Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
Neuropsychology ; 38(4): 368-378, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38300579

RESUMO

OBJECTIVE: Although early diagnosis and treatment prevent the severe impairments associated with untreated phenylketonuria (PKU), individuals with early treated PKU (ETPKU) nonetheless experience significant neurocognitive and psychological sequelae, including difficulties in working memory (WM) and increased risk of anxiety. The primary objective of the present study was to examine the extent to which anxiety may moderate the relationship between ETPKU and WM performance. METHOD: A sample of 40 adults with ETPKU and a demographically comparable sample of 40 healthy adults without PKU completed a comprehensive assessment of WM performance and anxiety symptomatology. Data were collected using a variety of remote assessment methods (e.g., web-based neurocognitive tests, semistructured interview, report-based measures). RESULTS: The ETPKU group demonstrated significantly poorer WM performance as compared to the non-PKU group. The groups did not differ significantly in anxiety; however, high anxiety was more common in the ETPKU group (53% of sample) than the non-PKU group (33%). A significant interaction between anxiety, metabolic control (as reflected by Phe levels), and WM performance was observed for the ETPKU group. Individuals with high anxiety and/or high Phe levels (> 360 µmol/L) performed poorer than the non-PKU group. Individuals with low anxiety and relatively low Phe levels (< 360 µmol/L) performed comparably to the non-PKU group. CONCLUSIONS: Anxiety was found to moderate the relationship between Phe levels and WM performance in individuals with ETPKU. This finding underscores the importance of accounting for anxiety when evaluating neurocognitive performance in individuals with ETPKU whether for research or clinical purposes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Ansiedade , Memória de Curto Prazo , Fenilcetonúrias , Humanos , Fenilcetonúrias/psicologia , Fenilcetonúrias/complicações , Masculino , Memória de Curto Prazo/fisiologia , Feminino , Adulto , Ansiedade/etiologia , Adulto Jovem , Testes Neuropsicológicos , Adolescente
2.
Obesity (Silver Spring) ; 32(1): 80-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37861062

RESUMO

OBJECTIVE: Neural activity in food reward- and appetite-related regions was examined in response to high-calorie (HC), low-calorie, and non-food pictures after exposure to written weight stigma (WS) content. Relationships with eating behavior (by Three-Factor Eating Questionnaire [TFEQ]), blood glucose, and subjective appetite were also explored. METHODS: Adults with overweight and obesity were randomized to read either a WS (n = 20) or control (n = 20) article and subsequently underwent brain scans while they rated pleasantness of food pictures. Fasting glucose, TFEQ, stigma experiences, and appetite were measured before reading the article, appetite after reading, and glucose and appetite again after the scan. RESULTS: A priori region of interest analyses revealed significant group differences in activation to HC > low-calorie food cues in the caudate and thalamus whereas exploratory whole-brain analyses suggested significant differences in regions including left insula, left thalamus, left inferior temporal gyrus, right lingual gyrus, and bilateral middle occipital gyrus and superior parietal lobule (p < 0.005 uncorrected, k ≥ 200 m3 ). No significant relationships were observed between the pattern of activation and TFEQ, glucose, or subjective appetite in the WS group. CONCLUSIONS: Exposure to WS was associated with increased responsiveness to HC food content in the dorsal striatum and thalamus in individuals with overweight and obesity.


Assuntos
Sobrepeso , Estereotipagem , Adulto , Humanos , Imageamento por Ressonância Magnética , Encéfalo/fisiologia , Apetite/fisiologia , Alimentos , Obesidade , Glucose , Recompensa , Sinais (Psicologia)
3.
Orphanet J Rare Dis ; 18(1): 222, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516884

