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1.
Alzheimers Dement ; 20(2): 1268-1283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985223

RESUMO

INTRODUCTION: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline. METHODS: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts. RESULTS: We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits. DISCUSSION: We discovered several novel loci, genes, and genetic correlations associated with late-life memory performance and decline. HIGHLIGHTS: Late-life memory has high heritability that is similar across ancestries. We discovered four novel variants associated with late-life memory. We identified four novel genes associated with late-life memory. Late-life memory shares genetic architecture with psychiatric/autoimmune traits.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Endofenótipos , Predisposição Genética para Doença/genética , Cognição , Transtornos da Memória/genética , Polimorfismo de Nucleotídeo Único/genética
2.
Alzheimers Dement ; 20(2): 1250-1267, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984853

RESUMO

BACKGROUND: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear. METHODS: We conducted the largest sex-aware genetic study on late-life memory to date (Nmales  = 11,942; Nfemales  = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants. RESULTS: We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits. DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory. HIGHLIGHTS: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits.


Assuntos
Doença de Alzheimer , Envelhecimento Cognitivo , Humanos , Masculino , Feminino , Estudo de Associação Genômica Ampla , Doença de Alzheimer/genética , Cognição , Caracteres Sexuais
3.
Mov Disord ; 37(2): 325-333, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724257

RESUMO

BACKGROUND: Rasagiline has received attention as a potential disease-modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question. OBJECTIVE: The main objective of this study was to determine whether rasagiline has disease-modifying effects in PD over 1 year. Secondarily we evaluated two diffusion magnetic resonance imaging pulse sequences to determine the best sequence to measure disease progression. METHODS: This prospective, randomized, double-blind, placebo-controlled trial assessed the effects of rasagiline administered at 1 mg/day over 12 months in early-stage PD. The primary outcome was 1-year change in free-water accumulation in posterior substantia nigra (pSN) measured using two diffusion magnetic resonance imaging pulse sequences, one with a repetition time (TR) of 2500 ms (short TR; n = 90) and one with a TR of 6400 ms (long TR; n = 75). Secondary clinical outcomes also were assessed. RESULTS: Absolute change in pSN free-water accumulation was not significantly different between groups (short TR: P = 0.346; long TR: P = 0.228). No significant differences were found in any secondary clinical outcomes between groups. Long TR, but not short TR, data show pSN free-water increased significantly over 1 year (P = 0.025). Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III increased significantly over 1 year (P = 0.009), and baseline free-water in the pSN correlated with the 1-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III (P = 0.004) and 1-year change in bradykinesia score (P = 0.044). CONCLUSIONS: We found no evidence that 1 mg/day rasagiline has a disease-modifying effect in PD over 1 year. We found pSN free-water increased over 1 year, and baseline free-water relates to clinical motor progression, demonstrating the importance of diffusion imaging parameters for detecting and predicting PD progression. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Método Duplo-Cego , Humanos , Indanos/farmacologia , Indanos/uso terapêutico , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Estudos Prospectivos
4.
Mov Disord ; 35(8): 1388-1395, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32357259

RESUMO

OBJECTIVE: Accurate diagnosis is particularly challenging in Parkinson's disease (PD), multiple system atrophy (MSAp), and progressive supranuclear palsy (PSP). We compare the utility of 3 promising biomarkers to differentiate disease state and explain disease severity in parkinsonism: the Automated Imaging Differentiation in Parkinsonism (AID-P), the Magnetic Resonance Parkinsonism Index (MRPI), and plasma-based neurofilament light chain protein (NfL). METHODS: For each biomarker, the area under the curve (AUC) of receiver operating characteristic curves were quantified for PD versus MSAp/PSP and MSAp versus PSP and statistically compared. Unique combinations of variables were also assessed. Furthermore, each measures association with disease severity was determined using stepwise multiple regression. RESULTS: For PD versus MSAp/PSP, AID-P (AUC, 0.900) measures had higher AUC compared with NfL (AUC, 0.747) and MRPI (AUC, 0.669), P < 0.05. For MSAp versus PSP, AID-P (AUC, 0.889), and MRPI (AUC, 0.824) measures were greater than NfL (AUC, 0.537), P < 0.05. We then combined measures to determine if any unique combination provided enhanced accuracy and found that no combination performed better than the AID-P alone in differentiating parkinsonisms. Furthermore, we found that the AID-P demonstrated the highest association with the MDS-UPDRS (Radj2 -AID-P, 26.58%; NfL,15.12%; MRPI, 12.90%). CONCLUSIONS: Compared with MRPI and NfL, AID-P provides the best overall differentiation of PD versus MSAp/PSP. Both AID-P and MRPI are effective in differentiating MSAp versus PSP. Furthermore, combining biomarkers did not improve classification of disease state compared with using AID-P alone. The findings demonstrate in the current sample that the AID-P and MRPI are robust biomarkers for PD, MSAp, and PSP. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Atrofia de Múltiplos Sistemas , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Diagnóstico Diferencial , Humanos , Filamentos Intermediários , Imageamento por Ressonância Magnética , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem
5.
Brain ; 142(6): 1644-1659, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30957839

