Instrumental control of cardioacceleration induced by central electrical stimulation.

Each of four monkeys (Macaca mulatta) was operantly conditioned to slow and to speed heart rate through a shock-avoidance procedure. During these sessions, electrical brain stimulation that produced tachycardia and pressor responses was delivered on alternate, 64-second segments to one of several brain regions. All animals were able to attenuate the increases in heart rate produced by brain stimulation during the slowing sessions when posterior hypothalamic and striatal regions were stimulated but not when anterior hypothalamic or subthalamic areas were stimulated. During speeding or control sessions during which heart rate was monitored, brain stimulation continued to increase heart rate.

Clinical biofeedback: a behavioral analysis.

Clinical biofeedback studies have shown that patients can learn to control highly specific physiological responses such as relaxation of the internal anal sphincter, contraction of the external anal sphincter, heart rate and intracardiac conduction patterns, or blood pressure. Findings from a number of studies indicate that the ability to learn to control abnormal responses is highly reinforcing and facilitates further learning. Other findings indicate that learning tends to be specific to the response being trained. If it is desirable to teach patients to control more than one response, it may be necessary to teach each response independently.

Age-Related Neostriatal Alterations in the Rat: Failure of L-DOPA to Alter Behavior.

Age differences in rotational behavior were examined in young (6 mo) and old (24 mo) Wistar rats lesioned in the left substantia nigra with 6-OHDA. Young animals showed a 50% increase in rotational behavior with L-DOPA pretreatment and a 15-20% increase following L-tyrosine pretreatment. However, neither L-DOPA nor L-tyrosine pretreatment potentiated amphetamine-induced rotational behavior of senescent animals. Pretreatment with tranylcypromine, an MAO inhibitor, did not enhance rotational behavior in either group. After assessing rotational responses to amphetamine, half of each age group was given L-DOPA 1 hr prior to sacrifice, and right (RS) and left striatal (LS) levels of dopamine (DA) were examined in all groups. Comparable LS depletion was found in both age groups. L-DOPA significantly raised DA levels in the RS of the young animals while causing no change effect in old animals although the amount of L-DOPA entering the striatum was even higher in the senescent animals. Striatal tyrosine hydroxylase showed only a small decrease (15%) in activity, while DOPA decarboxylase activity showed no significant age-related decline. Despite the lack of substantial decrease in enzyme activity, the results indicate an age-dependent decrease in the capacity for L-DOPA potentiation of rotational behavior. Defects may exist at the level of elevation of the functional pool of DA, the release of DA, or the interaction of DA with a decreasing number of a class of DA receptors involved in motor control.

Cardiovascular reactivity as behavior.

The word, behavior, means action or reaction. Thus, all physiologic responses meet this definition and are behavior. Furthermore, if the response is neurally mediated, then there are only 3 possible behavioral mechanisms that can be operating to determine it: (1) The response is part of a reflex, elicited by an adequate stimulus. In this case, in an intact animal the expression of the response will be modulated by a variety of situational factors. (2) The response is part of a reflex. However, the capacity of the stimulus to elicit the response is acquired through association with an adequate stimulus. Thus, the reflex is learned rather than innate. (3) The response is part of a "central command" and is emitted in anticipation of a consequence whose likelihood of occurrence has been learned. Neurally mediated responses of the circulation meet all these criteria. Thus, circulatory responses not only are passive reflexes, they also are reactive and proactive behaviors, which permit animals to interact effectively with their environments, and which change with practice. These principles explain a variety of cardiovascular effects observed in experimental or clinical settings. Furthermore, by applying well-established behavioral principles to circulatory responses, it is possible to achieve clinically significant effects. This presentation will characterize the way in which behavioral mechanisms are expressed in the circulation, it will describe a number of clinically significant findings that illustrate the importance of these mechanisms, and it will propose a number of applications of behavioral principles that can be used in clinical practice.

Autonomic behavior.

This article summarizes a body of work which collectively shows that autonomic responses meet the criteria for behavior. They can be modified reliably through the systematic use of antecedent (cues) and consequent (contingencies) stimuli. This means that autonomic responses, which are usually characterized as elicited reflexes, can be learned responses (viz., behaviors). This review cites a number of experimental and clinical studies in which autonomic learning has been shown to occur and to have clinical importance. Of special interest to gerontologists are the clinical studies which show that incontinent and hypertensive elderly patients can be trained to normalize their pathognomic responses.