RESUMO

BACKGROUND: Despite early diagnosis and compliance with phenylalanine (Phe)-restricted diets, many individuals with phenylketonuria (PKU) still exhibit neurological changes and experience deficits in working memory and other executive functions. Suboptimal choline intake may contribute to these impairments, but this relationship has not been previously investigated in PKU. The objective of this study was to determine if choline intake is correlated with working memory performance, and if this relationship is modified by diagnosis and metabolic control. METHODS: This was a cross-sectional study that included 40 adults with PKU and 40 demographically matched healthy adults. Web-based neurocognitive tests were used to assess working memory performance and 3-day dietary records were collected to evaluate nutrient intake. Recent and historical blood Phe concentrations were collected as measures of metabolic control. RESULTS: Working memory performance was 0.32 z-scores (95% CI 0.06, 0.58) lower, on average, in participants with PKU compared to participants without PKU, and this difference was not modified by total choline intake (F[1,75] = 0.85, p = 0.36). However, in a subgroup with complete historical blood Phe data, increased total choline intake was related to improved working memory outcomes among participants with well controlled PKU (Phe = 360 µmol/L) after adjusting for intellectual ability and mid-childhood Phe concentrations (average change in working memory per 100 mg change in choline = 0.11; 95% CI 0.02, 0.20; p = 0.02). There also was a trend, albeit nonsignificant (p = 0.10), for this association to be attenuated with increased Phe concentrations. CONCLUSIONS: Clinical monitoring of choline intake is essential for all individuals with PKU but may have important implications for working memory functioning among patients with good metabolic control. Results from this study should be confirmed in a larger controlled trial in people living with PKU.


Assuntos
Memória de Curto Prazo , Fenilcetonúrias , Humanos , Adulto , Criança , Estudos Transversais , Cognição , Colina
4.
Mol Genet Metab ; 139(1): 107579, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37099821

RESUMO

Among researchers and clinicians, there is a call for the development and validation of new measures to better assess and characterize neurocognitive difficulties associated with early-treated phenylketonuria (ETPKU) and other metabolic disorders. The NIH Toolbox represents a relatively new computer-administered assessment tool and provides a sampling of performance across multiple cognitive domains, several of which (e.g., executive function, processing speed) are at risk for disruption in ETPKU. The goal of the present study was to provide an initial evaluation of the value and sensitivity of the NIH Toolbox for use with individuals with ETPKU. To this end, a sample of adults with ETPKU and a demographically-matched comparison group without PKU completed the cognitive and motor batteries of the Toolbox. Results indicate that overall performance (as reflected by the Fluid Cognition Composite) was sensitive to both group differences (ETPKU vs non-PKU) as well as blood Phe levels (a marker of metabolic control). The present findings offer preliminary support for the utility of the NIH Toolbox as a measure of neurocognitive functioning in individuals with ETPKU. Future research including a larger sample size and broader age range is needed to fully validate the Toolbox for clinical and research use with individuals with ETPKU.


Assuntos
Cognição , Fenilcetonúrias , Humanos , Adulto , Testes Neuropsicológicos , Função Executiva , Velocidade de Processamento
5.
Dev Neuropsychol ; 47(8): 369-383, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36537866

RESUMO

The present study examined potential sex- and age-related differences in inhibitory control in adolescents with and without ASD. A computerized flanker visual filtering task and a go/no-go task were used to assess the ability to resist interference from visual distractors (RIVD) and prepotent response inhibition, respectively. Overall, the ASD and non-ASD groups performed comparably on both tasks and no sex-related differences or interactions (group-by-sex) were apparent. Consistent with past research, however, we did observe a significant age-related improvement in RIVD performance among the ASD group (but not the non-ASD group).


Assuntos
Transtorno do Espectro Autista , Adolescente , Feminino , Humanos , Masculino
6.
Mol Genet Metab ; 137(3): 249-256, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36209659

RESUMO

Abnormalities of the cortical white matter are the most prominent and widely-reported neurological findings in individuals with early-treated phenylketonuria (ETPKU). Much less is known regarding the effects of ETPKU on gray matter structures in the brain such as the basal ganglia. Previous findings on basal ganglia in ETPKU have been mixed. The current study was designed to further elucidate the effects of ETPKU and elevated phe levels on the morphometry of basal ganglia structures (i.e., putamen, caudate nucleus, nucleus accumbens, and globus pallidus). High resolution magnetic resonance imaging (MRI) data was collected from a sample of 37 adults with ETPKU and a demographically-matched comparison group of 33 individuals without PKU. No overall group differences (ETPKU vs. non-PKU) in basal ganglia volumes were observed. However, within the ETPKU group, poorer metabolic control (as reflected by higher blood phenylalanine levels) was associated with larger putamen volume. Vertex-wise shape analysis revealed that the volume increase was accompanied by shape changes in the middle left putamen. Consistent with this area's role in motor control, a significant correlation between left putamen volume and motor performance was also observed. Additional research is needed to fully understand the cellular level processes underlying this effect as well as to better understand the clinical impact of these morphometric changes and their potential relation to treatment response.