RESUMO

Dystonia is a movement disorder characterized by involuntary muscle co-contractions that give rise to disabling movements and postures. A recent expert consensus labelled the incidence of tremor as a core feature of dystonia that can affect body regions both symptomatic and asymptomatic to dystonic features. We are only beginning to understand the neural network-level signatures that relate to clinical features of dystonic tremor. At the same time, clinical features of dystonic tremor can resemble that of essential tremor and present a diagnostic confound for clinicians. Here, we examined network-level functional activation and connectivity in patients with dystonic tremor and essential tremor. The dystonic tremor group included primarily cervical dystonia patients with dystonic head tremor and the majority had additional upper-limb tremor. The experimental paradigm included a precision grip-force task wherein online visual feedback related to force was manipulated across high and low spatial feedback levels. Prior work using this paradigm in essential tremor patients produced exacerbation of grip-force tremor and associated changes in functional activation. As such, we directly compared the effect of visual feedback on grip-force tremor and associated functional network-level activation and connectivity between dystonic tremor and essential tremor patient cohorts to better understand disease-specific mechanisms. Increased visual feedback similarly exacerbated force tremor during the grip-force task in dystonic tremor and essential tremor cohorts. Patients with dystonic tremor and essential tremor were characterized by distinct functional activation abnormalities in cortical regions but not in the cerebellum. We examined seed-based functional connectivity from the sensorimotor cortex, globus pallidus internus, ventral intermediate thalamic nucleus, and dentate nucleus, and observed abnormal functional connectivity networks in dystonic tremor and essential tremor groups relative to controls. However, the effects were far more widespread in the dystonic tremor group as changes in functional connectivity were revealed across cortical, subcortical, and cerebellar regions independent of the seed location. A unique pattern for dystonic tremor included widespread reductions in functional connectivity compared to essential tremor within higher-level cortical, basal ganglia, and cerebellar regions. Importantly, a receiver operating characteristic determined that functional connectivity z-scores were able to classify dystonic tremor and essential tremor with 89% area under the curve, whereas combining functional connectivity with force tremor yielded 94%. These findings point to network-level connectivity as an important feature that differs substantially between dystonic tremor and essential tremor and should be further explored in implementing appropriate diagnostic and therapeutic strategies.


Assuntos
Distonia/congênito , Distúrbios Distônicos/fisiopatologia , Tremor Essencial/fisiopatologia , Vias Neurais/fisiopatologia , Tremor/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cerebelo/fisiopatologia , Distonia/fisiopatologia , Globo Pálido/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia
6.
Neuroimage ; 200: 302-312, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260838

