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1.
Am J Psychiatry ; : appiajp201919060583, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32046535

RESUMO

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

2.
J Neurotrauma ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931657

RESUMO

There are no validated, objective diagnostic or prognostic biomarkers for sports-related concussion, which hinders evidence-based treatment for concussed athletes. While quantitative electrophysiology and diffusion tensor imaging are promising technologies for providing objective biomarkers for concussion, the degree to which they are related has not been systematically investigated in concussed athletes. This study examined whether diffusion metrics differentiated concussed athletes with prolonged recovery (n = 18) from nonconccused athletes (n = 13), and whether observed diffusion alterations related to electrophysiology. Collegiate athletes (N = 31) completed electrophysiology, neurocognitive, and magnetic resonance imaging. White matter diffusivity differed between the groups in multiple white matter tracts, including the corpus callosum, cingulum bundle, thalamic radiations, and the inferior fronto-occipital, inferior longitudinal, and uncinate fasciculi, but not after correction for multiple comparisons. The enhanced brain function index, a measure that combines electrophysiology and neurocognitive data, significantly correlated with altered diffusion in the concussed athletes. These preliminary findings suggest that the absolute deviation of diffusion metrics in concussed versus nonconcussed athletes may have clinically utility. Results also suggested that the enhanced brain function index may be sensitive to early changes from sports-related concussion.

3.
Mol Psychiatry ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358905

RESUMO

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

5.
Neuroimage Clin ; 25: 102106, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31896466

RESUMO

INTRODUCTION: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). MATERIALS AND METHODS: Children aged 8-16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons. RESULTS: No significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group. CONCLUSIONS: Post-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

6.
Int J Psychophysiol ; 132(Pt A): 99-104, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30040986

RESUMO

This investigation explored whether differences in cortical thickness could be detected in children who sustained a mild traumatic brain injury (mTBI) compared to those with orthopedic injury (OI) and whether cortical thickness related parental reporting of symptoms. To achieve this objective, FreeSurfer®-based cortical thickness measures were obtained in 330 children, 8 to 15 years of age, with either a history of mTBI or OI. Imaging was performed in all participants with the same 3 Tesla MRI scanner at six-months post-injury, where a parent-rated Post-Concussion Symptom Inventory (PCSI) was also obtained. Robust age-mediated reductions in cortical thickness were observed, but no consistent group-based differences between the mTBI and OI groups were observed. Also, the relation between mechanism of injury (i.e., sports-related, recreational, fall, motor vehicle accident or other) and cortical thickness was examined. Injuries associated with any type of abuse were excluded and children with OI could not have experienced a MVA. Mechanism of injury did not differentially relate to cortical thickness, although in the fall group, parental rating using the PCSI showed increased symptom reporting to be associated with reduced cortical thickness in the left interior frontal, temporal pole and lateral temporal lobe as well as in the right temporal pole. Results from these preliminary findings are discussed in terms of injury variables and developmental factors associated with mTBI in childhood.


Assuntos
Desenvolvimento do Adolescente , Traumatismos em Atletas/patologia , Concussão Encefálica/patologia , Córtex Cerebral/patologia , Desenvolvimento Infantil , Adolescente , Desenvolvimento do Adolescente/fisiologia , Traumatismos em Atletas/diagnóstico por imagem , Traumatismos em Atletas/fisiopatologia , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Desenvolvimento Infantil/fisiologia , Feminino , Humanos , Masculino
7.
Mol Psychiatry ; 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29895892

RESUMO

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

8.
Hum Brain Mapp ; 39(1): 232-248, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28990258

RESUMO

Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS. Hum Brain Mapp 39:232-248, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Encéfalo/fisiopatologia , Conectoma , Síndrome de DiGeorge/fisiopatologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Criança , Análise por Conglomerados , Conectoma/métodos , Síndrome de DiGeorge/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Estudos Longitudinais , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia
9.
J Neurosci Res ; 96(4): 626-641, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28984377

RESUMO

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Adolescente , Anisotropia , Encéfalo/anatomia & histologia , Encéfalo/patologia , Lesões Encefálicas Traumáticas/patologia , Criança , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia
10.
Sports Med Arthrosc Rev ; 24(3): e42-52, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27482782

RESUMO

Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Imagem por Ressonância Magnética , Neuroimagem/métodos , Tomografia Computadorizada por Raios X , Adolescente , Traumatismos em Atletas/diagnóstico por imagem , Criança , Humanos , Centros de Traumatologia
11.
Psychiatry Res ; 232(1): 106-14, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25748884

RESUMO

The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population.


