Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 162
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Int J Eat Disord ; 57(2): 223-248, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38041221

RESUMO

OBJECTIVE: This study aimed to quantify the prevalence of non-suicidal self-injury across eating disorders (EDs) and within diagnostic categories through systematic review and proportional, or so-called prevalence, meta-analysis. METHOD: Included studies had to contain individuals with a verified diagnosis of an ED. The last literature search was conducted on September 11, 2023, for studies published on or before September 2023 without a restriction on earliest publication year. Results were synthesized and analyzed using the "metaprop" package in R and presented using forest plots. Bias was assessed by a Peters' regression test and funnel plot. RESULTS: 79 studies published between 1985 and 2023 were included encompassing 32,334 individuals with an ED. Importantly, 42 studies were not included in any other meta-analyses on self-injury in EDs to date. Overall prevalence of non-suicidal self-injury was 34.59% (95%CI = 30.49-38.81). Prevalence in anorexia nervosa restrictive type, binge/purge type, bulimia nervosa, binge eating disorder and other specified feeding/eating disorder were 23.19% (95%CI = 16.96-30.03%), 41.98% (95%CI = 32.35-51.91%), 36.97% (95%CI = 30.69-43.46%), 21.21% (95%CI = 14.93-28.12%) and 37.65% (95%CI = 28.59-47.09%), respectively. Prevalence estimations could not be estimated for other ED categories due to lack of a sufficient number of studies. DISCUSSION: Non-suicidal self-injury is prevalent across both binge/purge and restrictive EDs. Considering the transdiagnostic nature of self-injurious behaviors in ED, the results highlight the importance of assessment and monitoring of self-injury in people with ED, irrespective of specific diagnoses. The method of determining self-injury varied across studies and may limit this study. PUBLIC SIGNIFICANCE: This study highlights the prevalence of self-injury across eating disorders irrespective of diagnosis and within specific EDs. While diagnoses known to exhibit self-injurious behaviors (e.g., bulimia nervosa, anorexia nervosa binge/purge subtype) demonstrated the highest prevalence of self-injury, all diagnoses were found to have a prevalence greater than 20%. These findings suggest the importance of assessing and monitoring all individuals with an eating disorder for the presence of self-injury.


OBJETIVO: Este estudio tuvo como objetivo cuantificar la prevalencia de la autolesión no suicida en los trastornos de la conducta alimentaria (TCA) y dentro de las categorías diagnósticas mediante una revisión sistemática y un metaanálisis proporcional, también llamado metaanálisis de prevalencia. MÉTODO: Los estudios incluidos debían contener individuos con un diagnóstico verificado de un TCA. La última búsqueda bibliográfica se realizó el 11 de septiembre de 2023, para estudios publicados en o antes de septiembre de 2023 sin restricción en el año de publicación más temprano. Los resultados fueron sintetizados y analizados utilizando el paquete "metaprop" en R y presentados mediante gráficos de bosque. El sesgo se evaluó mediante una prueba de regresión de Peters y un gráfico de embudo. RESULTADOS: Se incluyeron 79 estudios publicados entre 1985 y 2023 que abarcaron a 32,334 individuos que padecían un TCA. Es importante destacar que 42 estudios no se incluyeron en ningún otro metaanálisis sobre autolesión en TCA hasta la fecha. La prevalencia general de la autolesión no suicida fue del 34.59% (IC del 95% = 30.49-38.81). La prevalencia en la anorexia nerviosa subtipo restrictivo, subtipo atracones/purga, bulimia nerviosa, trastorno de atracones y otros trastornos especificados de la conducta alimentaria y de la alimentación fue del 23.19% (IC del 95% = 16.96-30.03%), 41.98% (IC del 95% = 32.35-51.91%), 36.97% (IC del 95% = 30.69-43.46%), 21.21% (IC del 95% = 14.93-28.12%) y 37.65% (IC del 95% = 28.59-47.09%), respectivamente. No se pudieron estimar las estimaciones de prevalencia para otras categorías de TCA debido a la falta de un número suficiente de estudios. DISCUSIÓN: La autolesión no suicida es prevalente tanto en los TCA subtipo de atracón/purgación como en los restrictivos. Dada la naturaleza transdiagnóstica de los comportamientos autolesivos en los TCA, los resultados resaltan la importancia de la evaluación y el monitoreo de la autolesión en personas que padecen TCA, independientemente de los diagnósticos específicos. El método para determinar la autolesión varió entre los estudios y puede limitar este estudio.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Comportamento Autodestrutivo , Humanos , Prevalência , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Bulimia Nervosa/diagnóstico , Transtorno da Compulsão Alimentar/diagnóstico , Comportamento Autodestrutivo/epidemiologia , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/diagnóstico
2.
Alzheimers Dement ; 20(3): 1753-1770, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38105605

RESUMO

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.


