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Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors.

The thalamus relays sensory information to cortex, but this information may be influenced by excitatory feedback from cortical layer VI. The full importance of this feedback has only recently been explored, but among its possible functions are influences on the processing of sensory features, synchronization of thalamic firing, and transitions in response mode of thalamic relay cells. Uncontrolled, corticothalamic feedback has also been implicated in pathological thalamic rhythms associated with certain neurological disorders. We have found a form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by a Group II metabotropic glutamate receptor (mGluR) and activated by high-frequency corticothalamic activity. We tested putative retinogeniculate and corticogeniculate synapses for Group II mGluR modulation within the dorsal lateral geniculate nucleus of the ferret thalamus. Stimulation of optic-tract fibers elicited paired-pulse depression of excitatory postsynaptic currents (EPSCs), whereas stimulation of the optic radiations elicited paired-pulse facilitation. Paired-pulse responses were subsequently used to characterize the pathway of origin of stimulated synapses. Group II mGluR agonists (LY379268 and DCG-IV) applied to thalamic neurons under voltage-clamp conditions reduced the amplitude of corticogeniculate EPSCs. Stimulation with high-frequency trains produced a facilitating response that was reduced by Group II mGluR agonists, but was enhanced by the selective antagonist LY341495, revealing a presynaptic, mGluR-mediated reduction of high-frequency corticogeniculate feedback. Agonist treatment did not affect EPSCs from stimulation of the optic tract. NAAG (reported to be selective for mGluR3) was ineffective at the corticogeniculate synapse, implicating mGluR2 in the observed effects. Our data are the first to show a synaptically elicited form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by presynaptic action of mGluR2. This presynaptic inhibition may partially mute sensory feedback and prevent reentrant excitation from initiating abnormal thalamic rhythms.

Amino Acids↗

Human midbrain sensitivity to cognitive feedback and uncertainty during classification learning.

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the "prediction error") and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.

Adult↗

Temporal contrast enhancement via GABAC feedback at bipolar terminals in the tiger salamander retina.

Most retinal amacrine (ACs) and ganglion cells (GCs) express temporal contrast by generating action potentials at only the onset and offset of the light stimulus. This study investigated the neural mechanisms that underlie this temporal contrast enhancement. Whole cell patch recordings were made from bipolar cells (BCs), ACs, and GCs in the retinal slice preparation. The cells were identified by the locations of their somas in the inner nuclear layer and ganglion cell layers, their characteristic light responses, and morphology revealed by Lucifer yellow staining. Depolarizing a single BC with a brief voltage pulse elicited a Cl- tail current that was completely abolished when Ca2+ entry to bipolar terminals was prevented, by either removing Ca2+ from the Ringer solution or blocking Ca2+ channels with Co2+. This suggests that the Cl- current is Ca2+-dependent. In those bipolar cells whose axon terminals were cutoff during slicing no Cl- current was observed, indicating that this current is generated at the synaptic terminals. The Cl- current consists of a predominant synaptic component that can be blocked by the non-N-methyl--aspartate (NMDA) glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or by the gamma-aminobutyric acid-C (GABAC) receptor antagonist picrotoxin. There also exists a relatively small nonsynaptic component. Thus both glutamatergic and GABAergic transmission were involved in the generation of this Cl- current, suggesting that it is mediated by a recurrent feedback to bipolar cells. Picrotoxin, which blocks both GABAC receptors at BC terminals and GABAA receptors on the dendrites of ACs and GCs, converted the light-elicited voltage response in most - ACs and GCs from transient to sustained. Bicuculline, which blocks only the GABAA receptors, did not prolong the transient response in - ACs and GCs. This suggests that a negative feedback mediated by the GABAC receptor on the bipolar terminals is responsible for making these responses transient. After the GABAergic feedback was blocked with picrotoxin the light-elicited voltage responses (recorded under current clamp) were more sustained than the current responses (recorded under voltage clamp) to the same light stimuli. This suggests that a voltage-dependent conductance converts the relatively transient current responses to more sustained voltage responses. Our results imply a synaptically driven local GABAergic feedback at bipolar terminals, mediated by GABAC receptors. This feedback appears to be a significant component of the mechanism underlying temporal contrast enhancement in - ACs and GCs.