RESUMO

Understanding the architecture of transcallosal connections would allow for more specific assessments of neurodegeneration across many fields of neuroscience, neurology, and psychiatry. To map these connections, we conducted probabilistic tractography in 100 Human Connectome Project subjects in 32 cortical areas using novel post-processing algorithms to create a spatially precise Trancallosal Tract Template (TCATT). We found robust transcallosal tracts in all 32 regions, and a topographical analysis in the corpus callosum largely agreed with well-established subdivisions of the corpus callosum. We then obtained diffusion MRI data from a cohort of patients with Alzheimer's disease (AD) and another with progressive supranuclear palsy (PSP) and used a two-compartment model to calculate free-water corrected fractional anisotropy (FAT) and free-water (FW) within the TCATT. These metrics were used to determine between-group differences and to determine which subset of tracts was best associated with cognitive function (Montreal Cognitive Assessment (MoCA)). In AD, we found robust between-group differences in FW (31/32 TCATT tracts) in the absence of between-group differences in FAT. FW in the inferior temporal gyrus TCATT tract was most associated with MoCA scores in AD. In PSP, there were widespread differences in both FAT and FW, and MoCA was predicted by FAT in the inferior frontal pars triangularis, preSMA, and medial frontal gyrus TCATT tracts as well as FW in the inferior frontal pars opercularis TCATT tract. The TCATT improves spatial localization of corpus callosum measurements to enhance the evaluation of treatment effects, as well as the monitoring of brain microstructure in relation to cognitive dysfunction and disease progression. Here, we have shown its direct relevance in capturing between-group differences and associating it with the MoCA in AD and PSP.


Assuntos
Doença de Alzheimer/patologia , Atlas como Assunto , Conectoma , Corpo Caloso/patologia , Imagem de Tensor de Difusão/métodos , Rede Nervosa/patologia , Paralisia Supranuclear Progressiva/patologia , Adulto , Doença de Alzheimer/diagnóstico por imagem , Água Corporal/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Adulto Jovem
7.
Hum Brain Mapp ; 40(17): 5094-5107, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403737

RESUMO

Neurite orientation dispersion and density imaging (NODDI) uses a three-compartment model to probe brain tissue microstructure, whereas free-water (FW) imaging models two-compartments. It is unknown if NODDI detects more disease-specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi- and single-shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi-shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single-shell; FW; free-water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neuritos , Doença de Parkinson/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Mov Disord ; 34(1): 95-104, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30345712

RESUMO

BACKGROUND: Evidence from functional imaging in essential tremor suggests that activity within parietal and motor cortices may be associated with worsening of tremor at increased visual feedback. OBJECTIVES: Examine how cortical oscillations within these regions and the connectivity between these regions is associated with worsening of tremor in essential tremor in response to high visual feedback. METHOD: The study included 24 essential tremor participants and 17 controls. We measured cortical activity and tremor magnitude at low and high feedback conditions. Cortical activity was measured using high-density electroencephalogram and isolated using source localization. RESULTS: Changes in power across feedback in the 4-12 Hz and 12-30 Hz bands were reduced within the contralateral motor cortex of essential tremor patients compared to controls. The 12-30 Hz bidirectional connectivity between the parietal and contralateral motor cortex was decreased in essential tremor patients. Worsening of tremor from low to high visual feedback was associated with 4-12 Hz activity in contralateral motor cortex. The greatest separation between groups was found when using the difference of the contralateral motor cortex activity at high and low feedback, rather than either feedback condition alone. CONCLUSION: Our findings provide new evidence that tremor in essential tremor is associated with reduced power across feedback in the motor cortex and reduced connectivity between the parietal and motor cortices. Combined with previous work on the cerebellar-thalamo-cortical motor circuit, our findings suggest that the network level disturbances associated with essential tremor extend to the cortico-cortical pathway between the parietal cortex and motor cortex. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Tremor Essencial/fisiopatologia , Retroalimentação Sensorial/fisiologia , Córtex Motor/fisiopatologia , Tremor/fisiopatologia , Idoso , Mapeamento Encefálico , Cerebelo/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
9.
Brain ; 141(2): 472-485, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29293948

