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1.
J Comput Assist Tomogr ; 45(2): 294-299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661154

RESUMO

OBJECTIVE: To determine whether there is a difference between healthy control group and children with neurofibromatosis type 1 (NF1) in terms of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in different regions of the brain associated with neurocognitive functions and to investigate the correlation between diffusion tensor imaging parameters and neurocognitive dysfunctions. METHODS: The study included 28 children with NF1 and 21 controls. Nine distinct areas related to cognitive functions were selected for the analysis. The ADC and FA values were compared. RESULTS: There was a significant difference between NF1 and healthy control in terms of ADC values obtained from all areas. The ADC values at obtained from thalamus and striatum were positively correlated with the full-scale intelligence quotient (IQ), verbal IQ, and performance IQ. CONCLUSIONS: We are speculated that the development of microstructural damage in the thalamostriatal pathway may lead to neurocognitive dysfunction.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Imagem de Tensor de Difusão , Neurofibromatose 1/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adolescente , Estudos de Casos e Controles , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Corpo Estriado/fisiopatologia , Feminino , Humanos , Masculino , Neurofibromatose 1/complicações , Neurofibromatose 1/fisiopatologia , Tálamo/fisiopatologia
2.
Nat Med ; 27(2): 232-238, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462447

RESUMO

Nearly one billion people worldwide suffer from obsessive-compulsive behaviors1,2, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive-compulsive behaviors as maladaptive habit learning3,4, which may be associated with abnormal beta-gamma neurophysiology of the orbitofrontal-striatal circuitry during reward processing5,6. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta-gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive-compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive-compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive-compulsive behavior, suggest a unifying functional role of rhythms in the beta-gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.


Assuntos
Corpo Estriado/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/terapia , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Elétrica Nervosa Transcutânea , Adulto , Mapeamento Encefálico , Comportamento Compulsivo/diagnóstico por imagem , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/terapia , Corpo Estriado/fisiopatologia , Corpo Estriado/efeitos da radiação , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/efeitos da radiação
4.
J Stroke Cerebrovasc Dis ; 29(10): 105153, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912549

RESUMO

BACKGROUND: Concomitant asymptomatic striatocapsular slit-like hemorrhage (SSH) is occasionally found in patients of spontaneous intracerebral hemorrhage (ICH), but was seldomly described in the literature. In this study, we described the clinico-radiological features of asymptomatic SSH in ICH patients with hypertensive microangiopathy. METHODS AND RESULTS: 246 patients with strictly deep or mixed deep and lobar ICH/microbleeds were included. SSH was defined as hypointense lesions involving the lateral aspect of lentiform nucleus or external capsule in slit shape (>1.5 cm) on susceptibility-weighted imaging without history of associated symptoms. Demographics and neuroimaging markers were compared between patients with SSH and those without. Patients with SSH (n=24, 10%) and without SSH had comparable age (62.0 ± 12.6 vs. 62.3 ± 13.5, p = 0.912) and vascular risk factor profiles including the diagnosis of chronic hypertension, diabetes, and dyslipidemia (all p>0.05). SSH was associated with more common lobar microbleeds (79.2% vs 48.2%, p = 0.005), lacunes (75% vs. 41.4%, p = 0.002) and higher white matter hyperintensity (WMH) volumes (24.1 [10.4-46.3] vs. 13.9 [7.0-24.8] mL, p = 0.012) on MRI, as well as more frequent left ventricular hypertrophy (LVH) (50.0% vs. 20.5%, p = 0.004) and albuminuria (41.7% vs. 19.4%, p = 0.018). In multivariable analyses, SSH remains independently associated with LVH (p = 0.017) and albuminuria (p = 0.032) after adjustment for age, sex, microbleed, lacune and WMH volume. CONCLUSIONS: Asymptomatic SSH is associated with more severe cerebral small vessel disease-related change on brain MRI, and hypertensive cardiac and renal injury, suggesting a more advanced stage of chronic hypertension.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Cápsula Externa/diagnóstico por imagem , Hipertensão/complicações , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Idoso , Doenças Assintomáticas , Doenças de Pequenos Vasos Cerebrais/etiologia , Estudos Transversais , Feminino , Humanos , Hemorragia Intracraniana Hipertensiva/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença
5.
Acta Neurol Scand ; 142(4): 385-391, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32914881