An improved cold stress test for aging mice.

Tolerance to cold stress is a simple and reliable test which can be used longitudinally to study age-related differences or changes in thermoregulation of C57BL/6J mice. Neither prior food deprivation nor permanently inserted thermoprobes are necessary conditions for eliciting reliable age differences. However, restraint during the test is important and does elicit reliable age differences.

Heat loss during cold exposure in adult and aged C57BL/6J mice.

Metabolic heat production (MHP), colonic temperature (Tco), and nonevaporative (dry) heat loss were measured in ADULT and AGED C57BL/6J male mice during cold exposure. Dry heat loss was assessed as a differential temperature (Td) between incoming and outgoing air through the chamber for indirect calorimetry. The average Td during cold exposure normalized to surface area for ADULT mice was significantly higher than that for the AGED animals (0.0618 +/- 0.0003 degree C/cm2 and 0.0553 +/- 0.0005 degree C/cm2, respectively). Linear regression analysis showed that at the same Tco AGED mice showed lower values of Td normalized to surface area, indicating that at the same body temperature they were losing less heat than ADULT animals. It was concluded that age-related decline in cold tolerance in mice is not due to a lack of ability to reduce heat loss during cold exposure. On the contrary, AGED animals had lower heat loss in comparison with ADULT. We suggest that augmentation of heat conservation mechanisms is an adaptive response to diminishing cold-induced heat production.

Nonshivering thermogenesis during acute cold exposure in adult and aged C57BL/6J mice.

In C57BL/6J adult and aged mice, housed at room temperature (22.5 +/- 1 degrees C), we measured O2 consumption and CO2 production and calculated metabolic heat production under conditions of anesthesia and myorelaxation during acute cold stimulation when body temperature was lowered 7.5 degrees C below control level. An independent group of mice was subjected to a three hour partial physical restraint at 6 degrees C and concentration of uncoupling protein (thermogenin) was measured in interscapular brown adipose tissue mitochondria at different times after cold exposure. Heat production under anesthesia and myorelaxation was about 57-66% lower than in nonanesthetized conditions, but increased significantly during cold stimulation in both age groups. Under anesthesia and myorelaxation before and during cold stimulation aged mice produced about 20% more heat than adult mice. Because in these experiments all sources of facultative thermogenesis, except nonshivering, were suppressed by anesthesia and myorelaxation, and because brown adipose tissue is the major source of nonshivering thermoproduction, we concluded that aged mice housed at room temperature have an increased thermogenesis in brown adipose tissue. This conclusion was also supported by the finding that the concentration of uncoupling protein measured in the mitochondria of brown adipose tissue after single cold exposure was significantly higher in aged than in adult mice. Therefore, we propose that the lower, cold-induced, heat production typically observed in nonanesthetized aged mice may reflect reduced thermogenic capacity of skeletal muscles. While aged mice have less brown adipose tissue than adult animals, the remaining brown adipose tissue may compensate by increasing the concentration of uncoupling protein.

Biofeedback treatment of fecal incontinence in geriatric patients.

Eighteen fecally incontinent geriatric patients were first treated for constipation as a possible cause of incontinence, and the 13 who remained incontinent were provided sphincter biofeedback training. Half the patients were instructed to perform 50 sphincter exercises per day for a four-week period prior to the start of biofeedback training to determine whether such exercises would improve bowel control in the absence of biofeedback training. Sphincter exercises alone did not produce clinical improvements and did not significantly increase the strength of sphincter contractions. Biofeedback training did significantly augment sphincter strength and was associated with greater than 75 per cent decreases in incontinence for 10 (77 per cent) of the patients. Improvements were maintained in 60 per cent at six months and in 42 per cent at one year. Thus biofeedback training appears to be of specific value in the treatment of fecal incontinence in geriatric patients.

Behavioral training for urinary incontinence in elderly ambulatory patients.

