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1.
Commun Biol ; 7(1): 700, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849518

RESUMO

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca's area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca's area, during language processing.


Assuntos
Afasia , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral , Tálamo , Núcleos Ventrais do Tálamo , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Núcleos Ventrais do Tálamo/fisiopatologia , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Afasia/fisiopatologia , Afasia/etiologia , Afasia/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Tálamo/fisiopatologia , Tálamo/diagnóstico por imagem , Idoso , Adulto , Conectoma , Lobo Frontal/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Vias Neurais/fisiopatologia
2.
Alzheimers Res Ther ; 16(1): 119, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822365

RESUMO

BACKGROUND: Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aß)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology. METHODS: 142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aß)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates. RESULTS: At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity. CONCLUSIONS: Our findings demonstrate that the LC can provide resilience against Aß-related attention decline. However, when Aß accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aß-related cognitive decline.


Assuntos
Doença de Alzheimer , Locus Cerúleo , Imageamento por Ressonância Magnética , Lobo Parietal , Humanos , Feminino , Masculino , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Doença de Alzheimer/fisiopatologia , Idoso , Locus Cerúleo/diagnóstico por imagem , Locus Cerúleo/patologia , Imageamento por Ressonância Magnética/métodos , Lobo Parietal/diagnóstico por imagem , Idoso de 80 Anos ou mais , Atenção/fisiologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Tomografia por Emissão de Pósitrons , Estudos Transversais , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos
3.
Brain Nerve ; 76(6): 715-720, 2024 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-38853499

RESUMO

The concept of attention in cognitive science encompasses a bidirectional nature: bottom-up attention based on the salience of sensory stimuli, and top-down attention, which involves voluntary control over aspects such as intensity, allocation, selectivity, and duration. Top-down attention is believed to be primarily realized through the frontal lobes that monitor on-going information processing. This monitoring helps detect situations requiring intervention and manipulates lower-level information processing systems as a part of executive functions.


Assuntos
Atenção , Lobo Frontal , Humanos , Atenção/fisiologia , Lobo Frontal/fisiologia , Função Executiva/fisiologia
4.
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
5.
Nat Commun ; 15(1): 4802, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839745

RESUMO

Staying engaged is necessary to maintain goal-directed behaviors. Despite this, engagement exhibits continuous, intrinsic fluctuations. Even in experimental settings, animals, unlike most humans, repeatedly and spontaneously move between periods of complete task engagement and disengagement. We, therefore, looked at behavior in male macaques (macaca mulatta) in four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement. We identified task general patterns of neural activity linked to impending sudden task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of performance across tasks. Importantly, we carefully controlled for task-specific factors such as the reward history and other motivational effects, such as response vigor, in our analyses. Moreover, we showed pgACC activity had a causal link to task engagement: transcranial ultrasound stimulation of pgACC changed task engagement patterns.


Assuntos
Giro do Cíngulo , Macaca mulatta , Imageamento por Ressonância Magnética , Recompensa , Animais , Masculino , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , Comportamento Animal/fisiologia , Mapeamento Encefálico , Motivação/fisiologia
6.
Brain Res Bull ; 214: 111003, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852652

RESUMO

An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.


Assuntos
Atenção , Lobo Frontal , Lateralidade Funcional , Lobo Parietal , Tempo de Reação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Atenção/fisiologia , Idoso , Lateralidade Funcional/fisiologia , Adulto , Tempo de Reação/fisiologia , Lobo Frontal/fisiopatologia , Transtornos da Percepção/etiologia , Transtornos da Percepção/fisiopatologia , Sinais (Psicologia) , Percepção Espacial/fisiologia , Lesões Encefálicas/fisiopatologia
7.
J Neuroeng Rehabil ; 21(1): 101, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872209

RESUMO

BACKGROUND: In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery outcomes. However, the interrelationship between FC, MRCP, gait activities, and bipedal distinguishability have yet to be investigated. METHODS: Ten participants were equipped with EEG devices and inertial measurement units (IMUs) while performing lower limb motor preparation (MP) and motor execution (ME) tasks. MRCP, FCs, and bipedal distinguishability were extracted from the EEG signals, while the change in knee degree during the ME phase was calculated from the gait data. FCs were analyzed with pairwise Pearson's correlation, and the brain-wide FC was fed into support vector machine (SVM) for bipedal classification. RESULTS: Parietal-frontocentral connectivity (PFCC) dysconnection and MRCP desynchronization were related to the MP and ME phases, respectively. Hemiplegic limb movement exhibited higher PFCC strength than nonhemiplegic limb movement. Bipedal classification had a short-lived peak of 75.1% in the pre-movement phase. These results contribute to a better understanding of the neurophysiological functions during motor tasks, with respect to localized MRCP and nonlocalized FC activities. The difference in PFCCs between both limbs could be a marker to understand the motor function of the brain of post-stroke patients. CONCLUSIONS: In this study, we discovered that PFCCs are temporally dependent on lower limb gait movement and MRCP. The PFCCs are also related to the lower limb motor performance of post-stroke patients. The detection of motor intentions allows the development of bipedal brain-controlled exoskeletons for lower limb active rehabilitation.


Assuntos
Eletroencefalografia , Marcha , Lobo Parietal , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Feminino , Pessoa de Meia-Idade , Marcha/fisiologia , Lobo Parietal/fisiopatologia , Lobo Parietal/fisiologia , Potencial Evocado Motor/fisiologia , Lobo Frontal/fisiopatologia , Lobo Frontal/fisiologia , Idoso , Adulto , Córtex Motor/fisiopatologia , Córtex Motor/fisiologia , Máquina de Vetores de Suporte
8.
J Am Soc Mass Spectrom ; 35(6): 1310-1319, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38780475

RESUMO

The accumulation of amyloid beta (Aß1-42) results in neurotoxicity and is strongly related to neurodegenerative disorders, especially Alzheimer's disease (AD), but the underlying molecular mechanism is still poorly understood. Therefore, there is an urgent need for researchers to discover the proteins that interact with Aß1-42 to determine the molecular basis. Previously, we developed peptide-ligand-induced changes in the abundance of proTeinS (PACTS)-assisted thermal proteome profiling (TPP) to identify proteins that interact with peptide ligands. In the present study, we applied this technique to analyze clinical samples to identify Aß1-42-interacting proteins. We detected 115 proteins that interact with Aß1-42 in human frontal lobe tissue. Pathway enrichment analysis revealed that the differentially expressed proteins were involved mainly in neurodegenerative diseases. Further orthogonal validation revealed that Aß1-42 interacted with the AD-associated protein mitogen-activated protein kinase 3 (MAPK3), and knockdown of the Aß1-42 amyloid precursor protein (APP) inhibited the MAPK signaling pathway, suggesting potential functional roles for Aß1-42 in interacting with MAPK3. Overall, this study demonstrated the application of the PACTS-TPP in clinical samples and provided a valuable data source for research on neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Fragmentos de Peptídeos , Proteômica , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/análise , Proteômica/métodos , Doença de Alzheimer/metabolismo , Proteoma/análise , Proteoma/metabolismo , Lobo Frontal/metabolismo , Lobo Frontal/química , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/química , Ligação Proteica
9.
Nat Commun ; 15(1): 4669, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821963

RESUMO

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.


Assuntos
Tonsila do Cerebelo , Imageamento por Ressonância Magnética , Córtex Pré-Frontal , Imageamento por Ressonância Magnética/métodos , Masculino , Animais , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/diagnóstico por imagem , Vias Neurais/fisiologia , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , Sistema Límbico/fisiologia , Sistema Límbico/diagnóstico por imagem , Mapeamento Encefálico/métodos , Descanso/fisiologia , Macaca mulatta , Drogas Desenhadas/farmacologia , Clozapina/análogos & derivados , Clozapina/farmacologia , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem
10.
Neurocase ; 30(1): 32-38, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38752838

RESUMO

We report a patient with behavioral variant frontotemporal dementia who developed agraphia, irritability, perseverative and stereotyped behavior, and dietary changes. MRI revealed bilateral frontal convexity atrophy. Neuropsychological examination showed fluent aphasia with perseverative allographic agraphia, mild semantic impairment, and dysexecutive syndrome. Allographic agraphia featured unidirectional conversion from hiragana (cursive form of Japanese phonograms) and kanji (Japanese morphograms) to katakana (square form of Japanese phonograms), as opposed to mutual (bidirectional) conversion between hiragana and katakana in parieto-occipital gyri lesions. Furthermore, all letters of the word were converted and this whole-word conversion may be characteristic of perseverative behavior in frontotemporal dementia.


