RESUMEN
Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery.
Asunto(s)
Alcoholismo , Mapeo Encefálico , Electroencefalografía , Humanos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Estimulación Magnética TranscranealRESUMEN
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact on cognition. Inhibitory processes and cognitive flexibility were examined in FRDA by assessing the ability to suppress a predictable verbal response. We administered the Hayling Sentence Completion Test (HSCT), the Trail Making Test, and the Stroop Test to 43 individuals with FRDA and 42 gender- and age-matched control participants. There were no significant group differences in performance on the Stroop or Trail Making Test whereas significant impairment in cognitive flexibility including the ability to predict and inhibit a pre-potent response as measured in the HSCT was evident in individuals with FRDA. These deficits did not correlate with clinical characteristics of FRDA (age of disease onset, disease duration, number of guanine-adenine-adenine repeats on the shorter or larger FXN allele, or Friedreich Ataxia Rating Scale score), suggesting that such impairment may not be related to the disease process in a straightforward way. The observed specific impairment of inhibition and predictive capacity in individuals with FRDA on the HSCT task, in the absence of impairment in associated executive functions, supports cerebellar dysfunction in conjunction with disturbance to cortico-thalamo-cerebellar connectivity, perhaps via inability to access frontal areas necessary for successful task completion.
Asunto(s)
Cognición , Función Ejecutiva , Ataxia de Friedreich/psicología , Inhibición Psicológica , Adolescente , Adulto , Edad de Inicio , Análisis de Varianza , Femenino , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Ataxia de Friedreich/fisiopatología , Humanos , Proteínas de Unión a Hierro/genética , Lenguaje , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Habla , Expansión de Repetición de Trinucleótido , Adulto Joven , FrataxinaRESUMEN
While Major Depressive Disorder (MDD) is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS), a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC) can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS) were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART) at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n = 21) and after 4 weeks (n = 13) of high-frequency (20 Hz) repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n = 26) were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer-term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment.
Asunto(s)
Atención/fisiología , Trastorno Depresivo Mayor/psicología , Corteza Prefrontal/fisiopatología , Adulto , Afecto/fisiología , Cognición/fisiología , Trastorno Depresivo Mayor/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Estimulación Magnética TranscranealRESUMEN
OBJECTIVES: Preclinical studies suggest that cortical alterations within the prefrontal cortex (PFC) are critical to the pathophysiology of alcohol dependence. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows direct assessment of cortical excitability and inhibition within the PFC of human subjects. We report the first application of TMS-EEG to measure these indices within the PFC of alcohol-dependent (ALD) patients post-detoxification. METHODS: Cortical inhibition was assessed in 12 ALD patients and 14 healthy controls through single and paired-pulse TMS paradigms. Long-interval cortical inhibition indexed cortical inhibition in the PFC. In the motor cortex (MC), short- interval intracortical inhibition and cortical silent period determined inhibition, while intracortical facilitation measured facilitation, resting and active motor threshold indexed cortical excitability. RESULTS: ALD patients demonstrated altered cortical inhibition across the bilateral frontal cortices relative to controls. There was evidence of altered cortical excitability in ALD patients; however, no significant differences in MC inhibition. CONCLUSIONS: Our study provides first direct evidence of reduced cortical inhibition in the PFC of ALD patients post-detoxification. Altered cortical excitability in the MC may reflect hyper-excitability within the cortex associated with chronic alcohol consumption. These findings provide initial neurophysiological evidence of disrupted cortical excitability within the PFC of ALD patients.