RESUMO

BACKGROUND: Idiopathic Parkinson's disease (PD) is characterized by clinical motor symptoms including hypokinesia, rigidity and tremor. In addition to the movement disorder, cognitive deficits are commonly described. In the present study, we applied FP-CIT SPECT to investigate the impact of nigrostriatal dopaminergic degeneration on cognitive function in PD patients. METHODS: Fifty-four PD patients underwent [123I]FP-CIT SPECT and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) testing. FP-CIT SPECT visualized the density of presynaptic dopamine transporters in both striata, each subdivided into a limbic, executive and sensorimotor subregion according to the atlas of Tziortzi et al (Cereb Cortex 24, 2014, 1165). CERAD testing quantified cognitive function. RESULTS: In the CERAD testing, PD patients exhibited deficits in the domains of semantic memory, attention, visuospatial function, non-verbal memory and executive function. After correction for multiple testing, the performance of the subtests Figure Recall and Trail-Making Test A correlated significantly with FP-CIT uptake into the ipsilateral executive subregion. The performance of the subtest Figure Saving correlated significantly with FP-CIT uptake into the contralateral executive subregion. CONCLUSIONS: The significant correlation between cognitive function and density of nigrostriatal dopamine transporters, as assessed by FP-CIT SPECT, indicate that striatal dopaminergic pathways-primarily the executive striatal subregion-are relevant to cognitive processing in PD.


Assuntos
Cognição , Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Corpo Estriado/metabolismo , Feminino , Humanos , Masculino , Doença de Parkinson/fisiopatologia , Tremor
6.
PLoS Biol ; 18(8): e3000800, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776945

RESUMO

Studies of neural processes underlying delay of gratification usually focus on prefrontal networks related to curbing affective impulses. Here, we provide evidence for an alternative mechanism that facilitates delaying gratification by mental orientation towards the future. Combining continuous theta-burst stimulation (cTBS) with functional neuroimaging, we tested how the right temporoparietal junction (rTPJ) facilitates processing of future events and thereby promotes delay of gratification. Participants performed an intertemporal decision task and a mental time-travel task in the MRI scanner before and after receiving cTBS over the rTPJ or the vertex (control site). rTPJ cTBS led to both stronger temporal discounting for longer delays and reduced processing of future relative to past events in the mental time-travel task. This finding suggests that the rTPJ contributes to the ability to delay gratification by facilitating mental representation of outcomes in the future. On the neural level, rTPJ cTBS led to a reduction in the extent to which connectivity of rTPJ with striatum reflected the value of delayed rewards, indicating a role of rTPJ-striatum connectivity in constructing neural representations of future rewards. Together, our findings provide evidence that the rTPJ is an integral part of a brain network that promotes delay of gratification by facilitating mental orientation to future rewards.


Assuntos
Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Desvalorização pelo Atraso/fisiologia , Rede Nervosa/fisiologia , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Corpo Estriado/anatomia & histologia , Corpo Estriado/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/anatomia & histologia , Lobo Parietal/diagnóstico por imagem , Recompensa , Lobo Temporal/anatomia & histologia , Lobo Temporal/diagnóstico por imagem , Estimulação Magnética Transcraniana
7.
BMC Neurol ; 20(1): 277, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652959

RESUMO

BACKGROUND: Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. METHODS: In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. RESULTS: Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. CONCLUSION: Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.


Assuntos
Corpo Estriado , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Dopamina/metabolismo , Hidrocefalia de Pressão Normal , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Diagnóstico por Imagem , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/metabolismo
8.
Neurology ; 95(3): e280-e290, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32616674