Assuntos
Síndrome de DiGeorge/patologia , Fórnice/patologia , Hipocampo/patologia , Adolescente , Anisotropia , Criança , Síndrome de DiGeorge/genética , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Tamanho do Órgão , Esquizofrenia/genética
12.
Neuropsychology ; 28(4): 571-584, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24773414

RESUMO

OBJECTIVE: Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. METHOD: Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. RESULTS: Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII. CONCLUSION: Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/genética , Transtornos da Motilidade Ocular/etiologia , Insuficiência Ovariana Primária/complicações , Insuficiência Ovariana Primária/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Córtex Cerebelar/patologia , Transtornos Cognitivos/etiologia , Função Executiva/fisiologia , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/diagnóstico , Testes Psicológicos , Tempo de Reação/genética , Expansão das Repetições de Trinucleotídeos/genética , Adulto Jovem
13.
Hum Brain Mapp ; 35(9): 4518-30, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24578183

RESUMO

Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon (for nodal efficiency), and in the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task.


Assuntos
Encéfalo/patologia , Cromossomos Humanos X/genética , Proteína do X Frágil de Retardo Mental/genética , Expansão das Repetições de Trinucleotídeos , Adolescente , Adulto , Ataxia/genética , Conectoma , Imagem de Difusão por Ressonância Magnética , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Modelos Neurológicos , Vias Neurais/patologia , Tamanho do Órgão , Testes Psicológicos , Caracteres Sexuais , Tremor/genética , Adulto Jovem
14.
J Neurodev Disord ; 6(1): 45, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25937844

RESUMO

BACKGROUND: Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (fragile X-associated tremor/ataxia syndrome (FXTAS)) often accompanied by cognitive decline. Several broad domains are implicated as core systems of dysfunction in fXPCs, including perceptual processing of spatial information, orienting of attention to space, and inhibiting attention to irrelevant distractors. We tested whether orienting of spatial attention is impaired in fXPCs. METHODS: Participants were fXPCs or healthy controls (HCs) asymptomatic for FXTAS. In experiment 1, they were male and female children and adults (aged 7-45 years). They oriented attention in response to volitional (endogenous) and reflexive (exogenous) cues. In experiment 2, the participants were men (aged 18-48 years). They oriented attention in an endogenous cueing task that manipulated the amount of information in the cue. RESULTS: In women, fXPCs exhibited slower reaction times than HCs in both the endogenous and exogenous conditions. In men, fXPCs exhibited slower reaction times than HCs in the exogenous condition and in the challenging endogenous cueing task with probabilistic cues. In children, fXPCs did not differ from HCs. CONCLUSIONS: Because adult fXPCs were slower even when controlling for psychomotor speed, results support the interpretation that a core dysfunction in fXPCs is the allocation of spatial attention, while perceptual processing and attention orienting are intact. These findings indicate the importance of considering age and sex when interpreting and generalizing studies of fXPCs.

15.
J Neurodev Disord ; 4(1): 26, 2012 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-23148490

RESUMO

BACKGROUND: A previous study reported enhanced psychomotor speed, and subtle but significant cognitive impairments, modulated by age and by mutations in the fragile X mental retardation 1 (FMR1) gene in adult female fragile X premutation carriers (fXPCs). Because male carriers, unlike females, do not have a second, unaffected FMR1 allele, male fXPCs should exhibit similar, if not worse, impairments. Understanding male fXPCs is of particular significance because of their increased risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS). METHODS: Male fXPCs (n = 18) and healthy control (HC) adults (n = 26) aged less than 45 years performed two psychomotor speed tasks (manual and oral) and two visuospatial tasks (magnitude comparison and enumeration). In the magnitude comparison task, participants were asked to compare and judge which of two bars was larger. In the enumeration task, participants were shown between one and eight green bars in the center of the screen, and asked to state the total number displayed. Enumeration typically proceeds in one of two modes: subitizing, a fast and accurate process that works only with a small set of items, and counting, which requires accurate serial-object detection and individuation during visual search. We examined the associations between the performance on all tasks and the age, full-scale intelligent quotient, and CGG repeat length of participants. RESULTS: We found that in the magnitude comparison and enumeration tasks, male fXPCs exhibited slower reaction times relative to HCs, even after controlling for simple reaction time. CONCLUSIONS: Our results indicate that male fXPCs as a group show impairments (slower reaction times) in numerical visuospatial tasks, which are consistent with previous findings. This adds to a growing body of literature characterizing the phenotype in fXPCs who are asymptomatic for FXTAS. Future longitudinal studies are needed to determine how these impairments relate to risk of developing FXTAS.

