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1.
PLoS One ; 15(9): e0239125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991590

RESUMO

A mesoscale network model is proposed for the development of spike and wave discharges (SWDs) in the cortico-thalamo-cortical (C-T-C) circuit. It is based on experimental findings in two genetic models of childhood absence epilepsy-rats of WAG/Rij and GAERS strains. The model is organized hierarchically into two levels (brain structures and individual neurons) and composed of compartments for representation of somatosensory cortex, reticular and ventroposteriomedial thalamic nuclei. The cortex and the two thalamic compartments contain excitatory and inhibitory connections between four populations of neurons. Two connected subnetworks both including relevant parts of a C-T-C network responsible for SWD generation are modelled: a smaller subnetwork for the focal area in which the SWD generation can take place, and a larger subnetwork for surrounding areas which can be only passively involved into SWDs, but which is mostly responsible for normal brain activity. This assumption allows modeling of both normal and SWD activity as a dynamical system (no noise is necessary), providing reproducibility of results and allowing future analysis by means of theory of dynamical system theories. The model is able to reproduce most time-frequency changes in EEG activity accompanying the transition from normal to epileptiform activity and back. Three different mechanisms of SWD initiation reported previously in experimental studies were successfully reproduced in the model. The model incorporates also a separate mechanism for the maintenance of SWDs based on coupling analysis from experimental data. Finally, the model reproduces the possibility to stop ongoing SWDs with high frequency electrical stimulation, as described in the literature.


Assuntos
Epilepsia Tipo Ausência/fisiopatologia , Modelos Neurológicos , Neurônios/fisiologia , Córtex Somatossensorial/fisiopatologia , Núcleos Talâmicos/fisiopatologia , Animais , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/terapia , Masculino , Vias Neurais/fisiopatologia , Ratos , Ratos Transgênicos , Córtex Somatossensorial/citologia , Núcleos Talâmicos/citologia , Estimulação Transcraniana por Corrente Contínua/métodos
2.
Immunity ; 52(5): 753-766, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32433948

RESUMO

Although the medical definition of itch has been in existence for 360 years, only in the last 20 years have we begun to understand the basic mechanisms that underlie this unique sensation. Therapeutics that specifically target chronic itch as a pathologic entity are currently still not available. Recent seminal advances in itch circuitry within the nervous system have intersected with discoveries in immunology in unexpected ways to rapidly inform emerging treatment strategies. The current review aims to introduce these basic concepts in itch biology and highlight how distinct immunologic pathways integrate with recently identified itch-sensory circuits in the nervous system to inform a major new paradigm of neuroimmunology and therapeutic development for chronic itch.


Assuntos
Gânglios Espinais/imunologia , Prurido/imunologia , Células Receptoras Sensoriais/imunologia , Pele/imunologia , Córtex Somatossensorial/imunologia , Animais , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Humanos , Modelos Imunológicos , Modelos Neurológicos , Prurido/diagnóstico , Prurido/fisiopatologia , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Pele/inervação , Córtex Somatossensorial/fisiopatologia
3.
Acta Neurol Scand ; 142(2): 181-185, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32392619

RESUMO

BACKGROUND: After cardiac arrest (CA), present cortical somatosensory evoked potentials (N20 response of SSEPs) have low predictive value for good outcome and might be redundant with EEG. AIMS: To determine whether specific features, or rather global, standardized EEG assessments, are reliably associated with cortical SSEP occurrence after cardiac arrest (CA). METHODS: In a prospective CA registry, EEGs recorded within 72 hours were scored according to the ACNS nomenclature, and also categorized into "benign," "malignant," and "highly malignant." Correlations between EEGs and SSEPs (bilaterally absent vs present), and between EEGs/SSEPs and outcome (good: CPC 1-2) were assessed. RESULTS: Among 709 CA episodes, 532 had present N20 and 366 "benign EEGs." While EEG categories as well as background, epileptiform features, and reactivity differed significantly between patients with and without N20 (each P < .001), only "benign EEG" was almost universally associated with present N20: 99.5% (95%CI: 97.9%-99.9%) PPV. The combination of "benign EEG" and present N20 showed similar PPV for good outcome as "benign" EEG alone: 69.0% (95% CI: 65.2-72.4) vs 68.6% (95% CI: 64.9-72.0). CONCLUSION: Global EEG ("benign") assessment, rather than single EEG features, can reliably predict cortical SSEP occurrence. SSEP adjunction does not increase EEG prognostic performance toward good outcome. SSEP could therefore be omitted in patients with "benign EEG."