RESUMO

Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback. Here, we directly manipulated visual feedback during a functional MRI grip force task in patients with essential tremor and control participants, and hypothesized that an increase in visual feedback would exacerbate tremor in the 4-12 Hz range in essential tremor patients. Further, we hypothesized that this exacerbation of tremor would be associated with dysfunctional changes in BOLD signal and entropy within, and beyond, the cerebello-thalamo-cortical pathway. We found that increases in visual feedback increased tremor in the 4-12 Hz range in essential tremor patients, and this increase in tremor was associated with abnormal changes in BOLD amplitude and entropy in regions within the cerebello-thalamo-motor cortical pathway, and extended to visual and parietal areas. To determine if the tremor severity was associated with single or multiple brain region(s), we conducted a birectional stepwise multiple regression analysis, and found that a widespread functional network extending beyond the cerebello-thalamo-motor cortical pathway was associated with changes in tremor severity measured during the imaging protocol. Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant. Since increased visual feedback also reduced force error, this network was evaluated in relation to force error but the model was not significant, indicating it is associated with force tremor but not force error. This study therefore provides new evidence that a widespread functional network is associated with the severity of tremor in patients with essential tremor measured simultaneously at the hand during functional imaging, and is also associated with the clinical severity of tremor. These findings support the idea that the severity of tremor is exacerbated by increased visual feedback, suggesting that designers of new computing technologies should consider using lower visual feedback levels to reduce tremor in essential tremor.


Assuntos
Mapeamento Encefálico , Tremor Essencial/complicações , Tremor Essencial/patologia , Retroalimentação Sensorial/fisiologia , Vias Neurais/fisiopatologia , Visão Ocular/fisiologia , Adulto , Idoso , Cerebelo/diagnóstico por imagem , Conectoma , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Córtex Motor/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Oxigênio/sangue , Desempenho Psicomotor/fisiologia , Análise de Regressão , Tálamo/diagnóstico por imagem
10.
Cereb Cortex ; 28(5): 1685-1699, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334314

RESUMO

The purpose of this study was to develop a high-resolution sensorimotor area tract template (SMATT) which segments corticofugal tracts based on 6 cortical regions in primary motor cortex, dorsal premotor cortex, ventral premotor cortex, supplementary motor area (SMA), pre-supplementary motor area (preSMA), and primary somatosensory cortex using diffusion tensor imaging. Individual probabilistic tractography analyses were conducted in 100 subjects using the highest resolution data currently available. Tractography results were refined using a novel algorithm to objectively determine slice level thresholds that best minimized overlap between tracts while preserving tract volume. Consistent with tracing studies in monkey and rodent, our observations show that cortical topography is generally preserved through the internal capsule, with the preSMA tract remaining most anterior and the primary somatosensory tract remaining most posterior. We combine our results into a freely available white matter template named the SMATT. We also provide a probabilistic SMATT that quantifies the extent of overlap between tracts. Finally, we assess how the SMATT operates at the individual subject level in another independent data set, and in an individual after stroke. The SMATT and probabilistic SMATT provide new tools that segment and label sensorimotor tracts at a spatial resolution not previously available.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Algoritmos , Córtex Cerebral/fisiologia , Conectoma , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Probabilidade , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto Jovem
11.
Brain ; 140(8): 2183-2192, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28899020

RESUMO

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies.


Assuntos
Progressão da Doença , Doença de Parkinson/metabolismo , Água/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Corpo Estriado/metabolismo , Imagem de Difusão por Ressonância Magnética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuroimagem , Substância Negra/metabolismo
12.
J Neurophysiol ; 117(2): 786-795, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27903639

RESUMO

The translation of brief, millisecond-long pain-eliciting stimuli to the subjective perception of pain is associated with changes in theta, alpha, beta, and gamma oscillations over sensorimotor cortex. However, when a pain-eliciting stimulus continues for minutes, regions beyond the sensorimotor cortex, such as the prefrontal cortex, are also engaged. Abnormalities in prefrontal cortex have been associated with chronic pain states, but conventional, millisecond-long EEG paradigms do not engage prefrontal regions. In the current study, we collected high-density EEG data during an experimental paradigm in which subjects experienced a 4-s, low- or high-intensity pain-eliciting stimulus. EEG data were analyzed using independent component analyses, EEG source localization analyses, and measure projection analyses. We report three novel findings. First, an increase in pain perception was associated with an increase in gamma and theta power in a cortical region that included medial prefrontal cortex. Second, a decrease in lower beta power was associated with an increase in pain perception in a cortical region that included the contralateral sensorimotor cortex. Third, we used machine learning for automated classification of EEG data into low- and high-pain classes. Theta and gamma power in the medial prefrontal region and lower beta power in the contralateral sensorimotor region served as features for classification. We found a leave-one-out cross-validation accuracy of 89.58%. The development of biological markers for pain states continues to gain traction in the literature, and our findings provide new information that advances this body of work.NEW & NOTEWORTHY The development of a biological marker for pain continues to gain traction in literature. Our findings show that high- and low-pain perception in human subjects can be classified with 89% accuracy using high-density EEG data from prefrontal cortex and contralateral sensorimotor cortex. Our approach represents a novel neurophysiological paradigm that advances the literature on biological markers for pain.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Processamento Eletrônico de Dados , Percepção da Dor/fisiologia , Dor/fisiopatologia , Adolescente , Eletroencefalografia , Feminino , Humanos , Masculino , Estimulação Física/efeitos adversos , Escalas de Graduação Psiquiátrica , Temperatura , Escala Visual Analógica , Adulto Jovem
13.
Hum Brain Mapp ; 38(9): 4546-4562, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28590584

