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1.
Am J Psychiatry ; 178(10): 952-964, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407624

RESUMO

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.


Assuntos
Vias Auditivas/fisiopatologia , Transtorno Bipolar , Eletroencefalografia/métodos , Vias Neurais/fisiopatologia , Transtornos Psicóticos , Estimulação Acústica/métodos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Cognição , Correlação de Dados , Diagnóstico Diferencial , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Técnicas Psicológicas , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Índice de Gravidade de Doença
2.
Medicine (Baltimore) ; 100(31): e26840, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397854

RESUMO

RATIONALE: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). PATIENT CONCERNS: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. DIAGNOSIS: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. INTERVENTION: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). OUTCOMES: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. LESSONS: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.


Assuntos
Afasia , Encéfalo , Área de Broca , Infarto da Artéria Cerebral Média , Área de Wernicke , Adulto , Afasia/diagnóstico , Afasia/etiologia , Afasia/reabilitação , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/reabilitação , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Reabilitação Neurológica/métodos , Tratos Piramidais/patologia , Recuperação de Função Fisiológica , Fonoterapia/métodos , Resultado do Tratamento
3.
Nat Neurosci ; 24(10): 1402-1413, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373644

RESUMO

Pain decreases the activity of many ventral tegmental area (VTA) dopamine (DA) neurons, yet the underlying neural circuitry connecting nociception and the DA system is not understood. Here we show that a subpopulation of lateral parabrachial (LPB) neurons is critical for relaying nociceptive signals from the spinal cord to the substantia nigra pars reticulata (SNR). SNR-projecting LPB neurons are activated by noxious stimuli and silencing them blocks pain responses in two different models of pain. LPB-targeted and nociception-recipient SNR neurons regulate VTA DA activity directly through feed-forward inhibition and indirectly by inhibiting a distinct subpopulation of VTA-projecting LPB neurons thereby reducing excitatory drive onto VTA DA neurons. Correspondingly, ablation of SNR-projecting LPB neurons is sufficient to reduce pain-mediated inhibition of DA release in vivo. The identification of a neural circuit conveying nociceptive input to DA neurons is critical to our understanding of how pain influences learning and behavior.


Assuntos
Neurônios Dopaminérgicos , Mesencéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Dor/fisiopatologia , Núcleos Parabraquiais/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Comportamento Animal , Mapeamento Encefálico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Nociceptividade , Optogenética , Dor/psicologia , Manejo da Dor , Substância Negra/fisiopatologia , Área Tegmentar Ventral/fisiopatologia
4.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263737

RESUMO

Anxiety-related disorders can be treated by cognitive therapies and transcranial magnetic stimulation, which involve the medial prefrontal cortex (mPFC). Subregions of the mPFC have been implicated in mediating different and even opposite roles in anxiety-related behaviors. However, precise causal targets of these top-down connections among diverse possibilities have not been established. Here, we show that the lateral septum (LS) and the central nucleus of the amygdala (CeA) represent 2 direct targets of the infralimbic cortex (IL), a subregion of the mPFC that modulates anxiety and fear. Two projections were unexpectedly found to exert opposite effects on the anxious state and learned freezing: the IL-LS projection promoted anxiety-related behaviors and fear-related freezing, whereas the IL-CeA projection exerted anxiolytic and fear-releasing effects for the same features. Furthermore, selective inhibition of corresponding circuit elements showed opposing behavioral effects compared with excitation. Notably, the IL-CeA projection implemented top-down control of the stress-induced high-anxiety state. These results suggest that distinct IL outputs exert opposite effects in modulating anxiety and fear and that modulating the excitability of these projections with distinct strategies may be beneficial for the treatment of anxiety disorders.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Ansiedade/fisiopatologia , Medo , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Humanos , Camundongos
5.
Neuron ; 109(16): 2590-2603.e13, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34197733

RESUMO

Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.