Assuntos
Agrafia , Demência Frontotemporal , Humanos , Demência Frontotemporal/patologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/fisiopatologia , Demência Frontotemporal/complicações , Agrafia/etiologia , Agrafia/fisiopatologia , Masculino , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Atrofia/patologia
11.
Brain ; 147(6): 2214-2229, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38802114

RESUMO

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.


Assuntos
Aquaporina 4 , Traumatismos por Explosões , Sistema Glinfático , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Aquaporina 4/metabolismo , Traumatismos por Explosões/complicações , Traumatismos por Explosões/patologia , Traumatismos por Explosões/metabolismo , Concussão Encefálica/metabolismo , Concussão Encefálica/complicações , Concussão Encefálica/patologia , Concussão Encefálica/fisiopatologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Lobo Frontal/diagnóstico por imagem , Sistema Glinfático/metabolismo , Sistema Glinfático/patologia , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Veteranos
12.
Cortex ; 176: 94-112, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763111

RESUMO

The ability to weigh a reward against the effort required to acquire it is critical for decision-making. However, extant experimental paradigms oftentimes confound increased effort demand with decreased reward probability, thereby obscuring neural correlates underlying these cognitive processes. To resolve this issue, we designed novel tasks that disentangled probability of success - and therefore reward probability - from effort demand. In Experiment 1, reward magnitude and effort demand were varied while reward probability was kept constant. In Experiment 2, effort demand and reward probability were varied while reward magnitude remained fixed. Electroencephalogram (EEG) data was recorded to explore how frontal midline theta (FMT; an electrophysiological index of mPFC function) and component P3 (an index of incentive salience) respond to effort demand, and reward magnitude and probability. We found no evidence that FMT tracked effort demands or net value during cue evaluation. At feedback, however, FMT power was enhanced for high compared to low effort trials, but not modulated by reward magnitude or probability. Conversely, P3 was sensitive to reward magnitude and probability at both cue and feedback phases and only integrated expended effort costs at feedback, such that P3 amplitudes continued to scale with reward magnitude and probability but were also increased for high compared to low effort reward feedback. These findings suggest that, when likelihood of success is equal, FMT power does not track net value of prospective effort-based rewards. Instead, expended cognitive effort potentiates FMT power and enhances the saliency of rewards at feedback. SIGNIFICANCE STATEMENT: The way the brain weighs rewards against the effort required to achieve them is critical for understanding motivational disorders. Current paradigms confound increased effort demand with decreased reward probability, making it difficult to disentangle neural activity associated with effort costs from those associated with reward likelihood. Here, we explored the temporal dynamics of effort-based reward (via frontal midline theta (FMT) and component P3) while participants underwent a novel paradigm that kept probability of reward constant between mental effort demand conditions. Our findings suggest that the FMT does not track net value and that expended effort enhances, instead of attenuates, the saliency of rewards.


Assuntos
Tomada de Decisões , Eletroencefalografia , Recompensa , Ritmo Teta , Humanos , Masculino , Feminino , Ritmo Teta/fisiologia , Adulto Jovem , Adulto , Tomada de Decisões/fisiologia , Motivação/fisiologia , Probabilidade , Lobo Frontal/fisiologia , Sinais (Psicologia) , Córtex Pré-Frontal/fisiologia , Adolescente
13.
Food Funct ; 15(10): 5579-5595, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38713055

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder and dopaminergic dysfunction in the prefrontal cortex (PFC) may play a role. Our previous research indicated that theobromine (TB), a methylxanthine, enhances cognitive function in rodents via the PFC. This study investigates TB's effects on hyperactivity and cognitive function in stroke-prone spontaneously hypertensive rats (SHR), an ADHD animal model. Male SHRs (6-week old) received a diet containing 0.05% TB for 40 days, while control rats received normal diets. Age-matched male Wistar-Kyoto rats (WKY) served as genetic controls. During the TB administration period, we conducted open-field tests and Y-maze tasks to evaluate hyperactivity and cognitive function, then assessed dopamine concentrations and tyrosine hydroxylase (TH), dopamine receptor D1-5 (DRD1-5), dopamine transporter (DAT), vesicular monoamine transporter-2 (VMAT-2), synaptosome-associated protein-25 (SNAP-25), and brain-derived neurotrophic factor (BDNF) expressions in the PFC. Additionally, the binding affinity of TB for the adenosine receptors (ARs) was evaluated. Compared to WKY, SHR exhibited hyperactivity, inattention and working memory deficits. However, chronic TB administration significantly improved these ADHD-like behaviors in SHR. TB administration also normalized dopamine concentrations and expression levels of TH, DRD2, DRD4, SNAP-25, and BDNF in the PFC of SHR. No changes were observed in DRD1, DRD3, DRD5, DAT, and VMAT-2 expression between SHR and WKY rats, and TB intake had minimal effects. TB was found to have affinity binding to ARs. These results indicate that long-term TB supplementation mitigates hyperactivity, inattention and cognitive deficits in SHR by modulating dopaminergic nervous function and BDNF levels in the PFC, representing a potential adjunctive treatment for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Dopamina , Memória de Curto Prazo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Teobromina , Animais , Masculino , Ratos , Teobromina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Dopamina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Lobo Frontal/metabolismo , Lobo Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Modelos Animais de Doenças , Proteína 25 Associada a Sinaptossoma/metabolismo
14.
Physiol Meas ; 45(5)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38697205

RESUMO

Objectives.The purpose of this study is to investigate the age dependence of bilateral frontal electroencephalogram (EEG) coupling characteristics, and find potential age-independent depth of anesthesia monitoring indicators for the elderlies.Approach.We recorded bilateral forehead EEG data from 41 patients (ranged in 19-82 years old), and separated into three age groups: 18-40 years (n= 12); 40-65 years (n= 14), >65 years (n= 15). All these patients underwent desflurane maintained general anesthesia (GA). We analyzed the age-related EEG spectra, phase amplitude coupling (PAC), coherence and phase lag index (PLI) of EEG data in the states of awake, GA, and recovery.Main results.The frontal alpha power shows age dependence in the state of GA maintained by desflurane. Modulation index in slow oscillation-alpha and delta-alpha bands showed age dependence and state dependence in varying degrees, the PAC pattern also became less pronounced with increasing age. In the awake state, the coherence in delta, theta and alpha frequency bands were all significantly higher in the >65 years age group than in the 18-40 years age group (p< 0.05 for three frequency bands). The coherence in alpha-band was significantly enhanced in all age groups in GA (p< 0.01) and then decreased in recovery state. Notably, the PLI in the alpha band was able to significantly distinguish the three states of awake, GA and recovery (p< 0.01) and the results of PLI in delta and theta frequency bands had similar changes to those of coherence.Significance.We found the EEG coupling and synchronization between bilateral forehead are age-dependent. The PAC, coherence and PLI portray this age-dependence. The PLI and coherence based on bilateral frontal EEG functional connectivity measures and PAC based on frontal single-channel are closely associated with anesthesia-induced unconsciousness.


Assuntos
Desflurano , Eletroencefalografia , Humanos , Desflurano/farmacologia , Adulto , Pessoa de Meia-Idade , Idoso , Eletroencefalografia/efeitos dos fármacos , Adulto Jovem , Masculino , Feminino , Idoso de 80 Anos ou mais , Adolescente , Envelhecimento/fisiologia , Envelhecimento/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Isoflurano/análogos & derivados , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Anestesia Geral
15.
Schizophr Res ; 269: 123-129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772324

RESUMO

BACKGROUND: Persistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ. METHODS: 76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups. RESULTS: Compared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (ß = -0.29, p = 0.001) and right fusiform (ß = -0.21, p = 0.01) were significantly associated with the severity of pAVHs. CONCLUSIONS: Widespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ.


Assuntos
Substância Cinzenta , Alucinações , Imageamento por Ressonância Magnética , Esquizofrenia , Lobo Temporal , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Alucinações/diagnóstico por imagem , Alucinações/etiologia , Alucinações/patologia , Alucinações/fisiopatologia , Masculino , Feminino , Adulto , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Doença Crônica , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Pessoa de Meia-Idade , Adulto Jovem , China , População do Leste Asiático
16.
Neurosci Biobehav Rev ; 162: 105696, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723734

RESUMO

Human brain activity consists of different frequency bands associated with varying functions. Oscillatory activity of frontal brain regions in the theta range (4-8 Hz) is linked to cognitive processing and can be modulated by neurofeedback - a technique where participants receive real-time feedback about their brain activity and learn to modulate it. However, criticism of this technique evolved, and high heterogeneity of study designs complicates a valid evaluation of its effectiveness. This meta-analysis provides the first systematic overview over studies attempting to modulate frontal midline theta with neurofeedback in healthy human participants. Out of 1261 articles screened, 14 studies were eligible for systematic review and 11 for quantitative meta-analyses. Studies were evaluated following the DIAD model and the PRISMA guidelines. A significant across-study effect of medium size (Hedges' g = .66; 95%-CI [-0.62, 1.73]) with substantial between-study heterogeneity (Q(16) = 167.43, p < .001) was observed and subanalysis revealed effective frontal midline theta upregulation. We discuss moderators of effect sizes and provide guidelines for future research in this dynamic field.


Assuntos
Lobo Frontal , Neurorretroalimentação , Ritmo Teta , Humanos , Ritmo Teta/fisiologia , Neurorretroalimentação/fisiologia , Neurorretroalimentação/métodos , Lobo Frontal/fisiologia
17.
Res Dev Disabil ; 150: 104760, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795555

RESUMO

BACKGROUND: Pain perception mechanisms in cerebral palsy remain largely unclear. AIMS: This study investigates brain activity in adults with cerebral palsy during painful and non-painful stretching to elucidate their pain processing characteristics. METHODS AND PROCEDURES: Twenty adults with cerebral palsy and 20 controls underwent EEG in three conditions: rest, non-painful stretching, and painful stretching. Time-frequency power density of theta, alpha, and beta waves in somatosensory and frontal cortices was analyzed, alongside baseline pressure pain thresholds. OUTCOMES AND RESULTS: Cerebral palsy individuals exhibited higher theta, alpha, and beta power density in both cortices during painful stretching compared to rest, and lower during non-painful stretching. Controls showed higher power density during non-painful stretching but lower during painful stretching. Cerebral palsy individuals had higher pain sensitivity, with those more sensitive experiencing greater alpha power density. CONCLUSIONS AND IMPLICATIONS: These findings confirm alterations in the cerebral processing of pain in individuals with cerebral palsy. This knowledge could enhance future approaches to the diagnosis and treatment of pain in this vulnerable population.


Assuntos
Paralisia Cerebral , Eletroencefalografia , Limiar da Dor , Humanos , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/complicações , Masculino , Feminino , Adulto , Limiar da Dor/fisiologia , Estudos de Casos e Controles , Adulto Jovem , Exercícios de Alongamento Muscular , Percepção da Dor/fisiologia , Dor/fisiopatologia , Dor/etiologia , Lobo Frontal/fisiopatologia , Córtex Somatossensorial/fisiopatologia
18.
PLoS One ; 19(5): e0301267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753768