Asunto(s)
Alcoholismo/terapia , Electroencefalografía , Lóbulo Frontal/fisiopatología , Inhibición Neural , Estimulación Magnética Transcraneal , Adulto , Alcoholismo/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Although the experience of vicarious sensations when observing another in pain have been described postamputation, the underlying mechanisms are unknown. We investigated whether vicarious sensations are related to posttraumatic stress disorder (PTSD) symptoms and chronic pain. In Study 1, 236 amputees completed questionnaires about phantom limb phenomena and vicarious sensations to both innocuous and painful sensory experiences of others. There was a 10.2% incidence of vicarious sensations, which was significantly more prevalent in amputees reporting PTSD-like experiences, particularly increased arousal and reexperiencing the event that led to amputation (φ = .16). In Study 2, 63 amputees completed the Empathy for Pain Scale and PTSD Checklist-Civilian Version. Cluster analyses revealed 3 groups: 1 group did not experience vicarious pain or PTSD symptoms, and 2 groups were vicarious pain responders, but only 1 had increased PTSD symptoms. Only the latter group showed increased chronic pain severity compared with the nonresponder group (p = .025) with a moderate effect size (r = .35). The findings from both studies implicated an overlap, but also divergence, between PTSD symptoms and vicarious pain reactivity postamputation. Maladaptive mechanisms implicated in severe chronic pain and physical reactivity posttrauma may increase the incidence of vicarious reactivity to the pain of others.
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Amputación Quirúrgica/psicología , Desgaste por Empatía/epidemiología , Dolor/epidemiología , Sensación , Trastornos por Estrés Postraumático/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/efectos adversos , Amputados/psicología , Dolor Crónico/psicología , Desgaste por Empatía/psicología , Empatía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/psicología , Dimensión del Dolor , Miembro Fantasma/etiología , Prevalencia , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/psicologíaRESUMEN
OBJECTIVE: To determine the extent and nature of driving self-regulation in drivers with Parkinson disease (PD) and factors associated with self-regulatory practices. BACKGROUND: Although people with PD have consistently been shown to have driving impairments, few studies have examined self-regulatory driving practices and their relationship to driving performance. METHODS: We used a self-report driving questionnaire to examine driving self-regulation in 37 drivers with PD and 37 healthy age-matched controls. We also analyzed factors associated with self-regulatory practices, primarily demographic, disease-related, psychological, and simulated driving performance variables. RESULTS: The drivers with PD reported significantly higher rates of self-perceived decline in their driving ability (P=0.008) and driving significantly shorter distances per week (P=0.004) than controls. Unfamiliar situations (P=0.009), in-car distractions (P<0.001), low visibility conditions (P=0.004), and long journeys (P=0.003) were particularly challenging for the drivers with PD, and their pattern of driving avoidance mirrored these difficulties. The use of self-regulatory strategies among drivers with PD was associated with female sex (rho=0.42, P=0.009) and perceived decline in driving ability (rho=-0.55, P<0.001), but not with age or objective measures of disease severity, cognition, or simulated driving performance. CONCLUSIONS: Drivers with PD reported driving less overall and restricting their driving to avoid particularly difficult circumstances. Further research is warranted on effective use of self-regulation strategies to improve driving performance in people with PD.
Asunto(s)
Conducción de Automóvil/psicología , Enfermedad de Parkinson/psicología , Desempeño Psicomotor , Autoinforme , Autocontrol , Accidentes de Tránsito , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Encuestas y CuestionariosRESUMEN
Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women.
Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/fisiopatología , Actividad Motora/genética , Equilibrio Postural/genética , Postura/fisiología , ARN Mensajero/genética , Cognición , Función Ejecutiva , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/epidemiología , Síndrome del Cromosoma X Frágil/psicología , Humanos , Mutación , Riesgo , Factores SexualesRESUMEN
OBJECTIVE: This study investigated the relationship between motor performance and social-communicative impairment in children with ADHD-combined type (ADHD-CT). METHOD: An upper limb Fitts' aiming task was used as a measure of motor performance and the Social Responsiveness Scale as a measure of social-communicative/autistic impairment in the following groups: ADHD-CT (n = 11) and typically developing (TD) controls (n = 10). RESULTS: Children with ADHD-CT displayed greater variability in their movements, reflected in increased error variance over repeated aiming trials compared with TD controls. Motor performance variability was associated with social-communicative deficits in the ADHD-CT but not in the TD group. CONCLUSION: Social-communicative impairments further complicate the clinical picture of ADHD-CT; therefore, further research in this area is warranted to ascertain whether a particular pattern of motor disturbance in children with ADHD-CT may be clinically useful in identifying and assessing children with a more complex ADHD presentation.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno Autístico/complicaciones , Comunicación , Percepción de Movimiento/fisiología , Trastornos de la Destreza Motora/complicaciones , Destreza Motora/fisiología , Trastornos del Movimiento/diagnóstico , Adolescente , Brazo/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno Autístico/diagnóstico , Fenómenos Biomecánicos , Niño , Femenino , Humanos , Masculino , Trastornos de la Destreza Motora/diagnóstico , Trastornos del Movimiento/etiología , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Análisis y Desempeño de Tareas , Escalas de WechslerRESUMEN
OBJECTIVE: We sought to quantify subtle changes in motor control in multiple sclerosis (MS) using a Fitts law reciprocal aiming task presented on a computer touchscreen. BACKGROUND: Upper-limb motor control is impaired in MS. However, many commonly used motor assessments do not detect subtle changes in motor function or differentiate between aspects of movement such as planning and online control. Fitts law states that movement time varies as a function of task difficulty, with smaller targets and greater distances making the task more difficult. METHODS: We gave a Fitts aiming task to 22 patients with MS and 22 matched controls. We manipulated movement difficulty by changing the targets' size and distance apart. RESULTS: The patients spent a significantly longer time than the controls stationary in each target before starting the next movement, and had a lower peak velocity, suggesting deficits in movement planning. The patients also spent longer in the deceleration phase of each movement, indicating deficits in the online control of movement. CONCLUSIONS: The computerized Fitts task allows quick, easy, and sensitive measurement of subtle aspects of movement. This task should be useful in clinical and research settings for assessing MS motor symptoms, disease progression, and treatment efficacy.
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Movimiento , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Desempeño Psicomotor , Adulto , Estudios de Casos y Controles , Simulación por Computador , Progresión de la Enfermedad , Femenino , Humanos , Modelos Lineales , MasculinoRESUMEN
Recent studies report a higher risk of dementia and motor symptoms in females with the fragile X mental retardation 1 premutation (PM-carriers) than has hitherto been appreciated. Here, we use dual-task gait paradigms to identify potential markers of cognitive and motor decline in female PM-carriers. Spatiotemporal gait characteristics and variability of gait were assessed during single- and dual-task conditions in 28 female PM-carriers (mean age 41.32 ± 8.03 years) and 31 female controls with normal fragile X mental retardation 1 alleles (mean age 41.61 ± 8.30 years). Despite comparable gait characteristics at baseline, gait performance was significantly poorer for PM-carriers when performing concurrent working memory tasks (counting backwards by 3's or 7's) when compared with controls. Correlational analyses showed that low working memory capacity was significantly associated with dual-task interference for the gait domains of pace (speed, step length) and variability (step time, swing time) in PM-carriers. Multiple regression analyses further showed that the interaction between age and CGG repeat length was strongly predictive of gait variability during dual-task performance. These findings indicate for the first time that vulnerability in specific domains of gait control may act as sensitive surrogate markers of future decline in female PM-carriers.