Research questions addressed by this study were: 1) Is the treatment of chronic urinary incontinence (UI) in elderly, nondemented ambulatory patients using bladder-sphincter biofeedback as effective when performed by an internist/geriatrician and a nurse practitioner as that reported by behavioral scientists?; and 2) how does bladder-sphincter biofeedback compare to a program of behavioral training that does not utilize biofeedback? Twenty-seven patients with UI were assigned based on the number of baseline accidents documented in a self-maintained log, their sex, and the predominant pattern of symptoms (urge or stress) to one of two treatment groups: biofeedback (13 patients) or behavioral training not utilizing biofeedback (14 patients). Patients were given up to six treatments. Patients in both groups achieved a highly significant (P less than .001) reduction in urinary accidents 1 month following treatments compared with their baseline number of accidents. The average reduction of accidents over this time period was 79% for the biofeedback group and 82% for the group receiving behavioral training without biofeedback. All patients showed improvement and no patient experienced any side effect. A internist/geriatrician and a geriatric nurse practitioner may achieve success utilizing behavioral therapy with or without biofeedback for the treatment of chronic urinary incontinence for ambulatory elderly patients.

The effects of changing prompted voiding schedules in the treatment of incontinence in nursing home residents.

OBJECTIVE: To determine the effects of different prompted voiding schedules on urinary incontinence on a continence unit (CU) and the maintenance of benefits on normal nursing units. DESIGN: Multiphase study with both intra- and inter-subject comparisons. PARTICIPANTS: Subjects were 41 consenting incontinent nursing home residents. Based on clinical criteria, subjects were assigned to one of four treatment groups that varied as to the schedule of prompted voiding received. MEASUREMENT: The study used chart review, Katz ADL, and MMSE. Urologic status, self-initiated toileting, urine volumes voided, and incontinence assessed by pad/pants checks were measured by research nurses. Baseline pad check data were collected on residents' normal nursing units. Residents were transferred to the CU where baseline measurement was repeated, and the effects of different prompted voiding schedules were then assessed. Indigenous staff were trained to use prompted voiding, and nurse supervisors were instructed in special procedures for enhancing maintenance of the intervention. Residents were returned to their normal units and the maintenance of improvements in continence status was assessed at 2 weeks and 3 months post-CU discharge. RESULTS: One of the four groups showed significant improvement on the CU in response to the 2-hour schedule; two groups improved on the less intensive 3-hour schedule (P < 0.05). Two groups maintained this improvement on their normal nursing units (P < 0.05); one group showed a non-significant trend toward improvement. Self-initiated toileting decreased (P < 0.05) and volume voids in an appropriate receptacle increased (P < 0.05) during training. CONCLUSIONS: Prompted voiding is an effective treatment for urinary incontinence, and a less intensive 3-hour schedule may be superior to the standard 2-hour schedule for some residents. These improvements in dryness can be maintained by normal nursing home staff if formal staff management procedures are utilized by nurse supervisors.

Learned control of heart rate during dynamic exercise in nonhuman primates.

The purpose of this study was to describe an animal model to test the relationships among the cardiovascular, pulmonary, and somatomotor command systems during exercise. Using operant conditioning, three chronically chaired monkeys (Macaca mulatta) were trained to exercise (to lift weights repeatedly), to attenuate their heart rate responses, and finally, both conditions were combined so that the animals were required to exercise and attenuate their heart rates. Heart rate, systolic and diastolic blood pressure, rate-pressure product, O2 and CO2 concentration in expired air, and number of weight lifts were recorded and compared between the two conditions, i.e., exercise only and combined exercise and heart rate slowing. In all animals heart rate increases in response to exercise were significantly less (P less than 0.05) during combined conditions than during exercise only: the mean heart rate increase was 41 beats/min less during combined sessions than during exercise only sessions for monkey 1, 13.5 beats/min less for monkey 2, and 9 beats/min less for monkey 3. Rate-pressure product showed a consistent difference across animals paralleling the heart rate differences. This acquired response did not involve other cardiovascular and pulmonary parameters, which did not change systematically across animals. However, the pattern of cardiovascular reactivity in relation to O2 consumption (linear regression of heart rate and systolic or diastolic blood pressure on change in O2 consumption over many experiments) was attenuated during combined sessions relative to exercise only experiments. The relative attenuation of heart rate during combined sessions also remained significant when both experimental conditions were equated on the basis of work done. Therefore, this animal model shows a dissociation of cardiovascular, somatomotor, and pulmonary effects of central command.

