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1.
Artigo em Inglês | MEDLINE | ID: mdl-38374692

RESUMO

OBJECTIVES: Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume. METHODS: Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia. RESULTS: Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals. DISCUSSION: Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors.


Assuntos
Demência , Depressão Vascular , Humanos , Pessoa de Meia-Idade , Idoso , Prevalência , Imageamento por Ressonância Magnética , Encéfalo , Demência/epidemiologia
2.
Brain Imaging Behav ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340285

RESUMO

While one can characterize mental health using questionnaires, such tools do not provide direct insight into the underlying biology. By linking approaches that visualize brain activity to questionnaires in the context of individualized prediction, we can gain new insights into the biology and behavioral aspects of brain health. Resting-state fMRI (rs-fMRI) can be used to identify biomarkers of these conditions and study patterns of abnormal connectivity. In this work, we estimate mental health quality for individual participants using static functional network connectivity (sFNC) data from rs-fMRI. The deep learning model uses the sFNC data as input to predict four categories of mental health quality and visualize the neural patterns indicative of each group. We used guided gradient class activation maps (guided Grad-CAM) to identify the most discriminative sFNC patterns. The effectiveness of this model was validated using the UK Biobank dataset, in which we showed that our approach outperformed four alternative models by 4-18% accuracy. The proposed model's performance evaluation yielded a classification accuracy of 76%, 78%, 88%, and 98% for the excellent, good, fair, and poor mental health categories, with poor mental health accuracy being the highest. The findings show distinct sFNC patterns across each group. The patterns associated with excellent mental health consist of the cerebellar-subcortical regions, whereas the most prominent areas in the poor mental health category are in the sensorimotor and visual domains. Thus the combination of rs-fMRI and deep learning opens a promising path for developing a comprehensive framework to evaluate and measure mental health. Moreover, this approach had the potential to guide the development of personalized interventions and enable the monitoring of treatment response. Overall this highlights the crucial role of advanced imaging modalities and deep learning algorithms in advancing our understanding and management of mental health.

3.
Cerebellum ; 23(2): 802-832, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37428408

RESUMO

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.


Assuntos
Transtorno Depressivo Maior , Adulto , Humanos , Idoso , Estudos Transversais , Consenso , Qualidade de Vida , Cerebelo/patologia , Envelhecimento , Imageamento por Ressonância Magnética/métodos
4.
Neuroimage ; 285: 120485, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38110045

RESUMO

In recent years, deep learning approaches have gained significant attention in predicting brain disorders using neuroimaging data. However, conventional methods often rely on single-modality data and supervised models, which provide only a limited perspective of the intricacies of the highly complex brain. Moreover, the scarcity of accurate diagnostic labels in clinical settings hinders the applicability of the supervised models. To address these limitations, we propose a novel self-supervised framework for extracting multiple representations from multimodal neuroimaging data to enhance group inferences and enable analysis without resorting to labeled data during pre-training. Our approach leverages Deep InfoMax (DIM), a self-supervised methodology renowned for its efficacy in learning representations by estimating mutual information without the need for explicit labels. While DIM has shown promise in predicting brain disorders from single-modality MRI data, its potential for multimodal data remains untapped. This work extends DIM to multimodal neuroimaging data, allowing us to identify disorder-relevant brain regions and explore multimodal links. We present compelling evidence of the efficacy of our multimodal DIM analysis in uncovering disorder-relevant brain regions, including the hippocampus, caudate, insula, - and multimodal links with the thalamus, precuneus, and subthalamus hypothalamus. Our self-supervised representations demonstrate promising capabilities in predicting the presence of brain disorders across a spectrum of Alzheimer's phenotypes. Comparative evaluations against state-of-the-art unsupervised methods based on autoencoders, canonical correlation analysis, and supervised models highlight the superiority of our proposed method in achieving improved classification performance, capturing joint information, and interpretability capabilities. The computational efficiency of the decoder-free strategy enhances its practical utility, as it saves compute resources without compromising performance. This work offers a significant step forward in addressing the challenge of understanding multimodal links in complex brain disorders, with potential applications in neuroimaging research and clinical diagnosis.


