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1.
Acta Neuropathol Commun ; 12(1): 111, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956662

RESUMO

The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.


Assuntos
Redes Reguladoras de Genes , Neurônios , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Neurônios/metabolismo , Neurônios/patologia , Masculino , Feminino , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Idoso , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo , Estudo de Associação Genômica Ampla , Transcriptoma , Análise de Célula Única , Lobo Temporal/metabolismo , Lobo Temporal/patologia , Pessoa de Meia-Idade , Regulação da Expressão Gênica/genética , Multiômica
2.
Hum Brain Mapp ; 45(10): e26749, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38989605

RESUMO

The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions.


Assuntos
Cerebelo , Imageamento por Ressonância Magnética , Humanos , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/patologia , Masculino , Feminino , Adulto Jovem , Adulto , Conectoma/métodos , Habilidades Sociais , Adolescente , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem
3.
Nat Commun ; 15(1): 5369, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987235

RESUMO

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.


Assuntos
Neurônios , Lobo Temporal , Animais , Masculino , Lobo Temporal/fisiologia , Neurônios/fisiologia , Macaca mulatta , Memória/fisiologia , Imageamento por Ressonância Magnética , Lobo Frontal/fisiologia , Memória de Curto Prazo/fisiologia , Mapeamento Encefálico , Córtex Pré-Frontal/fisiologia
4.
Nat Commun ; 15(1): 5531, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982092

RESUMO

In everyday life, people need to respond appropriately to many types of emotional stimuli. Here, we investigate whether human occipital-temporal cortex (OTC) shows co-representation of the semantic category and affective content of visual stimuli. We also explore whether OTC transformation of semantic and affective features extracts information of value for guiding behavior. Participants viewed 1620 emotional natural images while functional magnetic resonance imaging data were acquired. Using voxel-wise modeling we show widespread tuning to semantic and affective image features across OTC. The top three principal components underlying OTC voxel-wise responses to image features encoded stimulus animacy, stimulus arousal and interactions of animacy with stimulus valence and arousal. At low to moderate dimensionality, OTC tuning patterns predicted behavioral responses linked to each image better than regressors directly based on image features. This is consistent with OTC representing stimulus semantic category and affective content in a manner suited to guiding behavior.


Assuntos
Emoções , Imageamento por Ressonância Magnética , Lobo Occipital , Semântica , Lobo Temporal , Humanos , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Lobo Temporal/fisiologia , Lobo Temporal/diagnóstico por imagem , Adulto , Lobo Occipital/fisiologia , Lobo Occipital/diagnóstico por imagem , Adulto Jovem , Emoções/fisiologia , Mapeamento Encefálico , Estimulação Luminosa , Afeto/fisiologia , Nível de Alerta/fisiologia
5.
Nat Commun ; 15(1): 5738, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982106

RESUMO

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here, we have male macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area's ability for cross-context decoding. Lastly, correlational analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between neurons in prefrontal cortex maintain a stable population code and context-invariant beliefs during naturalistic behavior.


Assuntos
Macaca mulatta , Neurônios , Córtex Pré-Frontal , Animais , Masculino , Córtex Pré-Frontal/fisiologia , Neurônios/fisiologia , Lobo Temporal/fisiologia , Lobo Parietal/fisiologia , Comportamento Animal/fisiologia
7.
Sci Rep ; 14(1): 16569, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019949

RESUMO

This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.


Assuntos
Estudos Cross-Over , Alucinações , Esquizofrenia , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Masculino , Feminino , Alucinações/terapia , Alucinações/fisiopatologia , Adulto , Esquizofrenia/terapia , Esquizofrenia/fisiopatologia , Adulto Jovem , Córtex Pré-Frontal Dorsolateral/fisiologia , Lobo Temporal/fisiopatologia , Lobo Temporal/fisiologia
8.
Proc Natl Acad Sci U S A ; 121(28): e2321346121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38954551