RESUMO

OBJECTIVE: To investigate whether the patterns of striatal dopamine depletion on dopamine transporter (DAT) scans could provide information on the long-term prognosis in Parkinson disease (PD). METHODS: We enrolled 205 drug-naive patients with early-stage PD, who underwent 18F-FP-CIT PET scans at initial assessment and received PD medications for 3 or more years. After quantifying the DAT availability in each striatal subregion, factor analysis was conducted to simplify the identification of striatal dopamine depletion patterns and to yield 4 striatal subregion factors. We assessed the effect of these factors on the development of levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia during the follow-up period (6.84 ± 1.80 years). RESULTS: The 4 factors indicated which striatal subregions were relatively preserved: factor 1 (caudate), factor 2 (more-affected sensorimotor striatum), factor 3 (less-affected sensorimotor striatum), and factor 4 (anterior putamen). Cox regression analyses using the composite scores of these striatal subregion factors as covariates demonstrated that selective dopamine depletion in the sensorimotor striatum was associated with a higher risk for developing LID. Selective dopamine loss in the putamen, particularly in the anterior putamen, was associated with early development of wearing-off. Selective involvement of the anterior putamen was associated with a higher risk for dementia conversion. However, the patterns of striatal dopamine depletion did not affect the risk of FOG. CONCLUSIONS: These findings suggested that the patterns of striatal dopaminergic denervation, which were estimated by the equation derived from the factor analysis, have a prognostic implication in patients with early-stage PD.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/tendências , Idoso , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
Nat Commun ; 11(1): 3111, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561725

RESUMO

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation. DA projections are misguided and fail to innervate the striatum in both constitutive and striatal-specific Nolz1 mutant embryos. The lack of striatal Nolz1 expression results in nigral to pallidal lineage conversion of striatal projection neuron subtypes. This lineage switch alters the composition of secreted factors influencing DA axonal tract formation and renders the striatum non-permissive for dopaminergic and other forebrain tracts. Furthermore, transcriptomic analysis of wild-type and Nolz1-/- mutant striatal tissue led to the identification of several secreted factors that underlie the observed guidance defects and proteins that promote DA axonal outgrowth. Together, our data demonstrate the involvement of the striatum in orchestrating dopaminergic circuitry formation.


Assuntos
Orientação de Axônios/fisiologia , Axônios/fisiologia , Corpo Estriado/crescimento & desenvolvimento , Neurônios Dopaminérgicos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Carbocianinas/administração & dosagem , Corpo Estriado/diagnóstico por imagem , Embrião de Mamíferos , Feminino , Corantes Fluorescentes/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microscopia Intravital , Camundongos Knockout , Técnicas Analíticas Microfluídicas , Microinjeções , Microscopia Confocal , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Técnicas de Cultura de Tecidos
10.
Psychiatry Res Neuroimaging ; 301: 111086, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32464340

RESUMO

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT. Eight inpatients (7 patients with major depressive disorder and 1 patient with bipolar disorder with a DSM-IV diagnosis) received a series of 7-15(11.3±5.2) bilateral ECT sessions.The severity of symptoms was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Severity (CGI-S). All patients were examined with [18F]FE-PE2I positron emission tomography (PET) at pre-ECT, after the 10th ECT, and at post-ECT. Striatal DAT-binding potential (BPND) of all patients was reduced, with an average change ratio of DAT-BPND of -13.1±5.6%. In the 2 cases with 15 ECT sessions, the ratio change of DAT-BPND after the 15th ECT was larger than that after the 10th ECT. Also, HDRS and CGI-S were reduced. These results indicate that the dopamine nervous system is part of themechanism of action of ECT.


Assuntos
Transtorno Bipolar/metabolismo , Corpo Estriado/metabolismo , Transtorno Depressivo Maior/terapia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Eletroconvulsoterapia/métodos , Adulto , Idoso , Transtorno Bipolar/terapia , Corpo Estriado/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Resultado do Tratamento , Adulto Jovem
11.
J Neurol Neurosurg Psychiatry ; 91(6): 631-637, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32381639