Assuntos
Gânglios da Base , Fenilcetonúrias , Adulto , Humanos , Gânglios da Base/diagnóstico por imagem , Putamen/diagnóstico por imagem , Núcleo Caudado , Imageamento por Ressonância Magnética/métodos
7.
Mol Genet Metab ; 137(1-2): 114-126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36027720

RESUMO

BACKGROUND: Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited. METHODS: Two meetings were held with a multidisciplinary international panel of 25 experts in PKU and comorbidities frequently experienced by patients with PKU. Based on the outcomes of the first meeting, a set of statements were developed. During the second meeting, these statements were voted on for consensus generation (≥70% agreement), using a modified Delphi approach. RESULTS: A total of 37 consensus recommendations were developed across five areas that were deemed important in the management of adolescents and young adults with PKU: (1) general physical health, (2) mental health and neurocognitive functioning, (3) blood Phe target range, (4) PKU-specific challenges, and (5) transition to adult care. The consensus recommendations reflect the personal opinions and experiences from the participating experts supported with evidence when available. Overall, clinicians managing adolescents and young adults with PKU should be aware of the wide variety of PKU-associated comorbidities, initiating screening at an early age. In addition, management of adolescents/young adults should be a joint effort between the patient, clinical center, and parents/caregivers supporting adolescents with gradually gaining independent control of their disease during the transition to adulthood. CONCLUSIONS: A multidisciplinary international group of experts used a modified Delphi approach to develop a set of consensus recommendations with the aim of providing guidance and offering tools to clinics to aid with supporting adolescents and young adults with PKU.


Assuntos
Fenilcetonúrias , Criança , Adolescente , Adulto Jovem , Humanos , Adulto , Consenso , Fenilcetonúrias/diagnóstico , Programas de Rastreamento
8.
Neuroimage Clin ; 34: 102974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35248901

RESUMO

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters. The aim of the present study was to examine neural correlates of working memory and its association with metabolic parameters in early-treated adults with PKU. METHODS: This cross-sectional study included 20 early-treated adults with PKU (mean age: 31.4 years ± 9.0) and 40 healthy controls with comparable age, sex, and education (mean age: 29.8 years ± 8.2). All participants underwent functional magnetic resonance imaging (fMRI) of working memory to evaluate the fronto-parietal working memory network. Fasting blood samples were collected from the individuals with PKU to acquire a concurrent plasma amino acid profile, and retrospective Phe concentrations were obtained to estimate an index of dietary control. RESULTS: On a cognitive level, early-treated adults with PKU displayed significantly lower accuracy but comparable reaction time in the working memory task compared to the control group. Whole-brain analyses did not reveal differences in working memory-related neural activation between the groups. Exploratory region-of-interest (ROI) analyses indicated reduced neural activation in the left and right middle frontal gyri and the right superior frontal gyrus in the PKU group compared to the control group. However, none of the ROI analyses survived correction for multiple comparisons. Neural activation was related to concurrent Phe, tyrosine, and tryptophan concentrations but not to retrospective Phe concentrations. CONCLUSION: In early-treated adults with PKU, cognitive performance and neural activation are slightly altered, a result that is partly related to metabolic parameters. This study offers a rare insight into the complex interplay between metabolic parameters, neural activation, and cognitive performance in a sample of individuals with PKU.


Assuntos
Memória de Curto Prazo , Fenilcetonúrias , Adulto , Estudos Transversais , Humanos , Fenilalanina/metabolismo , Fenilcetonúrias/diagnóstico por imagem , Estudos Retrospectivos , Tirosina
9.
J Autism Dev Disord ; 52(4): 1896-1902, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34009548

RESUMO

The present study evaluated the hypothesis that the strength of the relationship between executive function (EF) and repetitive behaviors and restricted interests (RBRI) symptomatology is moderated by the degree to which concurrent demands are placed on multiple aspects of EF. An eye movement task was used to evaluate inhibition and task switching ability (both together and in isolation) in a sample of 22 children with autism spectrum disorder (ASD). The Repetitive Behavior Scale-Revised (RBS-R) was used to assess the severity of RBRI symptoms. Results provide preliminary support for the aforementioned hypothesis. RBS-R scores were significantly correlated with task performance when simultaneous demands were placed on switching and inhibition; however, no such relationship was found for inhibition-only or switching-only task conditions.


