RESUMEN
Disrupted sensorimotor gating has been found in various neuropsychiatric conditions which are characterized by impaired attention, poor impulse control, dysfunctional dopamine neurotransmission, and neurodevelopmental deficits. We investigated sensorimotor gating by prepulse inhibition (PPI) of the acoustic startle eyeblink reflex in 23 young adults diagnosed with attention deficit hyperactivity disorder (ADHD) as children and still symptomatic at the time of testing and 29 age-matched healthy control subjects. Sensorimotor gating was assessed in a passive listening task at prepulse-to-startle probe intervals of 30, 60, 120, 240, and 480 ms, and subsequently at prepulse-to-startle probe intervals of 60, 120, 240, and 480 ms whilst participants were performing a two-tone auditory discrimination task on the prepulse. Consistent with increased neural maturity and partially remitted symptomatology, our results indicate intact sensorimotor gating for both tasks in adult ADHD with no comorbidity, independent of the subjects' gender and whether ADHD subjects were receiving ongoing stimulant treatment or not. Reduced PPI at 120-ms lead intervals, on the other hand, was recorded in a subset of 10 ADHD subjects who were taken off their prescribed regular stimulants for 24 h and tested in a randomized counterbalanced order for on vs. off medication. However, our data remained inconclusive as to whether this observation constitutes beneficial treatment or acute stimulant withdrawal effects on sensorimotor gating.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Filtrado Sensorial/fisiología , Estimulación Acústica/métodos , Adolescente , Parpadeo/fisiología , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: A reduction in the size of the auditory event-related potential component known as mismatch negativity (MMN) is a consistent finding in schizophrenia. This study was designed to test the hypothesis that sound intensity and duration might be more sensitive to MMN reduction early in the development of schizophrenia because of the computational complexity in extracting these two sound dimensions. METHODS: The MMN elicited to sounds deviating in duration, frequency, or intensity was measured in participants with a short (n = 14, mean 2.6 years) and longer length of illness (n = 29, mean 18.9 years) relative to healthy age-matched control subjects. RESULTS: For participants early in the illness, a clear reduction was evident in MMN to duration and intensity but not frequency deviants. A different pattern was observed in patients with a longer length of illness--that is, a reduction in frequency and in duration to a lesser degree but not intensity MMN. CONCLUSIONS: The results indicate a pronounced age-related decline in duration and intensity MMN in control subjects that might reduce the sensitivity of these indices in schizophrenia when measured later in the course of the illness. The MMN elicited to changes in different sound properties provides potentially complementary information on the onset and progression of neuropathological changes that underlie the reduction in MMN in schizophrenia.
Asunto(s)
Variación Contingente Negativa , Potenciales Evocados Auditivos , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Estimulación Acústica/métodos , Adolescente , Adulto , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Relación Dosis-Respuesta en la Radiación , Electroencefalografía , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMG-recorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.
Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Imagen por Resonancia Magnética , Inhibición Neural/fisiología , Reflejo de Sobresalto/fisiología , Estimulación Acústica/métodos , Adulto , Estimulación Eléctrica , Electromiografía/métodos , Potenciales Evocados Auditivos/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Red Nerviosa/irrigación sanguínea , Red Nerviosa/fisiología , Oxígeno/sangre , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
BACKGROUND: Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. METHODS: The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. RESULTS: Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. CONCLUSIONS: In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.