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative diseases for which at present no cure is available. Despite the extensive research the progress from diagnosis to prognosis in ALS and frontotemporal dementia (FTD) has been slow which represents suboptimal understanding of disease pathophysiological processes. In recent studies, several genes have been associated with the ALS and FTD diseases such as SOD1, TDP43, and TBK1, whereas the hexanucleotide GGGGCC repeat expansion (HRE) in C9orf72 gene is a most frequent cause of ALS and FTD, that has changed the understanding of these diseases. METHODS: The goal of this study was to identify and spatially determine differential gene expression signature differences between cerebellum and frontal cortex in C9orf72-associated ALS (C9-ALS), to study the network properties of these differentially expressed genes, and to identify miRNAs targeting the common differentially expressed genes in both the tissues. This study thus highlights underlying differential cell susceptibilities to the disease mechanisms in C9-ALS and suggesting therapeutic target selection in C9-ALS. RESULTS: In this manuscript, we have identified that the genes involved in neuron development, protein localization and transcription are mostly enriched in cerebellum of C9-ALS patients, while the UPR-related genes are enriched in the frontal cortex. Of note, UPR pathway genes were mostly dysregulated both in the C9-ALS cerebellum and frontal cortex. Overall, the data presented here show that defects in normal RNA processing and the UPR pathway are the pathological hallmarks of C9-ALS. Interestingly, the cerebellum showed more strong transcriptome changes than the frontal cortex. CONCLUSION: Interestingly, the cerebellum region showed more significant transcriptomic changes as compared to the frontal cortex region suggesting its active participation in the disease process. This nuanced understanding may offer valuable insights for the development of targeted therapeutic strategies aimed at mitigating disease progression in C9-ALS.


Assuntos
Esclerose Lateral Amiotrófica , Cerebelo , Lobo Frontal , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/metabolismo , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Cerebelo/metabolismo , Cerebelo/patologia , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Demência Frontotemporal/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
19.
J Affect Disord ; 359: 269-276, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38795776

RESUMO

Changes in EEG have been reported in both major depressive disorder (MDD) and bipolar disorder (BD). Specifically, power changes in EEG alpha and theta frequency bands during rest and task are known in both disorders. This leaves open whether there are changes in yet another component of the electrophysiological EEG signal, namely phase-related processes that may allow for distinguishing MDD and BD. For that purpose, we investigate EEG-based spontaneous phase in the resting state of MDD, BD and healthy controls. Our main findings show: (i) decreased spontaneous phase variability in frontal theta of both MDD and BD compared to HC; (ii) decreased spontaneous phase variability in central-parietal alpha in MDD compared to both BD and HC; (iii) increased delays or lags of alpha phase cycles in MDD (but not in BD), which (iv) correlate with the decreased phase variability in MDD. Together, we show similar (decreased frontal theta variability) and distinct (decreased central-parietal alpha variability with increased lags or delays) findings in the spontaneous phase dynamics of MDD and BD. This suggests potential relevance of theta and alpha phase dynamics in distinguishing MDD and BD in clinical differential-diagnosis.


Assuntos
Ritmo alfa , Transtorno Bipolar , Transtorno Depressivo Maior , Eletroencefalografia , Lobo Frontal , Ritmo Teta , Humanos , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Adulto , Masculino , Feminino , Ritmo Teta/fisiologia , Ritmo alfa/fisiologia , Lobo Frontal/fisiopatologia , Diagnóstico Diferencial , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Adulto Jovem , Descanso/fisiologia , Córtex Cerebral/fisiopatologia
20.
Nat Commun ; 15(1): 3941, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729937

RESUMO

A relevant question concerning inter-areal communication in the cortex is whether these interactions are synergistic. Synergy refers to the complementary effect of multiple brain signals conveying more information than the sum of each isolated signal. Redundancy, on the other hand, refers to the common information shared between brain signals. Here, we dissociated cortical interactions encoding complementary information (synergy) from those sharing common information (redundancy) during prediction error (PE) processing. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded synergistic and redundant information about PE processing. The information conveyed by ERPs and BB signals was synergistic even at lower stages of the hierarchy in the auditory cortex and between auditory and frontal regions. Using a brain-constrained neural network, we simulated the synergy and redundancy observed in the experimental results and demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback, and feedforward connections. These results indicate that distributed representations of PE signals across the cortical hierarchy can be highly synergistic.


Assuntos
Estimulação Acústica , Córtex Auditivo , Callithrix , Eletrocorticografia , Animais , Córtex Auditivo/fisiologia , Callithrix/fisiologia , Masculino , Feminino , Potenciais Evocados/fisiologia , Lobo Frontal/fisiologia , Potenciais Evocados Auditivos/fisiologia , Percepção Auditiva/fisiologia , Mapeamento Encefálico/métodos
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