Animals↗

Contribution of sensory feedback to the generation of extensor activity during walking in the decerebrate Cat.

In this investigation we have estimated the afferent contribution to the generation of activity in the knee and ankle extensor muscles during walking in decerebrate cats by loading and unloading extensor muscles, and by unilateral deafferentation of a hind leg. The total contribution of afferent feedback to extensor burst generation was estimated by allowing one hind leg to step into a hole in the treadmill belt on which the animal was walking. In the absence of ground support the level of activity in knee and ankle extensor muscles was reduced to approximately 70% of normal. Activity in the ankle extensors could be restored during the "foot-in-hole" trials by selectively resisting extension at the ankle. Thus feedback from proprioceptors in the ankle extensor muscles probably makes a large contribution to burst generation in these muscles during weight-bearing steps. Similarly, feedback from proprioceptors in knee extensor appears to contribute substantially to the activation of knee extensor muscles because unloading and loading these muscles, by lifting and dropping the hindquarters, strongly reduced and increased, respectively, the level of activity in the knee extensors. This conclusion was supported by the finding that partial deafferentation of one hind leg by transection of the L4-L6 dorsal roots reduced the level of activity in the knee extensors by approximately 50%, but did not noticeably influence the activity in ankle extensor muscles. However, extending the deafferentation to include the L7-S2 dorsal roots decreased the ankle extensor activity. We conclude that afferent feedback contributes to more than one-half of the input to knee and ankle extensor motoneurons during the stance phase of walking in decerebrate cats. The continuous contribution of afferent feedback to the generation of extensor activity could function to automatically adjust the intensity of activity to meet external demands.

Afferent Pathways↗

Basal hypothalamo-pituitary-adrenal axis activity and corticotropin feedback in young and older men: relationships to magnetic resonance imaging-derived hippocampus and cingulate gyrus volumes.

Alterations in basal cortisol secretion and feedback sensitivity are reported in aging. However, it is not known whether these hypothalamus-pituitary-adrenal (HPA) axis alterations are related to structural brain changes. This study was designed to investigate these relationships in the human. Nine young (24.0 +/- 1.2 years; mean +/- SE; range: 19-30) and 11 older (69.0 +/- 1.8 years; range: 59-76) men, in addition to having standardized magnetic resonance imaging of their brains, were given 0.5 mg/kg cortisol or placebo intravenously in a double-blind, crossover study. As expected, older men had significantly smaller volumes for all brain regions. Although the groups did not differ in baseline HPA axis activity, there were significant and specific relationships between the brain volumes and the baseline measures of HPA activity. Namely, for young and older subjects combined and after controlling for age and cerebral vault size, hippocampal volumes were inversely associated with 24-hour urinary cortisol and basal corticotropin (ACTH) levels, and the anterior cingulate gyrus volume was negatively correlated with baseline ACTH. Elderly subjects had a slower decrease in ACTH levels (percent of baseline level) during the first 30 min after cortisol administration. However, no associations were observed between the ACTH feedback indices and any brain measure. This report, although based on a small number of subjects, supports previous studies showing a blunted ACTH fast feedback during normal aging. Hippocampal atrophy appears to be related to increased basal measures of HPA axis activity, but not to fast ACTH feedback. It remains possible that age-associated changes in fast feedback may be related to changes to other brain sites, such as hypothalamus or pituitary.

Adrenocorticotropic Hormone↗

Differential regulation of luteinizing hormone and follicle-stimulating hormone expression during ovarian development and under sexual steroid feedback in the European eel.

Pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are, in teleosts as in mammals, under the control of hypothalamic factors and steroid feedbacks. In teleosts, feedback regulations largely vary depending on species and physiological stage. In the present study the regulation of FSH and LH expression was investigated in the European eel, a fish of biological and phylogenetical interest as a representative of an early group of teleosts. The eel FSHbeta subunit was cloned, sequenced and together with earlier isolated eel LHbeta and glycoprotein hormone alpha (GPalpha) subunits used to study the differential regulation of LH and FSH. In situ hybridization indicated that FSHbeta and LHbeta are expressed by separate cells of the proximal pars distalis of the adenohypophysis, differently from the situation in mammals. The profiles of LHbeta and FSHbeta subunit expression were compared during experimental ovarian maturation, using dot-blot assays. Expression levels for LHbeta and GPalpha increased throughout ovarian development with a positive correlation between these two subunits. Conversely, FSHbeta mRNA levels decreased. To understand the role of sex steroids in these opposite variations, immature eels were treated with estradiol (E2)and testosterone (T), both steroids being produced in eel ovaries during gonadal development. E2 treatment induced increases in both LHbeta and GPalpha mRNA levels, without any significant effect on FSHbeta. In contrast, T treatment induced a decrease in FSHbeta mRNA levels, without any significant effect on the other subunits. These data demonstrate that steroids exert a differential feedback on eel gonadotropin expression, with an E2-specific positive feedback on LH and a T-specific negative feedback on FSH, leading to an opposite regulation of LH and FSH during ovarian development.

Analysis of Variance↗

A prey-type dependent hypoglossal feedback system in the frog Rana pipiens.

Nerve transection experiments combined with high-speed videography and electromyography were used to characterize a prey-type dependent hypoglossal feedback system which coordinates mouth opening and tongue protraction in the common leopard frog, Rana pipiens. When feeding on small prey, sensory feedback from the tongue through the hypoglossal nerve is necessary to trigger mouth opening. If sensory feedback is prevented from reaching the brain by transection of the hypoglossal nerve, then the mouth fails to open although the feeding behavior appears otherwise normal. However, when feeding on large prey, the mouth opens normally even after the hypoglossal nerve has been transected. Thus, peripheral feedback is not necessary to trigger mouth opening when feeding on large prey, and presumably a central coordination mechanism is used. In Rana pipiens, the evolution of a new tongue morphology and a new motor pattern for feeding on small prey has been accompanied by the evolution of a novel, peripheral mechanism for coordinating tongue protraction and mouth opening. However, the primitive motor pattern for feeding on large prey and the primitive coordinating mechanism have been retained. These results imply that the neural circuits producing the different motor patterns for large and small prey are anatomically distinct at some level in the central nervous system. If they are not anatomically distinct, then sensory feedback should be necessary to trigger mouth opening regardless of which motor pattern is being expressed. While the anatomy of these distinct pathways remains to be elucidated, these results suggest that novel neural circuits may in fact underlie different behaviors even when they seem, superficially, to be relatively similar.

Animals↗

Glucocorticoid feedback inhibition of adrenocorticotropic hormone secretagogue release. Relationship to corticosteroid receptor occupancy in various limbic sites.

Feedback inhibition of the adrenocortical axis by circulating glucocorticoids occurs at the pituitary and CNS sites. In the CNS, both hypothalamic and suprahypothalamic sites have been implicated as mediators of glucocorticoid feedback activity. In the present experiments, we have attempted to identify specific CNS regions mediating the feedback and to characterize which hypothalamic adrenocorticotropic hormone secretagogues are under glucocorticoid inhibitory control. Adrenalectomized rats were presented with a delayed feedback signal in the form of systemic infusion with corticosterone or dexamethasone. Hypophysialportal concentrations of corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and oxytocin (OT) were determined before and during a hypotensive stressor in the face of varying levels of feedback. The rats were then killed, and the extent of total, type I, and type II corticosteroid receptor occupancy in hippocampus, hypothalamus, and amygdala was determined. The following observations were made: (1) increased hippocampal corticosteroid receptor occupancy was associated with suppressed adrenocorticotropic hormone secretagogue concentrations; (2) the major, significant predictor of initial (prehypotensive) concentrations of CRF, AVP, and OT was the extent of occupancy of hippocampal type II receptors, often in combination with occupancy of hippocampal type I or hypothalamic receptors; (3) secretion of CRF induced by hypotension was best predicted by hippocampal type I and type II receptor occupancy (stress-induced OT secretion was best predicted by hippocampal type II and hypothalamic receptor occupancy), and (4) the 'shape' of the hippocampal type II receptor occupancy versus initial AVP concentration curve suggested a nonlinear, threshold type of relationship, implying tight hippocampal regulation of AVP secretion.