Asunto(s)
Envejecimiento , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Estudios de Asociación Genética , Mutación , Trastornos Psicomotores/genética , Repeticiones de Trinucleótidos , Adulto , Femenino , Marcha , Heterocigoto , Humanos , Memoria a Corto Plazo , Persona de Mediana Edad , Trastornos Psicomotores/fisiopatología , Trastornos Psicomotores/psicología , Desempeño Psicomotor , Análisis de Regresión , RiesgoRESUMEN
This study aimed to compare the gait of children with ADHD - Combined Type (ADHD-CT) to typically developing (TD) children. Children with ADHD-CT (n=14; mean age 10 years 4 months) and a TD group (n=13; mean age 10 years 9 months) walked at self-selected slow, preferred and fast speed on an electronic walkway system. Participants completed a total of 15 walking trials; 5 trials per walking condition. Groups were matched on age, intellectual functioning, height and weight. In the preferred walking condition, there was no difference in spatio-temporal gait variables between the ADHD-CT and TD control groups. At self-selected fast speed, children with ADHD-CT were faster and walked with a higher cadence. The subtle alterations in gait pattern that may reflect a timing deficit is consistent with previous ADHD motor studies. In addition, this study extends previous studies in characterising the unique gait profile of non-medicated children with ADHD-CT where a diagnosis of autism spectrum disorder has been ruled out.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastornos Neurológicos de la Marcha/diagnóstico , Marcha , Equilibrio Postural , Caminata , Adolescente , Análisis de Varianza , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Estudios de Casos y Controles , Niño , Trastornos Generalizados del Desarrollo Infantil/complicaciones , Femenino , Trastornos Neurológicos de la Marcha/etiología , Humanos , MasculinoRESUMEN
Impulsivity is considered a core feature of problem gambling; however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports betting) and nonstrategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task, and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and nonstrategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers.
Asunto(s)
Función Ejecutiva/fisiología , Juego de Azar/fisiopatología , Conducta Impulsiva , Inhibición Psicológica , Adulto , Femenino , Juego de Azar/clasificación , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , AutoinformeRESUMEN
AIMS: To analyse problem gamblers' decision-making under conditions of risk and ambiguity, investigate underlying psychological factors associated with their choice behaviour and examine whether decision-making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. DESIGN: Cross-sectional study. SETTING: Out-patient treatment centres and university testing facilities in Victoria, Australia. PARTICIPANTS: Thirty-nine problem gamblers and 41 age, gender and estimated IQ-matched controls. MEASUREMENTS: Decision-making tasks included the Iowa Gambling Task (IGT) and a loss aversion task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. FINDINGS: Overall, problem gamblers performed more poorly than controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and their IGT decisions were associated with heightened attention to gains (P = 0.003) and less consistency (P = 0.002). Strategic problem gamblers did not differ from matched controls on either decision-making task, but non-strategic problem gamblers performed worse on both the IGT (P = 0.006) and the loss aversion task (P = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. CONCLUSIONS: Problem gamblers demonstrated poor decision-making under conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non-strategic (e.g. electronic gaming machines) problem gamblers differed in decision-making and the underlying psychological processes associated with their decisions.
Asunto(s)
Conducta Adictiva/psicología , Toma de Decisiones , Juego de Azar/psicología , Adulto , Atención , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Motivación , Pruebas Neuropsicológicas , Recompensa , Riesgo , Asunción de Riesgos , VictoriaRESUMEN
There is evidence which demonstrates that a subset of males with a premutation CGG repeat expansion (between 55 and 200 repeats) of the fragile X mental retardation 1 gene exhibit subtle deficits of executive function that progressively deteriorate with increasing age and CGG repeat length. However, it remains unclear whether similar deficits, which may indicate the onset of more severe degeneration, are evident in female PM-carriers. In the present study we explore whether female PM-carriers exhibit deficits of executive function which parallel those of male PM-carriers. Fourteen female fragile X premutation carriers without fragile X-associated tremor/ataxia syndrome and fourteen age, sex, and IQ matched controls underwent ocular motor and neuropsychological tests of select executive processes, specifically of response inhibition and working memory. Group comparisons revealed poorer inhibitory control for female premutation carriers on ocular motor tasks, in addition to demonstrating some difficulties in behaviour self-regulation, when compared to controls. A negative correlation between CGG repeat length and antisaccade error rates for premutation carriers was also found. Our preliminary findings indicate that impaired inhibitory control may represent a phenotype characteristic which may be a sensitive risk biomarker within this female fragile X premutation population.