RESUMO

Measures from diffusion MRI have been used to characterize the corticospinal tract in chronic stroke. However, diffusivity can be influenced by partial volume effects from free-water, region of interest placement, and lesion masking. We collected diffusion MRI from a cohort of chronic stroke patients and controls and used a bitensor model to calculate free-water corrected fractional anisotropy (FAT ) and free water (FW) in the primary motor corticospinal tract (M1-CST) and the dorsal premotor corticospinal tract (PMd-CST). Region of interest analyses and whole-tract slice-by-slice analyses were used to assess between-group differences in FAT and FW in each tract. Correlations between FAT and FW and grip strength were also examined. Following lesion masking and correction for multiple comparisons, relative increases in FW were found for the stroke group in large portions of the M1-CST and PMd-CST in the lesioned hemisphere. FW in cortical regions was the strongest predictor of grip strength in the stroke group. Our findings also demonstrated that FAT is sensitive to the direct effects of the lesion itself, thus after controlling for the lesion, differences in FAT in nonlesioned tissue were small and generally similar between hemispheres and groups. Our observations suggest that FW may be a robust biological measurement that can be used to assess microstructure in residual white matter after stroke. Hum Brain Mapp 38:4546-4562, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Córtex Motor/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Água Corporal/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Doença Crônica , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Substância Branca/diagnóstico por imagem
14.
Hum Brain Mapp ; 37(6): 2039-54, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26920656

RESUMO

Microstructural properties of the corticospinal tract (CST) descending from the motor cortex predict strength and motor skill in the chronic phase after stroke. Much less is known about the relation between brain microstructure and visuomotor processing after stroke. In this study, individual's poststroke and age-matched controls performed a unimanual force task separately with each hand at three levels of visual gain. We collected diffusion MRI data and used probabilistic tractography algorithms to identify the primary and premotor CSTs. Fractional anisotropy (FA) within each tract was used to predict changes in force variability across different levels of visual gain. Our observations revealed that individuals poststroke reduced force variability with an increase in visual gain, performed the force task with greater variability as compared with controls across all gain levels, and had lower FA in the primary motor and premotor CSTs. Our results also demonstrated that the CST descending from the premotor cortex, rather than the primary motor cortex, best predicted force variability. Together, these findings demonstrate that the microstructural properties of the premotor CST predict visual gain-related changes in force variability in individuals poststroke. Hum Brain Mapp 37:2039-2054, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Córtex Motor/diagnóstico por imagem , Destreza Motora , Tratos Piramidais/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Doença Crônica , Retroalimentação Sensorial/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Destreza Motora/fisiologia , Análise Multivariada , Tratos Piramidais/fisiopatologia , Análise de Regressão , Percepção Visual/fisiologia
16.
Neurocase ; 21(6): 674-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25360766

RESUMO

Poststroke central pain (PSCP) can be a debilitating medication-refractory disorder. We report a single case where right unilateral ventral capsule/ventral striatum (VC/VS) deep brain stimulation was used to treat PSCP and inadvertently induced a smile without euphoria. The patient was a 69 year-old woman who had a stroke with resultant dysesthesia and allodynia in her left hemibody and also a painful left hemibody dystonia. In her case, VC/VS stimulation induced a smile phenomenon, but without a euphoric sensation. This phenomenon was different from the typical smile responses we have observed in obsessive-compulsive disorder cases. This difference was considered to be possibly attributable to impairment in the emotional smile pathway.