RESUMO

How does the brain process the faces of familiar people? Neuropsychological studies have argued for an area of the temporal pole (TP) linking faces with person identities, but magnetic susceptibility artifacts in this region have hampered its study with fMRI. Using data acquisition and analysis methods optimized to overcome this artifact, we identify a familiar face response in TP, reliably observed in individual brains. This area responds strongly to visual images of familiar faces over unfamiliar faces, objects, and scenes. However, TP did not just respond to images of faces, but also to a variety of high-level social cognitive tasks, including semantic, episodic, and theory of mind tasks. The response profile of TP contrasted with a nearby region of the perirhinal cortex that responded specifically to faces, but not to social cognition tasks. TP was functionally connected with a distributed network in the association cortex associated with social cognition, while PR was functionally connected with face-preferring areas of the ventral visual cortex. This work identifies a missing link in the human face processing system that specifically processes familiar faces, and is well placed to integrate visual information about faces with higher-order conceptual information about other people. The results suggest that separate streams for person and face processing reach anterior temporal areas positioned at the top of the cortical hierarchy.


Assuntos
Imageamento por Ressonância Magnética , Lobo Temporal , Humanos , Imageamento por Ressonância Magnética/métodos , Lobo Temporal/fisiologia , Lobo Temporal/diagnóstico por imagem , Masculino , Feminino , Adulto , Reconhecimento Facial/fisiologia , Mapeamento Encefálico/métodos , Reconhecimento Psicológico/fisiologia , Face/fisiologia , Adulto Jovem , Reconhecimento Visual de Modelos/fisiologia
9.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38858838

RESUMO

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.


Assuntos
Mapeamento Encefálico , Idioma , Lobo Temporal , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , População do Leste Asiático , Estimulação Elétrica , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Japão , Imageamento por Ressonância Magnética , Lobo Temporal/fisiologia
10.
Zhonghua Yi Xue Za Zhi ; 104(21): 1994-1997, 2024 Jun 04.
Artigo em Chinês | MEDLINE | ID: mdl-38825943

RESUMO

The patients with temporal lobe epilepsy (TLE) admitted in the Department of Neurology, Zhongshan Hospital, Fudan University from June 2009 to February 2012 were prospectively enrolled. The diffusion tensor imaing was performed on the patients at the time of enrollment and 3 years later. The fractional anisotropy (FA) values of the white matter connecting fibers(bilateral hooked, arcuate, cingulate, and superior longitudinal tracts), the connecting fibers of both hemispheres(anterior union, anterior callosal forceps, posterior forceps, and bilateral fornix), and fibers of perirhinal cortices system(bilateral radiating crown and anterior limb of the internal capsule) were measured by the region of interest method. The severity of epilepsy was evaluated using the Veterans Administration Seizure Type and Frequency Rating Scale(VA-2) and National Hospital Seizure Severity Scale (NHS3). A total of 51 patients with TLE were screened, with 27 patients completing the 3-year follow-up. There were 13 males and 14 females with an age of (32±11) years and a follow-up duration of (39.1±1.1) months. During the follow-up, 6 patients had increased/unchanged NHS3 or VA-2 scores, while 21 patients had decreased scores. Three years later, the FA values of the bilateral arcuate fasciculus, the right superior longitudinal fasciculus, the right radial coronal and corpus callosum anterior forceps in TLE patients decreased compared to baseline(P<0.05). However, compared to the patients with decreased VA-2 scores during the follow-up, the degree of increase in FA values (ΔFA, follow-up FA value-baseline FA value) of the ipsilateral hook bundle caused by epilepsy was more significant in the group with increased/unchanged VA-2 scores (decreased score group vs increased/unchanged score group:-0.032±0.063 vs 0.018±0.043, t=2.305, P=0.035). The value of ΔFA in epileptic patients with increased/unchanged NHS3 scores (0.075±0.113) was higher compared to those with decreased scores (-0.079±0.099, t=2.804, P=0.010). Correlation analysis also showed the changes in FA values of epileptic lateral fasciculus (r=0.503, P=0.009) and arcuate fasciculus (r=0.602, P=0.001)were positively correlated with the changes in VA-2 and HNS3 scores, respectively. The seizure severity in patients with TLE was closely associated with the microstructure changes in the frontal and temporal white matter, especially the arcuate and uncinate tracts, on the same side that caused seizures, which may indicate the white matter remodeling and abnormal network reformation associated with seizures.