Assuntos
Núcleos Anteriores do Tálamo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Vias Neurais/fisiopatologia , Núcleos Talâmicos/fisiopatologia , Animais , Núcleos Anteriores do Tálamo/fisiologia , Córtex Cerebral/fisiopatologia , Cognição/fisiologia , Camundongos , Vias Neurais/fisiologia , Núcleos Talâmicos/fisiologia
6.
Sci Rep ; 11(1): 15045, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294803

RESUMO

Emotion dysregulation is common in attention-deficit/hyperactivity disorder (ADHD). It is highly prevalent in young adult ADHD and related to reduced well-being and social impairments. Neuroimaging studies reported neural activity changes in ADHD in brain regions associated with emotion processing and regulation. It is however unknown whether deficits in emotion regulation relate to changes in functional brain network topology in these regions. We used a combination of graph analysis and structural equation modelling (SEM) to analyze resting-state functional connectivity in 147 well-characterized young adults with ADHD and age-matched healthy controls from the NeuroIMAGE database. Emotion dysregulation was gauged with four scales obtained from questionnaires and operationalized through a latent variable derived from SEM. Graph analysis was applied to resting-state data and network topology measures were entered into SEM models to identify brain regions whose local network integration and connectedness differed between subjects and was associated with emotion dysregulation. The latent variable of emotion dysregulation was characterized by scales gauging emotional distress, emotional symptoms, conduct symptoms, and emotional lability. In individuals with ADHD characterized by prominent hyperactivity-impulsivity, the latent emotion dysregulation variable was related to an increased clustering and local efficiency of the right insula. Thus, in the presence of hyperactivity-impulsivity, clustered network formation of the right insula may underpin emotion dysregulation in young adult ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Córtex Cerebral/fisiopatologia , Emoções , Vias Neurais/fisiopatologia , Estudos de Casos e Controles , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Neuroimagem/métodos
7.
Neuroimage ; 239: 118282, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34146711

RESUMO

Hypnotic suggestions can produce a broad range of perceptual experiences, including hallucinations. Visual hypnotic hallucinations differ in many ways from regular mental images. For example, they are usually experienced as automatic, vivid, and real images, typically compromising the sense of reality. While both hypnotic hallucination and mental imagery are believed to mainly rely on the activation of the visual cortex via top-down mechanisms, it is unknown how they differ in the neural processes they engage. Here we used an adaptation paradigm to test and compare top-down processing between hypnotic hallucination, mental imagery, and visual perception in very highly hypnotisable individuals whose ability to hallucinate was assessed. By measuring the N170/VPP event-related complex and using multivariate decoding analysis, we found that hypnotic hallucination of faces involves greater top-down activation of sensory processing through lateralised neural mechanisms in the right hemisphere compared to mental imagery. Our findings suggest that the neural signatures that distinguish hypnotically hallucinated faces from imagined faces lie in the right brain hemisphere.


Assuntos
Dominância Cerebral/fisiologia , Alucinações/fisiopatologia , Hipnose , Imaginação/fisiologia , Vias Neurais/fisiopatologia , Córtex Visual/fisiopatologia , Adolescente , Adulto , Eletroencefalografia , Potenciais Evocados , Face , Reconhecimento Facial/fisiologia , Pessoas Famosas , Feminino , Utensílios Domésticos , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação , Adulto Jovem
8.
Neuroimage ; 238: 118205, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34077804

RESUMO

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed "hold-your-horses" role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC.


Assuntos
Ritmo Gama/fisiologia , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Ritmo Teta/fisiologia , Adulto , Idoso , Atenção/fisiologia , Eletroencefalografia , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Tempo de Reação/fisiologia , Teste de Stroop
9.
Nat Rev Neurosci ; 22(8): 458-471, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34127843

RESUMO

The sensory, associative and limbic neocortical structures play a critical role in shaping incoming noxious inputs to generate variable pain perceptions. Technological advances in tracing circuitry and interrogation of pathways and complex behaviours are now yielding critical knowledge of neocortical circuits, cellular contributions and causal relationships between pain perception and its abnormalities in chronic pain. Emerging insights into neocortical pain processing suggest the existence of neocortical causality and specificity for pain at the level of subdomains, circuits and cellular entities and the activity patterns they encode. These mechanisms provide opportunities for therapeutic intervention for improved pain management.


Assuntos
Analgesia , Neocórtex/fisiopatologia , Percepção da Dor/fisiologia , Dor/fisiopatologia , Animais , Humanos , Vias Neurais/fisiopatologia , Manejo da Dor
10.
Sci Rep ; 11(1): 11951, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099768

RESUMO

Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive-compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD > SIB > HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.