Assuntos
Transtorno do Espectro Autista , Função Executiva , Transtorno do Espectro Autista/diagnóstico , Criança , Cognição , Função Executiva/fisiologia , Humanos , Inibição Psicológica
10.
Neuropsychology ; 35(7): 731-741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34323564

RESUMO

OBJECTIVE: Although past studies have documented motor control impairments in individuals with early-treated phenylketonuria (ETPKU), much less is known regarding motor learning in ETPKU. The goal of the present study was to advance our understanding on this front. METHOD: We isolated and examined motor kinematics associated with the learning of a rapid aimed limb movement in a sample of 40 individuals (13-34 years of age) with ETPKU and a matched comparison group of 40 individuals without phenylketonuria (PKU). Indices of motor learning included overall movement duration as well as the relative proportion of movement time devoted to ballistic and corrective submovements. (Note that practice of motor movements in nonclinical populations is associated with, not only improvements in overall speed, but also reduction in the proportion of movement time devoted to corrective submovements relative to an initial ballistic submovement.) Results: A group-by-time interaction was found. With practice, the non-PKU group showed a significant reduction in the proportion of movement time devoted to the corrected (as compared to the ballistic) submovement. A similar change was not observed for the ETPKU group. In addition, within the ETPKU group, the rate of improvement in total movement duration was correlated with recent blood phenylalanine levels (an indicator of treatment adherence). CONCLUSIONS: Motor learning is adversely affected in individuals with ETPKU. Further investigation into the behavioral and neural mechanisms of motor learning in ETPKU will advance our understanding of the etiologic basis for this disruption as well as how it relates to the broader neurocognitive profile of ETPKU. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Fenilcetonúrias , Humanos , Fenilcetonúrias/complicações , Fenilcetonúrias/psicologia , Aprendizagem
11.
Mol Genet Metab ; 132(1): 11-18, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334682

RESUMO

Even with early and continuous treatment, individuals with phenylketonuria (PKU) may exhibit abnormalities of cortical white matter (WM). The present study utilizes a new analysis approach called Automated Fiber-Tract Quantification (AFQ) to advance our understanding of the tract-specific patterns of change in WM abnormalities in individuals with early-treated PKU (ETPKU). Diffusion Tensor Imaging (DTI) data from a sample of 22 individuals with ETPKU and a demographically-matched sample of 21 healthy individuals without PKU was analyzed using AFQ. In addition, a subsample of 8 individuals with ETPKU was reevaluated six months later after demonstrating a significant reduction in blood phe levels following initiation of sapropterin treatment. Within-tract AFQ analyses revealed significant location-by-group interactions for several WM tracts throughout the brain. In most cases, ETPKU-related disruptions in mean diffusivity (MD) were more apparent in posterior (as compared to anterior) aspects of a given tract. Reduction in blood phe levels with the aforementioned ETPKU subsample was associated with a similar pattern of improvement (posterior-to-anterior) within most tracts. Taken together, these findings suggest that there is a systematic pattern of change in WM abnormalities in individuals with ETPKU in a posterior-to-anterior manner along individual WM tracts.


Assuntos
Encéfalo/metabolismo , Leucoencefalopatias/diagnóstico , Fenilcetonúrias/diagnóstico , Substância Branca/metabolismo , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Cognição/fisiologia , Imagem de Tensor de Difusão , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/metabolismo , Masculino , Fenilcetonúrias/diagnóstico por imagem , Fenilcetonúrias/metabolismo , Fenilcetonúrias/patologia , Substância Branca/anormalidades , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
12.
JCI Insight ; 5(20)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055427

RESUMO

Phenylalanine hydroxylase-deficient (PAH-deficient) phenylketonuria (PKU) results in systemic hyperphenylalaninemia, leading to neurotoxicity with severe developmental disabilities. Dietary phenylalanine (Phe) restriction prevents the most deleterious effects of hyperphenylalaninemia, but adherence to diet is poor in adult and adolescent patients, resulting in characteristic neurobehavioral phenotypes. Thus, an urgent need exists for new treatments. Additionally, rodent models of PKU do not adequately reflect neurocognitive phenotypes, and thus there is a need for improved animal models. To this end, we have developed PAH-null pigs. After selection of optimal CRISPR/Cas9 genome-editing reagents by using an in vitro cell model, zygote injection of 2 sgRNAs and Cas9 mRNA demonstrated deletions in preimplantation embryos, with embryo transfer to a surrogate leading to 2 founder animals. One pig was heterozygous for a PAH exon 6 deletion allele, while the other was compound heterozygous for deletions of exon 6 and of exons 6-7. The affected pig exhibited hyperphenylalaninemia (2000-5000 µM) that was treatable by dietary Phe restriction, consistent with classical PKU, along with juvenile growth retardation, hypopigmentation, ventriculomegaly, and decreased brain gray matter volume. In conclusion, we have established a large-animal preclinical model of PKU to investigate pathophysiology and to assess new therapeutic interventions.