Assuntos
Imagem de Tensor de Difusão , Epilepsia do Lobo Temporal , Convulsões , Substância Branca , Humanos , Masculino , Feminino , Adulto , Substância Branca/diagnóstico por imagem , Estudos Prospectivos , Anisotropia , Pessoa de Meia-Idade , Lobo Temporal
11.
J Affect Disord ; 361: 399-408, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897307

RESUMO

BACKGROUND: While it is well-established that humans possess an innate need for social belonging, the neural mechanisms underlying motivation for connection are still largely unknown. We propose that inclusion motivation - measured through the effort that individuals are willing to invest to be included in social interactions - may serve as one of the basic building blocks of social behavior and may change in lonely individuals. METHODS: Following the screening of 303 participants, we scanned 30 low- and 28 high-loneliness individuals with functional magnetic resonance imaging while they performed the Active Inclusion Task (AIT). The AIT assesses the participants' levels of effort invested in influencing their inclusion during classic Cyberball conditions of fair play and exclusion. RESULTS: High- compared to low-loneliness individuals showed higher urgency for inclusion, specifically during fair play, which correlated with higher activity in the right thalamus. Furthermore, in high-loneliness individuals, we found increased functional connectivity between the thalamus and the temporoparietal junction, putamen, and insula. LIMITATIONS: Participants interacted with computerized avatars, reducing ecological validity. Additionally, although increasing inclusion in the task required action, the physical demand was not high. Additional limitations are discussed. CONCLUSIONS: Inclusion motivation in loneliness is heightened during fair but not exclusionary interactions, and is linked to activity in brain regions implicated in appetitive behavior and social cognition. The findings indicate that lonely individuals may view threat in inclusionary interactions, prompting them to take action to regain connection. This suggests that inclusion motivation may help explain social difficulties in loneliness.


Assuntos
Solidão , Imageamento por Ressonância Magnética , Motivação , Humanos , Solidão/psicologia , Motivação/fisiologia , Masculino , Feminino , Adulto , Adulto Jovem , Tálamo/diagnóstico por imagem , Tálamo/fisiologia , Interação Social , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/fisiologia , Putamen/diagnóstico por imagem , Putamen/fisiologia , Putamen/fisiopatologia , Córtex Insular/diagnóstico por imagem , Córtex Insular/fisiologia , Córtex Insular/fisiopatologia , Mapeamento Encefálico , Comportamento Social , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Cognição Social
12.
Int Immunopharmacol ; 137: 112374, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38851162

RESUMO

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neurological disorder, characterized by cognitive deficits as one of its vital features. The nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome is a key contributor to neuroinflammation and cognitive deficits in neurological diseases. However, the underlying mechanism of anti-NMDAR encephalitis remains unclear, and the biological function of the NLRP3 inflammasome in this condition has not been elucidated. In this study, a mouse model of anti-NMDAR encephalitis was induced by active immunization with the GluN1356-385 peptide (NEA model). The NLRP3 inflammasome in the hippocampus and temporal cortex was investigated using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence staining. The impact of MCC950 on cognitive function and NLRP3 inflammation was assessed. Confocal immunofluorescence staining and Sholl analysis were employed to examine the function and morphology of microglia. In the current study, we discovered overactivation of the NLRP3 inflammasome and an enhanced inflammatory response in the NEA model, particularly in the hippocampus and temporal cortex. Furthermore, significant cognitive dysfunction was observed in the NEA model. While, MCC950, a selective inhibitor of the NLRP3 inflammasome, sharply attenuated the inflammatory response in mice, leading to mitigated cognitive deficits of mice and more regular arrangements of neurons and reduced number of hyperchromatic cells were also observed in the hippocampus area. In addition, we found that the excess elevation of NLRP3 inflammasome was mainly expressed in microglia accompanied with the overactivation of microglia, while MCC950 treatment significantly inhibited the increased number and activated morphological changes of microglia in the NEA model. Altogether, our study reveals the vital role of overactivated NLRP3 signaling pathway in aggravating the inflammatory response and cognitive deficits and the potential protective effect of MCC950 in anti-NMDAR encephalitis. Thus, MCC950 represents a promising strategy for anti-inflammation in anti-NMDAR encephalitis and our study lays a theoretical foundation for it to become a clinically targeted drug.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Disfunção Cognitiva , Modelos Animais de Doenças , Hipocampo , Indenos , Inflamassomos , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sulfonamidas , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/etiologia , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/imunologia , Camundongos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Hipocampo/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Indenos/uso terapêutico , Sulfonamidas/uso terapêutico , Sulfonamidas/farmacologia , Microglia/efeitos dos fármacos , Microglia/imunologia , Furanos/uso terapêutico , Furanos/farmacologia , Sulfonas/uso terapêutico , Sulfonas/farmacologia , Camundongos Endogâmicos C57BL , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Masculino , Lobo Temporal/patologia
13.
J Affect Disord ; 361: 256-267, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38862077

