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Biomedical subjects

G G Berntson

Publications and source records attributed to G G Berntson.

At least 19 recordsLinked to original sources

Blockade of epinephrine priming of the cerebral auditory evoked response by cortical cholinergic deafferentation.

The present study tested hypotheses derived from a neurobehavioral model of anxiety that posits an important role of the basal forebrain cholinergic system in the cortical processing of anxiety-associated stimuli and contexts. We hypothesized that visceral afferent activity induced by systemic administration of epinephrine would enhance the processing of auditory stimuli as evidenced by the cerebral auditory evoked response. We further predicted that selective lesions of the basal forebrain cortical cholinergic projection system would disrupt this processing, and would further block the effects of epinephrine. Results confirmed these hypotheses. Epinephrine was found to enhance the amplitude of the P70 component of the auditory evoked response in rats. Selective lesions of the basal forebrain corticopetal cholinergic projection, by intrabasalis infusions of 192 IgG saporin, delayed and reduced the amplitude of the P70 component, and blocked the potentiating effects of epinephrine on the auditory evoked response. The present results are consistent with the view that visceral afferent input may modulate cortical processing of sensory signals via the basal forebrain cholinergic system. These considerations emphasize the potential importance of ascending, bottom-up modulation of processing by telencephalic circuits that may impact on a wide range of behavioral functions.

Acetylcholine↗

Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour.

The present study examined the role of the basal forebrain corticopetal cholinergic projection in the regulation of cortical electroencephalographic activity across sleep/wake states in rats. Selective lesions of this projection were effected by local intraparenchymal infusions of the immunotoxin 192 IgG-saporin. Lesions spared the septo-hippocampal cholinergic system, as well as p75-receptor-bearing noncholinergic neurons in the suprachiasmatic nucleus. Relative to sham-lesioned control animals, rats with lesions of basal forebrain cholinergic neurons displayed a significant reduction in high frequency EEG activity, characterized especially by a reduction in gamma EEG power. Lesions did not significantly alter the overall proportion of sleeping and waking states as defined behaviourally, but the attenuation of high frequency EEG activity was apparent across all stages, including REM-like periods. Results are consistent with the view that the basal forebrain corticopetal cholinergic system exerts a general activational effect on the cortical mantle. Although this system may not be essential for sleep/wake stage-switching, it does impact on the cortical states associated with those stages.

Action Potentials↗

Psychotogenic properties of benzodiazepine receptor inverse agonists.

The neurochemical, behavioral, and cognitive effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug traditionally described as exhibiting 'anxiogenic' effects, are proposed to model core components of present theories of the neuronal mechanisms of schizophrenia. FG activates the mesolimbic dopaminergic system and, via increases in dopaminergic activity in the nucleus accumbens, disinhibits corticopetal cholinergic projections. The latter effect of FG is hypothesized to mediate the hyperattentional impairments that contribute to the development of psychotic cognition. Furthermore, the FG-induced abnormal overprocessing of conditioned stimuli and contexts provides an explanation of the 'anxiogenic' effects of FG. The FG-induced increases in the activity of cortical cholinergic inputs and the FG-induced cognitive impairments in rats and monkeys were demonstrated to be attenuated by the administration of typical and atypical antipsychotic drugs. Compared to the classic psychotogenic drugs amphetamine and phencyclidine, the effects of FG serve as an alternative psychotogenic manipulation in research focusing on the cortical and cognitive aspects of current theories of schizophrenia.

Acetylcholine↗

Size matters: impact of item size and quantity on array choice by chimpanzees (Pan troglodytes).

The authors previously reported that chimpanzees (Pan troglodytes) showed a striking bias to select the larger of 2 candy arrays, despite a reversed reward contingency in which the animals received the smaller, nonselected array as a reward, except when Arabic numerals were used as stimuli. A perceptual or incentive-based interference occurred that was overcome by symbolic stimuli. The authors of the present study examined the impact of element size in choice arrays, using 1 to 5 large and small candies. Five test-sophisticated chimpanzees selected an array from the 2 presented during each trial. Their responses were not optimal, as animals generally selected arrays with larger total mass; thus, they received the smaller remaining array as a reward. When choice stimuli differed in size and quantity, element size was more heavily weighted, although choices reflected total candy mass. These results replicate previous findings showing chimpanzees' difficulties with quantity judgments under reverse reward contingencies and also show that individual item size exerts a more powerful interference effect.

Animals↗

Cardiovascular and endocrine reactivity in older females: intertask consistency.

Age-related structural and functional changes in the cardiovascular, sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA) systems may affect the ability to reliably identify individual differences in response to stress. Heart rate, preejection period, respiratory sinus arrhythmia, respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol were assessed in 64 healthy older women (mean = 67 years) in response to a mental arithmetic and public-speaking task. All cardiovascular and endocrine measures changed significantly during the tasks. All measures were consistent across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this sample exhibited cross-task consistency in the relative activation of the autonomic, SAM, and HPA systems (i.e., response profiles). Further research is recommended to examine the significance of consistent individual differences in response profile.