Assuntos
Fígado/metabolismo , Fenilalanina Hidroxilase/genética , Fenilalanina/genética , Fenilcetonúrias/genética , Adolescente , Adulto , Animais , Sistemas CRISPR-Cas/genética , Dieta , Modelos Animais de Doenças , Edição de Genes , Humanos , Fígado/efeitos dos fármacos , Fenótipo , Fenilalanina/metabolismo , Fenilalanina/farmacologia , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/metabolismo , Fenilcetonúrias/patologia , Suínos
13.
Mol Genet Metab Rep ; 25: 100647, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32995290

RESUMO

Past murine studies of phenylketonuria (PKU) have documented significant effects on cerebellum at both the gross and cellular levels. The profile of neurocognitive and motor difficulties associated with early-treated PKU (ETPKU) is also consistent with potential cerebellar involvement. Previous neuroanatomical studies of cerebellum in patients with PKU, however, have yielded mixed results. The objective of the present study was to further examine potential differences in cerebellar morphometry between individuals with and without ETPKU. To this end, we analyzed high resolution T1-weighted MR images from a sample of 20 individuals with ETPKU and an age-matched comparison group of 20 healthy individuals without PKU. Measurements of whole brain volume, whole cerebellum volume, cerebellar gray matter volume, and cerebellar white matter volume were collected by means of semiautomatic volumetric analysis. Data analysis revealed no significant group differences in whole brain volume, whole cerebellar volume, or cerebellar white matter volume. A significant reduction in cerebellar gray matter volume, however, was observed for the ETPKU group compared to the non-PKU comparison group. These findings expand on previous animal work suggesting that cerebellar gray matter is impacted by PKU. It is also consistent with the hypothesis that the cognitive difficulties experienced by individuals with ETPKU may be related to disruptions in gray matter. Additional studies are needed to fully elucidate the timing and extent of the impact of ETPKU on cerebellum and the associated neurocognitive consequences.

14.
Neuropsychology ; 34(4): 456-466, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32202818

RESUMO

OBJECTIVE: Previous research has documented executive function (EF) impairments in individuals with early treated phenylketonuria (ETPKU). It remains unclear, however, whether some aspects of EF may be more affected than others. A number of factors, including small sample sizes and variability in EF tasks, have likely contributed to past mixed findings. The present objective was to elucidate further the EF profile associated with ETPKU, particularly as it relates to report-based assessment of EF. METHOD: Data from 286 individuals (5-48 years of age) with ETPKU on the child and adult versions of the Behavior Rating Inventory of Executive Function (BRIEF), a well-established report-based assessment tool, were analyzed. RESULTS: The Working Memory scale showed the largest effect size in both young and older ETPKU samples, with 19% of children and 29% of adults scoring in the "abnormally elevated" range. In addition, EF impairment appeared more general (i.e., affecting more domains) in the adult sample as compared to the child sample. Exploratory analyses also suggested that the presence/absence of overall impairment on the BRIEF among our ETPKU participants could be predicted based on a small subset of items. A 10-item subset showed total classification accuracy values of 90% and above for both groups. CONCLUSIONS: Working memory represents an aspect of EF that appears to be particularly affected in individuals with ETPKU. Findings also provide preliminary support of the viability for the development and/or adoption of an abbreviated screening measure for EF difficulties in children and adults with ETPKU. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Função Executiva , Testes Neuropsicológicos , Fenilcetonúrias/psicologia , Adolescente , Adulto , Envelhecimento/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Resolução de Problemas , Adulto Jovem
15.
Autism ; 24(3): 795-801, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31416333

RESUMO

Beta-adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol (beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Vias Neurais/efeitos dos fármacos , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Transtorno do Espectro Autista/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Propranolol/farmacologia , Adulto Jovem
16.
Neuroimage ; 208: 116407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809888

RESUMO

AIM: Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect. METHODS: Forty-five healthy participants (Mean age: 19.6 â€‹± â€‹1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task. RESULTS: There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene â€‹× â€‹stress interaction on solution latency was also observed. DISCUSSION: Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.