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) and rapid eye movement sleep behavioural disorder (RBD) are risk factors for Parkinson's disease (PD). Dopaminergic abnormalities are often seen after TBI, but patients usually lack parkinsonian features. We test whether TBI, PD and RBD have distinct striatal dopamine abnormalities using dopamine transporter (DaT) imaging. METHODS: 123I-ioflupane single-photon emission CT scans were used in a cross-sectional study to measure DaT levels in moderate/severe TBI, healthy controls, patients with early PD and RBD. Caudate and putamen DaT, putamen to caudate ratios and left-right symmetry of DaT were compared. RESULTS: 108 participants (43 TBI, 26 PD, 8 RBD, 31 controls) were assessed. Patients with early PD scored significantly higher on the Unified Parkinson's Disease Rating Scale motor subscale than other groups. Patients with TBI and PD had reduced DaT levels in the caudate (12.2% and 18.7%, respectively) and putamen (9.0% and 42.6%, respectively) compared with controls. Patients with RBD had reduced DaT levels in the putamen (12.8%) but not in the caudate compared with controls. Patients with PD and TBI showed distinct patterns of DaT reduction, with patients with PD showing a lower putamen to caudate ratio. DaT asymmetry was greater in the PD group than other groups. CONCLUSIONS: The results show that patients with early PD and TBI have distinct patterns of striatal dopamine abnormalities. Patients with early PD and moderate/severe TBI showed similar reductions in caudate DaT binding, but patients with PD showed a greater reduction in putamen DaT and a lower putamen to caudate ratio. The results suggest that parkinsonian motor signs are absent in these patients with TBI because of relatively intact putaminal dopamine levels.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Adulto , Idoso , Lesões Encefálicas Traumáticas/metabolismo , Corpo Estriado/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Transtorno do Comportamento do Sono REM/metabolismo , Fatores de Risco , Tomografia Computadorizada de Emissão de Fóton Único
12.
Psychiatry Res Neuroimaging ; 301: 111089, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32442837

RESUMO

It is thought that altered connectivity between the striatum and the cortex could contribute to psychosis. However, whether psychosis risk is associated with altered white matter connectivity between the striatum and any cortical region is still unclear. Further, no previous study has directly examined whether psychosis risk is associated with altered striatal connectivity with specific cortical networks. The current study examined the integrity of corticostriatal white matter tracts in psychosis risk (n=18) and in non-psychosis risk comparison participants (n=19). We used probabilistic tractography to identify white matter tracts connecting each of four different striatal subregions with their most functionally connected cortical network: limbic, default mode, frontoparietal, and motor networks. We then compared groups on fractional anisotropy in these four tracts. Psychosis risk was associated with decreased fractional anisotropy in white matter tracts connecting the limbic striatum with the limbic cortical network, especially in an anterior right external capsule segment and in tracts specifically connected to the right prefrontal cortex. In contrast, psychosis risk was not associated with decreased white matter integrity in other corticostriatal tracts. Hence, the current research suggests that psychosis risk is especially associated with decreased corticostriatal white matter integrity involved in processing emotional and personally relevant information.


Assuntos
Corpo Estriado/diagnóstico por imagem , Imagem de Tensor de Difusão , Sistema Límbico/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos Psicóticos/etiologia , Substância Branca/diagnóstico por imagem , Adolescente , Anisotropia , Estudos de Casos e Controles , Corpo Estriado/patologia , Feminino , Humanos , Sistema Límbico/patologia , Masculino , Córtex Pré-Frontal/patologia , Medição de Risco , Fatores de Risco , Substância Branca/patologia , Adulto Jovem
13.
Psychiatry Res Neuroimaging ; 300: 111081, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32344156

RESUMO

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants. We then examined relationships between OCD neural network connectivity and OCD symptom severity in OCD participants. OCD relative to healthy participants showed significantly greater connectivity between the left caudate and bilateral dorsolateral prefrontal cortex. We also found a positive correlation between left caudate-bilateral dorsolateral prefrontal cortex connectivity and depression scores in OCD participants, such that greater positive connectivity was associated with more severe symptoms. This study makes a significant contribution to our understanding of functional networks and their relationship with depression in OCD.


Assuntos
Imagem por Ressonância Magnética , Rede Nervosa/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Índice de Gravidade de Doença , Adulto , Tonsila do Cerebelo/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia , Adulto Jovem
14.
Nat Med ; 26(4): 558-565, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32251404

RESUMO

Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia1-5. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.


Assuntos
Biomarcadores , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Neuroimagem/métodos , Esquizofrenia/diagnóstico , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Biomarcadores/análise , Biomarcadores Farmacológicos/análise , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Projetos de Pesquisa , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Sensibilidade e Especificidade , Máquina de Vetores de Suporte , Adulto Jovem
15.
Nat Hum Behav ; 4(5): 531-543, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231281

RESUMO

Curiosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in harmful situations. Here, using a set of behavioural and neuroimaging experiments with stimuli that strongly trigger curiosity (for example, magic tricks), we examine the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrate that across different samples, people are indeed willing to gamble, subjecting themselves to electric shocks to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of hunger for food. In particular, we show that acceptance (compared to rejection) of curiosity-driven or incentive-driven gambles is accompanied by enhanced activity in the ventral striatum when curiosity or hunger was elicited, which extends into the dorsal striatum when participants made a decision.