Assuntos
Doença de Alzheimer , Doenças Cardiovasculares , Disfunção Cognitiva , Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Atividades Cotidianas , Peptídeos beta-Amiloides , Ontário , Cognição , Biomarcadores , Proteínas tau
3.
J Neurosci ; 42(1): 69-80, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34759032

RESUMO

When presented with a periodic stimulus, humans spontaneously adjust their movements from reacting to predicting the timing of its arrival, but little is known about how this sensorimotor adaptation changes across development. To investigate this, we analyzed saccade behavior in 114 healthy humans (ages 6-24 years) performing the visual metronome task, who were instructed to move their eyes in time with a visual target that alternated between two known locations at a fixed rate, and we compared their behavior to performance in a random task, where target onsets were randomized across five interstimulus intervals (ISIs) and thus the timing of appearance was unknown. Saccades initiated before registration of the visual target, thus in anticipation of its appearance, were labeled predictive [saccade reaction time (SRT) < 90 ms] and saccades that were made in reaction to its appearance were labeled reactive (SRT > 90 ms). Eye-tracking behavior including saccadic metrics (e.g., peak velocity, amplitude), pupil size following saccade to target, and blink behavior all varied as a function of predicting or reacting to periodic targets. Compared with reactive saccades, predictive saccades had a lower peak velocity, a hypometric amplitude, smaller pupil size, and a reduced probability of blink occurrence before target appearance. The percentage of predictive and reactive saccades changed inversely from ages 8-16, at which they reached adult-levels of behavior. Differences in predictive saccades for fast and slow target rates are interpreted by differential maturation of cerebellar-thalamic-striatal pathways.SIGNIFICANCE STATEMENT From the first moments of life, humans are exposed to rhythm (i.e., mother's heartbeat in utero), but the timeline of brain development to promote the identification and anticipation of a rhythmic stimulus, known as temporal prediction, remains unknown. Here, we used saccade reaction time (SRT) in the visual metronome task to differentiate between temporally predictive and reactive responses to a target that alternated at a fixed rate in humans aged 6-24. Periods of age-related change varied little by target rate, with matured predictive performance evident by mid-adolescence for fast and slow rates. A strong correlation among saccade, pupil, and blink responses during target prediction provides evidence of oculomotor coordination and dampened noradrenergic neuronal activity when generating rhythmic motor responses.


Assuntos
Adaptação Fisiológica/fisiologia , Piscadela/fisiologia , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Estimulação Luminosa , Pupila , Adulto Jovem
4.
J Cogn Neurosci ; 35(2): 180-199, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36473104

RESUMO

Visual fixation (i.e., holding gaze on a specific visual object or location of interest) has been shown to be influenced by activity in the rostral pole of the intermediate layers of the superior colliculus (SCi)-a sensory-motor integration nucleus in the midbrain involved in visual fixation and saccadic eye movement generation. Neurons in the rostral SCi discharge tonically during visual fixation and pause during saccades to locations beyond their foveal visual-sensory or saccadic-motor response fields. Injection of muscimol to deactivate rostral SCi neurons also leads to an increase in fixation instability. However, the precise role of rostral SCi activity for controlling visual fixation has not been established and is actively debated. Here, we address whether this activity reflects signals related to task demands (i.e., maintaining visual fixation) or foveal visual stimulus properties. Two non-human primates performed an oculomotor task that required fixation of a central fixation point (FP) of varying luminance at the start of each trial. During this fixation period, we measured fixational saccades (≤ 2° of the FP, including microsaccades) and fixation-error saccades (> 2° from the FP) in combination with activity from the rostral SCi. Fixation of the lowest FP luminance increased the latency (onset time relative to initial FP foveation) for both fixational and fixation-error saccades. Fifty percent of the rostral SCi neurons exhibited activity that opposed the change in FP luminance and correlated with delayed fixational saccades and increased fixation-error saccades. Twenty-two percent of rostral SCi neurons exhibited activity that followed the change in FP luminance and correlated with earlier fixational saccades and decreased fixation-error saccades. This suggests the rostral SCi contains both sensory-driven and task-related motor signals related to foveal sensory stimuli and visual fixation. This evidence supports a role for the rostral SCi in gaze stabilization and can help inform artificial computational models of vision.