Assuntos
Encefalopatias , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Imagem Multimodal/métodos
5.
Curr Neurol Neurosci Rep ; 23(12): 937-946, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37999830

RESUMO

PURPOSE OF REVIEW: Over the last decade, evidence suggests that a combination of behavioral and neuroimaging findings can help illuminate changes in functional dysconnectivity in schizophrenia. We review the recent connectivity literature considering several vital models, considering connectivity findings, and relationships with clinical symptoms. We reviewed resting state fMRI studies from 2017 to 2023. We summarized the role of two sets of brain networks (cerebello-thalamo-cortical (CTCC) and the triple network set) across three hypothesized models of schizophrenia etiology (neurodevelopmental, vulnerability-stress, and neurotransmitter hypotheses). RECENT FINDINGS: The neurotransmitter and neurodevelopmental models best explained CTCC-subcortical dysfunction, which was consistently connected to symptom severity and motor symptoms. Triple network dysconnectivity was linked to deficits in executive functioning, and the salience network (SN)-default mode network dysconnectivity was tied to disordered thought and attentional deficits. This paper links behavioral symptoms of schizophrenia (symptom severity, motor, executive functioning, and attentional deficits) to various hypothesized mechanisms.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Neurotransmissores , Vias Neurais/diagnóstico por imagem
6.
Neurotherapeutics ; 20(4): 1019-1036, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37490246

RESUMO

It is well known that vascular factors and specific social determinants of health contribute to dementia risk and that the prevalence of these risk factors differs according to race and sex. In this review, we discuss the intersection of sex and race, particularly female sex and Black American race. Women, particularly Black women, have been underrepresented in Alzheimer's disease clinical trials and research. However, in recent years, the number of women participating in clinical research has steadily increased. A greater prevalence of vascular risk factors such as hypertension and type 2 diabetes, coupled with unique social and environmental pressures, puts Black American women particularly at risk for the development of Alzheimer's disease and related dementias. Female sex hormones and the use of hormonal birth control may offer some protective benefits, but results are mixed, and studies do not consistently report the demographics of their samples. We argue that as a research community, greater efforts should be made to not only recruit this vulnerable population, but also report the demographic makeup of samples in research to better target those at greatest risk for the disease.


Assuntos
Doença de Alzheimer , Negro ou Afro-Americano , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Diabetes Mellitus Tipo 2/epidemiologia , Enquadramento Interseccional , Prevalência , Estados Unidos/epidemiologia , Fatores Sexuais , Seleção de Pacientes , Ensaios Clínicos como Assunto
7.
Psychiatry Res Neuroimaging ; 333: 111655, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37201216

RESUMO

Clinicians often face a dilemma in diagnosing bipolar disorder patients with complex symptoms who spend more time in a depressive state than a manic state. The current gold standard for such diagnosis, the Diagnostic and Statistical Manual (DSM), is not objectively grounded in pathophysiology. In such complex cases, relying solely on the DSM may result in misdiagnosis as major depressive disorder (MDD). A biologically-based classification algorithm that can accurately predict treatment response may help patients suffering from mood disorders. Here we used an algorithm to do so using neuroimaging data. We used the neuromark framework to learn a kernel function for support vector machine (SVM) on multiple feature subspaces. The neuromark framework achieves up to 95.45% accuracy, 0.90 sensitivity, and 0.92 specificity in predicting antidepressant (AD) vs. mood stabilizer (MS) response in patients. We incorporated two additional datasets to evaluate the generalizability of our approach. The trained algorithm achieved up to 89% accuracy, 0.88 sensitivity, and 0.89 specificity in predicting the DSM-based diagnosis on these datasets. We also translated the model to distinguish responders to treatment from nonresponders with up to 70% accuracy. This approach reveals multiple salient biomarkers of medication-class of response within mood disorders.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtornos do Humor/diagnóstico por imagem , Transtornos do Humor/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Antipsicóticos/uso terapêutico , Neuroimagem
8.
J Psychiatr Res ; 160: 78-85, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36780803

RESUMO

Depression and cardiovascular disease are common and associated with one another in HIV disease. This study aimed to determine the frequency and everyday functioning implications of the clinical syndrome of vascular depression among people living with HIV (PLWH). Participants in this cross-sectional study included 536 PLWH and 272 seronegative individuals who completed a biomedical and psychiatric research evaluation. Vascular depression was operationalized as the current presence of: 1) two or more vascular conditions; and 2) depression as determined by a normative elevation on the Depression/Dejection subscale of the Profile of Mood States or a diagnosis of Major Depressive Disorder per the Composite International Diagnostic Interview. Everyday functioning was measured by both self- and clinician-rated activities of daily living. A logistic regression model showed that HIV was associated with a three-fold increased risk of vascular depression, independent of potential confounding factors. A second logistic regression model within the PLWH sample showed that PLWH with vascular depression had significantly greater odds of dependence in everyday functioning as compared to PLWH with either vascular disease or depression alone. The elevated frequency of vascular depression in PLWH is consistent with the vascular depression hypothesis from the late-life depression literature. The high rate of functional dependence among PLWH with vascular depression highlights the clinical importance of prospective work on this syndrome in the context of HIV disease.


Assuntos
Transtorno Depressivo Maior , Infecções por HIV , Depressão Vascular , Humanos , Transtorno Depressivo Maior/complicações , Atividades Cotidianas/psicologia , Estudos Transversais , Estudos Prospectivos , Infecções por HIV/psicologia
9.
Transl Neurodegener ; 9: 8, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099645

RESUMO

Background: Older African Americans are more likely to develop Alzheimer's disease (AD) than older Caucasians, and this difference cannot be readily explained by cerebrovascular and socioeconomic factors alone. We previously showed that mild cognitive impairment and AD dementia were associated with attenuated increases in the cerebrospinal fluid (CSF) levels of total and phosphorylated tau in African Americans compared to Caucasians, even though there was no difference in beta-amyloid 1-42 level between the two races. Methods: We extended our work by analyzing early functional magnetic resonance imaging (fMRI) biomarkers of the default mode network in older African Americans and Caucasians. We calculated connectivity between nodes of the regions belonging to the various default mode network subsystems and correlated these imaging biomarkers with non-imaging biomarkers implicated in AD (CSF amyloid, total tau, and cognitive performance). Results: We found that race modifies the relationship between functional connectivity of default mode network subsystems and cognitive performance, tau, and amyloid levels. Conclusion: These findings provide further support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and identifies key inter-subsystem connections for deep imaging and neuropathologic characterization.


Assuntos
Doença de Alzheimer/fisiopatologia , Grupos Raciais , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/psicologia , Amiloide/líquido cefalorraquidiano , Biomarcadores , Cognição , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Rede de Modo Padrão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Desempenho Psicomotor , População Branca , Proteínas tau/líquido cefalorraquidiano
10.
J Huntingtons Dis ; 8(2): 199-219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932891

RESUMO

BACKGROUND: Gray matter (GM) atrophy in the striatum and across the brain is a consistently reported feature of the Huntington Disease (HD) prodrome. More recently, widespread prodromal white matter (WM) degradation has also been detected. However, longitudinal WM studies are limited and conflicting, and most analyses comparing WM and clinical functioning have also been cross-sectional. OBJECTIVE: We simultaneously assessed changes in WM and cognitive and motor functioning at various prodromal HD stages. METHODS: Data from 1,336 (1,047 prodromal, 289 control) PREDICT-HD participants were analyzed (3,700 sessions). MRI images were used to create GM, WM, and cerebrospinal fluid probability maps. Using source-based morphometry, independent component analysis was applied to WM probability maps to extract covarying spatial patterns and their subject profiles. WM profiles were analyzed in two sets of linear mixed model (LMM) analyses: one to compare WM profiles across groups cross-sectionally and longitudinally, and one to concurrently compare WM profiles and clinical variables cross-sectionally and longitudinally within each group. RESULTS: Findings illustrate widespread prodromal changes in GM-adjacent-WM, with premotor, supplementary motor, middle frontal and striatal changes early in the prodrome that subsequently extend sub-gyrally with progression. Motor functioning agreed most with WM until the near-onset prodromal stage, when Stroop interference was the best WM indicator. Across groups, Trail-Making Test part A outperformed other cognitive variables in its similarity to WM, particularly cross-sectionally. CONCLUSIONS: Results suggest that distinct regions coincide with cognitive compared to motor functioning. Furthermore, at different prodromal stages, distinct regions appear to align best with clinical functioning. Thus, the informativeness of clinical measures may vary according to the type of data available (cross-sectional or longitudinal) as well as age and CAG-number.


Assuntos
Encéfalo/patologia , Doença de Huntington/patologia , Sintomas Prodrômicos , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Estudos Transversais , Humanos , Doença de Huntington/diagnóstico por imagem , Estudos Longitudinais , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem
11.
J Int Neuropsychol Soc ; 25(5): 462-469, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30806337

RESUMO

OBJECTIVES: Apathy is a debilitating symptom of Huntington's disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington's disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. METHODS: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. RESULTS: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. CONCLUSIONS: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462-469).


Assuntos
Apatia/fisiologia , Núcleo Caudado/patologia , Função Executiva/fisiologia , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Sintomas Prodrômicos , Putamen/patologia , Adulto , Núcleo Caudado/diagnóstico por imagem , Feminino , Humanos , Doença de Huntington/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Putamen/diagnóstico por imagem
12.
Hum Brain Mapp ; 40(6): 1955-1968, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30618191

RESUMO

Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] and N = 78 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs-fMRI data to obtain whole-brain resting state networks. FNC was defined as the correlation between RSN time-courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k-means clustering algorithm. HDgmc individuals spent significantly more time in State-1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State-4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State-1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.


Assuntos
Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Doença de Huntington/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
13.
Brain Sci ; 8(7)2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29932126

RESUMO

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington's disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF's TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.

14.
Front Neurol ; 9: 190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29651271

RESUMO

Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion mutation of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene. Decline in cognitive and motor functioning during the prodromal phase has been reported, and understanding genetic influences on prodromal disease progression beyond CAG will benefit intervention therapies. From a prodromal HD cohort (N = 715), we extracted gray matter (GM) components through independent component analysis and tested them for associations with cognitive and motor functioning that cannot be accounted for by CAG-induced disease burden (cumulative effects of CAG expansion and age). Furthermore, we examined genetic associations (at the genomic, HD pathway, and candidate region levels) with the GM components that were related to functional decline. After accounting for disease burden, GM in a component containing cuneus, lingual, and middle occipital regions was positively associated with attention and working memory performance, and the effect size was about a tenth of that of disease burden. Prodromal participants with at least one dystonia sign also had significantly lower GM volume in a bilateral inferior parietal component than participants without dystonia, after controlling for the disease burden. Two single-nucleotide polymorphisms (SNPs: rs71358386 in NCOR1 and rs71358386 in ADORA2B) in the HD pathway were significantly associated with GM volume in the cuneus component, with minor alleles being linked to reduced GM volume. Additionally, homozygous minor allele carriers of SNPs in a candidate region of ch15q13.3 had significantly higher GM volume in the inferior parietal component, and one minor allele copy was associated with a total motor score decrease of 0.14 U. Our findings depict an early genetical GM reduction in prodromal HD that occurs irrespective of disease burden and affects regions important for cognitive and motor functioning.

15.
Brain Connect ; 8(3): 166-178, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29291624

RESUMO

Huntington's disease (HD) is an inherited brain disorder characterized by progressive motor, cognitive, and behavioral dysfunctions. It is caused by abnormally large trinucleotide cytosine-adenine-guanine (CAG) repeat expansions on exon 1 of the Huntingtin gene. CAG repeat length (CAG-RL) inversely correlates with an earlier age of onset. Region-based studies have shown that HD gene mutation carrier (HDgmc) individuals (CAG-RL ≥36) present functional connectivity alterations in subcortical (SC) and default mode networks. In this analysis, we expand on previous HD studies by investigating associations between CAG-RL and connectivity in the whole brain, as well as between CAG-dependent connectivity and motor and cognitive performances. We used group-independent component analysis on resting-state functional magnetic resonance imaging scans of 261 individuals (183 HDgmc and 78 healthy controls) from the PREDICT-HD study, to obtain whole-brain resting state networks (RSNs). Regression analysis was applied within and between RSNs connectivity (functional network connectivity [FNC]) to identify CAG-RL associations. Connectivity within the putamen RSN is negatively correlated with CAG-RL. The FNC between putamen and insula decreases with increasing CAG-RL, and also shows significant associations with motor and cognitive measures. The FNC between calcarine and middle frontal gyri increased with CAG-RL. In contrast, FNC in other visual (VIS) networks declined with increasing CAG-RL. In addition to observed effects in SC areas known to be related to HD, our study identifies a strong presence of alterations in VIS regions less commonly observed in previous reports and provides a step forward in understanding FNC dysfunction in HDgmc.


Assuntos
Encéfalo/fisiopatologia , Conectoma/métodos , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Heterozigoto , Humanos , Doença de Huntington/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
16.
J Int Neuropsychol Soc ; 23(2): 159-170, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28205498

RESUMO

OBJECTIVES: Huntington's disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis. METHODS: The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements. RESULTS: Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning. CONCLUSIONS: Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159-170).


