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1.
Nat Commun ; 12(1): 1080, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597538

RESUMO

Clinicians have long been interested in functional brain monitoring, as reversible functional losses often precedes observable irreversible structural insults. By characterizing neonatal functional cerebral networks, resting-state functional connectivity is envisioned to provide early markers of cognitive impairments. Here we present a pioneering bedside deep brain resting-state functional connectivity imaging at 250-µm resolution on human neonates using functional ultrasound. Signal correlations between cerebral regions unveil interhemispheric connectivity in very preterm newborns. Furthermore, fine-grain correlations between homologous pixels are consistent with white/grey matter organization. Finally, dynamic resting-state connectivity reveals a significant occurrence decrease of thalamo-cortical networks for very preterm neonates as compared to control term newborns. The same method also shows abnormal patterns in a congenital seizure disorder case compared with the control group. These results pave the way to infants' brain continuous monitoring and may enable the identification of abnormal brain development at the bedside.


Assuntos
Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Algoritmos , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imagem por Ressonância Magnética/métodos , Masculino , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Ultrassonografia Doppler/métodos , Substância Branca/fisiopatologia
2.
Medicine (Baltimore) ; 100(3): e24302, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546056

RESUMO

RATIONALE: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. PATIENT CONCERNS: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. DIAGNOSES: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. INTERVENTIONS: The patient underwent in-patient stroke rehabilitation therapy for 2 months. OUTCOMES: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. LESSONS: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.


Assuntos
Córtex Auditivo/anormalidades , Perda Auditiva Central/etiologia , Rede Nervosa/anormalidades , Córtex Sensório-Motor/anormalidades , Adulto , Córtex Auditivo/fisiopatologia , Feminino , Perda Auditiva Central/fisiopatologia , /fisiopatologia , Humanos , Testes de Estado Mental e Demência , Rede Nervosa/fisiopatologia , Hemorragia Putaminal/complicações , Hemorragia Putaminal/fisiopatologia , Córtex Sensório-Motor/fisiopatologia
3.
Neurology ; 96(9): e1334-e1346, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33441453

RESUMO

OBJECTIVE: To determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses. METHODS: We acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing. RESULTS: We observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = -0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%). CONCLUSIONS: These results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.


Assuntos
Núcleo Basal de Meynert/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Idoso , Nível de Alerta/fisiologia , Núcleo Basal de Meynert/diagnóstico por imagem , Cognição , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/psicologia , Feminino , Lateralidade Funcional , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Modelos Logísticos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Testes Neuropsicológicos , Adulto Jovem
4.
Nat Med ; 27(1): 174-182, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398159

RESUMO

Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation.


Assuntos
Biomarcadores/análise , Neuroimagem Funcional/métodos , Medição da Dor/métodos , Adolescente , Adulto , Agentes Aversivos/toxicidade , Capsaicina/toxicidade , Conectoma/métodos , Conectoma/estatística & dados numéricos , Dor Facial/fisiopatologia , Feminino , Neuroimagem Funcional/estatística & dados numéricos , Humanos , Dor Lombar/fisiopatologia , Imagem por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/estatística & dados numéricos , Masculino , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Dor/fisiopatologia , Medição da Dor/estatística & dados numéricos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Paladar/efeitos dos fármacos , Paladar/fisiologia , Adulto Jovem
5.
Neuroimage ; 228: 117705, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33385550

RESUMO

The relationship between anatomic and resting state functional connectivity of large-scale brain networks is a major focus of current research. In previous work, we introduced a model based on eigen decomposition of the Laplacian which predicts the functional network from the structural network in healthy brains. In this work, we apply the eigen decomposition model to two types of epilepsy; temporal lobe epilepsy associated with mesial temporal sclerosis, and MRI-normal temporal lobe epilepsy. Our findings show that the eigen relationship between function and structure holds for patients with temporal lobe epilepsy as well as normal individuals. These results suggest that the brain under TLE conditions reconfigures and rewires the fine-scale connectivity (a process which the model parameters are putatively sensitive to), in order to achieve the necessary structure-function relationship.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Processamento de Imagem Assistida por Computador/métodos , Rede Nervosa/fisiopatologia , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino
6.
Psychopharmacology (Berl) ; 238(4): 1059-1068, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388819

