ABSTRACT
Evaluation of the magnitudes of intrinsically rewarding stimuli is essential for assigning value and guiding behavior. By combining parametric manipulation of a primary reward, medial forebrain bundle (MFB) microstimulation, with functional magnetic imaging (fMRI) in rodents, we delineated a broad network of structures activated by behaviorally characterized levels of rewarding stimulation. Correlation of psychometric behavioral measurements with fMRI response magnitudes revealed regions whose activity corresponded closely to the subjective magnitude of rewards. The largest and most reliable focus of reward magnitude tracking was observed in the shell region of the nucleus accumbens (NAc). Although the nonlinear nature of neurovascular coupling complicates interpretation of fMRI findings in precise neurophysiological terms, reward magnitude tracking was not observed in vascular compartments and could not be explained by saturation of region-specific hemodynamic responses. In addition, local pharmacological inactivation of NAc changed the profile of animals' responses to rewards of different magnitudes without altering mean reward response rates, further supporting a hypothesis that neural population activity in this region contributes to assessment of reward magnitudes.
Subject(s)
Nucleus Accumbens/physiology , Reward , Animals , Brain/physiology , Brain Mapping , Electric Stimulation , Magnetic Resonance Imaging , Male , Medial Forebrain Bundle/physiology , Psychometrics , Rats, Inbred LewABSTRACT
Uno de los problemas clave que se plantean en el trastorno de estrés postraumático (TEPT) es la incapacidad de inhibir el temor, incluso estando en unas condiciones seguras. Los fundamentos neurales que subyacen en el temor son clínicamente relevantes pero no se conocen bien. En este estudio se evaluó la potenciación y la inhibición del temor con el empleo del sobresalto potenciado por el temor en un procedimiento de discriminación condicionada (AX+/BX). Nuestra hipótesis fue que los pacientes con TEPT mostrarían una potenciación del temor normal, pero con un deterioro de su inhibición. Se estudió a 28 voluntarios sanos y 27 pacientes con TEPT (14 con síntomas actuales bajos, 13 con síntomas actuales altos) a los que se presentó un conjunto de luces de colores (ensayos AX) emparejadas con chorros de aire aversivos en la garganta, y una serie diferente de luces (ensayos BX) presentadas sin chorros de aire. A continuación se les presentaron conjuntamente A y B (ensayos AB) con objeto de determinar si B inhibía la potenciación del temor que se producía con A. Todos los grupos mostraron una potenciación clara del temor, por cuanto la magnitud del sobresalto fue significativamente mayor en los ensayos AX que en los ensayos con ruido solo. Sin embargo, el grupo de TEPT de síntomas altos no mostró una inhibición del temor: estos pacientes mostraban una potenciación del temor en los ensayos AB significativamente superior a la de los controles y a la de los pacientes con TEPT de síntomas bajos (AU)
One of the central problems in posttraumatic stress disorder (PTSD) is the inability to suppress fear even under safe conditions. The neural underpinnings of fear are clinically relevant but poorly understood. This study assessed fear potentiation and fear inhibition using fear-potentiated startle in a conditional discrimination procedure (AX+/BX). We hypothesized that patients with PTSD would show normal fear potentiation and impaired fear inhibition. Subjects comprised 28 healthy volunteers and 27 PTSD patients (14 with low current symptoms, 13 with high current symptoms) who were presented with one set of colored lights (AX trials) paired with aversive air blasts to the throat, and a different series of lights (BX trials) presented without air blasts. We then presented A and B together (AB trials) to see whether B would inhibit fear potentiation to A. All groups showed robust fear potentiation in that they had significantly greater startle magnitude on AX trials than on noise-alone trials. However, the highsymptom PTSD group did not show fear inhibition: these subjects had significantly greater fear potentiation on the AB trials than both the controls and the low-symptom PTSD patients (AU)
Subject(s)
Humans , Male , Female , Biological Psychiatry/methods , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/therapy , Electromyography , Combat Disorders/diagnosis , Combat Disorders/therapy , Stress Disorders, Post-Traumatic/epidemiology , Electromyography/methods , Electromyography/trends , Informed Consent/statistics & numerical data , Combat Disorders , 28599 , Analysis of VarianceABSTRACT
One of the central problems in posttraumatic stress disorder (PTSD) is the inability to suppress fear even under safe conditions. The neural underpinnings of fear are clinically relevant but poorly understood. This study assessed fear potentiation and fear inhibition using fear-potentiated startle in a conditional discrimination procedure (AX+/BX-). We hypothesized that patients with PTSD would show normal fear potentiation and impaired fear inhibition. Subjects comprised 28 healthy volunteers and 27 PTSD patients (14 with low current symptoms, 13 with high current symptoms) who were presented with one set of colored lights (AX trials) paired with aversive air blasts to the throat, and a different series of lights (BX trials) presented without air blasts. We then presented A and B together (AB trials) to see whether B would inhibit fear potentiation to A. All groups showed robust fear potentiation in that they had significantly greater startle magnitude on AX trials than on noise-alone trials. However, the high-symptom PTSD group did not show fear inhibition: these subjects had significantly greater fear potentiation on the AB trials than both the controls and the low-symptom PTSD patients.
Subject(s)
Fear/physiology , Inhibition, Psychological , Reflex, Startle/physiology , Stress Disorders, Post-Traumatic/diagnosis , Acoustic Stimulation , Color Perception/physiology , Conditioning, Classical/physiology , Discrimination, Psychological/physiology , Electromyography , Galvanic Skin Response/physiology , Humans , Male , Middle Aged , Photic Stimulation , Severity of Illness Index , Stress Disorders, Post-Traumatic/physiopathologyABSTRACT
Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating.