Assuntos
Eletroencefalografia/tendências , Potenciais Somatossensoriais Evocados/fisiologia , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros
4.
J Headache Pain ; 21(1): 47, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375638

RESUMO

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.


Assuntos
Imagem por Ressonância Magnética/métodos , Enxaqueca sem Aura/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca sem Aura/fisiopatologia , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Dor/diagnóstico por imagem , Dor/fisiopatologia , Qualidade de Vida , Córtex Somatossensorial/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto Jovem
5.
Medicine (Baltimore) ; 99(16): e19835, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312005

RESUMO

RATIONALE: Pusher syndrome is a disorder of postural control. It is associated with unilateral lesions on central vestibular system. In the current study, we attempted to identify and investigate neural connectivity of the parieto-insular vestibular cortex in a patient with pusher syndrome, using diffusion tensor imaging. PATIENT CONCERNS: A 60-year-old male patient had left hemiplegia due to an infarction on right premotor cortex, primary motor cortex, corona radiata and temporal and occipital lobe. The patient had severe motor weakness in left upper and lower limb, left side neglect and significant pusher syndrome. DIAGNOSIS: Patient was diagnosed with left hemiplegia due to an infarction in the right middle cerebral artery territory at the neurology department of a university hospital. INTERVENTIONS: One patient and 5 control subjects of similar age participated. Diffusion tensor imaging data were acquired at 4-month and 12-month after the initial injury. OUTCOMES: Fractional anisotropy, mean diffusivity, and tract volume (TV) were measured. TV values in both affected and unaffected hemispheres of the patient were significantly decreased at 4-month compared to those of control subjects. In the unaffected hemisphere of the patient, TV value showed significant increase at 12-month compared to that at 4-month. Although the TV value at 12-month of the affected hemisphere was out of reference range, TV was considerably increased compared to that at 4-month. Mean values for fractional anisotropy or mean diffusivity in 2 hemispheres did not show significant difference compared to those of control subjects regardless of month. LESSONS: Restoration of an injured projection pathway between the vestibular nuclei and parieto-insular vestibular cortex with recovery of pusher syndrome was found in a patient with stroke.


Assuntos
Imagem de Tensor de Difusão/métodos , Hemiplegia/diagnóstico , Sistema Nervoso/diagnóstico por imagem , Equilíbrio Postural/fisiologia , Anisotropia , Infarto Encefálico , Córtex Cerebral/fisiopatologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Hemiplegia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/patologia , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Sistema Nervoso/fisiopatologia , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Lobo Parietal/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
6.
Dev Med Child Neurol ; 62(7): 778-783, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32277484

RESUMO

This review and synthesis discusses recent work that has utilized brain imaging methods, such as the electroencephalogram (EEG) and magnetoencephalogram, to provide insights into the ways that the body is represented in the infant brain. One aspect of body representation concerns somatotopic maps of the body surface in somatosensory cortex. A good deal is known about the properties of these maps in adults, but there has been relatively little developmental work. Recent studies have provided new insights into the organization of infant neural body maps and have laid the foundations for examining their plasticity in relation to behavioral development. Other work has suggested that neural body maps may be involved in the registration of correspondences between self and other, with implications for early social development. Here, body representations are discussed in the context of preterm birth and autism spectrum disorder, providing novel perspectives relevant to developmental medicine and child neurology. WHAT THIS PAPER ADDS: ●Somatotopic body maps develop prenatally through intrinsic and activity-dependent mechanisms. ●There is increasing interest in understanding postnatal plasticity in body maps. ●Body representations may be involved in the registration of preverbal, interpersonal relationships.