Asunto(s)
Función Ejecutiva , Movimientos Oculares , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Inhibición Psicológica , Adulto , Femenino , Humanos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
Alcohol dependence, a chronic relapsing disorder, is characterized by an impaired ability to regulate compulsive urges to consume alcohol. Very few empirical studies have examined the presence of these executive deficits, how they relate to craving, and the enduring nature of these deficits during abstinence. As such, the current study aimed to characterize these cognitive deficits within a sample of 24 alcohol-dependent participants post-detoxification and 23 non-alcohol-dependent participants. Participants were administered the Sustained Attention to Response Task to measure response inhibition and sustained attention and the Random Number Generation Task to examine executive deficits. Correlations between cognitive performance and clinical measures of alcohol dependence were examined. As predicted, the alcohol-dependent group exhibited poorer performance across the domains of response inhibition, executive function, and attentional control. Cognitive performance was related to clinical measures of craving and years of alcohol consumption, whereas the duration of abstinence was not associated with improved cognitive performance. These findings highlight the need for therapeutic strategies to target these enduring neurocognitive deficits in improving the treatment of alcohol dependence.
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Abstinencia de Alcohol/psicología , Alcoholismo/complicaciones , Alcoholismo/psicología , Trastornos del Conocimiento/etiología , Comportamiento de Búsqueda de Drogas , Adolescente , Adulto , Alcoholismo/rehabilitación , Análisis de Varianza , Atención/fisiología , Femenino , Estudios de Seguimiento , Humanos , Inhibición Psicológica , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Tiempo de Reacción , Estadística como Asunto , Encuestas y Cuestionarios , Escalas de Wechsler , Adulto JovenRESUMEN
Fragile X Mental Retardation 1 (FMR1) premutation carriers (PM-carriers) have a defective trinucleotide expansion on the FMR1 gene that is associated with continuum of neuropsychological and mental disorders. Currently, little is known about the distinct subcomponents of executive function potentially impaired in female PM-carriers, and there have been no investigations into associations between executive function and incidences of mental disorders. A total of 35 female PM-carriers confirmed by Asuragen triple primed PCR DNA testing and 35 age- and intelligence-matched controls completed tests of executive function (i.e., response inhibition and working memory) and self-reported on social anxiety, depression, and ADHD predominantly inattentive (ADHD-PI) symptoms. Compared to controls, PM-carriers were significantly elevated on self-reported social anxiety and ADHD-PI symptoms. Irrespective of mental symptoms, female PM-carries performed significantly worse than controls on a response inhibition test, and further investigations revealed significant correlations between executive function performance and self-reported symptoms of anxiety, depression and ADHD-PI. Critically, among PM-carriers with good executive function performance, no women exceeded threshold markers for probable caseness of mental disorder. However, rates of probable caseness were elevated in those with average performance (response inhibition: social anxiety: 41.7%; depression: 20%; ADHD: 44.4%; working memory: social anxiety: 27.3%; depression: 9.1%; ADHD: 18.2%) and highly elevated for those with poor executive function performance (response inhibition: social anxiety: 58.3%; depression: 80%; ADHD: 55.6%; working memory: social anxiety: 100%; depression: 50%; ADHD: 83.3%). These data suggest that subtle executive dysfunction may be a useful neuropsychological indicator for a range of mental disorders previously reported in female PM-carriers.