16.
Neuropsychologia ; 50(10): 2408-14, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22732491

RESUMO

Computational models of hippocampal function propose that the hippocampus is capable of rapidly storing distinct representations through a process known as pattern separation. This prediction is supported by electrophysiological data from rodents and neuroimaging data from humans. Here, we test the prediction that damage to the hippocampus would result in pattern separation deficits by having memory-impaired patients with bilateral hippocampal damage study a series of objects or faces and then perform a modified recognition memory test. In the test phase, participants viewed true repetitions, novel foils, and lures that were perceptually and semantically related to the studied stimuli. Patients with hippocampal damage were unimpaired relative to matched controls in their baseline recognition memory. However, patients were less likely to uniquely identify lures as "similar" than matched controls, indicating an impairment in pattern separation processes following damage to the hippocampus.


Assuntos
Hipocampo/fisiopatologia , Transtornos da Memória/fisiopatologia , Reconhecimento Visual de Modelos/fisiologia , /fisiologia , Adulto , Feminino , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos da Memória/patologia , Pessoa de Meia-Idade , Testes Neuropsicológicos
17.
Front Hum Neurosci ; 5: 63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21808616

RESUMO

The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Although as a group fXPCs did not differ from healthy controls (HCs), we show that young adult female fXPCs show subtle age- and significant fragile X mental retardation 1 (FMR1) gene mutation-modulated cognitive function as tested by a basic numerical enumeration task. These results indicate that older women with the premutation and fXPCs with greater CGG repeat lengths were at higher risk for difficulties in the deployment of volitional attention required to count 5-8 items, but spared performance when spatial shifts of attention were minimized to subitize a few (1-3). Results from the current study add to a growing body of evidence that suggests the premutation allele is associated with a subtle phenotype and implies that the cognitive demands necessary for counting are less effectively deployed in female fXPCs compared to HCs.

18.
J Int Neuropsychol Soc ; 17(4): 746-50, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21554789

RESUMO

A previous study reported preliminary results of enhanced processing of simple visual information in the form of faster reaction times, in female fragile X premutation carriers (fXPCs). In this study, we assessed manual and oral motor reaction times in 30 female fXPCs and 20 neurotypical (NT) controls. Participants completed two versions of the reaction time task; one version required a manual motor response and the other version required an oral motor response. Results revealed that the female fXPCs displayed faster reaction times for both manual and oral motor responses relative to NT controls. Molecular measures including CGG repeat length, FMR1 mRNA levels, and age were not associated with performance in either group. Given previously reported age and CGG repeat modulated performance on a magnitude comparison task in this same group of premutation carriers, results from the current study seem to suggest that female fXPCs may have spared basic psychomotor functionality.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/psicologia , Tempo de Reação/fisiologia , Adulto , Comportamento de Escolha , Cognição/fisiologia , Interpretação Estatística de Dados , Feminino , Heterozigoto , Humanos , Destreza Motora , Testes Neuropsicológicos , Reação em Cadeia da Polimerase , Adulto Jovem
19.
Behav Brain Res ; 222(1): 117-21, 2011 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-21440572

RESUMO

The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG trinucleotide repeat lengths between 70 and 350 has been developed and used to model the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial and temporal information. To characterize the motor deficits associated with the fragile X premutation, male and female CGG KI mice ranging from 2 to 16 months of age with trinucleotide repeats ranging from 72 to 240 CGG in length were tested for their ability to perform a skilled ladder rung walking test. The results demonstrate that both male and female CGG KI mice showed a greater number of foot slips as a function of increased CGG repeat length, independent of the age of the animal or general activity level.


Assuntos
Envelhecimento/genética , Proteína do X Frágil de Retardo Mental/genética , Transtornos dos Movimentos/genética , Desempenho Psicomotor/fisiologia , Caracteres Sexuais , Expansão das Repetições de Trinucleotídeos/genética , Análise de Variância , Animais , Comportamento Animal/fisiologia , Feminino , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transtornos dos Movimentos/fisiopatologia
20.
Brain Cogn ; 75(3): 255-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21295394

RESUMO

The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Here we show that young adult female fXPCs show subtle, yet significant, age- and FMR1 gene mutation-modulated cognitive impairments as tested by a quantitative magnitude comparison task. Our results begin to define the neurocognitive endophenotype associated with the premutation in adults, who are at risk for developing a neurodegenerative disorder associated with the fragile X premutation. Results from the present study may potentially be applied toward the design of early interventions wherein we might be able to target premutation carriers most at risk for degeneration for preventive treatment.


Assuntos
Transtornos Cognitivos/genética , Cognição/fisiologia , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Inteligência/genética , Adulto , Análise de Variância , Transtornos Cognitivos/complicações , Transtornos Cognitivos/psicologia , Endofenótipos , Feminino , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/psicologia , Heterozigoto , Humanos , Testes de Inteligência , Mutação , Testes Neuropsicológicos
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