMO
Neurons in the early stages of processing sensory information suffer transneuronal atrophy when deprived of their activating inputs. For over 40 y, members of our laboratory have studied the reorganization of the somatosensory cortex during and after recovering from different types of sensory loss. Here, we took advantage of the preserved histological material from these studies of the cortical effects of sensory loss to evaluate the histological consequences in the cuneate nucleus of the lower brainstem and the adjoining spinal cord. The neurons in the cuneate nucleus are activated by touch on the hand and arm, and relay this activation to the contralateral thalamus, and from the thalamus to the primary somatosensory cortex. Neurons deprived of activating inputs tend to shrink and sometimes die. We considered the effects of differences in species, type and extent of sensory loss, recovery time after injury, and age at the time of injury on the histology of the cuneate nucleus. The results indicate that all injuries that deprived part or all of the cuneate nucleus of sensory activation result in some atrophy of neurons as reflected by a decrease in nucleus size. The extent of the atrophy is greater with greater sensory loss and with longer recovery times. Based on supporting research, atrophy appears to involve a reduction in neuron size and neuropil, with little or no neuron loss. Thus, the potential exists for restoring the hand to cortex pathway with brain-machine interfaces, for bionic prosthetics, or biologically with hand replacement surgery.
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Tronco Encefálico , Primatas , Animais , Mãos , Extremidade Superior , AtrofiaRESUMO
PURPOSE: To calculate temperatures from T2 *-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. METHODS: fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T2 *-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. RESULTS: The temperature SD was 0.05°C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13°C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. CONCLUSION: The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.
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Imageamento por Ressonância Magnética , Optogenética , Imageamento por Ressonância Magnética/métodos , Calefação , Encéfalo/diagnóstico por imagem , Prótons , Lasers , Imagens de FantasmasRESUMO
In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical spinal cord deactivates the contralateral somatosensory hand cortex and impairs hand use in a reach-to-grasp task in squirrel monkeys. Nevertheless, considerable cortical reactivation and behavioral recovery occurs over the following weeks to months after lesion. This timeframe may also be a window for targeted therapies to promote cortical reactivation and functional reorganization, aiding in the recovery process. Here we asked if and how task specific training of an impaired hand would improve behavioral recovery and cortical reorganization in predictable ways, and if recovery related cortical changes would be detectable using noninvasive functional magnetic resonance imaging (fMRI). We further asked if invasive neurophysiological mapping reflected fMRI results. A reach-to-grasp task was used to test impairment and recovery of hand use before and after dorsal column lesions (DC-lesion). The activation and organization of the affected primary somatosensory cortex (area 3b) was evaluated with two types of fMRI - either blood oxygenation level dependent (BOLD) or cerebral blood volume (CBV) with a contrast agent of monocrystalline iron oxide nanocolloid (MION) - before and after DC-lesion. At the end of the behavioral and fMRI studies, microelectrode recordings in the somatosensory areas 3a, 3b and 1 were used to characterize neuronal responses and verify the somatotopy of cortical reactivations. Our results indicate that even after nearly complete DC lesions, monkeys had both considerable post-lesion behavioral recovery, as well as cortical reactivation assessed with fMRI followed by extracellular recordings. Generalized linear regression analyses indicate that lesion extent is correlated with the behavioral outcome, as well as with the difference in the percent signal change from pre-lesion peak activation in fMRI. Monkeys showed behavioral recovery and nearly complete cortical reactivation by 9-12 weeks post-lesion (particularly when the DC-lesion was incomplete). Importantly, the specific training group revealed trends for earlier behavioral recovery and had higher magnitude of fMRI responses to digit stimulation by 5-8 weeks post-lesion. Specific kinematic measures of hand movements in the selected retrieval task predicted recovery time and related to lesion characteristics better than overall task performance success. For measures of cortical reactivation, we found that CBV scans provided stronger signals to vibrotactile digit stimulation as compared to BOLD scans, and thereby may be the preferred non-invasive way to study the cortical reactivation process after sensory deprivations from digits. When the reactivation of cortex for each of the digits was considered, the reactivation by digit 2 stimulation as measured with microelectrode maps and fMRI maps was best correlated with overall behavioral recovery.
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Medula Cervical/lesões , Dedos/fisiopatologia , Bulbo/fisiologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Córtex Somatossensorial/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Microeletrodos , Reabilitação Neurológica , Estimulação Física , Saimiri , Córtex Somatossensorial/diagnóstico por imagemRESUMO
Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit B (CTB) into the hand representation in the cuneate nucleus (Cu) to label the spinal cord neurons, and related results to cortical reactivation in four squirrel monkeys (Saimiri boliviensis) at least 7 months after DCL. In two monkeys with complete DCLs, few CTB-labeled neurons were present below the lesion, and few neurons in the affected hand region in area 3b responded to touch on the hand. In two other cases with large but incomplete DCLs, CTB-labeled neurons were abundant below the lesion, and the area 3b hand cortex responded well to tactile stimulation in a roughly somatotopic organization. The proportions of labeled neurons in the spinal cord hand region reflected the extent of cortical reactivation to the hand. Comparing monkeys with short and long recovery times suggests that the numbers of labeled neurons below the lesion increase with time following incomplete DCLs (<95%) but decrease with time after nearly complete DCLs (≥95%). Taken together, these results suggest that the second-order spinal cord pathway facilitates cortical reactivation, likely through the potentiation of persisting tactile inputs from the hand to the Cu over months of postlesion recovery.
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Mãos/fisiopatologia , Células do Corno Posterior/fisiologia , Córtex Somatossensorial/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Percepção do Tato/fisiologia , Vias Aferentes/fisiopatologia , Animais , Transporte Axonal , Axônios/fisiologia , Toxina da Cólera/farmacocinética , Convalescença , Mãos/inervação , Hipestesia/fisiopatologia , Bulbo/fisiopatologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Saimiri , Tálamo/fisiopatologiaRESUMO
Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of somatosensory cortex of tactile activation. However, considerable cortical reactivation occurs over weeks to months of recovery. While most studies focused on the reactivation of primary somatosensory area 3b, here, for the first time, we address how the higher-order somatosensory cortex reactivates in the same monkeys after DCL that vary across cases in completeness, post-lesion recovery times, and types of treatments. We recorded neural responses to tactile stimulation in areas 3a, 3b, 1, secondary somatosensory cortex (S2), parietal ventral (PV), and occasionally areas 2/5. Our analysis emphasized comparisons of the responsiveness, somatotopy, and receptive field size between areas 3b, 1, and S2/PV across DCL conditions and recovery times. The results indicate that the extents of the reactivation in higher-order somatosensory areas 1 and S2/PV closely reflect the reactivation in primary somatosensory cortex. Responses in higher-order areas S2 and PV can be stronger than those in area 3b, thus suggesting converging or alternative sources of inputs. The results also provide evidence that both primary and higher-order fields are effectively activated after long recovery times as well as after behavioral and electrocutaneous stimulation interventions.
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Plasticidade Neuronal , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Percepção do Tato/fisiologia , Vias Aferentes/fisiopatologia , Animais , Mãos , Masculino , Estimulação Física , Recuperação de Função Fisiológica , Saimiri , Privação Sensorial/fisiologiaRESUMO
The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.
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Neocórtex/citologia , Neurônios/citologia , Pan troglodytes/fisiologia , Envelhecimento , Animais , Contagem de Células , Feminino , Córtex Motor/citologia , Córtex Somatossensorial/citologia , Córtex Visual/citologiaRESUMO
In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters. In 66% of our sample, neuron activity tended to display suppression of firing when regions of skin outside of the excitatory RF were stimulated. In a small proportion of neurons, single-site indentations suppressed firing without initial increases in response to any of the tested sites on the hand. Latencies of suppressive responses to skin indentation (usually 12-34 ms) were similar to excitatory response latencies. The duration of inhibition varied across neurons. Although most observations were from anesthetized animals, we also found similar neuron response properties in one awake galago. Notably, suppression of ongoing neuronal activity did not require conditioning stimuli or multi-site stimulation. The suppressive effects were generally seen following single-site skin indentations outside of the neuron's minimal RF and typically on different digits and palm pads, which have not often been studied in this context. Overall, the characteristics of widespread suppressive or inhibitory response properties with and without initial facilitative or excitatory responses add to the growing evidence that neurons in primary somatosensory cortex provide essential processing for integrating sensory stimulation from across the hand.