Assuntos
Fixação Ocular , Colículos Superiores , Animais , Colículos Superiores/fisiologia , Movimentos Oculares , Movimentos Sacádicos , Neurônios/fisiologia
5.
Alzheimers Dement ; 19(1): 226-243, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318754

RESUMO

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Masculino , Idoso , Doenças Neurodegenerativas/epidemiologia , Atividades Cotidianas , Ontário , Estudos de Coortes , Estudos Longitudinais
6.
J Cogn Neurosci ; 34(8): 1340-1354, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579984

RESUMO

The orienting response evoked by the appearance of a salient stimulus is modulated by arousal; however, neural underpinnings for the interplay between orienting and arousal are not well understood. The superior colliculus (SC), causally involved in multiple components of the orienting response including gaze and attention shifts, receives not only multisensory and cognitive inputs but also arousal-regulated inputs from various cortical and subcortical structures. To investigate the impact of moment-by-moment fluctuations in arousal on orienting saccade responses, we used microstimulation of the monkey SC to trigger saccade responses, and we used pupil size and velocity to index the level of arousal at stimulation onset because these measures correlate with changes in brain states and locus coeruleus activity. Saccades induced by SC microstimulation correlated with prestimulation pupil velocity, with higher pupil velocities on trials without evoked saccades than with evoked saccades. In contrast, prestimulation absolute pupil size did not correlate with saccade behavior. Moreover, pupil velocity correlated with evoked saccade latency and metrics. Together, our results demonstrated that small fluctuations in arousal, indexed by pupil velocity, can modulate the saccade response evoked by SC microstimulation in awake behaving monkeys.


Assuntos
Pupila , Colículos Superiores , Atenção , Estimulação Elétrica/métodos , Estimulação Luminosa/métodos , Pupila/fisiologia , Movimentos Sacádicos , Colículos Superiores/fisiologia
7.
Eur J Neurosci ; 55(1): 205-226, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791728

RESUMO

The removal of a fixation point (FP) prior to the appearance of a saccade target (gap effect) influences pre-motor circuits and reduces saccadic reaction time (SRT). Saccade preparation signals underlying the gap effect have been observed within the intermediate layers of the superior colliculus (SCi). Neurons in the caudal SCi, coding a target location, increase their activity during the gap, while neurons in the rostral SCi, with tonic activity related to visual fixation, decrease activity. However, the gap effect confounds two factors: (1) a goal-driven temporal warning component (upcoming saccade target appearance) and (2) a stimulus-driven sensory component (FP disappearance). These factors combine to reduce SRT and elicit pre-target responses in the SCi. To dissociate warning and sensory effects, we altered the luminance of the FP during the gap period (renamed warning period) such that it could increase, decrease, or stay the same. Faster SRTs resulted with larger decrements in FP luminance. Different categories of SCi warning period activity were evaluated: (1) always increasing or decreasing or (2) sensory-linked responses to changes in FP luminance. In the caudal SCi (at the location coding the target), all activity correlated negatively with SRT (i.e., saccade facilitation), and two categories of activity were observed (always increasing or opposing FP luminance changes). In the rostral SCi, four categories of activity were observed: activity that increased or followed the change in FP luminance correlated positively with SRT (i.e., saccade inhibition), while activity that decreased or opposed FP luminance changes correlated negatively with SRT. Such SCi activity reflected both goal-driven saccade preparation signals and FP sensory properties.


Assuntos
Objetivos , Colículos Superiores , Animais , Fixação Ocular , Macaca mulatta , Estimulação Luminosa , Tempo de Reação/fisiologia , Movimentos Sacádicos , Colículos Superiores/fisiologia
8.
Eur J Neurosci ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36453013

