Nelson H. Donegan

Amygdala Hyperreactivity in Borderline Personality Disorder: Implications for Emotional Dysregulation.

BACKGROUND Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder

RationaleAbnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets.ObjectivesThe aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses.MethodsFunctional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions.ResultsThe group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants.ConclusionsAlthough the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala–frontal neural system to emotional stimuli.

Evaluation of Blocking and Conditioned Inhibition to a CS Signaling a Decrease in US Intensity

Two experiments employing a conditioned emotional response procedure with rats evaluated the associative tendencies acquired by a target CS when a compound of that stimulus and another CS was reinforced by a low-intensity US whereas the latter CS alone was reinforced by a higher intensity US. Experiment 1 involved a blocking sequence in which the element and compound trials occurred in successive phases, followed by eventual testing of the responding to the target CS alone. Less evidence of excitatory conditioning was observed than in a comparison group which had the element and compound paired with the same low-intensity US. Experiment 2 included contemporaneous differential reinforcement of the element and compound CSs and periodic summation tests in which the target CS was compounded with another independently trained CS. Clear evidence was obtained of the development of inhibitory tendencies by the target CS. The results are consistent with the predictions of the Rescorla-Wagner model and are discussed in relation to the several determining assumptions of the model.

Sensory preconditioning versus protection from habituation.

Yale UniversitySensory preconditioning was demonstrated in two experiments, one using ratsin a conditioned-emotional-response paradigm, the other using rabbits in aheart-rate conditioning situation. In each case subjects were initially trainedwith two pairs of potential conditioned stimuli (CSs) : Si paired with S

Potentiation or Diminution of Discrete Motor Unconditioned Responses (Rabbit Eyeblink) to an Aversive Pavlovian Unconditioned Stimulus by Two Associative Processes: Conditioned Fear and a Conditioned Diminution of Unconditioned Stimulus Processing

In two experiments using the rabbit conditioned eyeblink preparation, the conditions under which a Pavlovian conditioned stimulus (CS) potentiates or diminishes the unconditioned response (UR) were examined. The results indicated that, after discrimination training (CS+ vs. CS-), the CS+ diminished UR amplitude at the training interstimulus interval (ISI). When CS+ trials were segregated into trials on which a conditioned response (CR) did or did not occur, the CS+ diminished the UR when it elicited a CR, but not when a CR failed to occur. When the CS-unconditioned stimulus (US) interval was lengthened to 10 s, the CS+ reliably potentiated the eyeblink UR on CR trials but did not potentiate responding on trials on which a CR was absent. The results are discussed in terms of the modulatory effects and temporal properties of conditioned fear and an associatively produced decrement in US processing.

Some Relationships Between a Computational Model (Sop) and a Neural Circuit for Pavlovian (Rabbit Eyeblink) Conditioning

Publisher Summary This chapter presents an introductory-level description of the sometimes opponent process (SOP), which is an abstract model of animal learning and performance that was developed in an attempt to integrate conceptually the principal behavioral regularities of Pavlovian conditioning, emphasizing the essence of its propositions and some of the fundamental regularities that it addresses. SOP is a connectionist model—that is, the knowledge system is conceived as a set of nodes that take on activity states and are capable of influencing each other according to the excitatory and/or inhibitory connections obtained among them. Performance is attributed to a presumed tendency of activity in certain nodes to drive overt behavior, and the acquisition of conditioned responding is interpreted in terms of a presumed change in the way some nodes do this via alterations in the linkages that they have with other nodes. The chapter reviews the current knowledge concerning the essential neural circuitry involved in eyeblink conditioning in the rabbit.

Conditioned diminution of the unconditioned response in rabbit eyeblink conditioning: identifying neural substrates in the cerebellum and brainstem.

Several models of Pavlovian conditioning assume that processing of an unconditioned stimulus (US) is diminished by a conditioned stimulus (CS) with which it had been paired. Two experiments evaluated the hypothesis that US processing may be diminished by CS-dependent activation of the cerebellum. Experiment 1 showed that electrical brain stimulation (EBS) of the cerebellar interpositus nucleus diminished the peak amplitude of the rabbits unconditioned eyeblink response. This effect was bilateral, was systematically related to the intensity of EBS, maximal 50 ms after the offset of EBS, and substantially reversed by naloxone. Experiment 2 showed that inactivating the contralateral red nucleus with gamma-D-glutamylglycine blocked the decremental effect of interpositus stimulation. Implications for neural systems mediating the inhibitory effects of cerebellar activation and the antinociceptive role of noradrenergic and opioid systems in Pavlovian conditioning phenomena are discussed.