Assuntos
Estimulação Encefálica Profunda , Euforia/fisiologia , Cápsula Interna/fisiopatologia , Sorriso/fisiologia , Estriado Ventral/fisiopatologia , Idoso , Feminino , Humanos , Cápsula Interna/cirurgia , Dor/etiologia , Dor/fisiopatologia , Manejo da Dor , Acidente Vascular Cerebral/complicações , Estriado Ventral/cirurgia
18.
J Arthroplasty ; 29(3): 541-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24290741

RESUMO

Limited experimental data exist comparing the mechanical response of the tibial cortex between fixed and rotating platform (RP) total knee arthroplasty (TKA), particularly in the revision setting. We asked if RP-TKA significantly affects tibiofemoral torque and cortical stain response in both the primary and revision settings. Fixed and RP tibial trays were implanted into analogue tibias and biomechanically tested under axial and torsional loading. Torque and strain response were analyzed using digital image correlation. Fixed bearing designs exhibited 13.8 times greater torque (P<0.01), and 69% (P<0.01) higher cortical strain than RP designs. Strain response was similar in the primary and revision cohorts. The decrease in torque transfer could act as a safeguard to reduce stress, micromotion and torsional fatigue in scenario of poor bone stock.


Assuntos
Artroplastia do Joelho , Articulação do Joelho/fisiopatologia , Prótese do Joelho , Tíbia/fisiopatologia , Fenômenos Biomecânicos , Humanos , Articulação do Joelho/cirurgia , Modelos Teóricos , Desenho de Prótese , Reoperação , Estresse Mecânico , Tíbia/cirurgia , Torque
19.
Artigo em Inglês | MEDLINE | ID: mdl-39220624

RESUMO

Multi-site diffusion MRI data is often acquired on different scanners and with distinct protocols. Differences in hardware and acquisition result in data that contains site dependent information, which confounds connectome analyses aiming to combine such multi-site data. We propose a data-driven solution that isolates site-invariant information whilst maintaining relevant features of the connectome. We construct a latent space that is uncorrelated with the imaging site and highly correlated with patient age and a connectome summary measure. Here, we focus on network modularity. The proposed model is a conditional, variational autoencoder with three additional prediction tasks: one for patient age, and two for modularity trained exclusively on data from each site. This model enables us to 1) isolate site-invariant biological features, 2) learn site context, and 3) re-inject site context and project biological features to desired site domains. We tested these hypotheses by projecting 77 connectomes from two studies and protocols (Vanderbilt Memory and Aging Project (VMAP) and Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) to a common site. We find that the resulting dataset of modularity has statistically similar means (p-value <0.05) across sites. In addition, we fit a linear model to the joint dataset and find that positive correlations between age and modularity were preserved.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39281711

RESUMO

Diffusion magnetic resonance imaging (dMRI) offers the ability to assess subvoxel brain microstructure through the extraction of biomarkers like fractional anisotropy, as well as to unveil brain connectivity by reconstructing white matter fiber trajectories. However, accurate analysis becomes challenging at the interface between cerebrospinal fluid and white matter, where the MRI signal originates from both the cerebrospinal fluid and the white matter partial volume. The presence of free water partial volume effects introduces a substantial bias in estimating diffusion properties, thereby limiting the clinical utility of DWI. Moreover, current mathematical models often lack applicability to single-shell acquisitions commonly encountered in clinical settings. Without appropriate regularization, direct model fitting becomes impractical. We propose a novel voxel-based deep learning method for mapping and correcting free-water partial volume contamination in DWI to address these limitations. This approach leverages data-driven techniques to reliably infer plausible free-water volumes across different diffusion MRI acquisition schemes, including single-shell acquisitions. Our evaluation demonstrates that the introduced methodology consistently produces more consistent and plausible results than previous approaches. By effectively mitigating the impact of free water partial volume effects, our approach enhances the accuracy and reliability of DWI analysis for single-shell dMRI, thereby expanding its applications in assessing brain microstructure and connectivity.

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