Assuntos
Corpo Estriado/fisiopatologia , Lobo Frontal/fisiopatologia , Modelos Neurológicos , Vias Neurais/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Cognição/fisiologia , Endofenótipos , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Análise de Regressão , Irmãos , Adulto Jovem
11.
Sci Rep ; 11(1): 12105, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103606

RESUMO

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtornos Cognitivos/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Sobreviventes de Câncer , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Cognição , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Projetos Piloto , Córtex Pré-Frontal
12.
Elife ; 102021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042586

RESUMO

Understanding how neuronal circuits control nociceptive processing will advance the search for novel analgesics. We use functional imaging to demonstrate that lateral hypothalamic parvalbumin-positive (LHPV) glutamatergic neurons respond to acute thermal stimuli and a persistent inflammatory irritant. Moreover, their chemogenetic modulation alters both pain-related behavioral adaptations and the unpleasantness of a noxious stimulus. In two models of persistent pain, optogenetic activation of LHPV neurons or their ventrolateral periaqueductal gray area (vlPAG) axonal projections attenuates nociception, and neuroanatomical tracing reveals that LHPV neurons preferentially target glutamatergic over GABAergic neurons in the vlPAG. By contrast, LHPV projections to the lateral habenula regulate aversion but not nociception. Finally, we find that LHPV activation evokes additive to synergistic antinociceptive interactions with morphine and restores morphine antinociception following the development of morphine tolerance. Our findings identify LHPV neurons as a lateral hypothalamic cell type involved in nociception and demonstrate their potential as a target for analgesia.


Assuntos
Comportamento Animal , Região Hipotalâmica Lateral/fisiopatologia , Nociceptividade , Dor/fisiopatologia , Dor/psicologia , Analgésicos Opioides/uso terapêutico , Animais , Animais Geneticamente Modificados , Comportamento Animal/efeitos dos fármacos , Sinalização do Cálcio , Modelos Animais de Doenças , Tolerância a Medicamentos , Feminino , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Morfina/farmacologia , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Técnicas de Rastreamento Neuroanatômico , Nociceptividade/efeitos dos fármacos , Optogenética , Dor/metabolismo , Dor/prevenção & controle , Parvalbuminas/genética , Parvalbuminas/metabolismo
13.
J Alzheimers Dis ; 82(1): 435-445, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024823

RESUMO

BACKGROUND: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. OBJECTIVE: To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magnetic resonance imaging. METHODS: Forty-nine participants with either SCD (n = 23, 12 females; mean age: 70.7 (5.5)) or who were cognitively unimpaired (CU; n = 26, 16 females, mean age: 71.42 (7.3)) completed the Memory Functioning Questionnaire, a measure of subjective memory, and underwent resting state functional MRI at 3 Tesla. Functional connectivity between the posterior cingulate cortex (PCC), as the key pDMN node, and MTL regions were compared between SCD and CU groups. Further, the association between pDMN-MTL connectivity and the Frequency of Forgetting subscale of the Memory Functioning Questionnaire was examined. RESULTS: Connectivity between the PCC-MTL was observed in the CU group but was absent in SCD (t(47) = 2.69, p = 0.01). Across all participants, self-perception of frequency of forgetting, but not objective memory, was strongly correlated with connectivity between the PCC-left parahippocampal gyrus (r = 0.43, p = 0.002). CONCLUSION: These findings support the hypothesis that increased AD risk in SCD may be mediated by disrupted pDMN-parahippocampal connectivity. In addition, these findings suggest that frequency of forgetting may serve as a potential biomarker of SCD due to incipient AD.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Transtornos da Memória/diagnóstico por imagem , Giro Para-Hipocampal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Idoso , Disfunção Cognitiva/fisiopatologia , Rede de Modo Padrão/fisiopatologia , Autoavaliação Diagnóstica , Feminino , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Giro Para-Hipocampal/fisiopatologia , Lobo Temporal/fisiopatologia
14.
J Alzheimers Dis ; 82(1): 447-460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024825

RESUMO

BACKGROUND: Language production deficits occur early in the course of Alzheimer's disease (AD); however, only a few studies have focused on language network's functional connectivity in mild cognitive impairment (MCI) due to AD. OBJECTIVE: The current study aims to uncover the extent of language alteration at the MCI stage, at a behavioral and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI. METHODS: Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks. RESULTS: MCI due to AD participants had language impairment during standardized language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multivariate pattern analyses could significantly predict participants' group. Language network's functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage, positively correlated with language performance. CONCLUSION: Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Idioma , Vias Neurais/diagnóstico por imagem , Fala , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Função Executiva , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Testes Neuropsicológicos
15.
J Neurosci ; 41(26): 5762-5770, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34021042