Assuntos
Imagem Corporal , Mapeamento Encefálico , Potenciais Somatossensoriais Evocados/fisiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Percepção Social , Córtex Somatossensorial/fisiopatologia , Percepção do Tato/fisiologia , Humanos , Lactente , Córtex Somatossensorial/crescimento & desenvolvimento
7.
Proc Natl Acad Sci U S A ; 117(16): 9094-9100, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32253308

RESUMO

Stem cell transplantation can improve behavioral recovery after stroke in animal models but whether stem cell-derived neurons become functionally integrated into stroke-injured brain circuitry is poorly understood. Here we show that intracortically grafted human induced pluripotent stem (iPS) cell-derived cortical neurons send widespread axonal projections to both hemispheres of rats with ischemic lesions in the cerebral cortex. Using rabies virus-based transsynaptic tracing, we find that at 6 mo after transplantation, host neurons in the contralateral somatosensory cortex receive monosynaptic inputs from grafted neurons. Immunoelectron microscopy demonstrates myelination of the graft-derived axons in the corpus callosum and that their terminals form excitatory, glutamatergic synapses on host cortical neurons. We show that the stroke-induced asymmetry in a sensorimotor (cylinder) test is reversed by transplantation. Light-induced inhibition of halorhodopsin-expressing, grafted neurons does not recreate the impairment, indicating that its reversal is not due to neuronal activity in the graft. However, we find bilateral decrease of motor performance in the cylinder test after light-induced inhibition of either grafted or endogenous halorhodopsin-expressing cortical neurons, located in the same area, and after inhibition of endogenous halorhodopsin-expressing cortical neurons by exposure of their axons to light on the contralateral side. Our data indicate that activity in the grafted neurons, probably mediated through transcallosal connections to the contralateral hemisphere, is involved in maintaining normal motor function. This is an example of functional integration of efferent projections from grafted neurons into the stroke-affected brain's neural circuitry, which raises the possibility that such repair might be achievable also in humans affected by stroke.


Assuntos
Células-Tronco Pluripotentes Induzidas/fisiologia , Infarto da Artéria Cerebral Média/terapia , Atividade Motora/fisiologia , Neurônios/transplante , Córtex Somatossensorial/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Técnicas de Observação do Comportamento , Comportamento Animal/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Neurônios/fisiologia , Optogenética , Técnicas de Patch-Clamp , Ratos , Recuperação de Função Fisiológica , Córtex Somatossensorial/citologia , Córtex Somatossensorial/patologia
8.
J Neurosci ; 40(17): 3478-3490, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32241836

RESUMO

Gamma-band oscillations (GBOs) elicited by transient nociceptive stimuli are one of the most promising biomarkers of pain across species. Still, whether these GBOs reflect stimulus encoding in the primary somatosensory cortex (S1) or nocifensive behavior in the primary motor cortex (M1) is debated. Here we recorded neural activity simultaneously from the brain surface as well as at different depths of the bilateral S1/M1 in freely-moving male rats receiving nociceptive stimulation. GBOs measured from superficial layers of S1 contralateral to the stimulated paw not only had the largest magnitude, but also showed the strongest temporal and phase coupling with epidural GBOs. Also, spiking of superficial S1 interneurons had the strongest phase coherence with epidural GBOs. These results provide the first direct demonstration that scalp GBOs, one of the most promising pain biomarkers, reflect neural activity strongly coupled with the fast spiking of interneurons in the superficial layers of the S1 contralateral to the stimulated side.SIGNIFICANCE STATEMENT Nociceptive-induced gamma-band oscillations (GBOs) measured at population level are one of the most promising biomarkers of pain perception. Our results provide the direct demonstration that these GBOs reflect neural activity coupled with the spike firing of interneurons in the superficial layers of the primary somatosensory cortex (S1) contralateral to the side of nociceptive stimulation. These results address the ongoing debate about whether nociceptive-induced GBOs recorded with scalp EEG or epidurally reflect stimulus encoding in the S1 or nocifensive behavior in the primary motor cortex (M1), and will therefore influence how experiments in pain neuroscience will be designed and interpreted.


