Ray W. Winters

Responsiveness to Threat and Incentive in Bipolar Disorder: Relations of the BIS/BAS Scales With Symptoms

Over the past 10 years, theorists have suggested that bipolar disorder symptoms result from increases and decreases in the activity of the Behavioral Activation or Facilitation System (BAS or BFS) and the Behavioral Inhibition System (BIS). These neurobehavioral systems are thought to determine the intensity of affective and behavioral responses to incentives and threats. This study examined cross-sectional and prospective associations of self-reported BIS and BAS with mania and depression in a sample of 59 individuals diagnosed with Bipolar I disorder. Depression was tied to BIS, pointing to the importance of sensitivity to threats in depression. However, links between BIS and depression appeared state-dependent. BAS subscales did not correlate with manic symptoms in a state-dependent manner; however, BAS (total scale and reward responsiveness subscale) predicted relative intensification of manic symptoms over time. Thus, evidence suggests that BAS sensitivity may constitute a vulnerability to mania among persons diagnosed with bipolar disorder. Discussion focuses on the integrative potential of the BIS/BAS constructs for linking psychosocial and biological research on bipolar disorder.

Increases in Manic Symptoms After Life Events Involving Goal Attainment

Bipolar disorder has been conceptualized as an outcome of dysregulation in the behavioral activation system (BAS), a brain system that regulates goal-directed activity. On the basis of the BAS model, the authors hypothesized that life events involving goal attainment would promote manic symptoms in bipolar individuals. The authors followed 43 bipolar I individuals monthly with standardized symptom severity assessments (the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale). Life events were assessed using the Goal Attainment and Positivity scales of the Life Events and Difficulties Schedule. As hypothesized, manic symptoms increased in the 2 months following goal-attainment events, but depressed symptoms were not changed following goal-attainment events. These results are congruent with a series of recent polarity-specific findings.

Auditory cortex lesions prevent the extinction of Pavlovian differential heart rate conditioning to tonal stimuli in rabbits

The present study examined the role of the auditory cortex in the extinction of differentially conditioned heart rate (HR) responses in rabbits. Lesions were placed bilaterally in either the auditory cortex or the visual cortex. Three days after recovery from surgery, the auditory cortex lesion group and the visual cortex lesion control group were habituated to the tonal conditioned stimuli (CSs), and then given 2 days of Pavlovian differential conditioning (60 trials per day) in which one tone (CS+) was always paired with the unconditioned stimulus and another tone (CS-) was never paired with the unconditioned stimulus. Animals that had demonstrated reliable differential conditioning (CS+ response at least 5 beats greater than the CS- response) were placed on an extinction schedule for 7 days. The extinction schedule was identical to the differential conditioning schedule with the exception that shock never followed the CS+. The results of the study indicate that auditory cortex lesions prevent the extinction of differential bradycardia conditioned responses (CRs) to tonal CSs. Whereas the bradycardia responses to the CS+ quickly extinguished in the group that had control lesions in the visual cortex, the auditory cortex lesion group continued to exhibit significantly larger bradycardiac HR CRs to the CS+ relative to the CS- during all 7 days of extinction. These results suggest that the animals in the auditory cortex lesioned group did not inhibit responses to a previously reinforced stimulus (i.e., CS+) as well as animals with control lesions in the visual cortex.

Afferents to the central nucleus of the amygdala and functional subdivisions of the periaqueductal gray: neuroanatomical substrates for affective behavior

Evidence suggests the periaqueductal gray (PAG) is involved in the integration of behavioral and autonomic components of affective behavior. Our laboratory has shown that electrical stimulation of the ventrolateral periaqueductal gray (vl PAG) versus the dorsolateral periaqueductal gray (dl PAG), in the rabbit, elicits two distinct behavioral/cardiorespiratory response patterns. Furthermore, evidence suggests that the amygdaloid central nucleus (ACe) may influence cardiovascular activity during emotional states. The purpose of this study was to delineate the topography and determine the origin of forebrain projections to the PAG and the ACe, as well as commonalties and differences in the pattern of afferents. Examination of common afferents may lend insights into their function as components of a forebrain system regulating autonomic activity during emotional states. Separate retrograde tracers were injected into functional subdivisions of the PAG and the ACe in rabbits. PAG injections led to neuronal labeling in numerous cortical regions including the ipsilateral medial prefrontal and insular cortices. Additionally, bilateral labeling was observed in several hypothalamic nuclei including the paraventricular nucleus, the dorsomedial nucleus and the ventromedial nucleus as well as the region lateral to the descending column of the fornix. Sparse labeling was also seen in various basal forebrain regions, thalamic nuclei and amygdaloid nuclei. Many of these regions were also labeled following injections in the ACe. Although double-labeled cells were never observed, afferents to the ACe were often proximal to PAG afferents. Implications of these findings are discussed in terms of two functionally distinct behavioral/cardiovascular response patterns.

Cardiovascular responses elicited by electrical and chemical stimulation of the rostral medullary raphe of the rabbit

Electrical stimulation of the rostral medullary raphe (RMR) of the rabbit elicited pressor responses that were accompanied by tachycardia or bradycardia. Stimulation of dorsal sites (the dorsal raphe obscurus) evoked a pressor/tachycardia response and stimulation of ventral sites (the ventral raphe obscurus, raphe magnus and raphe pallidus) produced a pressor/bradycardia response. Electrical stimulation of the RMR after sinoaortic denervation led to an increase in the magnitude of the pressor response elicited from all stimulation sites, a decrease in the magnitude of the bradycardia produced by stimulation at the ventral sites, but had no effect upon the magnitude of the tachycardia observed from stimulation of the dorsal sites. These findings suggest that electrical stimulation of the dorsal sites leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of vagal blockade experiments demonstrated that baroreceptor attenuation of the pressor responses at ventral sites was mediated primarily by parasympathetic input to the heart. Chemical stimulation of the RMR with L-glutamate also led to a pressor/tachycardia response at the dorsal sites and a pressor/brachycardia response at the ventral sites. This finding provides evidence that neuronal cell bodies, not axon of passage, mediated the responses elicited by electrical stimulation.

Cardiorespiratory Components of Defense Reaction Elicited from Paraventricular Nucleus

The present study was conducted to test the hypothesis that the paraventricular nucleus of the hypothalamus (PVN) is involved in the mediation or modulation of the cardiorespiratory components of the defense reaction (DR) in rabbits. Electrical stimulation of the PVN elicited increases in blood pressure and heart rate, hyperventilation, decreased blood flow to the visceral organs, and an increase in blood flow to the hindlimbs that was mediated by an atropine-sensitive vasodilation system. This response pattern is nearly identical to the one that is elicited by electrical stimulation of the hypothalamic defense area. In addition, the cardiomotor component of the baroreceptor reflex was observed to be suppressed during electrical stimulation of the PVN. Previous studies have shown that electrical stimulation of the hypothalamic defense area also leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of the present study provide evidence that the PVN is involved in the mediation or modulation of the defense reaction.

Hypothalamic, midbrain and bulbar areas involved in the defense reaction in rabbits ☆

The present study mapped neuroanatomical sites in the hypothalamus and periaqueductal gray (PAG) of the rabbit which, when stimulated electrically, evoked the cardiorespiratory components of the defense reaction (CRDR). This included increases in heart rate, blood pressure, hindlimb blood flow and respiration rate. All of the components of the CRDR were elicited by electrical stimulation of the posterior hypothalamus, at sites dorsal and medial to the fornix. Although there were regions throughout the PAG in which electrical stimulation elicited concomitant increases in blood pressure, hindlimb blood flow and respiration rate, only stimulation of the dorsal PAG evoked tachycardia. Injection of horseradish peroxidase into the rostral ventrolateral medulla (RVLM) led to heavy retrograde and anterograde labeling in the region of the hypothalamus that yielded the CRDR when stimulated electrically. Heavy labeling was also observed in the dorsal and ventral PAG. The results of this study provide evidence that the posterior hypothalamus and the dorsal PAG are nodal structures in the mediation of the CRDR and that cells in posterior hypothalamus, dorsal PAG and ventral PAG make monosynaptic connections with the RVLM.

Role of auditory cortex in the acquisition of differential heart rate conditioning.

Previous findings from our laboratory indicate that lesions of the auditory cortex disrupt the retention of differentially conditioned bradycardiac responses to tonal stimuli in rabbits. In the present experiment, the effect of lesions of the auditory cortex on the acquisition of differential bradycardiac conditioning was examined. The effect of lesions in the auditory cortex were compared to the effect produced by control lesions in the visual cortex. After 7 days of recovery, animals received 7 days of differential Pavlovian bradycardiac conditioning in which one tone (CS+) was paired with the unconditioned stimulus, and another tone (CS-) was never paired with the unconditioned stimulus. All animals demonstrated differential conditioning during the first 3 days of conditioning. On days 4-7, however, auditory cortex lesioned animals did not exhibit significant differential heart rate (HR) conditioning, whereas control animals with lesions in the visual cortex showed no loss of conditioning during this period. The loss of differential conditioning in animals with lesions in the auditory cortex appears to be due to an increase in the magnitude of the response to the CS-. These data support the hypothesis that the auditory cortex serves to inhibit the response to the CS- in differential conditioning of bradycardia to acoustic stimuli, and that the inhibition may be mediated by a descending corticothalamic or corticolimbic pathway.

Center-surround interactions in two types of on-center retinal ganglion cells in the cat

Abstract Center-surround interactions of Group I and Group II cells ( Winters , Hickey and Pollack , 1973) were studied by simultaneously presenting a small spot in the center of a units receptive field and an annulus in the receptive field periphery. The responses to this target configuration were compared to those elicited by the center spot alone and those elicited by presenting an annulus alone. Group I cells gave a transient response to a maintained central spot while Group II cells gave a sustained response for the same stimulus. Both Group I cells and Group II cells gave on-off responses to a center spot plus peripheral annulus but the on portion of the response was much weaker in Group II cells than in Group I cells, indicating greater peripheral suppression in these units. Linear summation of central and peripheral responses could be demonstrated for Group II cells but not Group I cells.

Temporal characteristics of peripheral inhibition of sustained and transient ganglion cells in cat retina

Abstract The temporal characteristics of transient and sustained retinal ganglion cells in the cat were assessed by varying the temporal relationship between a spot in the receptive field center and an annulus in the receptive field surround. The luminance of the annulus was also varied for some units. The maximum amount of suppression of the excitatory response from the center spot was produced when the annulus preceded the spot by about 38 msec for transient cells and by about 7 msec for sustained cells. The time course of peripheral inhibition for transient and sustained cells was also found to differ. These differences held at all luminance levels used but were minimized at both extremely low and extremely high contrast levels.