Assuntos
Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Comportamento Exploratório , Fome/fisiologia , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/fisiologia , Corpo Estriado/diagnóstico por imagem , Eletrochoque/psicologia , Comportamento Exploratório/fisiologia , Feminino , Jogo de Azar/diagnóstico por imagem , Jogo de Azar/fisiopatologia , Humanos , Magia/psicologia , Imagem por Ressonância Magnética , Masculino , Motivação/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Neuroimagem , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Adulto Jovem
16.
Nat Commun ; 11(1): 846, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051403

RESUMO

The development of the striatum dopamine (DA) system through human adolescence, a time of increased sensation seeking and vulnerability to the emergence of psychopathology, has been difficult to study due to pediatric restrictions on direct in vivo assessments of DA. Here, we applied neuroimaging in a longitudinal sample of n = 146 participants aged 12-30. R2', an MR measure of tissue iron which co-localizes with DA vesicles and is necessary for DA synthesis, was assessed across the sample. In the 18-30 year-olds (n = 79) we also performed PET using [11C]dihydrotetrabenazine (DTBZ), a measure of presynaptic vesicular DA storage, and [11C]raclopride (RAC), an indicator of D2/D3 receptor availability. We observed decreases in D2/D3 receptor availability with age, while presynaptic vesicular DA storage (as measured by DTBZ), which was significantly associated with R2' (standardized coefficient = 0.29, 95% CI = [0.11, 0.48]), was developmentally stable by age 18. Our results provide new evidence for maturational specialization of the striatal DA system through adolescence.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/crescimento & desenvolvimento , Corpo Estriado/metabolismo , Dopamina/metabolismo , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Fatores Etários , Criança , Neurociência Cognitiva , Feminino , Humanos , Cinética , Masculino , Modelos Biológicos , Neuroimagem , Racloprida , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Tetrabenazina/análogos & derivados , Adulto Jovem
17.
Sci Rep ; 10(1): 1594, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005905

RESUMO

Diabetic striatopathy (DS) is a rare medical condition with ambiguous nomenclature. We searched PubMed database from 1992 to 2018 for articles describing hyperglycemia associated with chorea/ballism and/or neuroimages of striatal abnormalities. Descriptive analysis was performed on demographic/clinical characteristics, locations of striatal abnormalities on neuroimages, pathology findings, treatment strategies, and outcomes. In total, 176 patients (male:female = 1:1.7) were identified from 72 articles with mean age 67.6 ± 15.9 (range, 8-92). Among them, 96.6% had type 2 DM with 17% being newly diagnosed. Average blood glucose and glycated hemoglobin concentrations were 414 mg/dL and 13.1%, respectively. Most patients (88.1%) presented with hemichorea/hemiballism. Isolated putamen and combined putamen-caudate nucleus involvements were most common on neuroimaging studies with discrepancies between CT and MRI findings in about one-sixth of patients. Unilateral arm-leg combination was the most frequent with bilateral chorea in 9.7% of patients. Chorea and imaging anomalies did not appear concomitantly in one-tenth of patients. Successful treatment rates of chorea with glucose-control-only and additional anti-chorea medications were 25.7% and 76.2%, respectively, with an overall recurrence rate being 18.2%. The most commonly used anti-chorea drug was haloperidol. To date, four out of six pathological studies revealed evidence of hemorrhage as a probable pathogenesis.