Assuntos
Ritmo Gama/fisiologia , Córtex Motor/fisiopatologia , Nociceptividade/fisiologia , Dor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Potenciais Somatossensoriais Evocados/fisiologia , Interneurônios/fisiologia , Masculino , Percepção da Dor/fisiologia , Ratos
9.
Sci Rep ; 10(1): 3771, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111927

RESUMO

Primary motor cortex (M1) infarctions sometimes cause sensory impairment. Because sensory signals play a vital role in motor control, sensory impairment compromises the recovery and rehabilitation of motor disability. However, the neural mechanism of the sensory impairment is poorly understood. We show that sensory processing in mouse primary somatosensory cortex (S1) was impaired in the acute phase of M1 infarctions and recovered in a layer-specific manner in the subacute phase. This layer-dependent recovery process and the anatomical connection pattern from M1 to S1 suggested that functional connectivity from M1 to S1 plays a key role in the sensory processing impairment. A simulation study demonstrated that the loss of inhibition from M1 to S1 in the acute phase of M1 infarctions could impair sensory processing in S1, and compensation for the inhibition could recover the temporal coding. Consistently, the optogenetic activation of M1 suppressed the sustained response in S1. Taken together, we revealed how focal stroke in M1 alters the cortical network activity of sensory processing, in which inhibitory input from M1 to S1 may be involved.


Assuntos
Infarto Encefálico/fisiopatologia , Sensação , Córtex Somatossensorial/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Infarto Encefálico/patologia , Masculino , Camundongos , Optogenética , Córtex Somatossensorial/patologia , Acidente Vascular Cerebral/patologia
10.
Nat Neurosci ; 23(4): 520-532, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32123378

RESUMO

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B-/- mouse model of ASD. Male and female Shank3B-/- mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.


Assuntos
Potenciais de Ação/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Neurônios GABAérgicos/fisiologia , Proteínas do Tecido Nervoso/genética , Córtex Somatossensorial/fisiopatologia , Percepção do Tato/fisiologia , Animais , Transtorno do Espectro Autista/genética , Modelos Animais de Doenças , Camundongos , Proteínas dos Microfilamentos , Estimulação Física , Células Piramidais/fisiologia , Limiar Sensorial/fisiologia , Tato/fisiologia
11.
Phys Ther ; 100(6): 946-962, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32201890

RESUMO

BACKGROUND: Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS). PURPOSE: This article provides an overview of the evidence relating to CNS changes (structural and functional) associated with pain in SCIs. DATA SOURCES: A systematic review was performed, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on PubMed, Embase, and Web of Science in March 2018. STUDY SELECTION: Studies were selected if they concerned changes in the CNS of patients with SCI, regardless of the type of imagery. DATA EXTRACTION: Data were extracted by 2 blinded reviewers. DATA SYNTHESIS: There is moderate evidence for impaired electroencephalographic function and metabolic abnormalities in the anterior cingulate in patients experiencing pain. There is preliminary evidence that patients with pain have morphological and functional changes to the somatosensory cortex and alterations to thalamic metabolism. There are conflicting data regarding the relationships between lesion characteristics and pain. In contrast, patients without pain can display protective neuroplasticity. LIMITATIONS AND CONCLUSION: Further studies are required to elucidate fully the relationships between pain and neuroplasticity in patients with SCIs. However, current evidence might support the use of physical therapist treatments targeting CNS plasticity in patients with SCI pain.


Assuntos
Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Dor Crônica/etiologia , Neuralgia/etiologia , Traumatismos da Medula Espinal/complicações , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/metabolismo , Dor Crônica/fisiopatologia , Eletroencefalografia/métodos , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Neuralgia/fisiopatologia , Neuroimagem/métodos , Plasticidade Neuronal/fisiologia , Viés de Seleção , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/patologia , Córtex Somatossensorial/fisiopatologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/metabolismo
12.
J Neurosci ; 40(11): 2228-2245, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32001612

RESUMO

Sensory cortex exhibits receptive field plasticity throughout life in response to changes in sensory experience and offers the experimental possibility of aligning functional changes in receptive field properties with underpinning structural changes in synapses. We looked at the effects on structural plasticity of two different patterns of whisker deprivation in male and female mice: chessboard deprivation, which causes functional plasticity; and all deprived, which does not. Using 2-photon microscopy and chronic imaging through a cranial window over the barrel cortex, we found that layer 2/3 neurones exhibit robust structural plasticity, but only in response to whisker deprivation patterns that cause functional plasticity. Chessboard pattern deprivation caused dual-component plasticity in layer 2/3 by (1) increasing production of new spines that subsequently persisted for weeks and (2) enlarging spine head sizes in the preexisting stable spine population. Structural plasticity occurred on basal dendrites, but not apical dendrites. Both components of plasticity were absent in αCaMKII-T286A mutants that lack LTP and experience-dependent potentiation in barrel cortex, implying that αCaMKII autophosphorylation is not only important for stabilization and enlargement of spines, but also for new spine production. These studies therefore reveal the relationship between spared whisker potentiation in layer 2/3 neurones and the form and mechanisms of structural plasticity processes that underlie them.SIGNIFICANCE STATEMENT This study provides a missing link in a chain of reasoning that connects LTP to experience-dependent functional plasticity in vivo We found that increases in dendritic spine formation and spine enlargement (both of which are characteristic of LTP) only occurred in barrel cortex during sensory deprivation that produced potentiation of sensory responses. Furthermore, the dendritic spine plasticity did not occur during sensory deprivation in mice lacking LTP and experience-dependent potentiation (αCaMKII autophosphorylation mutants). We also found that the dual-component dendritic spine plasticity only occurred on basal dendrites and not on apical dendrites, thereby resolving a paradox in the literature suggesting that layer 2/3 neurones lack structural plasticity in response to sensory deprivation.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Espinhas Dendríticas/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/enzimologia , Privação Sensorial/fisiologia , Córtex Somatossensorial/fisiopatologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/deficiência , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Tamanho Celular , Espinhas Dendríticas/ultraestrutura , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/ultraestrutura , Fosforilação , Processamento de Proteína Pós-Traducional , Técnica de Janela Cutânea , Córtex Somatossensorial/citologia , Distúrbios Somatossensoriais/fisiopatologia , Vibrissas/lesões , Vibrissas/inervação
13.
Epilepsia ; 61(2): 330-341, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31912497

RESUMO

OBJECTIVE: The neuronal underpinnings of impaired consciousness during absence seizures remain largely unknown. Spike-and-wave (SW) activity associated with absences imposes two extremely different states in cortical neurons, which transition from suprathreshold synaptic depolarizations during spike phases to membrane hyperpolarization and electrical silence during wave phases. To investigate whether this rhythmic alternation of neuronal states affects the processing of sensory information during seizures, we examined cortical and thalamic responsiveness to brief sensory stimuli in the different phases of the epileptic cycle. METHODS: Electrocorticographic (ECoG) monitoring from the primary somatosensory cortex combined with intracellular recordings of subjacent pyramidal neurons, or extracellular recordings of somatosensory thalamic neurons, were performed in the Genetic Absence Epilepsy Rat From Strasbourg. Sensory stimuli consisted of pulses of compressed air applied to the contralateral whiskers. RESULTS: Whisker stimuli delivered during spike phases evoked smaller depolarizing synaptic potentials and fewer action potentials in cortical neurons compared to stimuli occurring during wave phases. This spike-related attenuation of cortical responsiveness was accompanied by a reduced neuronal membrane resistance, likely due to the large increase in synaptic conductance. Sensory-evoked firing in thalamocortical neurons was also decreased during ECoG spikes as compared to wave phases, indicating that time-to-time changes in the thalamocortical volley may also contribute to the variability of cortical responses during seizures. SIGNIFICANCE: These findings demonstrate that thalamocortical sensory processing during absence seizures is nonstationary and strongly suggest that the cortical impact of a given environmental stimulus is conditioned by its exact timing relative to the SW cycle. The lack of stability of thalamic and cortical responses along seizures may contribute to impaired conscious sensory perception during absences.


Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/fisiopatologia , Sensação , Tálamo/fisiopatologia , Animais , Membrana Celular , Eletrocorticografia , Epilepsia Tipo Ausência/fisiopatologia , Neurônios , Células Piramidais , Ratos , Córtex Somatossensorial/fisiopatologia , Vibrissas/inervação
14.
J Neurosci ; 40(7): 1538-1548, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31896672

RESUMO

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.


