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1.
Nat Commun ; 10(1): 4699, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619680

RESUMO

Regaining the function of an impaired limb is highly desirable in paralyzed individuals. One possible avenue to achieve this goal is to bridge the interrupted pathway between preserved neural structures and muscles using a brain-computer interface. Here, we demonstrate that monkeys with subcortical stroke were able to learn to use an artificial cortico-muscular connection (ACMC), which transforms cortical activity into electrical stimulation to the hand muscles, to regain volitional control of a paralysed hand. The ACMC induced an adaptive change of cortical activities throughout an extensive cortical area. In a targeted manner, modulating high-gamma activity became localized around an arbitrarily-selected cortical site controlling stimulation to the muscles. This adaptive change could be reset and localized rapidly to a new cortical site. Thus, the ACMC imparts new function for muscle control to connected cortical sites and triggers cortical adaptation to regain impaired motor function after stroke.


Assuntos
Adaptação Fisiológica/fisiologia , Interfaces Cérebro-Computador , Estimulação Elétrica , Córtex Motor/fisiopatologia , Músculo Esquelético/fisiologia , Córtex Somatossensorial/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Braço , Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Eletrocorticografia , Mãos , Macaca mulatta , Córtex Motor/fisiologia , Vias Neurais/fisiopatologia , Paralisia , Córtex Somatossensorial/fisiologia , Reabilitação do Acidente Vascular Cerebral , Punho
2.
Exp Neurol ; 322: 113035, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31446080

RESUMO

The cortical reorganization after spinal cord injury (SCI) involves a series of physiological changes that drive the expansion of the intact cortical area to the deafferented cortical area. These changes have always been studied under a stimulus-response paradigm, which demonstrates that the deafferented cortex becomes more responsive to stimulation of body regions above the level of the lesion. However, less is known about how permanent large-scale deafferentation affects spontaneous activity in the somatosensory cortex, an important physiological feature related to the processing of peripheral inputs and perception. Here we studied the spontaneous activity at two sites of the somatosensory cortex, corresponding to forepaw and hindpaw, and at three different time points after SCI: acute SCI, one week post-SCI and chronic SCI (1-3 months after injury). Electrophysiological recordings from anesthetized rats were obtained in conditions of slow-wave activity in order to compare features of the neural populations in periods of cortical up-states. Our data demonstrate that acute SCI reduces the excitability of cortical neurons during up-states in both the forepaw and the hindpaw cortex. One week after SCI, the properties of cortical neurons were similar to those under control conditions, indicating a homeostatic plasticity. Finally, chronic SCI increased neural activity during up-states, while reduced up-state frequency in the cortex. We conclude that SCI induces different homeostatic changes in cortical slow-wave depending on the time after lesion. This temporal evolution of spontaneous activity could help better understand the cortical plasticity associated with acute or chronic SCI.


Assuntos
Homeostase/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Somatossensorial/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Masculino , Ratos , Ratos Wistar
3.
Exp Brain Res ; 237(9): 2297-2304, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273391

RESUMO

Incomplete recovery of sensory function is common after peripheral nerve injury (PNI). Despite reinnervation following injury, disorganized cortical representations persist and may contribute to functional deficits. There is a dearth of literature characterizing cortical responses after PNI in rodent models. Here we develop a quantitative electrophysiological method for mapping forepaw digit responses in primary somatosensory cortex (S1) of rats. We tested the hypothesis that PNI in the forelimb would generate significant, long lasting sensory deficits, and corresponding disorganization in S1. Rats underwent a transection of the proximal segment of the median and ulnar nerves in the forelimb followed by tubular repair. 4-12 months after nerve injury, we tested mechanosensory withdrawal thresholds and mapped S1 responses to mechanical stimulation of the digits. PNI produces persistent elevation of mechanical withdrawal thresholds, consistent with an impairment in sensory function. Assessment of cortical neurophysiology reveals a substantial disorganization of S1 somatotopy. Additionally, we document degraded timing and digit specificity of cortical responses. This quantitative measurement of long-term changes in S1 digit representations after forelimb nerve injury in rodents provides a framework for further studies focused on the development of therapeutic strategies to restore cortical and sensory function.


Assuntos
Membro Anterior/fisiopatologia , Nervo Mediano/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Limiar Sensorial/fisiologia , Córtex Somatossensorial/fisiopatologia , Dedos do Pé/fisiopatologia , Percepção do Tato/fisiologia , Nervo Ulnar/fisiopatologia , Animais , Modelos Animais de Doenças , Eletroencefalografia , Feminino , Nervo Mediano/lesões , Estimulação Física , Ratos , Ratos Sprague-Dawley , Nervo Ulnar/lesões
4.
Int J Mol Sci ; 20(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234472

RESUMO

Traumatic brain injury (TBI) can lead to impaired cognition and memory consolidation. The acute phase (24-48 h) after TBI is often characterized by neural dysfunction in the vicinity of the lesion, but also in remote areas like the contralateral hemisphere. Protein homeostasis is crucial for synaptic long-term plasticity including the protein degradation systems, proteasome and autophagy. Still, little is known about the acute effects of TBI on synaptic long-term plasticity and protein degradation. Thus, we investigated TBI in a controlled cortical impact (CCI) model in the motor and somatosensory cortex of mice ex vivo-in vitro. Late long-term potentiation (l-LTP) was induced by theta-burst stimulation in acute brain slices after survival times of 1-2 days. Protein levels for the plasticity related protein calcium/calmodulin-dependent protein kinase II (CaMKII) was quantified by Western blots, and the protein degradation activity by enzymatical assays. We observed missing maintenance of l-LTP in the ipsilateral hemisphere, however not in the contralateral hemisphere after TBI. Protein levels of CaMKII were not changed but, interestingly, the protein degradation revealed bidirectional changes with a reduced proteasome activity and an increased autophagic flux in the ipsilateral hemisphere. Finally, LTP recordings in the presence of pharmacologically modified protein degradation systems also led to an impaired synaptic plasticity: bath-applied MG132, a proteasome inhibitor, or rapamycin, an activator of autophagy, both administered during theta burst stimulation, blocked the induction of LTP. These data indicate that alterations in protein degradation pathways likely contribute to cognitive deficits in the acute phase after TBI, which could be interesting for future approaches towards neuroprotective treatments early after traumatic brain injury.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Potenciação de Longa Duração , Complexo de Endopeptidases do Proteassoma/metabolismo , Córtex Somatossensorial/fisiopatologia , Animais , Autofagia , Lesões Encefálicas Traumáticas/metabolismo , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Proteólise , Córtex Somatossensorial/metabolismo
5.
Neuroimage Clin ; 22: 101790, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31146320

RESUMO

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.


Assuntos
Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Enxaqueca sem Aura/fisiopatologia , Neostriado/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Percepção Social , Córtex Somatossensorial/fisiopatologia , Adulto , Medo/fisiologia , Feminino , Felicidade , Humanos , Imagem por Ressonância Magnética , Masculino , Enxaqueca sem Aura/diagnóstico por imagem , Enxaqueca sem Aura/etiologia , Neostriado/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Estresse Psicológico/complicações , Adulto Jovem
6.
Brain Topogr ; 32(3): 504-518, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30949863

RESUMO

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.


Assuntos
Síndrome de Asperger/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Síndrome de Asperger/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Criança , Potencial Evocado Motor/fisiologia , Exercício , Face , Lateralidade Funcional , Substância Cinzenta/diagnóstico por imagem , Mãos , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/fisiopatologia , Músculo Esquelético , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Substância Branca/diagnóstico por imagem
7.
Eur Radiol ; 29(9): 4904-4913, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30840103

RESUMO

OBJECTIVES: To identify regions causally influenced by thalamic stroke by measuring white matter integrity, cortical volume, and functional connectivity (FC) among patients with thalamic infarction (TI) and to determine the association between structural/functional alteration and somatosensory dysfunction. METHODS: Thirty-one cases with TI-induced somatosensory dysfunction and 32 healthy controls underwent magnetic resonance imaging scanning. We reconstructed the ipsilesional central thalamic radiation (CTR) and assessed its integrity using fractional anisotropy (FA), assessed S1 ipsilesional changes with cortical volume, and identified brain regions functionally connected to TI locations and regions without TI to examine the potential effects on somatosensory symptoms. RESULTS: Compared with controls, TI patients showed decreased FA (F = 17.626, p < 0.001) in the ipsilesional CTR. TI patients exhibited significantly decreased cortical volume in the ipsilesional top S1. Both affected CTR (r = 0.460, p = 0.012) and S1 volume (r = 0.375, p = 0.049) were positively correlated with somatosensory impairment in TI patients. In controls, the TI region was highly functionally connected to atrophic top S1 and less connected to the adjacent middle S1 region in FC mapping. However, T1 patients demonstrated significantly increased FC between the ipsilesional thalamus and middle S1 area, which was adjacent to the atrophic S1 region. CONCLUSIONS: TI induces remote changes in the S1, and this network of abnormality underlies the cause of the sensory deficits. However, our other finding that there is stronger connectivity in pathways adjacent to the damaged ones is likely responsible for at least some of the recovery of function. KEY POINTS: • TI led to secondary impairment in the CTR and cortical atrophy in the ipsilesional top of S1. • TI patients exhibited significantly higher functional connectivity with the ipsilateral middle S1 which was mainly located within the non-atrophic area of S1. • Our results provide neuroimaging markers for non-invasive treatment and predict somatosensory recovery.


Assuntos
Infarto Cerebral/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Tálamo/irrigação sanguínea , Anisotropia , Estudos Transversais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia
8.
Neuroscience ; 406: 626-636, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30825581

RESUMO

The medial prefrontal cortex (mPFC) has been implicated in novelty detection and attention. We studied the effect of mPFC electrical stimulation on whisker responses recorded in the ventroposterior medial thalamic nucleus (VPM), the posterior thalamic nucleus (POm) and the primary somatosensory (S1) cortex in urethane anesthetized rats. Field potentials and unit recordings were performed in the VPM or POm thalamic nuclei, in S1 cortex, and in the Zona Incerta (ZI). Somatosensory evoked potentials were elicited by whisker deflections. Current pulses were delivered by bipolar stimulating electrodes aimed at the prelimbic (PL) or infralimbic (IL) areas of mPFC. PL train stimulation (50 Hz, 500 ms) induced a facilitation of whisker responses in the VPM nucleus that lasted minutes and a short inhibition in the POm nucleus. IL stimulation induced a facilitation of whisker responses in both VPM and POm nuclei. Facilitation was due to corticofugal projections because it was reduced after S1 cortical inactivation with lidocaine, and by activation of NMDA glutamatergic receptors because it was blocked by APV. Paired stimulation of mPFC and whiskers revealed an inhibitory effect at short intervals (<100 ms), which was mediated by ZI inhibitory neurons since PL stimulation induced response facilitation in the majority of ZI neurons (42%) and muscimol injection into ZI nucleus reduced inhibitory effects, suggesting that the mPFC may inhibit the POm neurons by activation of GABAergic ZI neurons. In conclusion, the mPFC may control the flow of somatosensory information through the thalamus by activation of S1 and ZI neurons.


Assuntos
Estimulação Física , Córtex Pré-Frontal/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Tálamo/fisiopatologia , Vibrissas/fisiologia , Animais , Estimulação Elétrica/métodos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Masculino , Muscimol/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Ratos Sprague-Dawley , Córtex Somatossensorial/efeitos dos fármacos , Núcleos Talâmicos/efeitos dos fármacos , Núcleos Talâmicos/fisiopatologia , Tálamo/efeitos dos fármacos , Vibrissas/efeitos dos fármacos , Zona Incerta/efeitos dos fármacos , Zona Incerta/fisiopatologia
9.
Microbiome ; 7(1): 45, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898151

RESUMO

BACKGROUND AND AIMS: Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. METHODS: We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. RESULTS: We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. CONCLUSIONS: In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.


Assuntos
Mapeamento Encefálico/métodos , Clostridiaceae/fisiologia , Síndrome do Intestino Irritável/microbiologia , Córtex Sensório-Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Estudos de Casos e Controles , Clostridiaceae/isolamento & purificação , Fezes , Feminino , Microbioma Gastrointestinal , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Estudos Prospectivos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suécia , Adulto Jovem
10.
PLoS One ; 14(3): e0213371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845241

RESUMO

INTRODUCTION: Preoperative functional mapping in the vicinity of brain lesion is of high importance for avoiding complications in surgical management. However, space-occupying lesions may lead to functional reorganization or decreased BOLD activity. METHODS: Therefore in 13 patients with cerebral gliomas or brain arterio-venous malformations/ hemangioma fMRI- and MEG-based cortical localizations of motor and somatosensory cortical activation pattern were compared in order to investigate their congruency. RESULTS: Localization of cortical sensorimotor areas with fMRI and MEG showed good congruency with a mean spatial distance of around 10 mm, with differences depending on the localization method. The smallest mean differences for the centroids were found for MEF with MNE 8 mm and SEF with sLORETA 8 mm. Primary motor area (M1) reorganization was found in 5 of 12 patients in fMRI and confirmed with MEG data. In these 5 patients with M1-reorganization the distance between the border of the fMRI-based cortical M1-localization and the tumor border on T1w MR images varied between 0-4 mm, which was significant (P = 0.025) different to the distance in glioma patients without M1-reorganization (5-26 mm). CONCLUSION: Our multimodal preoperative mapping approach combining fMRI and MEG reveals a high degree of spatial congruence and provided high evidence for the presence of motor cortex reorganization.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Glioma/fisiopatologia , Córtex Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Idoso , Mapeamento Encefálico/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia
11.
Neuroimage ; 189: 615-630, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30708105

RESUMO

Despite the association between brainstem lesions and coma, a mechanistic understanding of coma pathogenesis and recovery is lacking. We developed a coma model in the rat mimicking human brainstem coma, which allowed multimodal analysis of a brainstem tegmentum lesion's effects on behavior, cortical electrophysiology, and global brain functional connectivity. After coma induction, we observed a transient period (∼1h) of unresponsiveness accompanied by cortical burst-suppression. Comatose rats then gradually regained behavioral responsiveness concurrent with emergence of delta/theta-predominant cortical rhythms in primary somatosensory cortex. During the acute stage of coma recovery (∼1-8h), longitudinal resting-state functional MRI revealed an increase in functional connectivity between subcortical arousal nuclei in the thalamus, basal forebrain, and basal ganglia and cortical regions implicated in awareness. This rat coma model provides an experimental platform to systematically study network-based mechanisms of coma pathogenesis and recovery, as well as to test targeted therapies aimed at promoting recovery of consciousness after coma.


Assuntos
Prosencéfalo Basal/fisiopatologia , Gânglios da Base/fisiopatologia , Mapeamento Encefálico/métodos , Tronco Encefálico/lesões , Córtex Cerebral/fisiopatologia , Coma/fisiopatologia , Rede Nervosa/fisiopatologia , Tálamo/fisiopatologia , Animais , Prosencéfalo Basal/diagnóstico por imagem , Gânglios da Base/diagnóstico por imagem , Comportamento Animal/fisiologia , Córtex Cerebral/diagnóstico por imagem , Coma/diagnóstico por imagem , Modelos Animais de Doenças , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Tálamo/diagnóstico por imagem
12.
Clin Neurophysiol ; 130(4): 439-444, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30769270

RESUMO

OBJECTIVE: The pathophysiology of epilepsia partialis continua (EPC) is still unclear, a thalamo-cortical circuit dysfunction has been hypothesized. The aim of present study is the functional evaluation of the thalamo-cortical network in EPC by means of the study of low- and high-frequency somatosensory evoked potentials (LF-SEP and HF-SEP). METHODS: Median LF-SEP and HF-SEP were recorded in 3 patients with EPC and in 2 patients with rolandic lesions without EPC (non-EPC). Recording electrodes were placed on P3, C3, F3 and P4, C4, F4 of scalp regions. HF-SEP were obtained by an offline 400-800 Hz filtering of P3-F3 and P4-F4 traces. RESULTS: In EPC patients, we found a significant suppression of post-synaptic HF-SEP burst and an amplitude reduction of the P24 wave of the LF-SEPs. Both these components are related to cortical inhibitory interneuron activity. HF-SEP and LF-SEP were normal in non-EPC patients. CONCLUSION: The different results obtained in patients with a rolandic lesion with and without EPC supports the hypothesis that EPC might be correlated to a dysfunction of gabaergic interneurons of a cortical sensory-motor network. SIGNIFICANCE: Our results might contribute to the understanding of the physiological basis of the cortical dysfunction causing epilepsia partialis continua.


Assuntos
Epilepsia Parcial Contínua/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Inibição Neural/fisiologia , Córtex Somatossensorial/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Eletroencefalografia , Feminino , Humanos , Masculino , Rede Nervosa/fisiopatologia
13.
eNeuro ; 6(1)2019.
Artigo em Inglês | MEDLINE | ID: mdl-30693315

RESUMO

The primary sensory cortex processes competitive sensory inputs. Ablation of these competitive inputs induces neuroplastic changes in local cortical circuits. However, information concerning cortical plasticity induced by a disturbance of competitive nociceptive inputs is limited. Nociceptive information from the maxillary and mandibular molar pulps converges at the border between the ventral secondary somatosensory cortex (S2) and insular oral region (IOR); therefore, S2/IOR is a suitable target for examining the cortical changes induced by a disturbance of noxious inputs, which often causes neuropathic pain and allodynia. We focused on the plastic changes in S2/IOR excitation in a model of rats subjected to inferior alveolar nerve transection (IANX). Our optical imaging using a voltage-sensitive dye (VSD) revealed that the maxillary molar pulp stimulation-induced excitatory propagation was expanded one to two weeks after IANX at the macroscopic level. At the cellular level, based on Ca2+ imaging using two-photon microscopy, the amplitude of the Ca2+ responses and the number of responding neurons in S2/IOR increased in both excitatory and inhibitory neurons. The in vitro laser scanning photostimulation (LSPS) revealed that Layer II/III pyramidal and GABAergic fast-spiking neurons in S2/IOR received larger excitatory inputs from Layer IV in the IANX models, which supports the findings obtained by the macroscopic and microscopic optical imaging. Furthermore, the inhibitory postsynaptic inputs to the pyramidal neurons were decreased in the IANX models, suggesting suppression of inhibitory synaptic transmission onto excitatory neurons. These results suggest that IANX induces plastic changes in S2/IOR by changing the local excitatory and inhibitory circuits.


Assuntos
Córtex Cerebral/fisiopatologia , Plasticidade Neuronal , Dor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Traumatismos do Nervo Trigêmeo/fisiopatologia , Animais , Polpa Dentária/inervação , Feminino , Masculino , Dente Molar/inervação , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Nociceptividade/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Ratos Transgênicos , Transmissão Sináptica/fisiologia , Técnicas de Cultura de Tecidos
14.
J Headache Pain ; 20(1): 3, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626318

RESUMO

BACKGROUND: Although altered neural networks have been demonstrated in recent MEG (magnetoencephalography) research in migraine patients during resting state, it is unknown whether this alteration can be detected in task-related networks. The present study aimed to investigate the abnormalities of the frequency-specific somatosensory-related network in migraine patients by using MEG. METHODS: Twenty-two migraineurs in the interictal phase and twenty-two sex- and age-matched healthy volunteers were studied using a whole-head magnetoencephalography (MEG) system. Electrical stimuli were delivered alternately to the median nerve on the right wrists of all subjects. MEG data were analyzed in a frequency range of 1-1000 Hz in multiple bands. RESULTS: The brain network patterns revealed that the patients with migraine exhibited remarkably increased functional connectivity in the high-frequency (250-1000 Hz) band between the sensory cortex and the frontal lobe. The results of quantitative analysis of graph theory showed that the patients had (1) an increased degree of connectivity in the theta (4-8 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands; (2) an increased connectivity strength in the beta (13-30 Hz) and gamma (30-80 Hz) bands; (3) an increased path length in the beta (13-30 Hz), gamma (30-80 Hz) and ripple (80-250 Hz) bands; and (4) an increased clustering coefficient in the theta (4-8 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands. CONCLUSIONS: The results indicate that migraine is associated with aberrant connections from the somatosensory cortex to the frontal lobe. The frequency-specific increases in connectivity in terms of strength, path length and clustering coefficients support the notion that migraineurs have elevated cortical networks. This alteration in functional connectivity may be involved in somatosensory processing in migraine patients and may contribute to understanding migraine pathophysiology and to providing convincing evidence for a spatially targeted migraine therapy.


Assuntos
Encéfalo/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Magnetoencefalografia , Masculino , Córtex Somatossensorial/fisiopatologia , Adulto Jovem
15.
Proc Natl Acad Sci U S A ; 116(5): 1782-1791, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30642968

RESUMO

Individuals exhibit considerable and unpredictable variability in painful percepts in response to the same nociceptive stimulus. Previous work has found neural responses that, while not necessarily responsible for the painful percepts themselves, can still correlate well with intensity of pain perception within a given individual. However, there is no reliable neural response reflecting the variability in pain perception across individuals. Here, we use an electrophysiological approach in humans and rodents to demonstrate that brain oscillations in the gamma band [gamma-band event-related synchronization (γ-ERS)] sampled by central electrodes reliably predict pain sensitivity across individuals. We observed a clear dissociation between the large number of neural measures that reflected subjective pain ratings at within-subject level but not across individuals, and γ-ERS, which reliably distinguished subjective ratings within the same individual but also coded pain sensitivity across different individuals. Importantly, the ability of γ-ERS to track pain sensitivity across individuals was selective because it did not track the between-subject reported intensity of nonpainful but equally salient auditory, visual, and nonnociceptive somatosensory stimuli. These results also demonstrate that graded neural activity related to within-subject variability should be minimized to accurately investigate the relationship between nociceptive-evoked neural activities and pain sensitivity across individuals.


Assuntos
Percepção da Dor/fisiologia , Dor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adolescente , Adulto , Animais , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Limiar da Dor/fisiologia , Ratos Sprague-Dawley , Sensação/fisiologia , Adulto Jovem
16.
Genes Brain Behav ; 18(7): e12556, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30653836

RESUMO

The nuclear receptor COUP TFI (also known as Nr2f1) plays major roles in specifying distinct neuronal subtypes during patterning of the neocortical motor and somatosensory cortex, as well as in regulating the longitudinal growth of the hippocampus during development. In humans, mutations in the NR2F1 gene lead to a global developmental delay and intellectual disabilities. While more than 30% of patients show behavioral features of autism spectrum disorder, 16% of haploinsufficient children show signs of hyperactivity and impulsivity. Loss of COUP-TFI in the cortical mouse primordium results in altered area organization and serotonin distribution, abnormal coordination of voluntary movements and learning and memory deficits. Here, we asked whether absence of COUP-TFI affects locomotor activity, anxiety, as well as depression. Mice mutant for COUP-TFI have normal motor coordination, but significant traits of hyperactivity, which does not seem to respond to N-Methyl-D-aspartate (NMDA) antagonists. However, no changes in anxiety, despite increased locomotor performances, were observed in the open field task. On the contrary, elevated plus maze and dark-light test explorations indicate a decreased anxiety-like behavior in COUP-TFI mutant mice. Finally, significantly reduced immobility in the forced swim test and no changes in anhedonia in the sucrose preference task suggest no particular depressive behaviors in mutant mice. Taken together, our study shows that loss of COUP-TFI leads to increased locomotor activity but less anxiety and contributes in further deciphering the pathophysiology of patients haploinsufficient for NR2F1.


Assuntos
Ansiedade/genética , Fator I de Transcrição COUP/genética , Agitação Psicomotora/genética , Córtex Somatossensorial/metabolismo , Animais , Fator I de Transcrição COUP/metabolismo , Feminino , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Somatossensorial/fisiopatologia
17.
Neuron ; 101(4): 648-661.e4, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30679017

RESUMO

Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide a systematic test of this hypothesis across 4 mouse models (Fmr1-/y, Cntnap2-/-, 16p11.2del/+, Tsc2+/-), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reduction in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization, and spontaneous spiking were largely normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype but appears to reflect homeostatic stabilization of synaptic drive rather than driving network hyperexcitability in autism.


Assuntos
Transtorno Autístico/fisiopatologia , Potenciais Somatossensoriais Evocados , Potenciais Pós-Sinápticos Excitadores , Potenciais Pós-Sinápticos Inibidores , Córtex Somatossensorial/fisiopatologia , Animais , Transtorno Autístico/genética , Cromossomos Humanos Par 16/genética , Proteína do X Frágil de Retardo Mental/genética , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Córtex Somatossensorial/fisiologia , Proteína 2 do Complexo Esclerose Tuberosa/genética
18.
Neuroimage Clin ; 21: 101674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30642754

RESUMO

OBJECTIVE: The main purpose of the present study was to investigate the possible somatosensory-related brain functional reorganization after traumatic spinal cord injury (SCI). METHODS: Thirteen patients with subacute incomplete cervical cord injury (ICCI) and thirteen age- and sex-matched healthy controls (HCs) were recruited. Eleven patients and all the HCs underwent both sensory task-related brain functional scanning and whole brain structural scanning on a 3.0 Tesla MRI system, and two patients underwent only structural scanning; the process of structural scanning was completed on thirteen patients, while functional scanning was only applied to eleven patients. We performed sensory task-related functional MRI (fMRI) to investigate the functional changes in the brain. In addition, voxel-based morphometry (VBM) was applied to explore whether any sensory-related brain structural changes occur in the whole brain after SCI. RESULTS: Compared with HCs, ICCI patients exhibited decreased activation in the left postcentral gyrus (postCG), the brainstem (midbrain and right pons) and the right cerebellar lobules IV-VI. Moreover, a significant positive association was found between the activation in the left PostCG and the activation in both the brainstem and the right cerebellar lobules IV-VI. Additionally, the decrease in gray matter volume (GMV) was detected in the left superior parietal lobule (SPL). The decrease of white matter volume (WMV) was observed in the right temporal lobe, the right occipital lobe, and the right calcarine gyrus. No structural change in the primary sensory cortex (S1), the secondary somatosensory cortex (S2) or the thalamus was detected. CONCLUSION: These functional and structural findings may demonstrate the existence of an alternative pathway in the impairment of somatosensory function after SCI, which consists of the ipsilateral cerebellum, the brainstem and the contralateral postCG. It provides a new theoretical basis for the mechanism of sensory-related brain alteration in SCI patients and the rehabilitation therapy based on this pathway in the future.


Assuntos
Mapeamento Encefálico , Medula Cervical/patologia , Substância Cinzenta/patologia , Traumatismos da Medula Espinal/patologia , Adulto , Idoso , Cerebelo/patologia , Cerebelo/fisiopatologia , Medula Cervical/fisiopatologia , Transtornos Cognitivos/patologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/patologia , Córtex Somatossensorial/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Tálamo/patologia , Adulto Jovem
19.
Clin EEG Neurosci ; 50(3): 188-195, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29877098

RESUMO

Transient global amnesia (TGA) is a clinical syndrome characterized by retrograde and anterograde amnesia without other neurological deficits. Although electroencephalography (EEG) methods are commonly used in both clinical and research setting with TGA patients, few studies have investigated neurophysiological pattern in TGA using quantitative EEG (qEEG). The main aim of the present study was to extend these previous findings by exploring EEG power spectra differences between patients with acute TGA and healthy controls using the exact low-resolution brain electromagnetic tomography software (eLORETA). EEG was recorded during 5 minutes of resting state. Sixteen patients (mean age: 66.81 ± 7.94 years) during acute TGA and 16 healthy subjects were enrolled. All patients showed hippocampal or parahippocampal signal abnormalities in diffusion-weighted magnetic resonance imaging performed from 2 to 5 days after the onset of TGA. Compared with healthy controls, TGA patients showed a decrease of theta power localized in the temporal lobe (Brodmann areas, BAs 21-22-38) and frontal lobe (BAs 8-9-44-45). A decrease of EEG beta power in the bilateral precuneus (BA 7) and in the bilateral postcentral gyrus (BAs 3-4-5) was also observed in TGA individuals. Taken together, our results could reflect the neurophysiological substrate of the severe impairment of both episodic memory and autobiographical memory which affect TGA patients during the acute phase.


Assuntos
Amnésia Global Transitória/fisiopatologia , Eletroencefalografia , Hipocampo/fisiopatologia , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Lobo Temporal/fisiopatologia
20.
Brain Struct Funct ; 224(1): 9-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30238209

RESUMO

In the present study, we mapped the spatio-temporal dynamics of cortical responses to ipsilateral median nerve stimulation using intracerebral recordings (stereo-EEG) in 38 drug-resistant epileptic patients. Furthermore, we compared the pattern of responsiveness obtained in the same leads across ipsilateral and contralateral stimulations. Ipsilateral responses were found mostly confined to SII and posterior insula, while no activity was found in ipsilateral SI. By examining the temporal profiles of activation, ipsilateral SII showed a prominent tonic pattern, while contralateral SII exhibited both phasic and tonic responses. Beyond the localization of the active cortical nodes, these data contributed to identify the cortico-cortical connections carrying the somatosensory information to the ipsilateral hemisphere, with a major role of transcallosal projections from contralateral SII. In light of previous literature and of its localization, the functional role possibly covered by long lasting discharge in SII and insular cortex is also discussed. Overall, the presence of tonic activities was neglected so far due to the impossibility to identify deep sources along with a resolved description of their time course. The use of stereo-EEG, instead, allows one to achieve a four-dimensional characterization, complementing the classical view about the somatosensory system organization.


Assuntos
Epilepsias Parciais/fisiopatologia , Potenciais Somatossensoriais Evocados , Nervo Mediano/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Anticonvulsivantes/uso terapêutico , Mapeamento Encefálico/métodos , Resistência a Medicamentos , Estimulação Elétrica , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/psicologia , Feminino , Humanos , Masculino , Fatores de Tempo , Tato , Percepção do Tato , Adulto Jovem
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