RESUMO

Misophonia is a common disorder characterized by the experience of strong negative emotions of anger and anxiety in response to certain everyday sounds, such as those generated by other people eating, drinking, and breathing. The commonplace nature of these "trigger" sounds makes misophonia a devastating disorder for sufferers and their families. How such innocuous sounds trigger this response is unknown. Since most trigger sounds are generated by orofacial movements (e.g., chewing) in others, we hypothesized that the mirror neuron system related to orofacial movements could underlie misophonia. We analyzed resting state fMRI (rs-fMRI) connectivity (N = 33, 16 females) and sound-evoked fMRI responses (N = 42, 29 females) in misophonia sufferers and controls. We demonstrate that, compared with controls, the misophonia group show no difference in auditory cortex responses to trigger sounds, but do show: (1) stronger rs-fMRI connectivity between both auditory and visual cortex and the ventral premotor cortex responsible for orofacial movements; (2) stronger functional connectivity between the auditory cortex and orofacial motor area during sound perception in general; and (3) stronger activation of the orofacial motor area, specifically, in response to trigger sounds. Our results support a model of misophonia based on "hyper-mirroring" of the orofacial actions of others with sounds being the "medium" via which action of others is excessively mirrored. Misophonia is therefore not an abreaction to sounds, per se, but a manifestation of activity in parts of the motor system involved in producing those sounds. This new framework to understand misophonia can explain behavioral and emotional responses and has important consequences for devising effective therapies.SIGNIFICANCE STATEMENT Conventionally, misophonia, literally "hatred of sounds" has been considered as a disorder of sound emotion processing, in which "simple" eating and chewing sounds produced by others cause negative emotional responses. Our data provide an alternative but complementary perspective on misophonia that emphasizes the action of the trigger-person rather than the sounds which are a byproduct of that action. Sounds, in this new perspective, are only a "medium" via which action of the triggering-person is mirrored onto the listener. This change in perspective has important consequences for devising therapies and treatment methods for misophonia. It suggests that, instead of focusing on sounds, which many existing therapies do, effective therapies should target the brain representation of movement.


Assuntos
Sintomas Afetivos/fisiopatologia , Córtex Cerebral/fisiopatologia , Neurônios-Espelho/fisiologia , Vias Neurais/fisiopatologia , Ruído , Estimulação Acústica , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
16.
Medicine (Baltimore) ; 100(21): e26078, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032740

RESUMO

ABSTRACT: Based on association studies on amounts of alcohol consumed and cortical and subcortical structural shrinkage, we investigated the effect of chronic alcohol consumption on white matter pathways using probabilistic tractography.Twenty-three alcohol-dependent men (with an average sobriety of 13.1 months) from a mental health hospital and 22 age-matched male healthy social drinkers underwent 3T magnetic resonance imaging. Eighteen major white matter pathways were reconstructed using the TRActs Constrained by UnderLying Anatomy tool (provided by the FreeSurfer). The hippocampal volumes were estimated using an automated procedure. The lifetime drinking history interview, Alcohol Use Disorder Identification Test, Brief Michigan Alcoholism Screening Test, and pack-years of smoking were also evaluated.Analysis of covariance controlling for age, cigarette smoking, total motion index indicated that there was no definite difference of diffusion parameters between the 2 groups after multiple comparison correction. As hippocampal volume decreased, the fractional anisotropy of the right cingulum-angular bundle decreased. Additionally, the axial diffusivity of right cingulum-angular bundle was positively correlated with the alcohol abstinence period.The results imply resilience of white matter in patients with alcohol dependence. Additional longitudinal studies with multimodal methods and neuropsychological tests may improve our findings of the changes in white matter pathways in patients with alcohol dependence.


Assuntos
Alcoolismo/complicações , Hipocampo/patologia , Imageamento por Ressonância Magnética , Substância Branca/fisiopatologia , Adulto , Abstinência de Álcool , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Anisotropia , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Tamanho do Órgão , Substância Branca/diagnóstico por imagem
17.
Brain ; 144(6): 1774-1786, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-33889943

RESUMO

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.