Assuntos
Gânglios da Base/patologia , Transtornos Cognitivos/etiologia , Doença de Huntington/complicações , Doença de Huntington/patologia , Deficiências da Aprendizagem/etiologia , Movimento/fisiologia , Adulto , Gânglios da Base/diagnóstico por imagem , Análise por Conglomerados , Feminino , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Repetições de Trinucleotídeos/genética
17.
Behav Brain Res ; 318: 71-81, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27816558

RESUMO

Among nonhuman primates, chimpanzees are well known for their sophistication and diversity of tool use in both captivity and the wild. The evolution of tool manufacture and use has been proposed as a driving mechanism for the development of increasing brain size, complex cognition and motor skills, as well as the population-level handedness observed in modern humans. Notwithstanding, our understanding of the neurological correlates of tool use in chimpanzees and other primates remains poorly understood. Here, we assessed the hand preference and performance skill of chimpanzees on a tool use task and correlated these data with measures of neuroanatomical asymmetries in the inferior frontal gyrus (IFG) and the pli-de-passage fronto-parietal moyen (PPFM). The IFG is the homolog to Broca's area in the chimpanzee brain and the PPFM is a buried gyrus that connects the pre- and post-central gyri and corresponds to the motor-hand area of the precentral gyrus. We found that chimpanzees that performed the task better with their right compared to left hand showed greater leftward asymmetries in the IFG and PPFM. This association between hand performance and PPFM asymmetry was particularly robust for right-handed individuals. Based on these findings, we propose that the evolution of tool use was associated with increased left hemisphere specialization for motor skill. We further suggest that lateralization in motor planning, rather than hand preference per se, was selected for with increasing tool manufacture and use in Hominid evolution.


Assuntos
Área de Broca/anatomia & histologia , Lobo Frontal/anatomia & histologia , Destreza Motora/fisiologia , Comportamento de Utilização de Ferramentas/fisiologia , Animais , Feminino , Lateralidade Funcional , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Pan troglodytes
18.
Neuropsychologia ; 93(Pt B): 325-334, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27055947

RESUMO

Increases brain size has been hypothesized to be inversely associated with the expression of behavioral and brain asymmetries within and between species. We tested this hypothesis by analyzing the relation between asymmetries in the planum temporale (PT) and different measures of the corpus callosum (CC) including surface area, streamline count as measured from diffusion tensor imaging, fractional anisotropy values and the ratio in the number of fibers to surface area in a sample of chimpanzees. We found that chimpanzees with larger PT asymmetries in absolute terms had smaller CC surface areas, fewer streamlines and a smaller ratio of fibers to surface area. These results were largely specific to male but not female chimpanzees. Our results partially support the hypothesis that brain asymmetries are linked to variation in corpus callosum morphology, although these associations may be sex-dependent.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Lateralidade Funcional , Pan troglodytes/anatomia & histologia , Caracteres Sexuais , Animais , Córtex Cerebral/fisiologia , Corpo Caloso/fisiologia , Imagem de Tensor de Difusão , Feminino , Imageamento por Ressonância Magnética , Masculino , Pan troglodytes/fisiologia
19.
Ann N Y Acad Sci ; 1359: 65-83, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26426409

RESUMO

Contrary to many historical views, recent evidence suggests that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence that genes play specific roles in determining left-right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the surface area of the corpus callosum in different primate species. Last, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field.


Assuntos
Comportamento Animal/fisiologia , Evolução Biológica , Encéfalo/fisiologia , Lateralidade Funcional/fisiologia , Animais , Percepção Auditiva/fisiologia , Expressão Facial , Humanos , Primatas , Especificidade da Espécie
20.
Front Psychol ; 5: 7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24523703

RESUMO

Clinical and experimental data have implicated the posterior superior temporal gyrus as an important cortical region in the processing of socially relevant stimuli such as gaze following, eye direction, and head orientation. Gaze following and responding to different socio-communicative signals is an important and highly adaptive skill in primates, including humans. Here, we examined whether individual differences in responding to socio-communicative cues was associated with variation in either gray matter (GM) volume and asymmetry in a sample of chimpanzees. Magnetic resonance image scans and behavioral data on receptive joint attention (RJA) was obtained from a sample of 191 chimpanzees. We found that chimpanzees that performed poorly on the RJA task had less GM in the right compared to left hemisphere in the posterior but not anterior superior temporal gyrus. We further found that middle-aged and elderly chimpanzee performed more poorly on the RJA task and had significantly less GM than young-adult and sub-adult chimpanzees. The results are consistent with previous studies implicating the posterior temporal gyrus in the processing of socially relevant information.

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