RESUMO

RATIONALE: The probability of structural remodeling in brain circuits may be modulated by molecules of perineuronal nets (PNNs) that restrict neuronal plasticity to stabilize circuits. Animal research demonstrates that addictive drugs can remodel PNNs in different brain regions, including the cerebellum. OBJECTIVE: This study aimed to investigate the effects of short versus extended access to cocaine self-administration on PNN expression around Golgi interneurons in the cerebellar cortex after different periods of abstinence. METHODS: After 1 week of training (2 h/day), Sprague-Dawley rats self-administered cocaine daily for 20 days under short (ShA) or extended (LgA) access. PNN expression in the cerebellum was assessed after 1 day, 7 days, and 28 days of forced abstinence. PNNs were immunolabeled using Wisteria floribunda agglutinin (WFA) and captured by confocal microscopy. RESULTS: WFA intensity increased in PNN-bearing Golgi neurons over the abstinence period and a higher proportion of more intense PNNs were formed throughout the first month of abstinence. After the first 24 h of cocaine abstinence, however, we found a reduction in WFA intensity in the cerebellar cortex of rats with ShA to cocaine as compared to naïve animals. When comparing with naïve rats, LgA rats showed consistent PNN upregulation at 28 days of cocaine abstinence. CONCLUSIONS: Our results suggest that cocaine self-administration produces modifications in PNN that enhance conditions for synaptic plasticity in the cerebellar cortex. These modifications are revealed shortly after the cessation of drug intake but PNNs become more intense during protracted abstinence in the LgA group, pointing to the stabilization of drug-induced synaptic changes. These findings indicate that extended access to cocaine self-administration dynamically regulates conditions for plasticity in the cerebellum during abstinence.


Assuntos
Córtex Cerebelar/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Rede Nervosa/fisiopatologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Cocaína , Interneurônios , Masculino , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Autoadministração
7.
J Clin Neurosci ; 84: 82-90, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358344

RESUMO

AIM: There is rapidly increasing evidence that remission of MDD is associated with substantial changes in functional brain connectivity. These New data have provided a holistic view on the mechanism of antidepressants on multiple levels that goes beyond their conventional effects on neurotransmitters. METHOD: The study was approved by the Local Ethics Committee of Istanbul Medipol University (10840098-604.01.01-E.65129) and followed the Helsinki Declaration principles. In our study, we have evaluated the effect of six weeks of treatment with antidepressants (escitalopram and duloxetine), and tested the underlying brain functional connectivity through a Graph analysis approach in a well-defined first-episode, drug-naive, and non-comorbid population with MDD. RESULTS: Beyond indicating that there was a significant correlation between the antidepressant response and topological characteristics of the brain, our results suggested that global rather than regional network alterations may be implicated in the antidepressant effect. CONCLUSION: Despite the small-sample size and non-controlled study design, our study provides important and relevant clinical data regarding the underlying mechanisms of the antidepressants on topological dynamics in the human brain.


Assuntos
Antidepressivos/uso terapêutico , Encéfalo/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Rede Nervosa/efeitos dos fármacos , Adulto , Encéfalo/fisiopatologia , Citalopram/uso terapêutico , Estudos Transversais , Cloridrato de Duloxetina/farmacologia , Cloridrato de Duloxetina/uso terapêutico , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiopatologia
8.
Proc Natl Acad Sci U S A ; 117(52): 33578-33585, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33318200

RESUMO

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture-word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.