Aged↗

New ambulatory impedance cardiograph validated against the Minnesota Impedance Cardiograph.

The validity and reliability of a new ambulatory impedance cardiograph (AZCG) was tested against the Minnesota Impedance Cardiograph (ZCG) during rest, orthostasis, and mental stress. Impedance cardiography allows noninvasive assessment of stroke volume, cardiac output, and systolic time intervals. A reliable ambulatory device would allow studies outside the lab. The devices were compared at two sites in healthy subjects. In both studies, the AZCG tracked changes across conditions closely with the ZCG (all Period x Device interactions were nonsignificant). Pearson rs, were .65 to .93, random intraclass correlation coefficients ranged from .80 to .98, indicating high degrees of shared measurement variance, and Cronbach's alpha indicated very good internal reliabilities (.91 to .99). Relative to the ZCG, the new AZCG appears to provide valid and reliable estimates of cardiac function at rest and during behavioral challenges in the lab.

Adult↗

Autonomic and neuroendocrine responses to mild psychological stressors: effects of chronic stress on older women.

We investigated autonomic and endocrine responses to acute stressors in 27 women who were or are presently caring for a spouse with a progressive dementia (high chronic stress) and 37 noncaregivers who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and in response to brief laboratory stressors (high acute stress). We replicated prior research showing that caregivers report greater stress, depression, and loneliness than the comparison groups, and acute stressors elevate autonomic and neuroendocrine activity. We also found that caregivers, relative to noncaregivers, exhibited shorter preejection periods and elevated blood pressure and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to the experimental stressors was comparable across these groups. This pattern of autonomic differentiation replicates prior research showing that caregivers are characterized by higher sympathetic activation than noncaregivers and suggests that the effects of chronic stress on physiological reactivity may be a less robust effect in older adults.

Adaptation, Psychological↗

Attenuation of the bidirectional effects of chlordiazepoxide and FG 7142 on conditioned response suppression and associated cardiovascular reactivity by loss of cortical cholinergic inputs.

RATIONALE: Basal forebrain cortical cholinergic projections have been hypothesized to mediate the enhanced cardiovascular defensive response initiated by the putative anxiogenic benzodiazepine receptor (BZR) partial inverse agonist FG 7142 (FG). The present study was designed to test the broader hypothesis that the integrity of this cholinergic projection is required for the mediation of the bidirectional modulatory effects of BZR agonists and inverse agonists on anxiety and associated cardiovascular reactivity. OBJECTIVES: The interactions between the effects of 192 IgG-saporin-induced lesions of basal forebrain corticopetal cholinergic neurons and of the BZR agonist chlordiazepoxide (CDP) and FG on the performance of rats tested in a conditioned suppression paradigm and on associated cardiovascular reactivity were assessed. METHODS: Lesioned and control animals were equipped with a telemetric device to record heart rate, trained in an operant lever task, and then tested for suppression of responding during presentation of a conditioned stimulus (CS) and a general contextual cue that was previously associated with shock. FG, CDP (8 mg/kg) and vehicle were administered IP in separate extinction sessions. RESULTS: In control animals, operant responding was suppressed during presentation of the CS and contextual cue. Administration of FG enhanced this suppression, while CDP attenuated it. Lesions attenuated overall response suppression as well as the modulatory effects of BZR ligands on responding during presentation of the contextual stimulus. Likewise, lesions attenuated the cardioacceleratory response to the contextual stimulus and the ability of the BZR ligands to modulate this response. CONCLUSIONS: The behavioral and autonomic responses to anxiety-related stimuli, as well as the modulatory effects of BZR ligands, are mediated in part via cortical cholinergic inputs.

Animals↗

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Humans↗

Multilevel integrative analyses of human behavior: social neuroscience and the complementing nature of social and biological approaches.

Social and biological explanations traditionally have been cast as incompatible, but advances in recent years have revealed a new view synthesized from these 2 very different levels of analysis. The authors review evidence underscoring the complementing nature of social and biological levels of analysis and how the 2 together can foster understanding of the mechanisms underlying complex behavior and the mind. Specifically, they review the utility of considering social influences on biological processes that are often viewed as outside the social domain including genetic constitution, gene expression, disease, and autonomic, neuroendocrine, and immune activity. This research underscores the unity of psychology and the importance of retaining multilevel integrative research that spans molar and molecular levels of analysis. Especially needed in the coming years is more research on the mechanisms linking social and biological events and processes.

Forecasting↗

Psychobiology and social psychology: past, present, and future.

Social psychology and psychobiology have a rich historical connection, although over the last half century these two disciplines have seemingly become estranged. To a significant extent, that alienation arose from an archaic and nonviable model of behavioral biology that retarded the development of both disciplines. With the emergence of modern biological perspectives, this impediment no longer limits fruitful collaborations among social psychologists and psychobiologists. Indeed, some of the most exciting contemporary developments are emerging from the areas of social neuroscience, cognitive neuroscience, and behavioral neuroscience. We review the history of links between social psychology and psychobiology, the factors that led to the segregation of these subdisciplines, and the modern biological perspectives that provide the basis for reintegration of these disciplines.