Assuntos
Estimulação Encefálica Profunda/métodos , Tremor Essencial/fisiopatologia , Tremor Essencial/cirurgia , Tremor/fisiopatologia , Tremor/cirurgia , Adulto , Distúrbios Distônicos/complicações , Distúrbios Distônicos/fisiopatologia , Distúrbios Distônicos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Núcleos Posteriores do Tálamo/fisiopatologia , Núcleos Posteriores do Tálamo/cirurgia , Estudos Retrospectivos , Tálamo/fisiopatologia , Tálamo/cirurgia , Tremor/etiologia
18.
Health Psychol ; 40(4): 285-294, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33856834

RESUMO

OBJECTIVE: Health-related norms in social networks can influence whether people are open to health behavior change. Yet, little is known about how social networks relate to the ways individual brains respond to persuasive health messaging. The current study focuses on ventromedial prefrontal cortex (VMPFC) activity as an index of neural receptivity to health messages that may be related to behavior change. The study tested whether health-related norms and perceived physical activity levels within participants' social networks are associated with neural receptivity to health messages. METHOD: Adults who initially reported under 200 minutes/week of physical activity (N = 146) rated the perceived physical activity levels of, and closeness to, each person in their core social network. VMPFC activity was monitored using fMRI while participants viewed persuasive health messages promoting physical activity. Longitudinal changes in sedentary behavior were objectively logged using wrist-worn accelerometers throughout a 2-week baseline and the month following the fMRI scan. RESULTS: Higher levels of perceived physical activity in participants' social networks were associated with greater VMPFC activity during message exposure, which in turn were associated with greater decreases in sedentary minutes. By contrast, greater closeness to physically inactive social ties was associated with lower VMPFC activity. CONCLUSIONS: Perceived norms in social networks relate to neural receptivity to health messaging. In particular, closeness to physically inactive ties is associated with lower neural receptivity to health messages encouraging physical activity, which may undermine the effectiveness of health messages. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Comportamentos Relacionados com a Saúde/fisiologia , Vias Neurais/fisiopatologia , Rede Social , Adulto , Feminino , Humanos , Masculino
19.
Toxins (Basel) ; 13(4)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923397

RESUMO

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.


Assuntos
Encéfalo/fisiopatologia , Distonia/fisiopatologia , Contração Muscular , Hipertonia Muscular/fisiopatologia , Tono Muscular , Músculo Esquelético/inervação , Medula Espinal/fisiopatologia , Animais , Distonia/diagnóstico , Humanos , Hipertonia Muscular/diagnóstico , Rigidez Muscular/diagnóstico , Rigidez Muscular/fisiopatologia , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/fisiopatologia , Vias Neurais/fisiopatologia
20.
Nutr Metab Cardiovasc Dis ; 31(6): 1860-1870, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33853721

RESUMO

BACKGROUND AND AIMS: Deep repetitive Transcranial Magnetic Stimulation (deep rTMS) over the bilateral insula and prefrontal cortex (PFC) can promote weight-loss in obesity, preventing cardiometabolic complications as Type 2 Diabetes (T2D). To investigate the changes in the functional brain integration after dTMS, we conducted a resting-state functional connectivity (rsFC) study in obesity. METHODS AND RESULTS: This preliminary study was designed as a randomized, double-blind, sham-controlled study: 9 participants were treated with high-frequency stimulation (realTMS group), 8 were sham-treated (shamTMS group). Out of the 17 enrolled patients, 6 were affected by T2D. Resting-state fMRI scans were acquired at baseline (T0) and after the 5-week intervention (T1). Body weight was measured at three time points [T0, T1, 1-month follow-up visit (FU1)]. A mixed-model analysis showed a significant group-by-time interaction for body weight (p = .04), with a significant decrease (p < .001) in the realTMS group. The rsFC data revealed a significant increase of degree centrality for the realTMS group in the medial orbitofrontal cortex (mOFC) and a significant decrease in the occipital pole. CONCLUSION: An increase of whole-brain functional connections of the mOFC, together with the decrease of whole-brain functional connections with the occipital pole, may reflect a brain mechanism behind weight-loss through a diminished reactivity to bottom-up visual-sensory processes in favor of increased reliance on top-down decision-making processes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03009695.


Assuntos
Encéfalo/fisiopatologia , Comportamento de Escolha , Diabetes Mellitus Tipo 2/terapia , Comportamento Alimentar , Obesidade/terapia , Estimulação Magnética Transcraniana , Perda de Peso , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Obesidade/diagnóstico , Obesidade/fisiopatologia , Obesidade/psicologia , Recompensa , Estimulação Magnética Transcraniana/efeitos adversos , Resultado do Tratamento
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