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1.
Neurology ; 95(16): e2246-e2258, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32913023

RESUMO

OBJECTIVE: To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls. METHODS: Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences. RESULTS: Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups. CONCLUSION: Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.


Assuntos
Encéfalo/fisiopatologia , Distúrbios Distônicos/fisiopatologia , Adulto , Idoso , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia
2.
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
3.
PLoS One ; 15(8): e0231294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853207

RESUMO

Eigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer's disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network's dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain's functional networks develop and adapt when challenged by disease processes such as AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Mapeamento Encefálico/métodos , Disfunção Cognitiva/fisiopatologia , Idoso , Amnésia/fisiopatologia , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Modelos Teóricos , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia
4.
Neuron ; 107(6): 1113-1123.e4, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32679036

RESUMO

Disrupting memories that associate environmental cues with drug experiences holds promise for treating addiction, yet accessing the distributed neural network that stores such memories is challenging. Here, we show that the paraventricular nucleus of the thalamus (PVT) orchestrates the acquisition and maintenance of opiate-associated memories via projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). PVT→CeA activity associates morphine reward to the environment, whereas transient inhibition of the PVT→NAc pathway during retrieval causes enduring protection against opiate-primed relapse. Using brain-wide activity mapping, we revealed distributed network activities that are altered in non-relapsing mice, which enabled us to find that activating the downstream NAc→lateral hypothalamus (LH) pathway also prevents relapse. These findings establish the PVT as a key node in the opiate-associated memory network and demonstrate the potential of targeting the PVT→NAc→LH pathway for treating opioid addiction.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Núcleo Accumbens/fisiopatologia , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Priming de Repetição , Animais , Sinais (Psicologia) , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/fisiopatologia
5.
Neuron ; 107(6): 1095-1112.e6, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32697942

RESUMO

Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called "remapping." We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory. CA1 neurons, including place cells, showed disrupted remapping, although their spatial tuning was only mildly diminished. Medial entorhinal cortex (MEC) neurons severely lost their spatial tuning and grid cells were almost absent. Fast gamma oscillatory coupling between the MEC and CA1 was also impaired. Mild disruption of MEC grid cells emerged in younger APP-KI mice, although the spatial memory and CA1 remapping of the animals remained intact. These results point to remapping impairment in the hippocampus, possibly linked to grid cell disruption, as circuit mechanisms underlying spatial memory impairment in AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Região CA1 Hipocampal/fisiopatologia , Conectoma , Córtex Entorrinal/fisiopatologia , Neurônios/classificação , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Região CA1 Hipocampal/patologia , Córtex Entorrinal/patologia , Feminino , Ritmo Gama , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Neurônios/patologia , Neurônios/fisiologia
6.
Am J Otolaryngol ; 41(5): 102575, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32593047

RESUMO

PURPOSE: Approximately 1.3 billion people worldwide have vision impairment. The aim of the present study was to investigate the influence of Late-Onset blindness on cervical vestibular evoked myogenic potentials (cVEMP) responses. Accordingly, this study was performed to investigate and compare the parameters of the cVEMP test in sighted and late-onset blind individuals. MATERIALS AND METHOD: In this cross-sectional- comparative study, cVEMP was recorded by presenting a tone burst stimulus of 500 Hz with an intensity of 95 dBnHL in 20 sighted and 20 late-onset blind individuals aged between 18 and 30 years old. RESULTS: cVEMP was observed in all the individuals (100%). The average latency of P13 and N23, amplitude, amplitude ratio, and VEMP threshold did not differ significantly between the two groups (p > 0.05). CONCLUSION: The findings of the study revealed that the formation of the neural pathway and reflex arch of cVEMP is similar between late-onset blind and sighted individuals. Thus, cVEMP can be a suitable test for assessing the vestibular function of late-onset blind people.


Assuntos
Cegueira/fisiopatologia , Técnicas de Diagnóstico Otológico , Potenciais Evocados Miogênicos Vestibulares , Vestíbulo do Labirinto/fisiopatologia , Adolescente , Adulto , Idade de Início , Cegueira/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia , Tempo de Reação , Reflexo Vestíbulo-Ocular , Adulto Jovem
7.
J Neurosci ; 40(27): 5314-5326, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32527981

RESUMO

An epileptic seizure can trigger a headache during (ictal) or after (postictal) the termination of the event. Little is known about the pathophysiology of seizure-induced headaches. In the current study, we determined whether a seizure can activate nociceptive pathways that carry pain signals from the meninges to the spinal cord, and if so, to what extent and through which classes of peripheral and central neurons. To achieve these goals, we used single-unit recording techniques and an established animal model of seizure (picrotoxin) to determine the effects of epileptic seizure on the activity of trigeminovascular Aδ-, C-, wide-dynamic range, and high-threshold neurons in male and female rats. Occurrence of seizure activated 54%, 50%, 68%, and 39% of the Aδ-, C-, wide-dynamic range, and high-threshold neurons, respectively. Regardless of their class, activated neurons exhibited a twofold to fourfold increase in their firing, which started immediately (1 min) or up to 90 min after seizure initiation, and lasted as short as 10 min or as long as 120 min. Administration of lidocaine to the dura prevented activation of all neuronal classes but not the initiation or maintenance of the seizure. These findings suggest that all neuronal classes may be involved in the initiation and maintenance of seizure-induced headache, and that their activation patterns can provide a neural substrate for explaining the timing and duration of ictal and possibly postictal headaches. By using seizure, which is evident in humans, this study bypasses controversies associated with cortical spreading depression, which is less readily observed in humans.SIGNIFICANCE STATEMENT This preclinical study provides a neural substrate for ictal and postictal headache. By studying seizure effects on the activity of peripheral (C and Aδ) and central (wide dynamic range and high-threshold) trigeminovascular neurons in intact and anesthetized dura, the findings help resolve two outstanding questions about the pathophysiology of headaches of intracranial origin. The first is that abnormal brain activity (i.e., seizure) that is evident in human (unlike cortical spreading depression) gives rise to specific and selective activation of the different components of the trigeminovascular system, and the second is that the activation of all components of the trigeminovascular pathway (i.e., peripheral and central neurons) depends on activation of the meningeal nociceptors from their receptors in the dura.


Assuntos
Cefaleia/etiologia , Cefaleia/fisiopatologia , Neurônios , Convulsões/complicações , Convulsões/fisiopatologia , Nervo Trigêmeo/fisiopatologia , Anestésicos Locais/farmacologia , Animais , Sistema Nervoso Central/fisiopatologia , Eletroencefalografia , Feminino , Lidocaína/farmacologia , Masculino , Meninges/fisiopatologia , Fibras Nervosas Mielinizadas , Fibras Nervosas Amielínicas , Vias Neurais/fisiopatologia , Nociceptores , Sistema Nervoso Periférico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiopatologia
9.
ACS Chem Neurosci ; 11(11): 1520-1522, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: covidwho-324525

RESUMO

Accumulating data have now shown strong evidence that COVID-19 infection leads to the occurrence of neurological signs with different injury severity. Anosmia and agueusia are now well documented and included in the criteria list for diagnosis, and specialists have stressed that doctors screen COVID-19 patients for these two signs. The eventual brainstem dysregulation, due to the invasion of SARS CoV-2, as a cause of respiratory problems linked to COVID-19, has also been extensively discussed. All these findings lead to an implication of the central nervous system in the pathophysiology of COVID-19. Here we provide additional elements that could explain other described signs like appetite loss, vomiting, and nausea. For this, we investigated the role of brainstem structures located in the medulla oblongata involved in food intake and vomiting control. We also discussed the possible pathways the virus uses to reach the brainstem, i.e., neurotropic and hematogenous (with its two variants) routes.


Assuntos
Anorexia/fisiopatologia , Regulação do Apetite/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Ingestão de Alimentos/fisiologia , Náusea/fisiopatologia , Pneumonia Viral/fisiopatologia , Núcleo Solitário/fisiopatologia , Vômito/fisiopatologia , Ageusia/etiologia , Anorexia/etiologia , Área Postrema/fisiopatologia , Barreira Hematoencefálica , Infecções por Coronavirus/complicações , Humanos , Hipotálamo/fisiopatologia , Bulbo/fisiopatologia , Náusea/etiologia , Vias Neurais/fisiopatologia , Transtornos do Olfato/etiologia , Nervo Olfatório , Pandemias , Pneumonia Viral/complicações , Nervo Vago , Vômito/etiologia
10.
PLoS One ; 15(5): e0233780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469991

RESUMO

Gaming disorder, which is characterized by multiple cognitive and behavioral symptoms, often has comorbid psychiatric conditions such as depression and attention-deficit hyperactivity disorder. Neurobiological effects of the comorbid disorders so far reported are not converging, exhibiting positive and negative alterations of the connectivity in brain networks. In this study, we conducted resting-state functional magnetic-resonance imaging and whole brain functional connectivity analyses for young participants consisting of 40 patients diagnosed with the gaming disorder, with and without comorbid conditions, and 29 healthy controls. Compared to healthy controls, the gaming disorder-alone patients had partially diminished connectivities in the reward system and executive control network, within which there existed central nodes that served as a hub of diminished connections. In the gaming disorder patients who had comorbidity of autism spectrum disorder, the diminished connections were enlarged, with alteration of the hub nodes, to the entire brain areas involved in the reward system including cortical, subcortical and limbic areas that are crucial for reward processing, and to the whole cortical areas composing the executive control network. These observations suggest that the neurodevelopmental condition coexisting with the gaming disorder induced substantial impairment of the neural organizations associated with executive/cognitive and emotional functions, which are plausibly causal to the behavioral addiction, by rearranging and diminishing functional connectivities in the network.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Espectro Autista/complicações , Comportamento Aditivo/fisiopatologia , Encéfalo/fisiopatologia , Jogo de Azar , Vias Neurais/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Cognição , Emoções , Função Executiva , Jogo de Azar/complicações , Jogo de Azar/fisiopatologia , Humanos , Masculino , Recompensa , Adulto Jovem
11.
ACS Chem Neurosci ; 11(11): 1520-1522, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32427468

RESUMO

Accumulating data have now shown strong evidence that COVID-19 infection leads to the occurrence of neurological signs with different injury severity. Anosmia and agueusia are now well documented and included in the criteria list for diagnosis, and specialists have stressed that doctors screen COVID-19 patients for these two signs. The eventual brainstem dysregulation, due to the invasion of SARS CoV-2, as a cause of respiratory problems linked to COVID-19, has also been extensively discussed. All these findings lead to an implication of the central nervous system in the pathophysiology of COVID-19. Here we provide additional elements that could explain other described signs like appetite loss, vomiting, and nausea. For this, we investigated the role of brainstem structures located in the medulla oblongata involved in food intake and vomiting control. We also discussed the possible pathways the virus uses to reach the brainstem, i.e., neurotropic and hematogenous (with its two variants) routes.


Assuntos
Anorexia/fisiopatologia , Regulação do Apetite/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Ingestão de Alimentos/fisiologia , Náusea/fisiopatologia , Pneumonia Viral/fisiopatologia , Núcleo Solitário/fisiopatologia , Vômito/fisiopatologia , Ageusia/etiologia , Anorexia/etiologia , Área Postrema/fisiopatologia , Barreira Hematoencefálica , Infecções por Coronavirus/complicações , Humanos , Hipotálamo/fisiopatologia , Bulbo/fisiopatologia , Náusea/etiologia , Vias Neurais/fisiopatologia , Transtornos do Olfato/etiologia , Nervo Olfatório , Pandemias , Pneumonia Viral/complicações , Nervo Vago , Vômito/etiologia
12.
Dev Cogn Neurosci ; 42: 100775, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32452461

RESUMO

Both depression and substance use problems have their highest incidence during youth (i.e., adolescence and emerging adulthood), and are characterized by emotion regulation deficits. Influential neurodevelopmental theories suggest that alterations in the function of limbic and frontal regions render youth susceptible to these deficits. However, whether depression and substance use in youth are associated with similar alterations in emotion regulation neural circuitry is unknown. In this systematic review we synthesized the results of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of emotion regulation in youth depression and substance use. Resting-state fMRI studies focusing on limbic connectivity were also reviewed. While findings were largely inconsistent within and between studies of depression and substance use, some patterns emerged. First, youth depression appears to be associated with exaggerated amygdala activity in response to negative stimuli; second, both depression and substance use appear to be associated with lower functional connectivity between the amygdala and prefrontal cortex during rest. Findings are discussed in relation to support for existing neurodevelopmental models, and avenues for future work are suggested, including studying neurodevelopmental trajectories from a network perspective.


Assuntos
Depressão/psicologia , Neuroimagem Funcional/métodos , Vias Neurais/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem
13.
Brain ; 143(4): 1261-1277, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236540

RESUMO

Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate-in the spatial memory task, during memory recall-that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process.


Assuntos
Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Ritmo Teta/fisiologia , Adulto , Feminino , Humanos , Magnetoencefalografia , Masculino , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/metabolismo , Receptores de GABA-A/metabolismo , Esquizofrenia/metabolismo , Lobo Temporal/metabolismo
14.
J Neurosci ; 40(20): 3882-3895, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32291327

RESUMO

Neonatal tissue damage induces long-term deficits in inhibitory synaptic transmission within the spinal superficial dorsal horn (SDH) that include a reduction in primary afferent-evoked, feedforward inhibition onto adult projection neurons. However, the subpopulations of mature GABAergic interneurons which are compromised by early-life injury have yet to be identified. The present research illuminates the persistent effects of neonatal surgical injury on the function of inhibitory SDH interneurons derived from the prodynorphin (DYN) lineage, a population that synapses directly onto lamina I spinoparabrachial neurons and is known to suppress mechanical pain and itch in adults. The results demonstrate that hindpaw incision at postnatal day 3 (P3) significantly decreased the strength of primary afferent-evoked glutamatergic drive onto DYN neurons within the adult mouse SDH while increasing the appearance of afferent-evoked inhibition onto the same population. Neonatal injury also dampened the intrinsic membrane excitability of mature DYN neurons, and reduced their action potential discharge in response to sensory input, compared with naive littermate controls. Furthermore, P3 incision decreased the efficacy of inhibitory DYN synapses onto adult spinoparabrachial neurons, which reflected a prolonged reduction in the probability of GABA release. Collectively, the data suggest that early-life tissue damage may persistently constrain the ability of spinal DYN interneurons to limit ascending nociceptive transmission to the adult brain. This is predicted to contribute to the loss of feedforward inhibition onto mature projection neurons, and the "priming" of nociceptive circuits in the developing spinal cord, following injuries during the neonatal period.SIGNIFICANCE STATEMENT Neonatal injury has lasting effects on pain processing in the adult CNS, including a reduction in feedforward inhibition onto ascending projection neurons in the spinal dorsal horn. While it is clear that spinal GABAergic interneurons are comprised of multiple subpopulations that play distinct roles in somatosensation, the identity of those interneurons which are compromised by tissue damage during early life remains unknown. Here we document persistent deficits in spinal inhibitory circuits involving dynorphin-lineage interneurons previously implicated in gating mechanical pain and itch. Notably, neonatal injury reduced the strength of dynorphin-lineage inhibitory synapses onto mature lamina I spinoparabrachial neurons, a major output of the spinal nociceptive network, which could contribute to the priming of pain pathways by early tissue damage.


Assuntos
Dinorfinas , Membro Posterior/lesões , Inibição Neural , Vias Neurais/fisiopatologia , Corno Dorsal da Medula Espinal/lesões , Potenciais de Ação , Animais , Animais Recém-Nascidos , Análise por Conglomerados , Feminino , Glutamatos/fisiologia , Membro Posterior/inervação , Membro Posterior/fisiopatologia , Interneurônios , Camundongos , Neurônios Aferentes , Nociceptividade , Técnicas de Patch-Clamp , Medula Espinal/fisiopatologia , Corno Dorsal da Medula Espinal/fisiopatologia
15.
Nat Rev Neurosci ; 21(5): 264-276, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32269315

RESUMO

The very earliest stages of sensory processing have the potential to alter how we perceive and respond to our environment. These initial processing circuits can incorporate subcortical regions, such as the thalamus and brainstem nuclei, which mediate complex interactions with the brain's cortical processing hierarchy. These subcortical pathways, many of which we share with other animals, are not merely vestigial but appear to function as 'shortcuts' that ensure processing efficiency and preservation of vital life-preserving functions, such as harm avoidance, adaptive social interactions and efficient decision-making. Here, we propose that functional interactions between these higher-order and lower-order brain areas contribute to atypical sensory and cognitive processing that characterizes numerous neuropsychiatric disorders.


Assuntos
Tronco Encefálico/fisiopatologia , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Transtornos das Sensações/fisiopatologia , Tálamo/fisiopatologia , Animais , Humanos , Vias Neurais/fisiopatologia
16.
Nat Rev Neurosci ; 21(5): 277-295, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32269316

RESUMO

The past decade has witnessed exponentially growing interest in the lateral habenula (LHb) owing to new discoveries relating to its critical role in regulating negatively motivated behaviour and its implication in major depression. The LHb, sometimes referred to as the brain's 'antireward centre', receives inputs from diverse limbic forebrain and basal ganglia structures, and targets essentially all midbrain neuromodulatory systems, including the noradrenergic, serotonergic and dopaminergic systems. Its unique anatomical position enables the LHb to act as a hub that integrates value-based, sensory and experience-dependent information to regulate various motivational, cognitive and motor processes. Dysfunction of the LHb may contribute to the pathophysiology of several psychiatric disorders, especially major depression. Recently, exciting progress has been made in identifying the molecular and cellular mechanisms in the LHb that underlie negative emotional state in animal models of drug withdrawal and major depression. A future challenge is to translate these advances into effective clinical treatments.


Assuntos
Gânglios da Base/fisiologia , Gânglios da Base/fisiopatologia , Habenula/fisiologia , Habenula/fisiopatologia , Sistema Límbico/fisiologia , Sistema Límbico/fisiopatologia , Mesencéfalo/fisiologia , Mesencéfalo/fisiopatologia , Animais , Saúde , Humanos , Transtornos Mentais/fisiopatologia , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia
18.
Proc Natl Acad Sci U S A ; 117(18): 10015-10023, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312809

RESUMO

Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow-5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.


Assuntos
Dor nas Costas/fisiopatologia , Dor Crônica/fisiopatologia , Giro do Cíngulo/fisiopatologia , Núcleo Accumbens/fisiopatologia , Adulto , Dor nas Costas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Dor Crônica/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Núcleo Accumbens/diagnóstico por imagem , Fatores de Risco
19.
Neuron ; 107(1): 158-172.e4, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32333845

RESUMO

Overeating typically follows periods of energy deficit, but it is also sustained by highly palatable foods, even without metabolic demand. Dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the nucleus accumbens shell (NAcSh) project to the lateral hypothalamus (LH) to authorize feeding when inhibited. Whether plasticity at these synapses can affect food intake is unknown. Here, ex vivo electrophysiology recordings reveal that D1-MSN-to-LH inhibitory transmission is depressed in circumstances in which overeating is promoted. Endocannabinoid signaling is identified as the induction mechanism, since inhibitory plasticity and concomitant overeating were blocked or induced by CB1R antagonism or agonism, respectively. D1-MSN-to-LH projectors were largely non-overlapping with D1-MSNs targeting ventral pallidum or ventral midbrain, providing an anatomical basis for distinct circuit plasticity mechanisms. Our study reveals a critical role for plasticity at D1-MSN-to-LH synapses in adaptive feeding control, which may underlie persistent overeating of unhealthy foods, a major risk factor for developing obesity.


Assuntos
Hiperfagia/fisiopatologia , Região Hipotalâmica Lateral/fisiopatologia , Depressão Sináptica de Longo Prazo/fisiologia , Núcleo Accumbens/fisiopatologia , Transmissão Sináptica/fisiologia , Animais , Camundongos , Vias Neurais/fisiopatologia
20.
Nat Commun ; 11(1): 1898, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313055

RESUMO

Growing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, the neural correlates of this reciprocity and their influence on the subsequent development of PTSD are largely unknown. Here we investigated alterations in functional connectivity among brain networks related to low-grade inflammation and stress exposure using two large independent data sets. Functional couplings among the higher-order cognitive network system including the salience, default mode, and central executive networks were reduced in association with low-grade inflammation and stress exposure. This reduced functional coupling may also be related to subsequent posttraumatic stress symptom severity. The current findings propose functional couplings among the higher-order cognitive network system as neural correlates of low-grade inflammation and stress exposure, and suggest that low-grade inflammation, alongside with stress, may render individuals more vulnerable to PTSD.


Assuntos
Encéfalo/fisiopatologia , Inflamação/fisiopatologia , Redes Neurais de Computação , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Citocinas/sangue , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , República da Coreia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto Jovem
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