Assuntos
Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Processos Mentais/fisiologia , Noxas , Percepção da Dor/fisiologia , Adulto , Mapeamento Encefálico , Catastrofização , Cognição/fisiologia , Corpo Estriado/fisiopatologia , Sinais (Psicologia) , Feminino , Temperatura Alta/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Limiar da Dor/fisiologia , Sensação/fisiologia , Córtex Somatossensorial/fisiopatologia , Adulto Jovem
15.
Neurol Res ; 42(1): 76-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31900075

RESUMO

Objectives: Spreading depolarization (SD) is a well-recognized component of the stress response of the cortex to its acute injury. Cortical SD has been shown to occur in severe brain insults and standard neurosurgical procedures in patients and is supposed to promote delayed secondary brain injuries. Stereotactic surgery and site-specific intracerebral microinjections produce a small tissue injury when a thin needle is inserted directly into the brain parenchyma (via the cannula guide). The present study was designed to examine whether such a parenchymal damage can trigger SD.Methods: Experiments were performed in awake freely moving rats with simultaneous video-monitoring of behavior and recording of SD-related DC potentials in the cortex and striatum. A parenchymal damage was produced by 1-mm protruding of thin (0.3-mm diameter) cannula beyond the tip of cannula guide preliminary implanted into the amygdala or deep cortical layers.Results: We found that the micro-injury of the brain parenchyma the volume of which did not exceed 0.3 mm3 was sufficient to initiate SD in a very high proportion of rats (75-100%). The amygdala showed increased resistance against the injury-induced SD compared to the cortex. We further showed that SD triggered by the local micro-injury invaded remote intact regions of the cortico-striatal system and evoked specific changes in spontaneous animal behavior.Discussion: The findings indicate that SD may represent a previously unidentified side effect of local parenchymal injury during site-specific microinjections and stereotactic surgery.


Assuntos
Concussão Encefálica/fisiopatologia , Encéfalo/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Tecido Parenquimatoso/lesões , Tecido Parenquimatoso/fisiopatologia , Animais , Concussão Encefálica/complicações , Masculino , Microinjeções/efeitos adversos , Ratos , Ratos Wistar , Córtex Somatossensorial/fisiopatologia
16.
Am J Psychiatry ; 177(1): 37-46, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31416339

RESUMO

OBJECTIVE: Childhood maltreatment is a major risk factor for psychopathology associated with interpersonal problems in adulthood, but the etiological pathways involved are still unclear. The authors propose that childhood maltreatment confers risk for dysfunctional behavior in social interactions by altering interpersonal distance preference and the processing of social touch. METHODS: Ninety-two medication-free adults (64 of them female) with low, medium, and high levels of childhood maltreatment were tested with an interpersonal distance paradigm and subsequently underwent a social touch functional MRI task during which they rated the perceived comfort of slow touch (C-tactile [CT] optimal speed; 5 cm/s) and fast touch (non-CT-optimal speed; 20 cm/s). RESULTS: Participants with high childhood maltreatment levels preferred a larger interpersonal distance and experienced fast touch as less comforting compared with participants with no or moderate childhood maltreatment experiences. On the neural level, participants with severe childhood maltreatment exhibited exaggerated responses to fast touch in the right somatosensory and posterior insular cortex, which correlated with lower comfort ratings. Severe childhood maltreatment was associated with decreased activation in the right hippocampus in response to slow touch. This response pattern was not moderated or mediated by childhood maltreatment-associated region-specific reductions in gray matter volume. CONCLUSIONS: The study findings suggest that higher childhood maltreatment levels are associated with hypersensitivity characterized by a preference for larger interpersonal distance and discomfort of fast touch. These dysregulations were manifested in a sensory cortical hyperreactivity and limbic CT-related hypoactivation. These results may shed light on why individuals with severe childhood maltreatment exhibit an increased susceptibility to interpersonal dysfunctions and psychiatric disorders in adulthood.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Córtex Cerebral/fisiopatologia , Hipocampo/fisiopatologia , Relações Interpessoais , Córtex Somatossensorial/fisiopatologia , Adulto , Atrofia/patologia , Feminino , Neuroimagem Funcional , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Percepção do Tato/fisiologia , Adulto Jovem
17.
Cell Rep ; 29(12): 3847-3858.e5, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31851918

RESUMO

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamatergic neurons in the parafascicular nucleus (GluPF). These GluPF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABACeA→GluPF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABACeA→GluPF→S2 pathway in controlling at least some aspects of CP.