Assuntos
Corpo Estriado/patologia , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 2/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Corpo Estriado/diagnóstico por imagem , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/terapia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
Psychiatry Res Neuroimaging ; 298: 111046, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32106018

RESUMO

Recent neuroimaging studies in OCD have reported structural alterations in the brain, not limited to frontostriatal regions. While Diffusion Tensor Imaging (DTI) is typically used to interrogate WM microstructure in OCD, additional imaging metric, such as Magnetization Transfer Imaging (MTI), allows for further identification of subtle but important structural changes across both GM and WM. In this study, both MTI and DTI were utilised to investigate the structural integrity of the brain, in OCD in relation to healthy controls. 38 adult OCD patients were recruited, along with 41 age- and gender-matched controls. Structural T1, MTI and DTI data were collected. Case-control differences in Magnetization Transfer Ratio (MTR) and DTI metrics (FA, MD) were examined, along with MTR/DTI-related associations with symptom severity in patients. No significant group differences were found across MTR, FA, and MD. However, OCD symptom severity was positively correlated with MTR in a distributed network of brain regions, including the striatum, cingulate, orbitofrontal area and insula. Within the same regions, OCD symptoms were also positively correlated with FA in WM, and negatively correlated with MD in GM. These results indicate a greater degree of myelination in certain cortical and subcortical regions in the more severe cases of OCD.


Assuntos
Córtex Cerebral , Corpo Estriado , Imagem por Ressonância Magnética , Neuroimagem , Transtorno Obsessivo-Compulsivo , Índice de Gravidade de Doença , Adolescente , Adulto , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto Jovem
19.
Brain Dev ; 42(4): 363-368, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31932101

RESUMO

BACKGROUND: Biallelic variants in POLR3A encoding the largest subunit of RNA polymerase III cause POLR3-related (or 4H) leukodystrophy characterized by neurologic dysfunction, abnormal dentition, endocrine abnormalities and ocular abnormality. Recently, whole-exome sequencing enabled the discovery of POLR3A variants in cases lacking diffuse hypomyelination, the principal MRI phenotype of POLR3-related leukodystrophy. Homozygous c.1771-6C > G variants in POLR3A were recently suggested to cause striatal and red nucleus involvement without white matter involvement. CASE REPORT: Here, we report three cases in two families with biallelic POLR3A variants. We identified two sets of compound heterozygous variants in POLR3A, c.1771-6C > G and c.791C > T, p.(Pro264Leu) for family 1 and c.1771-6C > G and c.2671C > T, p.(Arg891*) for family 2. Both families had the c.1771-6C > G variant, which led to aberrant mRNA splicing. Neuropsychiatric regression and severe intellectual disability were identified in three patients. Two cases showed dystonia and oligodontia. Notably, characteristic bilateral symmetric atrophy and abnormal signal of the striatum without diffuse white matter signal change were observed in brain MRI of all three individuals. CONCLUSIONS: Striatum abnormalities may be another distinctive MRI finding associated with POLR3A variants, especially in cases including c.1771-6C > G variants and our cases can expand the phenotypic spectrum of POLR3A-related disorders.


Assuntos
Corpo Estriado/patologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , RNA Polimerase III/genética , Criança , Corpo Estriado/diagnóstico por imagem , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Masculino , Linhagem
20.
Curr Top Behav Neurosci ; 47: 53-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31907881

RESUMO

Molecular and functional imaging techniques have been used and combined with pharmacological probes to evaluate the role of dopamine in impulsivity. Overall, strong evidence links striatal dopaminergic function with impulsivity, measured by self-reports and laboratory tests of cognitive control and reward-based decision-making. The combination of molecular imaging using positron emission tomography (PET) with functional magnetic resonance imaging (fMRI) specifically implicates striatal D2-type dopamine receptors (i.e., D2 and D3) and corticostriatal connectivity in cognitive control. Low levels of striatal and midbrain D2-type receptor availability correlate with self-reported impulsivity, whereas striatal D2-type receptor availability shows positive correlation with motor response inhibition and cognitive flexibility. Impulsive choice on reward-based decision-making tasks also is related to deficits in striatal D2-type dopamine receptor availability, and there is evidence for an inverted U-shaped function in this relationship, reflecting an optimum of striatal dopaminergic activity. Findings from studies of clinical populations that present striatal dopamine D2-type receptor deficits as well as healthy control research participants identify D2-type receptors as therapeutic targets to improve cognitive control.


Assuntos
Corpo Estriado , Dopamina , Corpo Estriado/diagnóstico por imagem , Humanos , Comportamento Impulsivo , Imagem por Ressonância Magnética , Neuroimagem , Tomografia por Emissão de Pósitrons
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