Assuntos
Rede Nervosa/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Doença Aguda , Adolescente , Adulto , Idoso , Comportamento , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Síndrome , Análise e Desempenho de Tarefas , Fatores de Tempo , Adulto Jovem
9.
Brain ; 143(12): 3734-3747, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33320929

RESUMO

Impulse control disorders (ICDs) in Parkinson's disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson's disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson's disease with and without ICDs to track the spectral and dynamical signatures of different mechanisms involved in inhibitory control in a simple visuomotor task involving no selection between competing responses and no reward to avoid potential confounds with reward-based decision. Behaviourally, patients with Parkinson's disease with ICDs proved to be more impulsive than those without ICDs. This was associated with decreased beta activity in the precuneus and in a region of the medial frontal cortex centred on the supplementary motor area. The underlying dynamical patterns pinpointed dysfunction of proactive inhibitory control, an executive mechanism intended to gate motor responses in anticipation of stimulation in uncertain contexts. The alteration of the cortical drive of proactive response inhibition in Parkinson's disease ICDs pinpoints the neglected role the precuneus might play in higher order executive functions in coordination with the supplementary motor area, specifically for switching between executive settings. Clinical perspectives are discussed in the light of the non-dopaminergic basis of this function.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Inibição Psicológica , Transtornos Parkinsonianos/psicologia , Idoso , Ritmo beta , Mapeamento Encefálico , Comportamento de Escolha , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Eletroencefalografia , Função Executiva , Feminino , Humanos , Comportamento Impulsivo , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/fisiopatologia , Transtornos Parkinsonianos/complicações , Desempenho Psicomotor
10.
PLoS One ; 15(12): e0244516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382767

RESUMO

Research on face sensitivity is of particular relevance during the rapidly evolving Covid-19 pandemic leading to social isolation, but also calling for intact interaction and sharing. Humans possess high sensitivity even to a coarse face scheme, seeing faces in non-face images where real faces do not exist. The advantage of non-face images is that single components do not trigger face processing. Here by implementing a novel set of Face-n-Thing images, we examined (i) how face tuning alters with changing display orientation, and (ii) whether it is affected by observers' gender. Young females and males were presented with a set of Face-n-Thing images either with canonical upright orientation or inverted 180° in the image plane. Face impression was substantially impeded by display inversion. Furthermore, whereas with upright display orientation, no gender differences were found, with inversion, Face-n-Thing images elicited face impression in females significantly more often. The outcome sheds light on the origins of the face inversion effect in general. Moreover, the findings open a way for examination of face sensitivity and underwriting brain networks in neuropsychiatric conditions related to the current pandemic (such as depression and anxiety), most of which are gender/sex-specific.


Assuntos
Encéfalo/fisiopatologia , Reconhecimento Facial , Rede Nervosa/fisiopatologia , Orientação , Reconhecimento Visual de Modelos , Caracteres Sexuais , Adolescente , Adulto , Feminino , Humanos , Masculino
11.
BMC Neurol ; 20(1): 388, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33096988

RESUMO

BACKGROUND: Cerebral Palsy (CP) is a group of disorders that affect the development of movement and posture. CP results from injuries to the immature brain during the prenatal, perinatal, or postnatal stage of development. Neuroimaging research in CP has focused on the structural changes of the brain during early development, but little is known about brain's structural and functional changes during late adolescence and early adulthood, a period in time when individuals experience major changes as they transition into adulthood. The work reported here served as a feasibility study within a larger program of research (MyStory Study). We aimed to determine whether it would be feasible to scan and obtain good quality data without the use of sedation during a resting state condition for functional connectivity (FC) analyses in young adults with CP. Second, we aimed to identify the FC pattern(s) that are associated with depressive mood ratings, indices of pain and fatigue, and quality of life in this group. METHODS: Resting state functional images were collected from 9 young people with CP (18-29 years). We applied a stringent head motion correction and quality control methods following preprocessing. RESULTS: We were able to scan and obtain good quality data without the use of sedation from this group of young individuals with CP who demonstrated a range of gross motor ability. The functional connectivity networks of interest were identified in the data using standard seed regions. Our analyses further revealed that higher well-being scores were associated with higher levels of FC between the Medial Pre-Frontal Cortex and the right Lateral Parietal regions, which are implicated in prosocial and emotion regulations skills. The implications of this association are discussed. CONCLUSION: The findings of the present study demonstrate that it is feasible to conduct resting state functional connectivity in young adults with CP with different gross motor abilities without the use of sedation. Our results also highlight a neural circuitry that is associated with the self-report of quality of life and emotion regulation. These findings identify these regions/circuitries as important seeds for further investigations into mental health and wellbeing in CP.