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Potenciais Somatossensoriais Evocados , Inibição Neural , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Percepção do Tato , Vigília , Animais , Galago , Masculino , Tempo de Reação , Saimiri , Córtex Somatossensorial/citologia , TatoRESUMO
According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.
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Macaca/anatomia & histologia , Neocórtex/citologia , Neurônios/citologia , Córtex Visual/citologia , Animais , Contagem de Células , Feminino , Macaca mulatta/anatomia & histologia , Macaca nemestrina/anatomia & histologia , Macaca radiata/anatomia & histologia , Masculino , Córtex Motor/citologia , Neuroglia/citologia , Especificidade da EspécieRESUMO
Lesions of the dorsal columns at a mid-cervical level render the hand representation of the contralateral primary somatosensory cortex (area 3b) unresponsive. Over weeks of recovery, most of this cortex becomes responsive to touch on the hand. Determining functional properties of neurons within the hand representation is critical to understanding the neural basis of this adaptive plasticity. Here, we recorded neural activity across the hand representation of area 3b with a 100-electrode array and compared results from owl monkeys and squirrel monkeys 5-10 weeks after lesions with controls. Even after extensive lesions, performance on reach-to-grasp tasks returned to prelesion levels, and hand touches activated territories mainly within expected cortical locations. However, some digit representations were abnormal, such that receptive fields of presumably reactivated neurons were larger and more often involved discontinuous parts of the hand compared with controls. Hand stimulation evoked similar neuronal firing rates in lesion and control monkeys. By assessing the same monkeys with multiple measures, we determined that properties of neurons in area 3b were highly correlated with both the lesion severity and the impairment of hand use. We propose that the reactivation of neurons with near-normal response properties and the recovery of near-normal somatotopy likely supported the recovery of hand use. Given the near-completeness of the more extensive dorsal column lesions we studied, we suggest that alternate spinal afferents, in addition to the few spared primary axon afferents in the dorsal columns, likely have a major role in the reactivation pattern and return of function.
Assuntos
Neurônios/fisiologia , Desempenho Psicomotor/fisiologia , Recuperação de Função Fisiológica/fisiologia , Córtex Somatossensorial/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Aotidae , Comportamento Animal/fisiologia , Mapeamento Encefálico , Mãos/fisiopatologia , Plasticidade Neuronal/fisiologia , SaimiriRESUMO
PURPOSE: The degree and dynamic progression of neuroinflammation after traumatic spinal cord injuries (SCI) are crucial determinants of the severity of injury and potential for recovery. We used Positron Emission Tomography (PET) to monitor neuroinflammation longitudinally, correlating it with Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) and behavior in contusion-injured rats. These studies help validate CEST metrics and confirm how imaging may be used to evaluate the efficacy of therapies and understand their mechanisms of action. PROCEDURES: 12 SCI and 4 sham surgery rats were subjected to CEST MRI and PET-Translocator Protein (TSPO) scans for 8 weeks following injury. Z-spectra from the SCI were analyzed using a 5-Lorentzian pool model for fitting. Weekly motor and somatosensory behavior were correlated with imaging metrics, which were validated through post-mortem histological and immuo-staining using ionized calcium-binding adaptor protein-1 (iba-1, microglia) and glial fibrillary acidic protein (GFAP, astrocytes). RESULTS: PET-TSPO showed widespread inflammation and post-mortem histology confirmed the presence of activated microglia. Changes in CEST and nuclear Overhauser Effect (NOE) peaks at 3.5 ppm and -1.6 ppm respectively were largest within the first week after injury and more pronounced in rostral versus caudal segments. These temporal indices of neuroinflammation corresponded to the recovery of locomotor behaviors and somatic sensation in rats with moderate contusion injury. The results confirm that CEST MRI metrics are sensitive indices of states of neuroinflammation within injured spinal cords. CONCLUSIONS: The detection of dynamic spatiotemporal features of neuroinflammation progression underscores the importance of considering their timings and locations for neuroprotective and anti-inflammatory therapies. The availability of noninvasive MRI indices of neuroinflammation may facilitate clinical trials aimed at treatments that promote recovery after SCI.