Adrenocorticotropic Hormone↗

Decreased sensitivity to glucocorticoid fast feedback in chronically stressed rats.

A number of changes in anterior pituitary corticotrophs occur after chronic footshock. These include increased ACTH and beta-endorphin content and a loss of glucocorticoid negative feedback on corticotropin-releasing hormone (CRH)-stimulated ACTH and beta-endorphin secretion, without changes in sensitivity to ovine CRH examined in vitro. The present studies were undertaken to determine whether the in vitro changes were reflected by similar changes in vivo. We developed a fast feedback paradigm using a 5-min swim stress as challenge, with injection of saline or corticosterone immediately prior to swim. Corticosterone reliably decreased ACTH and beta-endorphin responses to swim over the 30-min period studied. This feedback inhibition did not occur in rats that were either exposed to 30 min of chronic footshock for 7 or 14 days or in rats that were treated with corticosterone daily for 14 days in a regimen that has been reported to decrease hippocampal glucocorticoid receptors. By contrast, in rats exposed to the less intense stimulus of 30 min swim for 14 days, the fast feedback action of corticosterone was intact. These results suggest that both fast and delayed feedback corticosterone-inhibitory mechanisms may be blocked by relatively high levels of chronic stress or by chronic treatment with corticosterone, possibly as a consequence of decreased hippocampal glucocorticoid receptor number.

Adrenocorticotropic Hormone↗

Lack of gonadotropin-positive feedback in the male rat is associated with lack of estrogen-induced synaptic plasticity in the arcuate nucleus.

We have demonstrated that estrogen induces synaptic reorganization in the hypothalamic arcuate nucleus of female rats during the ovarian cycle and proposed that estrogen-induced synaptic retraction plays a role in the disinhibition of gonadotropin secretion that occurs during the afternoon of proestrus. This so-called positive feedback of gonadotropins is developmentally determined. It is present in female rats and absent in males. To confirm the role of the estrogen-induced synaptic retraction in positive feedback, we tested whether administration of estrogen to male rats also fails to induce synaptic remodeling of the arcuate nucleus. Male and female rats were gonadectomized and studied as follows. One month following gonadectomy, animals received either a single injection of estradiol (100 micrograms/animal in sesame oil; 12 males and 12 females) or vehicle (6 males and 6 females). Twenty-four hours following injections, all animals in the vehicle-injected group and 6 animals of each sex in the treatment groups were sacrificed, while the rest of the animals were killed 48 h following the hormone injections (6 per group). As expected, quantitative electron microscopic analysis of the female arcuate nuclei revealed that compared to oil-injected controls, estradiol induced drastic decreases in the overall synapse counts by 24 h (121 +/- 10 vs. 74 +/- 5 synapses/1,000 microns membrane; p < 0.05). Synaptic counts had recovered to control levels by 48 h. On the contrary, in males, estradiol treatment did not cause changes in the total synapse counts at either time. As a further control, the lack of an estrogen-induced gonadotropin surge in long-term castrate males was also confirmed. Our study confirmed that in males estradiol does not alter the net synaptology of the arcuate nucleus or cause gonadotropin positive feedback. This is in clear contradistinction to females which show both synaptic plasticity and gonadotropin-positive feedback upon receiving exogenous or endogenous estrogen. The lack of estrogen-induced synaptic plasticity may be an underlying mechanism in the abolishment of positive gonadotropin, feedback in developing males and the development of constant estrus in aging female rats.

Animals↗

Effect of vocal feedback on Stroop Color-Word interference.

The present study tested the hypothesis that vocal feedback affects the interference obtained during performance on the Stroop Color-Word task. Two measures were studied as indicators of ability to name colors on the Stroop, speed (performance time) and accuracy (number of errors). Speed of performance on the interference task by 16 male college students was not aided by reduction of vocal feedback. Accuracy of performance in the interference condition was strongly facilitated by reduction of vocal feedback, while little change was noted with no interference. These results are consistent with a view that in vocal feedback on Stroop interference the experience of a mismatch between the auditory feedback produced by the weaker color-naming response in the presence of the prepotent tendency to make the reading response increases interference.

Adolescent↗

Effects of feedback on the vigilance task performance of hyperactive and hypoactive children.

Hyperactive and hypoactive children show attentional deficits. An effort was made to modify their approaches to a vigilance task by varying the feedback received for correct detections and false alarms. It was expected that hyperactive children would do better when receiving knowledge of false alarms; hypoactive children would do better when receiving knowledge of correct responses. 20 hyperactive and 20 hypoactive children, aged 6 to 10 yr., were each tested under three conditions with a vigilance task: (a) feedback for correct responses (KR+), (b) feedback for false alarms (KR-), (c) no feedback NKR). Feedback was given by a tone. For the total error score, hyperactive subjects committed more errors than hypoactive ones under KR+ and fewer errors under KR-. Hypoactive children committed fewer errors under KR+ than no knowledge. Partial support for the hypothesis was obtained. Hyperactive children generally to better when given knowledge of errors; they become more cautious in responding. Hypoactive children do best when given information regarding correct responses; they become less inhibited in responding.

Attention↗

Using self-monitoring with an adolescent with disruptive classroom behavior: preliminary analysis of the role of adult feedback.

Current research supports the effectiveness of self-monitoring strategies for addressing academic and behavioral challenges within educational settings. Although variations in procedures exist, frequently implementation of self-monitoring involves some form of adult feedback as a method of establishing accurate self-monitoring. To date, however, researchers have not systematically evaluated whether adult feedback is a necessary component for self-monitoring to be effective. In the current investigation, the influence of adult feedback on the effectiveness of self-monitoring was analyzed. The participant was a 13-year-old student receiving educational services in a special education school at a residential facility for youth with conduct problems. The effectiveness of self-monitoring with and without adult feedback was compared. Results suggest that adult feedback may be an important component for establishing self-monitoring as an effective intervention for behavior problems exhibited in academic settings.

Adolescent↗

Effects of adding on-the-job feedback to conventional analog staff training in a nursing home.

The aims of this study were to examine effects of on-the-job feedback after conventional analog staff training and to corroborate earlier findings of competent performance maintained without feedback from others. The study took place in a nursing home with four staff participants and a resident with problem behaviors. A multiple baseline design with measures of staff and resident behavior was used, supplemented with social validity reports. The staff training program consisted of conventional group workshops plus individual on-the-job feedback. During maintenance, staff members continued recording resident behaviors but without further on-the-job feedback. Results show that after workshop training, staff performance increased, but only one staff participant demonstrated competency. With on-the-job feedback, all staff participants achieved and maintained competency. Procedures were effective and acceptable, and resident behaviors showed corresponding changes.

Employment↗

In search of information that confirms a desired self-perception: motivated processing of social feedback and choice of social interactions.

The present studies examined how the motivation to see oneself as characterized by desirable attributes may influence feedback seeking and social preferences. In Study 1, participants were first led to believe that extraversion or introversion is conducive of success. Next, they received false feedback about themselves, related to extraversion and to introversion. In a surprise recall, extraversion-success participants remembered extraversion feedback more accurately and introversion feedback less, compared to introversion-success participants. Study 2 examined preferences for others as potential sources of feedback. The findings revealed that extraversion-success participants preferred others who perceived them as extraverted, whereas introversion-success participants preferred others who perceived them as introverted. Thus, people appear to rely on how others regard them to realize a desired self-perception. These processes, oriented more toward social and interpersonal aspects of the self, complement the more intrapersonal processes of motivated self-perception studied in the past.

Adult↗

Effects of performance feedback on patient pain outcomes.

The purpose of this study was to examine the effects of an individual feedback intervention provided to nurses on selected patient outcomes related to postoperative pain management Individual performance feedback served as the intervention. Thirty orthopedic staff nurses received feedback information on their past performance of recommended pain management practices. Data were collected preintervention and postintervention on selected patient pain outcomes from the medical records of 240 patients who had undergone total knee arthroplasty. The patient outcome measures were mean 4-hour pain intensity ratings, mean highest pain intensity ratings, mean number of times pain ratings exceeded patients' acceptable level of pain, mean administered morphine equivalents, and mean pain ratings on reassessment following analgesia administration. An improvement was noted in all pain outcomes following the feedback intervention. Results indicate that providing nurses with feedback on their past performance of pain management practices may contribute to decreased postoperative pain.

Aged↗

The effect on behavior and bone mineral density of individualized bone mineral density feedback and educational interventions in premenopausal women: a randomized controlled trial [NCT00273260].

BACKGROUND: Limited information is available on ways to influence osteoporosis risk in premenopausal women. This study tested four hypotheses regarding the effects of individualized bone density (BMD) feedback and different educational interventions on osteoporosis preventive behavior and BMD in pre-menopausal women, namely: that women are more likely to change calcium intake and physical activity if their BMD is low; that group education will be more efficacious at changing behavior than an information leaflet; that BMD feedback and group education have independent effects on behavior and BMD; and, that women who improve their physical activity or calcium intake will have a change in bone mass over 2 years that is better than those who do not alter their behavior. METHODS: We performed a 2-year randomized controlled trial of BMD feedback according to T-score and either an osteoporosis information leaflet or small group education in a population-based random sample of 470 healthy women aged 25-44 years (response rate 64%). Main outcome measures were dietary calcium intake, calcium supplement use, smoking behavior, physical activity, endurance fitness, lower limb strength and BMD. We used paired t-tests, one-way ANOVA and linear regression techniques for data analysis. RESULTS: Women who had feedback of low BMD had a greater increase in femoral neck BMD than those with normal BMD (1.6% p.a. vs. 0.7% p.a., p = 0.0001), but there was no difference in lumbar spine BMD change between these groups (0.1% p.a. vs. 0.08% p.a., p = 0.9). Both educational interventions had similar increases in femoral neck BMD (Leaflet = +1.0% p.a., Osteoporosis self-management course = + 1.3% p.a., p = 0.4). Femoral neck BMD change was only significantly associated with starting calcium supplements (1.3 % p.a, 95%CI +0.49, +2.17) and persistent self-reported change in physical activity levels (0.7% p.a., 95%CI +0.22, +1.22). CONCLUSION: Individualized BMD feedback combined with a minimal educational intervention is effective at increasing hip but not spine bone density in premenopausal women. The changes in behavior through which this was mediated are potentially important in the prevention of other diseases, thus measuring BMD at a young age may have substantial public health benefits, particularly if these changes are sustained.

Adult↗

Feedback on video recorded consultations in medical teaching: why students loathe and love it - a focus-group based qualitative study.

BACKGROUND: Feedback on videotaped consultations is a useful way to enhance consultation skills among medical students. The method is becoming increasingly common, but is still not widely implemented in medical education. One obstacle might be that many students seem to consider this educational approach a stressful experience and are reluctant to participate. In order to improve the process and make it more acceptable to the participants, we wanted to identify possible problems experienced by students when making and receiving feedback on their video taped consultations. METHODS: Nineteen of 75 students at the University of Bergen, Norway, participating in a consultation course in their final term of medical school underwent focus group interviews immediately following a video-based feedback session. The material was audio-taped, transcribed, and analysed by phenomenological qualitative analysis. RESULTS: The study uncovered that some students experienced emotional distress before the start of the course. They were apprehensive and lacking in confidence, expressing fear about exposing lack of skills and competence in front of each other. The video evaluation session and feedback process were evaluated positively however, and they found that their worries had been exaggerated. The video evaluation process also seemed to help strengthen the students' self esteem and self-confidence, and they welcomed this. CONCLUSION: Our study provides insight regarding the vulnerability of students receiving feedback from videotaped consultations and their need for reassurance and support in the process, and demonstrates the importance of carefully considering the design and execution of such educational programs.

Adult↗