Assuntos
Núcleo Central da Amígdala/fisiopatologia , Depressão/complicações , Neurônios GABAérgicos/patologia , Núcleos Intralaminares do Tálamo/fisiopatologia , Vias Neurais/fisiopatologia , Dor/patologia , Córtex Somatossensorial/fisiopatologia , Animais , Masculino , Camundongos , Optogenética , Dor/etiologia
18.
Sci Rep ; 9(1): 18213, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796805

RESUMO

The people with multiple sclerosis (MS) often report that fatigue restricts their life. Nowadays, pharmacological treatments are poorly effective accompanied by relevant side effects. A 5-day transcranial direct current stimulation (tDCS) targeting the somatosensory representation of the whole body (S1) delivered through an electrode personalized based on the brain MRI was efficacious against MS fatigue (FaReMuS treatment). This proof of principle study tested whether possible changes of the functional organization of the primary sensorimotor network induced by FaReMuS partly explained the effected fatigue amelioration. We measured the brain activity at rest through electroencephalography equipped with a Functional Source Separation algorithm and we assessed the neurodynamics state of the primary somatosensory (S1) and motor (M1) cortices via the Fractal Dimension and their functional connectivity via the Mutual Information. The dynamics of the neuronal electric activity, more distorted in S1 than M1 before treatment, as well as the network connectivity, altered maximally between left and right M1 homologs, reverted to normal after FaReMuS. The intervention-related changes explained 48% of variance of fatigue reduction in the regression model. A personalized neuromodulation tuned in on specific anatomo-functional features of the impaired regions can be effective against fatigue.


Assuntos
Fadiga/terapia , Córtex Motor/fisiopatologia , Esclerose Múltipla/terapia , Córtex Somatossensorial/fisiopatologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Eletrodos , Eletroencefalografia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Esclerose Múltipla/complicações , Estudo de Prova de Conceito , Córtex Somatossensorial/diagnóstico por imagem , Estimulação Transcraniana por Corrente Contínua/instrumentação , Resultado do Tratamento
19.
eNeuro ; 6(6)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31843753

RESUMO

Epidemiological studies have found an increased incidence of neurodevelopmental disorders in populations prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). Optical imaging provides a minimally invasive way to determine if perinatal SSRI exposure has long-term effects on cortical function. Herein we probed the functional neuroimaging effects of perinatal SSRI exposure in a fluoxetine (FLX)-exposed mouse model. While resting-state homotopic contralateral functional connectivity was unperturbed, the evoked cortical response to forepaw stimulation was altered in FLX mice. The stimulated cortex showed decreased activity for FLX versus controls, by both hemodynamic responses [oxyhemoglobin (HbO2)] and neuronal calcium responses (Thy1-GCaMP6f fluorescence). Significant alterations in both cortical HbO2 and calcium response amplitude were seen in the cortex ipsilateral to the stimulated paw in FLX as compared to controls. The cortical regions of largest difference in activation between FLX and controls also were consistent between HbO2 and calcium contrasts at the end of stimulation. Taken together, these results suggest a global loss of response signal amplitude in FLX versus controls. These findings indicate that perinatal SSRI exposure has long-term consequences on somatosensory cortical responses.


Assuntos
Cálcio/metabolismo , Potenciais Somatossensoriais Evocados/fisiologia , Fluoxetina/efeitos adversos , Hemodinâmica/fisiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Inibidores de Captação de Serotonina/efeitos adversos , Córtex Somatossensorial/fisiopatologia , Animais , Feminino , Camundongos , Imagem Óptica , Gravidez
20.
Sci Rep ; 9(1): 19776, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874978

RESUMO

We investigate changes in brain function before and after carpal tunnel release. Magnetoencephalography (MEG), during which we recorded somatosensory evoked cortical magnetic fields (SEFs), and a clinical evaluation were performed before surgery and 6 months after. The distance on the vertical axis between the equivalent current dipoles (ECDs) for the first and third digits before surgery was significantly less than after surgery. There were no significant differences in values between the control participant and patients after surgery. In terms of distal motor latency, there was a negative correlation with the distance. The recovery function of the root mean square (RMS) before surgery for the N20m was less suppressed at 10 ms of ISI in patients, compared to controls. There were no significant differences in the RMS values for patients before and after surgery. Our results indicate that treating peripheral nerve lesions, such as in carpal tunnel release, positively modifies brain function.


Assuntos
Síndrome do Túnel Carpal/fisiopatologia , Potenciais Somatossensoriais Evocados , Magnetoencefalografia , Córtex Somatossensorial/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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