RESUMO

BACKGROUND: Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions. METHODS: A general linear model was used for analysis of brain activation following task-state fNIRS from 131 patients with SCZ, 132 patients with MDD and 130 healthy controls (HCs). Subsequently, seventy-seven time-frequency analysis methods were used to construct new features of fNIRS, followed by the implementation of five machine learning algorithms to develop a differential diagnosis model for the three groups. This model was evaluated by comparing it to both a diagnostic model relying on traditional fNIRS features and assessments made by two psychiatrists. RESULTS: Brain activation analysis revealed significantly lower activation in Broca's area, the dorsolateral prefrontal cortex, and the middle temporal gyrus for both the SCZ and MDD groups compared to HCs. Additionally, the SCZ group exhibited notably lower activation in the superior temporal gyrus and the subcentral gyrus compared to the MDD group. When distinguishing among the three groups using independent validation datasets, the models utilizing new fNIRS features achieved an accuracy of 85.90 % (AUC = 0.95). In contrast, models based on traditional fNIRS features reached an accuracy of 52.56 % (AUC = 0.66). The accuracies of the two psychiatrists were 42.00 % (AUC = 0.60) and 38.00 % (AUC = 0.50), respectively. CONCLUSION: This investigation brings to light the shared and distinct neurobiological abnormalities present in SCZ and MDD, offering potential enhancements for extant diagnostic systems.


Assuntos
Transtorno Depressivo Maior , Esquizofrenia , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Feminino , Masculino , Adulto , Aprendizado de Máquina , Diagnóstico Diferencial , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Neuroimagem Funcional/métodos , Estudos de Casos e Controles , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Adulto Jovem
14.
Physiol Rep ; 12(11): e16084, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850124

RESUMO

Hypertension disproportionately affects African Americans and is a risk factor for Alzheimer's disease (AD). We investigated the relationship of blood pressure (BP) with medial temporal lobe (MTL) dynamic network flexibility (a novel AD biomarker) and cognitive generalization in older African Americans. In a cross-sectional study, 37 normotensive (systolic BP <130 mmHg, 82.5% F, 64.4 ± 4.9 years; 14.3 ± 2.1 years of education) versus 79 hypertensive (systolic BP ≥130 mmHg, 79.5% F, 66.8 ± 4.1 years; 14.0 ± 0.2 years of education) participants were enrolled. All participants completed a 10-min resting-state functional magnetic resonance imaging scan to assess MTL dynamic network flexibility and two generalization tasks to assess cognition. Anthropometrics and aerobic fitness (via 6-min walk test) were also determined. There was no difference in BMI (29.7 ± 6.4 vs. 31.9 ± 6.3 kg/m2, p = 0.083) or aerobic fitness (15.5 ± 2.6 vs. 15.1 ± 2.6 mL/kg/min; p = 0.445) between normotensive and hypertensive groups. However, normotensive participants had higher MTL dynamic network flexibility compared to hypertensive participants (0.42 ± 0.23 vs. 0.32 ± 0.25 mL, p = 0.040), and this was associated with higher mean arterial blood pressure (r = -0.21, p = 0.036). Therefore, hypertensive older African Americans demonstrated lower MTL dynamic network flexibility compared to their normotensive counterparts independent of BMI and aerobic fitness. Further studies are required to determine how blood pressure mediates AD risk in African Americans.


Assuntos
Negro ou Afro-Americano , Hipertensão , Imageamento por Ressonância Magnética , Lobo Temporal , Humanos , Masculino , Feminino , Idoso , Hipertensão/fisiopatologia , Hipertensão/etnologia , Pessoa de Meia-Idade , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Lobo Temporal/fisiologia , Estudos Transversais , Pressão Sanguínea/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Cognição/fisiologia
15.
Acta Neurochir (Wien) ; 166(1): 260, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858238

RESUMO

The aim of this case study was to describe differences in English and British Sign Language (BSL) communication caused by a left temporal tumour resulting in discordant presentation of symptoms, intraoperative stimulation mapping during awake craniotomy and post-operative language abilities. We report the first case of a hearing child of deaf adults, who acquired BSL with English as a second language. The patient presented with English word finding difficulty, phonemic paraphasias, and reading and writing challenges, with BSL preserved. Intraoperatively, object naming and semantic fluency tasks were performed in English and BSL, revealing differential language maps for each modality. Post-operative assessment confirmed mild dysphasia for English with BSL preserved. These findings suggest that in hearing people who acquire a signed language as a first language, topographical organisation may differ to that of a second, spoken, language.