Journal Article↗

Cholinergic inputs to the rat medial prefrontal cortex mediate potentiation of the cardiovascular defensive response by the anxiogenic benzodiazephine receptor partial inverse agonist FG 7142.

Consistent with its putative anxiogenic actions, administration of the benzodiazepine receptor partial inverse agonist FG 7142 has been shown to potentiate defensive-like cardiovascular reactivity to an acoustic stimulus in the rat, an effect that appears to be mediated by the basal forebrain cholinergic system. The present studies tested the hypothesis that the basal forebrain cholinergic projections to the medial prefrontal cortex, an area that has been implicated in both anxiety and autonomic control, may be a relevant pathway underlying this response potentiation. Infusions of the muscarinic receptor agonist carbachol into the medial prefrontal cortex, but not into the lateral prefrontal cortex or the basolateral amygdala, mimicked the effects of systemically administered FG 7142 on the cardioacceleratory response. Infusions of the muscarinic antagonist atropine blocked this effect, as well as the response-potentiating actions of FG 7142. The effects of FG 7142 were also blocked by lesions of the cholinergic inputs to the medial prefrontal cortex produced by local infusions of the immunotoxin 192 immunoglobulin G-saporin into this area. These findings indicate that cholinergic activation of the medial prefrontal cortex is sufficient to enhance the cardioacceleratory defensive response, and that cholinergic inputs to the medial prefrontal cortex are necessary for the response-potentiating effects of FG 7142. These results are consistent with a recent neurobiological model of anxiety and autonomic control that attributes the enhanced processing of anxiety-related stimuli and contexts to increases in activity in cortical cholinergic inputs.

Animals↗

Impedance pneumography: noise as signal in impedance cardiography.

Thoracic impedance is modulated by events within the respiratory cycle, which represents a source of "noise" in impedance cardiography. Respiration itself, however, is a physiological rhythm of interest to psychophysiologists. We report here methods and validation for deriving impedance pneumographic measures of respiration from impedance cardiography signals, based on standard tetrapolar band electrodes. We recorded the change in impedance (delta Z), the first derivative of the change in impedance (dZ/dt), output from a strain-gauge respirometer, and criterion spirometry from eight healthy adults during rest, paced breathing, abdominal breathing, thoracic breathing, and a mental arithmetic task. Transfer function analyses revealed that a delta Zd signal (derived by integration of the dZ/dt signal) provided the best estimate of the criterion spirometric measure for all parameters (coherence, phase, and gain), accounting for almost 90% of the variance in respiratory waveform morphology. The results document the potential utility of impedance pneumography, as derived from standard impedance cardiography signals.

Adult↗

Social stress and the reactivation of latent herpes simplex virus type 1.

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpesviruses.

Animals↗

Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis.

We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12-min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin-1 beta (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress-related changes in HPA activation also exhibited the greatest diminution in cellular immune response.

Autonomic Nervous System↗

Food intake in Prader-Willi syndrome and controls with obesity after administration of a benzodiazepine receptor agonist.

Benzodiazepine receptor (BZR) agonists, used extensively for their anxiolytic effects, have been shown to increase food intake in many mammalian species. Little information, however, is available on the effects of BZR agonists on feeding behaviors of humans. Food intake was evaluated in a 60-minute free-feeding standardized test after the acute administration of the BZR agonist chlordiazepoxide (CDP, Librium; 5 mg or 20 mg) or placebo. Subjects were 12 individuals with the Prader-Willi syndrome (PWS), a disorder characterized by extreme hyperphagia and morbid obesity, and 11 controls with obesity. PWS subjects showed the characteristic hyperphagia associated with the appetite disorder, consuming more than six times as many sandwiches as controls with obesity. Results revealed no significant effect of either dose of CDP on the food intake of either group. Serum assays revealed that dose-dependent, clinically effective levels of CDP and active metabolites were achieved. These results suggest that acute administration of the BZR agonist CDP, at the therapeutic levels used, may not increase food intake in populations with obesity. However, the chronic effects of CDP on appetite in human populations still need to be explored.

Adolescent↗

Cardiovascular and somatic startle and defense: concordant and discordant actions of benzodiazepine receptor agonists and inverse agonists.

Benzodiazepine receptor (BZR) agonists and inverse agonists yield generally opposing effects on GABAergic transmission, and the functional consequences of these ligands are often bidirectional. BZR agonists exert anxiolytic effects, whereas the BZR partial inverse agonist FG 7142 has been reported to have anxiogenic actions in a variety of paradigms. In keeping with this literature, we found that the cardioacceleratory defensive response is enhanced by FG 7142, and attenuated by the BZR agonist chlordiazepoxide. In contrast, both compounds attenuated basal and fear-potentiated somatic startle responses. This did not appear to reflect a global reduction of startle reactivity, however, as the cardiac startle response was not significantly altered. These findings support the view that multiple substrates underlie distinct aspects or features of fear and anxiety. The results are consistent with the suggestion that FG 7142 may selectively enhance those aspects of anxiety that depend on cortical-cognitive processing.

Aggression↗