Central control of cardiovascular adjustments to exercise.

Voluntary heart rate (HR) control during moderate exercise on a bicycle ergometer was studied in 10 healthy physically conditioned men (5 experimental and 5 control). The results showed that subjects could learn to attenuate the tachycardia of exercise while exercising at a steady work level of 60-70% of maximum HR. Experimental subjects who saw beat-to-beat displays of HR and were instructed to slow HR showed 22% less increase in HR than did control subjects who exercised without HR displays or instruction to slow HR (42.6 vs. 54.6 beats/min). When the control subjects were given feedback in additional sessions, they also decreased HR significantly by 9% (54.6 vs. 49.9 beats/min). Analyses of concomitant respiratory and metabolic data showed that HR attenuation was accompanied by decreased O2 consumption (P less than 0.06) and pulmonary ventilation (P less than 0.01). Rate pressure product also fell, indicating a decrease in myocardial O2 consumption. Comparisons among pre- and postsubmaximal and cardiovascular pulmonary and humoral responses during maximal test sessions suggested that the improvement in cardiopulmonary function during feedback training occurred with no sacrifice to working muscle requirements because blood lactate concentrations were similar. The attenuation of the HR response obtained in the present study indicates that feedback training in physically conditioned subjects can influence cardiovascular responses even under conditions of heavy local demands imposed by working muscles.

Central neural correlates of learned heart rate control during exercise: central command demystified.

To identify the brain areas involved in central command, four monkeys were trained to attenuate the tachycardia of exercise while different brain sites affecting heart rate (HR) were simultaneously stimulated electrically. Among 24 brain sites located mostly in the limbic structures, we have identified four types of control systems that mediate cardiovascular and motor behavior during exercise. One system increases HR equivalently during both exercise and operantly controlled HR, whereas another increases HR during both tasks and abolishes operant HR control. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but its effect is significantly attenuated during operant HR control. We believe that this last system, which includes the mediodorsal nucleus, nucleus ventralis anterior, and cingulate cortex, plays a significant role in central command.

Effect of nocturnal atrial demand cardiac pacing on diurnal hemodynamic patterns.

Heart rate (HR), stroke volume (SV), intra-arterial blood pressure, and central venous pressure were recorded on a beat-to-beat basis, 18 h/day (1800-1200 h the following day), for approximately 2 mo in four monkeys (Macaca mulatta). Cardiac output, left ventricular work, and total peripheral resistance were derived from these primary measurements. During the 1st mo we measured these parameters under control conditions, and during the 2nd mo the animals were studied while HR was paced by atrial demand pacing sufficient to prevent the normal nocturnal fall in HR (approximately 10 beats/min above the fastest hourly average rate recorded during the control condition). The main hypothesis of this study was that when HR is prevented from falling, SV, which normally does not fall overnight, would fall; this hypothesis was confirmed. In addition, we observed that, during the period of pacing, relative to the control period, SV was approximately 14% greater during the early evening and 4% lower during the early morning; total peripheral resistance was similar during the early evening but was 13% higher by morning. Throughout the night, systolic pressure was approximately 4% greater, diastolic pressure was 17% higher, central venous pressure was 43% greater, and left ventricular work was 27% higher. These findings show that when HR is prevented from falling overnight by atrial demand pacing, even to a relatively modest degree, there can be very significant sustained changes in cardiovascular function.

Systematic nocturnal atrial demand pacing results in high-output heart failure.

Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model.

Role of postural status in the nocturnal hemodynamic patterns of nonhuman primates.