Assuntos
Conectoma , Criatividade , Idioma , Imageamento por Ressonância Magnética , Resolução de Problemas/fisiologia , Estresse Psicológico/fisiopatologia , Lobo Temporal/fisiologia , Adolescente , Adulto , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Lobo Temporal/diagnóstico por imagem , Adulto Jovem
17.
Brain Imaging Behav ; 14(6): 2708-2723, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31833016

RESUMO

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6 ± 1.6 years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.


Assuntos
Idioma , Imageamento por Ressonância Magnética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Masculino , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Lobo Temporal , Adulto Jovem
18.
J Abnorm Psychol ; 128(8): 881-891, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599633

RESUMO

Past findings on working memory (WM) ability in individuals with autism spectrum disorder (ASD) are mixed. The present objective was to assess not only the integrity of WM capacity, but also the potential contribution of filtering ability and attentional selection to WM performance, in individuals with ASD. A sample of 24 participants with ASD (Mage = 19.6 years) and 24 typically developing participants without ASD (Mage = 20.3 years) participated. Participants completed a computerized paradigm designed to systematically assess WM capacity, visual filtering ability, and attentional selection. In brief, participants were shown visual arrays consisting of 2-8 colored stimuli (circles and/or squares). After a short delay, memory for one of the stimuli was probed. Importantly, participants were informed beforehand that one of the shape types (e.g., circles) was more likely to be probed compared to the other shape type (e.g., squares) - thus making it strategically advantageous to focus on the high frequency shapes and to filter/ignore the low frequency shapes. Eye tracking data were simultaneously collected. The ASD group demonstrated intact WM capacity and filtering ability, but disrupted ability to efficiently allocate capacity under the demands of high WM load. Analysis of eye tracking data suggests the groups may have differed in their strategic approach to encoding stimuli which may have, in turn, contributed to the aforementioned impairment. Findings support the assertion that disruptions in secondary processes such as strategy use and attentional selection may have played a role in previous reports of WM impairment in ASD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Atenção/fisiologia , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/fisiopatologia , Transtornos da Memória/complicações , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
J Autism Dev Disord ; 49(1): 422-428, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30259287

RESUMO

Recent research has documented impaired ability to resist interference from visual distractors in individuals with autism spectrum disorder (ASD) and suggests that this phenomenon may be more pronounced in young versus older children (Christ et al., Neuropsychology 25(6):690-701, 2011). The present study extends previous findings by examining visual filtering inhibitory ability within an older adolescent population. A flanker visual filtering task was administered to 36 adolescents with ASD and 44 adolescents without ASD (age: 11-20 years). Analysis revealed no evidence of group differences in visual filtering performance. Taken together with previous research, these results suggest that during early adolescence the previously observed impairment may resolve or compensatory strategies develop, allowing individuals with ASD to perform as well as their neurotypical peers.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Filtro Sensorial , Percepção Visual , Adolescente , Criança , Feminino , Humanos , Masculino , Adulto Jovem
20.
Autism Res Treat ; 2017: 5843851, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29075533

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication. It has been postulated that such difficulties are related to disruptions in underlying cognitive processes such as executive function. The present study examined potential changes in executive function performance associated with participation in the Social Competence Intervention (SCI) program, a short-term intervention designed to improve social competence in adolescents with ASD. Laboratory behavioral performance measures were used to separately evaluate potential intervention-related changes in individual executive function component processes (i.e., working memory, inhibitory control, and cognitive flexibility) in a sample of 22 adolescents with ASD both before and after intervention. For comparison purposes, a demographically matched sample of 14 individuals without ASD was assessed at identical time intervals. Intervention-related improvements were observed on the working memory task, with gains evident in spatial working memory and, to a slightly lesser degree, verbal working memory. Significant improvements were also found for a working memory-related aspect of the task switching test (i.e., mixing costs). Taken together, these findings provide preliminary support for the hypothesis that participation in the SCI program is accompanied by changes in underlying neurocognitive processes such as working memory.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA