Philip M. McCabe

Sensorimotor and cognitive consequences of middle cerebral artery occlusion in rats

Rats were subjected to either right proximal middle cerebral artery (MCA) occlusion or sham operation, and examined for an extended period on a battery of tests designed to measure simple motor function, sensorimotor integration and cognitive function. Rats with MCA occlusion showed extensive neuronal loss in the dorsolateral striatum and variable neuron loss in the parietal, temporal and frontolateral neocortex. MCA occluded animals exhibited significant impairments in tests of postural reflex, visual and tactile forelimb placing, locomotor coordination, and a test of simultaneous bilateral tactile extinction. The reflex and sensorimotor function deficits recovered to pre-operative levels by Day 30 post-ischemia. Five weeks following surgery, rats were tested in 2 versions of the Morris water task. Rats with MCA occlusion demonstrated significant impairments in their ability to navigate to a hidden platform, but were not significantly impaired on the visible (cued) version of the task. This general pattern of transient sensorimotor and reflex deficits, but with more persistent cognitive impairments, is similar to that seen in humans following MCA infarcts.

Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats

The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37 degrees C (4VO-37) or 30 degrees C (4VO-30). Behavioral tests designed to assess forelimb reflexes and sensorimotor function were given on post-operative weeks 2 and 4. Beginning in week 5, the rats were trained on a variety of navigation problems in the Morris water maze. Histopathological examination of the tissue 2 months following reperfusion revealed that 4VO-37 animals sustained substantial cell death in hippocampal region CA1 and moderate damage to the dorsolateral neostriatum. 4VO-30 animals showed minimal cell death in CA1 and neostriatum. There were no group differences for any of the sensorimotor measures, or for acquisition performance on either the simple place task or visible platform version of the water maze. In contrast, during acquisition of the learning set task, the performance of 4VO-37 animals was impaired relative to either of the other groups, whereas the performance of 4VO-30 animals was not significantly different from the sham controls. These data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia.

Effects of guided imagery and music (GIM) therapy on mood and cortisol in healthy adults.

Healthy adults (N = 28) participated in a randomized trial of Bonny Method of Guided Imagery and Music (GIM; a depth approach to music psychotherapy) sessions on mood and cortisol. Participants in both GIM and wait-list control conditions completed the Profile of Mood States (POMS) and donated 15 cc of blood before and after the 13-week intervention period and again at a 6-week follow-up. Split-plot factorial and post hoc analyses demonstrated that after 6 biweekly sessions GIM participants reported significant decreases between pre- and postsession depression, fatigue, and total mood disturbance and had significant decreases in cortisol level by follow-up. Pretest to follow-up decrease in cortisol was significantly associated with decrease in mood disturbance. A short series of GIM sessions may positively affect mood and reduce cortisol levels in healthy adults. Such changes in hormonal regulation may have health implications for chronically stressed people.

The role of amygdaloid central nucleus in the retention of differential pavlovian conditioning of bradycardia in rabbits

The present study examined the role of the amygdaloid central nucleus (ACE) in the retention of differential pavlovian conditioning of bradycardia in rabbits. Electrodes were implanted bilaterally in ACE or in control sites just dorsal and rostral to ACE. Following recovery, animals were subjected to differential pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS-) was presented alone. Subsequent electrolytic lesions abolished the heart rate (HR) conditioned response (CR), yet had no effect on HR orienting response, unconditioned response, or baseline. In a follow-up experiment, corneoretinal potential (CRP) and HR were recorded. Bilateral ACE lesions profoundly attenuated or abolished the HR CR without abolishing CRP CRs. The major finding of this study is that bilateral lesions of ACE selectively attenuate the HR CR while not necessarily abolishing other CRs.

Cognitive-behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men.

This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.

Involvement of cortical and thalamic auditory regions in retention of differential bradycardiac conditioning to acoustic conditioned stimuli in rabbits

Our previous findings indicate that lesions in the medial division of the medial geniculate nucleus (mMGN) prevent the acquisition of differential conditioning of bradycardia to acoustic stimuli in rabbits. In the present experiment, the effect of lesions in mMGN on retention of differential bradycardiac conditioning was examined. In addition, the possible involvement of auditory cortex in differential conditioning was investigated. Electrodes were chronically implanted in mMGN, the ventral division of the medial geniculate nucleus (vMGN), or auditory cortex. After 7 days of recovery, animals received one differential Pavlovian conditioning session. At the end of the session, lesions were produced through the implanted electrodes. All animals demonstrated differential bradycardiac conditioning during the prelesion session. Animals with vMGN lesions also demonstrated differential conditioning during the postlesion session. However, mMGN and auditory cortex lesion animals failed to demonstrate differential conditioning during the postlesion session due to an increased response magnitude to the unpaired tone (CS-). These data support the hypothesis that mMGN plays a role in differential conditioning of bradycardia to tonal stimuli. In addition, these findings suggest that a possible corticothalamic pathway may be involved in the inhibition of the response to the CS-.

Stress, Coping and Depression

Contents: Preface. Part I: Child Development. T.M. Field, Infants of Depressed Mothers. E.Z. Tronick, M.K. Weinberg, Gender Differences and Their Relation to Maternal Depression. P.J. Marshall, N.A. Fox, Emotion Regulation, Depression, and Hemispheric Asymmetry. S.L. Johnson, T. Jacob, Moderators of Child Outcome in Families With Depressed Mothers and Fathers. Part II: Basic Adult Psychopathology. C. Hammen, Interpersonal Factors in an Emerging Developmental Model of Depression. P.H. Blaney, Stress and Depression: A Personality-Situation Interaction Approach. I.H. Gotlib, D.L. Neubauer, Information-Processing Approaches to the Study of Cognitive Biases in Depression. W.D. Scott, R.W. Winters, C.G. Beevers, Affective Distress as a Central and Organizing Symptom in Depression: Psychological Mechanisms. R.W. Winters, W.D. Scott, C.G. Beevers, Affective Distress as a Central and Organizing Symptom in Depression: Neurobiological Mechanisms. Part III: Treatment. R.J. DeRubeis, T.Z. Tang, L.A. Gelfand, M. Feeley, Recent Findings Concerning the Processes and Outcomes of Cognitive Therapy for Depression. M.H. Antoni, Effects of Cognitive Behavioral Stress Management Intervention on Depressed Mood, Distress Levels, and Immune Status in HIV Infection. K. Kilbourn, P. Saab, N. Schneiderman, Depression and Negative Affect in Post-Myocardial Infarction Patients: Assessment and Treatment Implications. A.M. Hayes, M.S. Harris, The Development of an Integrative Therapy for Depression. E.L. George, J.C. Friedman, D.J. Miklowitz, Integrated Family and Individual Therapy for Bipolar Disorder.

Cognitive-behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol:DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men

This study examined the effects of a 10-week cognitive-behavioral stress management (CBSM) intervention on dehydroepiandrosterone sulfate (DHEA-S) levels and the ratio of cortisol to DHEA-S (cortisol/DHEA-S), potential surrogate adrenal markers of HIV disease progression, in relation to alterations in mood and distress. HIV-seropositive men were randomized to either a group-based CBSM intervention (n = 43) or to a wait-list control group (n = 24), with both hormonal and distress measures assessed just prior to and immediately following the 10-week period. Results showed that CBSM buffers decreases in DHEA-S and increases in the cortisol/DHEA-S ratio. Further examination also revealed that changes in the cortisol/DHEA-S ratio were significantly and positively related to changes in total mood disturbance and perceived stress over time. These findings demonstrate that a short-term CBSM intervention can buffer against decrements in DHEA-S and increments in the cortisol/DHEA-S ratio among symptomatic, HIV-positive men, and that alterations in the cortisol/DHEA-S ratio move in concert with changes in mood and distress observed during CBSM.

Psychophysiologic Strategies in Laboratory Research

Psychophysiologic laboratory research has begun to play an important role in the study of biobehavioral aspects of cardiovascular regulation and putative disease processes. Progress has been made both in specifying task characteristics (e. g., psychological versus physical Stressors; active coping versus passive tasks) and in defining the experimental context of these tasks (e. g., instructions; experimenter effects; sociocultural factors; social interactions). Nevertheless, discrepant findings often occur between ostensibly similar experiments, in part because important differences in task characteristics have not always been recognized.

Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats

The present study was designed to determine whether postischemic hypothermia, delayed MK-801 (dizocilpine) administration, or a combination of these treatments can provide lasting neurobehavioral protection following transient global ischemia in rats. Rats were subjected to 10 min of normothermic (37 degrees C) ischemia induced by 2-vessel occlusion and hypotension (50 mmHg) or sham procedures. Ischemia was followed by either: (a) 3 h at normothermic brain temperatures, (b) 3 h of postischemic brain hypothermia at 30 degrees C, (c) hypothermia coupled with MK-801 (4 mg/kg, i.p.) on postischemic days 3, 5 and 7, or (d) postischemic MK-801 treatment alone. Neurobehavioral evaluation 6-8 weeks following surgery showed that normothermic ischemia (NI) was associated with water maze navigational deficits, including performance on a simple place task involving finding a hidden platform maintained in one position for 6 days, and a learning set task in which the platform was moved to a different location each day (both Ps < 0.02 vs. sham). NI was also associated with increased locomotion in an open field (P < 0.01 vs. sham). A combination of postischemic hypothermia and delayed MK-801 injections provided partial protection from ischemic-associated hyperactivity in the open field (P < 0.02 vs. NI), and robust protection from simple place task deficits (P < 0.02 vs. NI). Evidence for significant protective effects of MK-801 or hypothermia alone was observed in the learning set, during the final trial blocks each day. These results provide further evidence for neuroprotective effects of these treatments at chronic survival intervals, and indicate that the therapeutic window for attenuating ischemic damage is considerably longer than has heretofore been appreciated.