We compared the nocturnal hemodynamic patterns of seven tethered monkeys (Macaca mulatta) with those of seven chaired animals to determine whether the overnight changes are comparable in the two conditions. In both groups, we found a consistent hemodynamic pattern characterized by an overnight fall in cardiac output and central venous pressure and a rise in total peripheral resistance that maintained blood pressure homeostasis. The pattern of overnight change occurred despite major differences in response levels: cardiac output and central venous pressure were significantly elevated, and total peripheral resistance was significantly reduced at all times (from 1800 to 1200 h the following day) in the chaired animals relative to the tethered animals. This difference was probably due to an expanded plasma volume in the chaired animals, because stroke volume was also significantly elevated. Because the nocturnal hemodynamic pattern occurred under both conditions, it is likely that it is a stable biologic effect, which is probably related to an overnight loss in fluid volume that is not replaced in animals that sleep throughout the night.

Habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.

Every two weeks for 12 weeks four groups of C57BL/6J male mice, initially 12 months old, were subjected to three-hour cold stress tests, which consisted of a partial physical restraint at an ambient temperature of 10 degrees C. The control group experienced six consecutive tests; one experimental group skipped the cold exposure during test No. 4 but was physically restrained at room temperature; the other two experimental groups omitted test No. 4. One of these groups spent the four weeks between test No. 3 and test No. 5 in their home cages, while the other was subjected to daily, 30-minute sessions of electrical stimulation of the hypothalamus through electrodes implanted in the "rewarding" area of the medial forebrain bundle. All animals in this group showed self-stimulating behavior in the test session which preceded cold stress test No. 1. During test No. 3, all four groups showed an improvement of cold tolerance relative to their first tests; body mass and colonic temperature prior to cold exposure remained unchanged. The two experimental groups that were not exposed to cold during test No. 4 and did not receive brain stimulation, demonstrated a significant worsening of cold tolerance during the subsequent test. Their body mass and baseline colonic temperatures did not change. The control group and the group which was subjected to brain stimulation during the interval between tests No. 3 and No. 5 did not demonstrate any changes in cold tolerance. These data demonstrated habituation to repeated mild cold exposures and dishabituation after interruption of cold exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic blockade does not prevent learned heart rate attenuation during exercise.

Each of three monkeys was operantly conditioned to slow its heart, to exercise (lift weights) and to attenuate the tachycardia of exercise by combining these two skills. Each was further tested during beta-adrenergic blockade (atenolol), combined alpha-adrenergic blockade (prazosin) and beta-adrenergic blockade, or cholinergic blockade (methylatropine). During all experiments heart rate, stroke volume, intraarterial blood pressure, O2 consumption, and CO2 production were recorded on a beat-to-beat basis. Each animal was able to attenuate the tachycardia of exercise under each of the drug conditions, indicating that "central command" is not the expression of fixed, cardiovascular and pulmonary reflexes elicited by somato-motor commands, but rather is an adaptive behavior, determined by environmental contingencies and mediated by cardiovascular and pulmonary as well as somato-motor commands. The ability of the animals to perform with greater cardiac efficiency during the combined exercise and heart rate slowing task relative to the exercise-only task was not affected by sympathetic blockade; however, parasympathetic blockade did reduce cardiac efficiency.

Effect of electrical stimulation of "rewarding" areas of the hypothalamus on habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.

Four groups of 12-month-old C57BL/6J male mice had chronic electrodes implanted in the median forebrain bundle. In three groups the "rewarding" property of electrical stimulation was determined during a single 30-min session of self-stimulation (ISS) before the beginning of the experiment. In the fourth group this test was postponed until the end of experiment. Every two weeks for 12 weeks all animals were subjected to repeated 3-hr cold stress tests consisting of partial physical restraint at an ambient temperature of 10 degrees C. The time interval between tests No. 3 and No. 4 was intentionally delayed up to four weeks. During the 4-week interval, animals of one of the groups tested for ISS remained in their home cages; mice of the second ISS-tested group received daily 30-min sessions of brain stimulation; and animals of the third ISS-tested group were placed daily for 30 min in the experimental chamber where they had been tested for ISS previously but received no brain stimulation. Animals of the fourth group, which were not tested for ISS prior to the experiment, also were placed daily in the experimental chamber without brain stimulation. Repeated cold testing resulted in improvement of cold tolerance (decrease of the rate of decline of colonic temperature during cold exposure) in the second and third tests relative to the first cold test in all groups (cold habituation).(ABSTRACT TRUNCATED AT 250 WORDS)