RESUMO

Decision-making during mixed-strategy games requires flexibly adapting choice strategies in response to others' actions and dynamically tracking outcomes. Such decisions involve diverse cognitive processes, including reinforcement learning, which are affected by disruptions to the striatal dopamine system. We therefore investigated how genetic variation in dopamine function affected mixed-strategy decision-making in Parkinson's disease (PD), which involves striatal dopamine pathology. Sixty-six PD patients (ages 49-85, Hoehn and Yahr Stages 1-3) and 22 healthy controls (ages 54-75) competed in a mixed-strategy game where successful performance depended on minimizing choice biases (i.e., flexibly adapting choices trial by trial). Participants also completed a fixed-strategy task that was matched for sensory input, motor outputs and overall reward rate. Factor analyses were used to disentangle cognitive from motor aspects within both tasks. Using a within-subject, multi-centre design, patients were examined on and off dopaminergic therapy, and genetic variation was examined via a multilocus genetic profile score representing the additive effects of three single nucleotide polymorphisms (SNPs) that influence dopamine transmission: rs4680 (COMT Val158 Met), rs6277 (C957T) and rs907094 (encoding DARPP-32). PD and control participants displayed comparable mixed-strategy choice behaviour (overall); however, PD patients with genetic profile scores indicating higher dopamine transmission showed improved performance relative to those with low scores. Exploratory follow-up tests across individual SNPs revealed better performance in individuals with the C957T polymorphism, reflecting higher striatal D2/D3 receptor density. Importantly, genetic variation modulated cognitive aspects of performance, above and beyond motor function, suggesting that genetic variation in dopamine signalling may underlie individual differences in cognitive function in PD.

9.
Exp Brain Res ; 240(6): 1873-1885, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35445861

RESUMO

The pupil responds to a salient stimulus appearing in the environment, in addition to its modulation by global luminance. These pupillary responses can be evoked by visual or auditory stimuli, scaled with stimulus salience, and enhanced by multisensory presentation. In addition, pupil size is modulated by various visual stimulus attributes, such as color, area, and motion. However, research that concurrently examines the influence of different factors on pupillary responses is limited. To explore how presentation of multiple visual stimuli influences human pupillary responses, we presented arrays of visual stimuli and systematically varied their luminance, color, and set size. Saliency level, computed by the saliency model, systematically changed with set size across all conditions, with higher saliency levels in larger set sizes. Pupillary constriction responses were evoked by the appearance of visual stimuli, with larger pupillary responses observed in larger set size. These effects were pronounced even though the global luminance level was unchanged using isoluminant chromatic stimuli. Furthermore, larger pupillary constriction responses were obtained in the blue, compared to other color conditions. Together, we argue that both cortical and subcortical areas contribute to the observed pupillary constriction modulated by set size and color.


Assuntos
Luz , Pupila , Humanos , Estimulação Luminosa , Pupila/fisiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-35633037

RESUMO

OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.


Assuntos
Transtornos Cerebrovasculares , Demência Frontotemporal , Doenças Neurodegenerativas , Atividades Cotidianas , Cuidadores/psicologia , Humanos , Ontário
11.
J Cogn Neurosci ; 33(5): 919-932, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449845

RESUMO

The appearance of a salient stimulus evokes saccadic eye movements and pupil dilation as part of the orienting response. Although the role of the superior colliculus (SC) in saccade and pupil dilation has been established separately, whether and how these responses are coordinated remains unknown. The SC also receives global luminance signals from the retina, but whether global luminance modulates saccade and pupil responses coordinated by the SC remains unknown. Here, we used microstimulation to causally determine how the SC coordinates saccade and pupil responses and whether global luminance modulates these responses by varying stimulation frequency and global luminance in male monkeys. Stimulation frequency modulated saccade and pupil responses, with trial-by-trial correlations between the two responses. Global luminance only modulated pupil, but not saccade, responses. Our results demonstrate an integrated role of the SC on coordinating saccade and pupil responses, characterizing luminance independent modulation in the SC, together elucidating the differentiated pathways underlying this behavior.


Assuntos
Movimentos Sacádicos , Colículos Superiores , Animais , Haplorrinos , Masculino , Estimulação Luminosa , Pupila
12.
Eur J Neurosci ; 54(10): 7560-7574, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34716728

RESUMO

Pupil size reflects a proxy for neural activity associated with global luminance, arousal and cognitive processing. Microsaccades are also modulated by arousal and cognitive processing. Are these effects of arousal and cognitive signals on pupil size and microsaccades coordinated? If so, via what neural mechanisms? We hypothesized that if pupil size and microsaccades are coordinately modulated by these processes, pupil size immediately before microsaccade onset, as an index for ongoing cognitive and arousal processing, should correlate with microsaccade responses during tasks alternating these signals. Here, we examined the relationship between pupil size and microsaccade responses in tasks that included variations in global luminance, arousal and inhibitory control. Higher microsaccade peak velocities correlated with larger pre-microsaccade pupil response related to arousal and inhibitory control signals. In contrast, pupil responses evoked by global luminance signals did not correlate with microsaccade responses. Given the central role of the superior colliculus in microsaccade generation, these results suggest the critical involvement of the superior colliculus to coordinate pupil and microsaccade responses for arousal and inhibitory control modulations, but not for the pupil luminance modulation.