Assuntos
Encéfalo/diagnóstico por imagem , Paralisia Cerebral/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Neuroimagem/métodos , Adolescente , Adulto , Encéfalo/fisiopatologia , Paralisia Cerebral/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiopatologia , Qualidade de Vida , Adulto Jovem
12.
Nat Commun ; 11(1): 5074, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033265

RESUMO

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressing Tachykinin 2-Cre (Tac2Cre) receive direct Aß low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition of Tac2Cre neurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch.


Assuntos
Rede Nervosa/fisiopatologia , Prurido/fisiopatologia , Tato/fisiologia , Animais , Comportamento Animal , Injeções Espinhais , Luz , Potenciais da Membrana , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores da Bombesina/metabolismo , Pele/patologia , Medula Espinal/fisiopatologia , Sinapses/metabolismo , Taquicininas/metabolismo
13.
PLoS One ; 15(9): e0234749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966291

RESUMO

Traumatic brain injury (TBI) can lead to neurodegeneration in the injured circuitry, either through primary structural damage to the neuron or secondary effects that disrupt key cellular processes. Moreover, traumatic injuries can preferentially impact subpopulations of neurons, but the functional network effects of these targeted degeneration profiles remain unclear. Although isolating the consequences of complex injury dynamics and long-term recovery of the circuit can be difficult to control experimentally, computational networks can be a powerful tool to analyze the consequences of injury. Here, we use the Izhikevich spiking neuron model to create networks representative of cortical tissue. After an initial settling period with spike-timing-dependent plasticity (STDP), networks developed rhythmic oscillations similar to those seen in vivo. As neurons were sequentially removed from the network, population activity rate and oscillation dynamics were significantly reduced. In a successive period of network restructuring with STDP, network activity levels returned to baseline for some injury levels and oscillation dynamics significantly improved. We next explored the role that specific neurons have in the creation and termination of oscillation dynamics. We determined that oscillations initiate from activation of low firing rate neurons with limited structural inputs. To terminate oscillations, high activity excitatory neurons with strong input connectivity activate downstream inhibitory circuitry. Finally, we confirm the excitatory neuron population role through targeted neurodegeneration. These results suggest targeted neurodegeneration can play a key role in the oscillation dynamics after injury.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Simulação por Computador , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Potenciais de Ação , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/complicações , Humanos , Rede Nervosa/fisiologia , Doenças Neurodegenerativas/etiologia , Plasticidade Neuronal , Neurônios/patologia , Neurônios/fisiologia
14.
PLoS One ; 15(9): e0238774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915832

RESUMO

Brain reward processing mechanisms that underlie complex decision-making are compromised in psychosis. The goal of this research was to advance our understanding of the underlying (1) neural mechanisms and (2) discrete neuro-economic/motivational processes that may be altered in complex decision-making in euthymic patients on the psychosis spectrum (PPS). Utilizing a functional magnetic resonance neuroimaging (fmri) paradigm of a well-validated laboratory measure of complex decision-making (Iowa Gambling Task-IGT), the brain activation patterns of a target group of PPS were compared to a demographically matched healthy comparison group (HMC). These two groups were also evaluated on real-life decision outcomes on day of scan. PPS primarily activate the Dorsal Attentional Network (DAN) in real-life decision outcomes and in achieving similar levels of performance on the IGT as the HMC, in-spite of dysregulated dopamine-based brain-reward circuit and salience network fmri activation patterns. However, PPS report more significant negative outcomes of their decision-making in real-life, compared to HMC. The differential engagement of brain networks by PPS on the IGT appear to be moderated by antipsychotic, dopamine antagonist, medication lifetime/daily dose levels. These findings may also be mediated by extent of dysregulation in brain reward circuitry and salience network associated with psychosis severity in the target PPS group. This is also evident in case studies of unmedicated PPS. We conclude by suggesting that the brain may adapt to this dysregulation by co-opting the DAN network, which is implicated in the related function of problem-solving, towards complex decision-making. The extent of utilization of the DAN network in complex decision-making may be moderated by psychosis severity.