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Contusões , Traumatismos da Medula Espinal , Ratos , Animais , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Inflamação/metabolismo , Proteínas de Transporte/metabolismoRESUMO
A mathematical model-based parcellation of magnetic resonance diffusion tensor images (DTI) has been developed to quantify progressive changes in three types of tissues - grey (GM), white matter (WM), and damaged spinal cord tissue, along with behavioral assessments over a 6 month period following targeted spinal cord injuries (SCI) in monkeys. Sigmoid Gompertz function based fittings of DTI metrics provide early indicators that correlate with, and predict, recovery of hand grasping behavior. Our three tissue pool model provided unbiased, data-driven segmentation of spinal cord images and identified DTI metrics that can serve as reliable biomarkers of severity of spinal cord injuries and predictors of behavioral outcomes.
Assuntos
Imagem de Tensor de Difusão , Traumatismos da Medula Espinal , Animais , Humanos , Saimiri , Imagem de Tensor de Difusão/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Imagem de Difusão por Ressonância Magnética , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/patologiaRESUMO
Resting-state fMRI based on analyzing BOLD signals is widely used to derive functional networks in the brain and how they alter during disease or injury conditions. Resting-state networks can also be used to study brain functional connectomes across species, which provides insights into brain evolution. The squirrel monkey (SM) is a non-human primate (NHP) that is widely used as a preclinical model for experimental manipulations to understand the organization and functioning of the brain. We derived resting-state networks from the whole brain of anesthetized SMs using Independent Component Analysis of BOLD acquisitions. We detected 15 anatomically constrained resting-state networks localized in the cortical and subcortical regions as well as in the white-matter. Networks encompassing visual, somatosensory, executive control, sensorimotor, salience and default mode regions, and subcortical networks including the Hippocampus-Amygdala, thalamus, basal-ganglia and brainstem region correspond well with previously detected networks in humans and NHPs. The connectivity pattern between the networks also agrees well with previously reported seed-based resting-state connectivity of SM brain. This study demonstrates that SMs share remarkable homologous network organization with humans and other NHPs, thereby providing strong support for their suitability as a translational animal model for research and additional insight into brain evolution across species.
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Multi-parametric MRI (mpMRI) technology enables non-invasive and quantitative assessments of the structural, molecular, and functional characteristics of various neurological diseases. Despite the recognized importance of studying spinal cord pathology, mpMRI applications in spinal cord research have been somewhat limited, partly due to technical challenges associated with spine imaging. However, advances in imaging techniques and improved image quality now allow longitudinal investigations of a comprehensive range of spinal cord pathological features by exploiting different endogenous MRI contrasts. This review summarizes the use of mpMRI techniques including blood oxygenation level-dependent (BOLD) functional MRI (fMRI), diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT), and chemical exchange saturation transfer (CEST) MRI in monitoring different aspects of spinal cord pathology. These aspects include cyst formation and axonal disruption, demyelination and remyelination, changes in the excitability of spinal grey matter and the integrity of intrinsic functional circuits, and non-specific molecular changes associated with secondary injury and neuroinflammation. These approaches are illustrated with reference to a nonhuman primate (NHP) model of traumatic cervical spinal cord injuries (SCI). We highlight the benefits of using NHP SCI models to guide future studies of human spinal cord pathology, and demonstrate how mpMRI can capture distinctive features of spinal cord pathology that were previously inaccessible. Furthermore, the development of mechanism-based MRI biomarkers from mpMRI studies can provide clinically useful imaging indices for understanding the mechanisms by which injured spinal cords progress and repair. These biomarkers can assist in the diagnosis, prognosis, and evaluation of therapies for SCI patients, potentially leading to improved outcomes.
Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Traumatismos da Medula Espinal , Animais , Humanos , Imagem de Tensor de Difusão/métodos , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/patologia , Imageamento por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Modelos AnimaisRESUMO
Purpose: The purpose of the study was to provide initial evidence for the internal consistency and convergent validity of the nine-item avoidant/restrictive food intake disorder screen (NIAS) in a sample of transgender and nonbinary (TGNB) youth and young adults. Methods: Returning patients at a Midwestern gender clinic (n=164) ages 12-23 completed the NIAS, sick, control, one stone, fat, food (SCOFF), patient health questionnaire 9 (PHQ-9), and generalized anxiety disorder 7 (GAD-7) during their clinic visit. Age, sex assigned at birth, gender identity, weight, and height were also collected. Confirmatory factor analysis was used to establish the hypothesized three-factor structure of the NIAS in this sample. Relationships between the NIAS subscales and anthropometric data, SCOFF, PHQ-9, GAD-7, and sex assigned at birth were explored for convergent and divergent validity, and proposed screening cutoff scores were used to identify the prevalence of likely avoidant/restrictive food intake disorder (ARFID) in this population. Results: The three-factor structure of the NIAS was an excellent fit to the current data. Approximately one in five (22%) of the participants screened positive for ARFID. Approximately one in four participants scored above the picky eating (27.4%) or appetite (23.9%) cutoffs. Assigned female at birth participants scored significantly higher on the NIAS-Total, Appetite, and Fear subscales than those assigned male at birth. NIAS-Total was significantly related to all convergent validity variables other than age, with a moderate-strong correlation with other symptom screeners (SCOFF, PHQ-9, GAD-7), and a small negative correlation with body mass index percentile. Conclusions: Evidence supports the NIAS as a valid measure to screen for ARFID among TGNB youth and young adults.
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BACKGROUND: MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. OBJECTIVE: To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. FINDINGS: BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. CONCLUSIONS: The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.
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Nociceptividade , Núcleos Talâmicos , Núcleos Talâmicos/fisiologia , Tálamo , Encéfalo , CogniçãoRESUMO
Despite the lack of ipsilateral receptive fields (RFs) for neurons in the hand representation of area 3b of primary somatosensory cortex, interhemispheric interactions have been reported to varying degrees. We investigated spatiotemporal properties of these interactions to determine the following: response types, timing between stimuli to evoke the strongest bimanual interactions, topographical distribution of effects, and their dependence on similarity of stimulus locations on the two hands. We analyzed response magnitudes and latencies of single neurons and multineuron clusters recorded from 100-electrode arrays implanted in one hemisphere of each of two anesthetized owl monkeys. Skin indentations were delivered to the two hands simultaneously and asynchronously at mirror locations (matched sites on each hand) and nonmirror locations. Since multiple neurons were recorded simultaneously, stimuli on the contralateral hand could be within or outside of the classical RFs of any given neuron. For most neurons, stimulation on the ipsilateral hand suppressed responses to stimuli on the contralateral hand. Maximum suppression occurred when the ipsilateral stimulus was presented 100 ms before the contralateral stimulus onset (p < 0.0005). The longest stimulus onset delay tested (500 ms) allowed contralateral responses to recover to control levels (p = 0.428). Stimulation on mirror digits did not differ from stimulation on nonmirror locations (p = 1.000). These results indicate that interhemispheric interactions are common in area 3b, somewhat topographically diffuse, and maximal when the suppressing ipsilateral stimulus precedes the contralateral stimulus. Our findings point to a neurophysiological basis for "interference" effects found in human psychophysical studies of bimanual stimulation.
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Lateralidade Funcional/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Tato/fisiologia , Animais , Aotidae , Distribuição de Qui-Quadrado , Eletrofisiologia , Neurônios/citologia , Estimulação Física , Tempo de Reação/fisiologia , Córtex Somatossensorial/citologia , Fatores de TempoRESUMO
The correlated discharges of cortical neurons in primary somatosensory cortex are a potential source of information about somatosensory stimuli. One aspect of neuronal correlations that has not been well studied is how the spatiotemporal properties of tactile stimuli affect the presence and magnitude of correlations. We presented single- and dual-point stimuli with varying spatiotemporal relationships to the hands of three anesthetized owl monkeys and recorded neuronal activity from 100-electrode arrays implanted in primary somatosensory cortex. Correlation magnitudes derived from joint peristimulus time histogram (JPSTH) analysis of single neuron pairs were used to determine the level of spike timing correlations under selected spatiotemporal stimulus conditions. Correlated activities between neuron pairs were commonly observed, and the proportions of correlated pairs tended to decrease with distance between the recorded neurons. Distance between stimulus sites also affected correlations. When stimuli were presented simultaneously at two sites, â¼37% of the recorded neuron pairs showed significant correlations when adjacent phalanges were stimulated, and â¼21% of the pairs were significantly correlated when nonadjacent digits were stimulated. Spatial proximity of paired stimuli also increased the average correlation magnitude. Stimulus onset asynchronies in the paired stimuli had small effects on the correlation magnitude. These results show that correlated discharges between neurons at the first level of cortical processing provide information about the relative locations of two stimuli on the hand.