Assuntos
Fixação Ocular , Movimentos Sacádicos , Nível de Alerta , Cognição , Estimulação Luminosa , Pupila , Percepção Visual
13.
J Neuroinflammation ; 18(1): 54, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33612100

RESUMO

BACKGROUND: The lack of effective treatments for Alzheimer's disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunction and has been associated with cognitive impairment in AD. Here, we investigated a possible link between pro-inflammatory interleukin-1 (IL-1), mitochondrial dysfunction, and cognitive impairment in AD models. METHODS: We exposed primary hippocampal cell cultures to amyloid-ß oligomers (AßOs) and carried out AßO infusions into the lateral cerebral ventricle of cynomolgus macaques to assess the impact of AßOs on proteins that regulate mitochondrial dynamics. Where indicated, primary cultures were pre-treated with mitochondrial division inhibitor 1 (mdivi-1), or with anakinra, a recombinant interleukin-1 receptor (IL-1R) antagonist used in the treatment of rheumatoid arthritis. Cognitive impairment was investigated in C57BL/6 mice that received an intracerebroventricular (i.c.v.) infusion of AßOs in the presence or absence of mdivi-1. To assess the role of interleukin-1 beta (IL-1ß) in AßO-induced alterations in mitochondrial proteins and memory impairment, interleukin receptor-1 knockout (Il1r1-/-) mice received an i.c.v. infusion of AßOs. RESULTS: We report that anakinra prevented AßO-induced alteration in mitochondrial dynamics proteins in primary hippocampal cultures. Altered levels of proteins involved in mitochondrial fusion and fission were observed in the brains of cynomolgus macaques that received i.c.v. infusions of AßOs. The mitochondrial fission inhibitor, mdivi-1, alleviated synapse loss and cognitive impairment induced by AßOs in mice. In addition, AßOs failed to cause alterations in expression of mitochondrial dynamics proteins or memory impairment in Il1r1-/- mice. CONCLUSION: These findings indicate that IL-1ß mediates the impact of AßOs on proteins involved in mitochondrial dynamics and that strategies aimed to prevent pathological alterations in those proteins may counteract synapse loss and cognitive impairment in AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Interleucina-1beta/biossíntese , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Dinâmica Mitocondrial/fisiologia , Fragmentos de Peptídeos/toxicidade , Animais , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Macaca fascicularis , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dinâmica Mitocondrial/efeitos dos fármacos , Ratos
14.
Mov Disord ; 36(7): 1720-1726, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33754406

RESUMO

BACKGROUND: Parkinson's disease (PD) patients exhibit deficits in saccade performance, pupil function, and blink rate. Isolated REM (rapid eye movement) Sleep Behavior Disorder (RBD) is a harbinger to PD making them candidates to investigate for early oculomotor abnormalities as PD biomarkers. OBJECTIVES: We tested whether saccade, pupillary, and blink responses in RBD were similar to PD. METHODS: RBD (n = 22), PD (n = 22) patients, and healthy controls (CTRL) (n = 74) were studied with video-based eye-tracking. RESULTS: RBD patients did not have significantly different saccadic behavior compared to CTRL, but PD patients differed from CTRL and RBD. Both patient groups had significantly lower blink rates, dampened pupil constriction, and dilation responses compared to CTRL. CONCLUSION: RBD and PD patients had altered pupil and blink behavior compared to CTRL. Because RBD saccade parameters were comparable to CTRL, pupil and blink brain areas may be impacted before saccadic control areas, making them potential prodromal PD biomarkers. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Transtorno do Comportamento do Sono REM , Encéfalo , Humanos , Doença de Parkinson/complicações , Pupila , Movimentos Sacádicos
15.
Proc Natl Acad Sci U S A ; 115(41): 10446-10451, 2018 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-30249636

RESUMO

Spatial attention enables us to focus visual processing toward specific locations or stimuli before the next fixation. Recent evidence has suggested that local luminance at the spatial locus of attention or saccade preparation influences pupil size independent of global luminance levels. However, it remains to be determined which neural pathways produce this location-specific modulation of pupil size. The intermediate layers of the midbrain superior colliculus (SC) form part of the network of brain areas involved in spatial attention and modulation of pupil size. Here, we demonstrated that pupil size was altered according to local luminance level at the spatial location corresponding to a microstimulated location in the intermediate SC (SCi) map of monkeys. Moreover, local SCi inactivation through injection of lidocaine reversed this local luminance modulation. Our findings reveal a causal role of the SCi in preparing pupil size for local luminance conditions at the next saccadic goal.