Assuntos
Neoplasias Encefálicas , Craniotomia , Glioblastoma , Língua de Sinais , Lobo Temporal , Humanos , Glioblastoma/cirurgia , Craniotomia/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Lobo Temporal/cirurgia , Lobo Temporal/diagnóstico por imagem , Mapeamento Encefálico/métodos , Masculino , Vigília/fisiologia , Fala/fisiologia , Multilinguismo , Idioma , Adulto
16.
Open Biol ; 14(6): 240063, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38864245

RESUMO

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.


Assuntos
Lobo Frontal , Transtornos Mentais , Psicotrópicos , Lobo Temporal , Humanos , Psicotrópicos/farmacologia , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Lobo Temporal/metabolismo , Lobo Temporal/patologia , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Predisposição Genética para Doença , Perfilação da Expressão Gênica , Transcriptoma , Regulação da Expressão Gênica , Esquizofrenia/genética , Esquizofrenia/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo
17.
Brain Res Bull ; 214: 110995, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38844172

RESUMO

Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Lobo Temporal , Língua , Humanos , Disfunção Cognitiva/fisiopatologia , Masculino , Feminino , Idoso , Lobo Temporal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Língua/fisiopatologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Testes Neuropsicológicos , Amnésia/fisiopatologia , Amnésia/diagnóstico por imagem , Rememoração Mental/fisiologia
18.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38897815

RESUMO

The left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialization in function, with the left ATL contributing preferentially to verbal semantic processing. We investigated the cognitive correlates of this organization, using resting-state functional connectivity as a measure of functional segregation between ATLs. We analyzed two independent resting-state fMRI datasets (n = 86 and n = 642) in which participants' verbal semantic expertise was measured using vocabulary tests. In both datasets, people with more advanced verbal semantic knowledge showed weaker functional connectivity between left and right ventral ATLs. This effect was highly specific. It was not observed for within-hemisphere connections between semantic regions (ventral ATL and inferior frontal gyrus (IFG), though it was found for left-right IFG connectivity in one dataset). Effects were not found for tasks probing semantic control, nonsemantic cognition, or face recognition. Our results suggest that hemispheric specialization in the ATLs is not an innate property but rather emerges as people develop highly detailed verbal semantic representations. We speculate that this effect is a consequence of the left ATL's greater connectivity with left-lateralized written word recognition regions, which causes it to preferentially represent meaning for advanced vocabulary acquired primarily through reading.


Assuntos
Mapeamento Encefálico , Lateralidade Funcional , Imageamento por Ressonância Magnética , Semântica , Lobo Temporal , Humanos , Lobo Temporal/fisiologia , Lobo Temporal/diagnóstico por imagem , Masculino , Feminino , Adulto , Lateralidade Funcional/fisiologia , Adulto Jovem , Mapeamento Encefálico/métodos , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem
19.
Nat Commun ; 15(1): 5249, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898100

RESUMO

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations.


Assuntos
Eletroencefalografia , Consolidação da Memória , Humanos , Masculino , Feminino , Adulto , Consolidação da Memória/fisiologia , Epilepsia/fisiopatologia , Fases do Sono/fisiologia , Adulto Jovem , Memória/fisiologia , Lobo Temporal/fisiologia , Sono/fisiologia , Sono de Ondas Lentas/fisiologia
20.
Biomed Eng Online ; 23(1): 59, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902700

RESUMO

BACKGROUND: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. METHODS: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. RESULTS: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. CONCLUSIONS: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Lobo Temporal , Zumbido , Humanos , Zumbido/fisiopatologia , Zumbido/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Masculino , Lobo Temporal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Feminino , Adulto , Estimulação Acústica , Pessoa de Meia-Idade , Oxigênio/sangue , Oxigênio/metabolismo , Estudos de Casos e Controles
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