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Ansiedad/genética , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno Depresivo/genética , Función Ejecutiva/fisiología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Adulto , Ansiedad/psicología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno Depresivo/psicología , Femenino , Humanos , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Psicológicas , Trastornos Psicóticos/genética , Trastornos Psicóticos/psicología , Conducta Social , Expansión de Repetición de Trinucleótido/genética , Adulto JovenRESUMEN
Atrophy of the dentate nucleus is one of the major neuropathological changes in Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM) degeneration in FRDA. In this study, we used advanced tractography techniques to quantitatively measure WM changes in the dentato-thalamic and dentato-rubral tracts, and correlated these changes with cognitive profiles of FRDA. We also analysed diffusivity changes of the thalamo-cortical tract to assess whether neurological degeneration of WM extends beyond the primary site of involvement in FRDA. Twelve genetically proven individuals with FRDA and 14 controls were recruited. Sixty directions diffusion tensor images were acquired. The WM bundles from the dentate nucleus were estimated using a constrained spherical deconvolution method and the diffusivity characteristics measured. The Simon task was used to assess cognitive profile of FRDA. The dentato-rubral, dentato-thalamic and thalamo-cortical tracts manifested significantly lower fractional anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA compared with controls. There was no difference in axial diffusivity between the two groups. The mean and radial diffusivity of the dentato-rubral tract was positively correlated with choice reaction time, congruent reaction time, incongruent reaction time and Simon effect reaction time and negatively with the larger GAA repeat. Significant changes in diffusivity characteristics were observed in the dentato-thalamic and thalamo-cortical tracts, suggesting extensive WM degeneration and affected WM structures in FRDA. Correlation of WM changes in the dentato-rubral tract with the cognitive assessment suggested that this tract is an important contributor to cognitive disturbances in FRDA.
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Núcleos Cerebelosos/patología , Trastornos del Conocimiento/patología , Ataxia de Friedreich/patología , Núcleo Rojo/patología , Adulto , Anisotropía , Corteza Cerebral/patología , Trastornos del Conocimiento/etiología , Imagen de Difusión Tensora , Femenino , Ataxia de Friedreich/complicaciones , Ataxia de Friedreich/genética , Humanos , Masculino , Degeneración Nerviosa , Fibras Nerviosas Mielínicas/patología , Vías Nerviosas/patología , Pruebas Neuropsicológicas , Tiempo de Reacción , Tálamo/patologíaRESUMEN
Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.
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Tronco Encefálico/patología , Cerebelo/patología , Ataxia de Friedreich/patología , Giro del Cíngulo/patología , Red Nerviosa/patología , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sustancia Blanca/patología , Adulto JovenRESUMEN
Motor overflow is overt involuntary movement that accompanies voluntary movement. This study investigated the change in overflow production across a timed trial and the factors that affected this profile. Seventeen children (aged 8-11 years), 17 young adults (aged 18-35 years), and 17 older adults (aged 60-80 years) performed a 5-s finger pressing task by exerting 33% or 66% of their maximal force output using either index finger. Overflow was recorded as force from the alternative index finger. Young adult overflow remained stable over the 5 s. The rate of overflow increase over time was significantly greater for children than young adults. There was also a tendency for a greater overflow increase in older adults than in young adults. This overflow gradient was also greater in the right hand, particularly for children. These findings indicate that the neurological processes underlying overflow production are age dependent. Overflow progressed in a dynamic fashion over the course of a trial in children and older adults, probably because of increased bilateral cortical activation and the facilitation of motor task performance. This study is unique in quantitatively capturing the dynamic profile of overflow production in healthy participants across the life span.
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Dedos/fisiología , Movimiento/fisiología , Contracción Muscular/fisiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis y Desempeño de Tareas , Factores de TiempoRESUMEN
Recent investigations report a higher risk of motor symptoms in females with the FMR1 premutation (PM-carriers) than has hitherto been appreciated. Here we examined basic sensorimotor and postural control under different sensory and attentional dual-task demands. Physiological performance and postural sway measures from the Physiological Profile Assessment (Lord et al., 2003 [39]) were conducted in 28 female PM-carriers (mean age: 41.32±8.03) and 31 female controls with normal FMR1 alleles (mean age: 41.61±8.3). Multiple regression analyses were conducted to examine the moderating role of CGG-repeat length on the relation between age and postural sway under dual-task interference. In female PM-carriers, our results showed significantly poorer proprioceptive awareness, slower reaction time, and greater postural displacement when performing a concurrent verbal fluency task. Significantly, these findings showed age- and genetically-modulated changes in dual-task postural displacement in the medio-lateral direction in female PM-carriers. These findings highlight the sensitivity of postural control paradigms in identifying early cerebellar postural changes that may act as surrogate markers of future decline in female PM-carriers.