Assuntos
Encéfalo/fisiopatologia , Tomada de Decisões/fisiologia , Rede Nervosa/fisiopatologia , Transtornos Psicóticos/psicologia , Adulto , Encéfalo/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia , Recompensa
15.
PLoS Comput Biol ; 16(8): e1007790, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841234

RESUMO

The impairment of cognitive function in Alzheimer's disease is clearly correlated to synapse loss. However, the mechanisms underlying this correlation are only poorly understood. Here, we investigate how the loss of excitatory synapses in sparsely connected random networks of spiking excitatory and inhibitory neurons alters their dynamical characteristics. Beyond the effects on the activity statistics, we find that the loss of excitatory synapses on excitatory neurons reduces the network's sensitivity to small perturbations. This decrease in sensitivity can be considered as an indication of a reduction of computational capacity. A full recovery of the network's dynamical characteristics and sensitivity can be achieved by firing rate homeostasis, here implemented by an up-scaling of the remaining excitatory-excitatory synapses. Mean-field analysis reveals that the stability of the linearised network dynamics is, in good approximation, uniquely determined by the firing rate, and thereby explains why firing rate homeostasis preserves not only the firing rate but also the network's sensitivity to small perturbations.


Assuntos
Doença de Alzheimer/fisiopatologia , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Sinapses/fisiologia , Homeostase/fisiologia , Humanos
16.
Nat Commun ; 11(1): 3948, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769984

RESUMO

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.


Assuntos
Córtex Cerebral/fisiopatologia , Dor Crônica/fisiopatologia , Núcleos Laterais do Tálamo/fisiopatologia , Dor Lombar/fisiopatologia , Núcleos Ventrais do Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico , Conjuntos de Dados como Assunto , Feminino , Humanos , Núcleos Laterais do Tálamo/diagnóstico por imagem , Dor Lombar/diagnóstico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Medição da Dor , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Adulto Jovem
17.
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
18.
Nat Commun ; 11(1): 4250, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843635

RESUMO

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Memória de Curto Prazo/fisiologia , Esquizofrenia/fisiopatologia , Sinapses/fisiologia , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Feminino , Humanos , Masculino , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Plasticidade Neuronal , Córtex Pré-Frontal/fisiopatologia , Receptores de N-Metil-D-Aspartato/fisiologia , Psicologia do Esquizofrênico , Adulto Jovem
19.
Neurology ; 95(17): e2427-e2441, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32847951

RESUMO

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality. METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality. RESULTS: Individuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS. CONCLUSIONS: In TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos Transversais , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/psicologia , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Lateralidade Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Desempenho Psicomotor , Curva ROC , Comportamento Verbal
20.
J Headache Pain ; 21(1): 93, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723299

RESUMO

BACKGROUND: Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. METHODS: Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. RESULTS: Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p < 0.0001; r = 0.655, p < 0.0001, respectively). CONCLUSION: Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Hipotálamo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Cefaleia Pós-Traumática/diagnóstico por imagem , Adulto , Concussão Encefálica/epidemiologia , Concussão Encefálica/fisiopatologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipotálamo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Cefaleia Pós-Traumática/epidemiologia , Cefaleia Pós-Traumática/fisiopatologia , Estudos Prospectivos
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