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Potenciais de Ação/fisiologia , Aotidae/fisiologia , Córtex Somatossensorial/fisiologia , Tato/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Masculino , Estimulação Física/métodos , Fatores de TempoRESUMO
Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.
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Aotidae/fisiologia , Córtex Somatossensorial/fisiologia , Tato/fisiologia , Potenciais de Ação , Animais , Estimulação Elétrica , Eletrodos Implantados , Retroalimentação Fisiológica , Mãos/inervação , Modelos Neurológicos , Rede Nervosa/fisiologia , Córtex Somatossensorial/anatomia & histologiaRESUMO
Recovery of responses to cutaneous stimuli in the area 3b hand cortex of monkeys after dorsal column lesions (DCLs) in the cervical spinal cord relies on neural rewiring in the cuneate nucleus (Cu) over time. To examine whether the corticocuneate projections are modified during recoveries after the DCL, we injected cholera toxin subunit B into the hand representation in Cu to label the cortical neurons after various recovery times, and related results to the recovery of neural responses in the affected area 3b hand cortex. In normal New World monkeys, labeled neurons were predominately distributed in the hand regions of contralateral areas 3b, 3a, 1 and 2, parietal ventral (PV), secondary somatosensory cortex (S2), and primary motor cortex (M1), with similar distributions in the ipsilateral cortex in significantly smaller numbers. In monkeys with short-term recoveries, the area 3b hand neurons were unresponsive or responded weakly to touch on the hand, while the cortical labeling pattern was largely unchanged. After longer recoveries, the area 3b hand neurons remained unresponsive, or responded to touch on the hand or somatotopically abnormal parts, depending on the lesion extent. The distributions of cortical labeled neurons were much more widespread than the normal pattern in both hemispheres, especially when lesions were incomplete. The proportion of labeled neurons in the contralateral area 3b hand cortex was not correlated with the functional reactivation in the area 3b hand cortex. Overall, our findings indicated that corticocuneate inputs increase during the functional recovery, but their functional role is uncertain.
Assuntos
Vias Aferentes/fisiopatologia , Bulbo/fisiopatologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , PlatirrinosRESUMO
Purpose: The purpose of this study was to describe the prevalence of and relationships among disordered eating, food insecurity, and weight status among transgender and gender nonbinary youth and young adults. Methods: This cross-sectional study involved a screening protocol to assess disordered eating and food insecurity risk from September to December of 2019 at a gender clinic using five validated measures: (1) previous eating disorder diagnosis (yes/no); (2) Sick, Control, One Stone, Fat, Food Questionnaire (SCOFF); (3) Adolescent Binge Eating Disorder Questionnaire (ADO-BED); (4) Nine-Item Avoidant/Restrictive Food Intake Disorder Screen (NIAS); and (5) Hunger Vital Sign. Age, assigned sex at birth, gender identity, stage of medical transition, and body mass index were collected. Pearson's r correlation coefficients, between-groups t-tests, one-way analysis of variance tests, and Tukey's honest significant difference test were used to characterize the relationships between variables. Results: A total of 164 participants ages 12-23 years completed the screener. Using assigned sex at birth, 1.8% were underweight, 53% were a healthy weight, 17.1% were overweight, and 28.0% were obese. An estimated 8.7% reported a previous eating disorder diagnosis, 28.0% screened positive on the SCOFF, 9.1% on the ADO-BED, 75.0% on the NIAS, and 21.2% on the Hunger Vital Sign. Transgender males scored higher on the NIAS than transgender females (p = 0.03). Those with a previous eating disorder diagnosis scored significantly higher on the Hunger Vital Sign (p < 0.05). Conclusion: Gender clinics should routinely screen for disordered eating, food insecurity, overweight, and obesity to identify patients in need of further evaluation and referral.