Assuntos
Rede Nervosa , Vias Neurais , Neurônios/fisiologia , Pupila/fisiologia , Movimentos Sacádicos/fisiologia , Colículos Superiores/fisiologia , Potenciais de Ação , Animais , Macaca mulatta , Masculino , Neurônios/citologia , Estimulação Luminosa , Colículos Superiores/citologia
16.
Eur J Neurosci ; 51(9): 1914-1927, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31596980

RESUMO

During competitive interactions, such as predator-prey or team sports, the outcome of one's actions is dependent on both their own choices and those of their opponents. Success in these rivalries requires that individuals choose dynamically and unpredictably, often adopting a mixed strategy. Understanding the neural basis of strategic decision making is complicated by the fact that it recruits various cognitive processes that are often shared with non-strategic forms of decision making, such as value estimation, working memory, response inhibition, response selection, and reward processes. Although researchers have explored neural activity within key brain regions during mixed-strategy games, how brain activity differs in the context of strategic interactions versus non-strategic choices is not well understood. We developed a novel behavioral paradigm to dissociate choice behavior during mixed-strategy interactions from non-strategic choices, and we used task-based functional magnetic resonance imaging (fMRI) to contrast brain activation. In a block design, participants competed in the classic mixed-strategy game, "matching pennies," against a dynamic computer opponent designed to exploit predictability in players' response patterns. Results were contrasted with a non-strategic task that had comparable sensory input, motor output, and reward rate; thus, differences in behavior and brain activation reflect strategic processes. The mixed-strategy game was associated with activation of a distributed cortico-striatal network compared to the non-strategic task. We propose that choosing in mixed-strategy contexts requires additional cognitive demands present to a lesser degree during the control task, illustrating the strength of this design in probing function of cognitive systems beyond core sensory, motor, and reward processes.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Tomada de Decisões , Humanos , Recompensa
17.
Eur J Neurosci ; 51(11): 2277-2298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31912932

RESUMO

We combined fMRI with eye tracking and speech recording to examine the neural and cognitive mechanisms that underlie reading. To simplify the study of the complex processes involved during reading, we used naming speed (NS) tasks (also known as rapid automatized naming or RAN) as a focus for this study, in which average reading right-handed adults named sets of stimuli (letters or objects) as quickly and accurately as possible. Due to the possibility of spoken output during fMRI studies creating motion artifacts, we employed both an overt session and a covert session. When comparing the two sessions, there were no significant differences in behavioral performance, sensorimotor activation (except for regions involved in the motor aspects of speech production) or activation in regions within the left-hemisphere-dominant neural reading network. This established that differences found between the tasks within the reading network were not attributed to speech production motion artifacts or sensorimotor processes. Both behavioral and neuroimaging measures showed that letter naming was a more automatic and efficient task than object naming. Furthermore, specific manipulations to the NS tasks to make the stimuli more visually and/or phonologically similar differentially activated the reading network in the left hemisphere associated with phonological, orthographic and orthographic-to-phonological processing, but not articulatory/motor processing related to speech production. These findings further our understanding of the underlying neural processes that support reading by examining how activation within the reading network differs with both task performance and task characteristics.


Assuntos
Leitura , Fala , Cognição , Linguística , Imageamento por Ressonância Magnética
18.
Hum Brain Mapp ; 41(7): 1934-1949, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31916374

RESUMO

Our ability to control and inhibit automatic behaviors is crucial for negotiating complex environments, all of which require rapid communication between sensory, motor, and cognitive networks. Here, we measured neuromagnetic brain activity to investigate the neural timing of cortical areas needed for inhibitory control, while 14 healthy young adults performed an interleaved prosaccade (look at a peripheral visual stimulus) and antisaccade (look away from stimulus) task. Analysis of how neural activity relates to saccade reaction time (SRT) and occurrence of direction errors (look at stimulus on antisaccade trials) provides insight into inhibitory control. Neuromagnetic source activity was used to extract stimulus-aligned and saccade-aligned activity to examine temporal differences between prosaccade and antisaccade trials in brain regions associated with saccade control. For stimulus-aligned antisaccade trials, a longer SRT was associated with delayed onset of neural activity within the ipsilateral parietal eye field (PEF) and bilateral frontal eye field (FEF). Saccade-aligned activity demonstrated peak activation 10ms before saccade-onset within the contralateral PEF for prosaccade trials and within the bilateral FEF for antisaccade trials. In addition, failure to inhibit prosaccades on anti-saccade trials was associated with increased activity prior to saccade onset within the FEF contralateral to the peripheral stimulus. This work on dynamic activity adds to our knowledge that direction errors were due, at least in part, to a failure to inhibit automatic prosaccades. These findings provide novel evidence in humans regarding the temporal dynamics within oculomotor areas needed for saccade programming and the role frontal brain regions have on top-down inhibitory control.


Assuntos
Fenômenos Fisiológicos do Sistema Nervoso , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Movimentos Sacádicos , Adulto , Mapeamento Encefálico , Potenciais Evocados/fisiologia , Movimentos Oculares/fisiologia , Feminino , Lobo Frontal/fisiologia , Lateralidade Funcional/fisiologia , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Campos Visuais , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 114(35): 9451-9456, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28808026

RESUMO

Models of visual attention postulate the existence of a bottom-up saliency map that is formed early in the visual processing stream. Although studies have reported evidence of a saliency map in various cortical brain areas, determining the contribution of phylogenetically older pathways is crucial to understanding its origin. Here, we compared saliency coding from neurons in two early gateways into the visual system: the primary visual cortex (V1) and the evolutionarily older superior colliculus (SC). We found that, while the response latency to visual stimulus onset was earlier for V1 neurons than superior colliculus superficial visual-layer neurons (SCs), the saliency representation emerged earlier in SCs than in V1. Because the dominant input to the SCs arises from V1, these relative timings are consistent with the hypothesis that SCs neurons pool the inputs from multiple V1 neurons to form a feature-agnostic saliency map, which may then be relayed to other brain areas.


Assuntos
Córtex Visual/fisiologia , Animais , Atenção/fisiologia , Macaca mulatta , Masculino , Neurônios/fisiologia , Estimulação Luminosa , Psicofísica , Tempo de Reação , Colículos Superiores , Vias Visuais/fisiologia
20.
J Neurophysiol ; 121(6): 2101-2111, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785808

RESUMO

We describe a novel behavioral method to accurately discriminate anticipatory (i.e., saccades not generated by visual input) from visually triggered saccades and to identify the minimal visual saccadic reaction time (SRT). This method can be used to calculate a feasible lower bound cutoff for latencies of visually triggered saccades within a certain experimental context or participant group. We apply this method to compute the minimal visual SRT for two different saccade target luminance levels. Three main findings are presented: 1) the minimal visual SRT for all participants was 46 ms shorter for bright targets than for dim targets, 2) the transition from non-visually triggered to visually triggered saccades occurred abruptly, independent of target luminance, and 3) although the absolute minimal visual SRTs varied between participants, the response pattern (response to bright targets being faster than to dim targets) was consistent across participants. These results are consistent with variability in saccadic and neural responses to luminance as has been reported in monkeys. On the basis of these results, we argue that differences in the minimal visual SRT can easily occur when stimuli vary in luminance or other saliency features. Applying an absolute cutoff (i.e., 70-90 ms) that approaches the minimal neuronal conduction delays, which is general practice in many laboratories, may result in the wrongful inclusion of saccades that are not visually triggered. It is suggested to assess the lower SRT bound for visually triggered saccades when piloting an experimental setup and before including saccades based on particular latency criteria. NEW & NOTEWORTHY We successfully developed an anticipation paradigm to discriminate between anticipatory and visually triggered saccades by measuring the minimal visual saccadic response time (SRT). We show that the 70- to 90-ms lower bound cutoff for visually triggered saccades should be applied in a flexible way and that the transitional interval is very short. The paradigm can be employed to investigate the effects of different stimulus features, experimental conditions, and participant groups on the minimal visual SRT in humans.


Assuntos
Antecipação Psicológica/fisiologia , Medições dos Movimentos Oculares/normas , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA