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Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus.

A gradual decrement in hypothalamic-pituitary-adrenal (HPA) activity is observed following repeated exposure to the same stressor, such as repeated restraint. This decrement, termed habituation, may be partly due to alterations in corticosterone-mediated negative feedback inhibition of the HPA axis. We have previously found that the posterior division of the paraventricular thalamus (pPVTh) regulates habituated HPA activity without altering HPA responses to acute stress. Therefore, in the present study, we examined the role of the pPVTh in delayed feedback inhibition of plasma corticosterone responses to repeated restraint. Dexamethasone was administered subcutaneously 2 h prior to 30 min restraint to induce delayed negative feedback inhibition of the HPA axis. In the first experiment, we determined that a 0.05-mg/kg dose of dexamethasone produced submaximal suppression of corticosterone responses to acute restraint and used this dose in the remainder of the experiments. In Experiment 2, we examined dexamethasone-induced feedback inhibition to corticosterone responses to a single or eighth restraint exposure since negative feedback functions in chronically stressed rats are not well studied. We found that corticosterone levels following dexamethasone treatment were similar in repeatedly restrained compared to acutely restrained rats. In Experiment 3, we lesioned the pPVTh and examined dexamethasone-induced feedback inhibition of corticosterone responses to a single or eighth exposure to restraint. pPVTh lesions attenuated dexamethasone-induced inhibition of corticosterone at 30 min in chronically stressed rats but had no effect in acutely stressed rats. These data suggest that negative feedback functions are maintained in rats exposed to repeated restraint and implicate the pPVTh as a site that contributes to these negative feedback functions specifically under chronic stress conditions.

Analysis of Variance↗

Cardiac concomitants of feedback processing.

This study examined the heart rate changes associated with positive and negative performance feedback in a probabilistic learning task derived from Holroyd and Coles (Psychological Review, 109 (2002) 679). In this task, subjects were presented with six stimuli and asked to respond by pressing a left versus right key. Responses were followed by positive or negative feedback. Subjects had to infer the S-R mapping rule on the basis of feedback provided to them. Two stimuli were consistently mapped onto the left versus right key (100% mapping). Two other stimuli were randomly mapped onto the keys (50% mapping) and responses to the two remaining stimuli received always positive or negative feedback (always condition). Negative feedback was associated with heart rate slowing in the 100% condition. Heart rate slowed following both positive and negative feedback in the 50% condition, but only when the previous encounter with the stimulus was followed by alternate feedback. Heart rate did not differentiate between positive and negative feedback in the always condition. The results were interpreted in support of the hypothesis assuming that heart rate slowing is elicited when performance-based expectations are violated.

Adult↗

Role of feedback in the development and maintenance of complex skill.

Three experiments examined the role of various sources of feedback in the development and maintenance of a complex ballistic skill, dart throwing, using extended practice. Even a brief delay of visual feedback initially affected accuracy and consistency adversely, though with practice performance gradually recovered. A total absence of visual feedback impelled subjects to use subtle cues such as crude auditory localization. When these cues were available, accuracy suffered to the same extent as with delayed visual feedback, but consistency in this case was unaffected. When all external feedback was removed, with subjects throwing in the dark at a luminous dot without hearing the dart land, consistency remained unimpaired, but accuracy suffered. However, on returning to full visual feedback both accuracy and consistency were found to have improved when compared to a control group. The independence of accuracy and consistency is discussed in terms of fixed and variable parameters of the skill. The effect of delayed visual feedback is attributed to the failure to integrate visual information with the fading proprioceptive trace. Central importance is attached to improvement in compentence when no external feedback is available, and possible underlying mechanisms for this improvement are described.

Auditory Perception↗

Acoustic phonetic effects of two types of verbal feedback in dysarthric subjects.

The effects of two different forms of verbal feedback on speech production were studied in 7 dysarthric speakers. Both forms of verbal feedback signaled that the listener failed to understand the message. The more general form of feedback gave no specific cues regarding the reason the listener failed to understand. The more specific feedback indicated that a voiceless initial consonant was perceived as its voiced cognate. The subjects studied had inconsistent voicing errors. Voice onset times (VOTs) and syllabic intensity, duration, and rate were measured in the phrases produced prior to and after verbal feedback. The results showed a significant change in VOT after the specific feedback and no significant change in VOT after the more general feedback. The use of specific feedback to induce articulatory change during speech treatment is discussed.

Adult↗

Plasticity and tuning by visual feedback of the stability of a neural integrator.

Persistent neural firing is of fundamental importance to working memory and other brain functions because it allows information to be held "online" following an input and to be integrated over time. Many models of persistent activity rely on some kind of positive feedback internal to the neural circuit concerned; however, too much feedback causes runaway firing (instability), and too little results in loss of persistence (leak). This parameter sensitivity leads to the hypothesis that the brain uses an error signal (external feedback) to tune the stability of persistent firing by adjusting the amount of internal feedback. We test this hypothesis by manipulating external visual feedback, a putative sensory error signal, in a model system for persistent firing, the goldfish oculomotor neural integrator. Over tens of minutes to hours, electronically controlled visual feedback consistent with a leaky or unstable integrator can drive the integrator progressively more unstable or leaky, respectively. Eye fixation time constants can be reduced >100-fold to <1 s. Normal visual feedback gradually retunes the integrator back to stability. Changes in the phase of the sinusoidal vestibulo-ocular response are consistent with integrator detuning, as are changes in ocular drift following eye position shifts compensating for brief passive head movements during fixations. Corresponding changes in persistent firing of integrator neurons are presented in the accompanying article. The presence, strength, and reversibility of the plasticity demonstrate that, in this system, external visual feedback plays a vital role in gradually tuning the stability of the neural integrator.

Animals↗

Estradiol feedback effects on the alpha-subunit mRNA in the sheep pituitary gland: correlation with serum and pituitary luteinizing hormone concentrations.

The effects of estradiol feedback on pituitary luteinizing hormone (LH) content, serum LH concentration, and in vitro-translated alpha subunit was examined in the ewe. Three animal models were used representing positive, negative, and no estradiol feedback. Two experiments were carried out: (i) anestrous ewes were treated acutely with five Silastic estradiol implants to induce a LH surge (positive feedback) and (ii) ovariectomized ewes were treated chronically with an estradiol implant (negative feedback) or were not treated (no feedback). Pituitary RNA was prepared and translated in a cell-free system; the alpha subunit was identified by immunoprecipitation and NaDodSO4/PAGE. cpm/microgram of RNA and immunoprecipitated growth hormone and prolactin were used to evaluate possible differences in RNA translational efficiencies among the treatment groups. In experiment 1, significantly higher amounts of the alpha subunit were observed in animals exhibiting an estradiol-induced LH surge than in normal anestrous ewes (P less than 0.001). Examination of values from individual animals suggested a correlation between the stage of the LH surge, pituitary LH, and translated alpha subunit. In experiment 2, the amount of alpha subunit observed in animals exposed to chronic estradiol negative feedback was significantly less (P less than 0.005) than that in the untreated ovariectomized animals (no feedback) and no different from that in intact anestrous ewes. These results suggest that both the negative and the positive feedback effects of estradiol include regulation of the amount of alpha-subunit mRNA.

Animals↗

A technology using feedback to manage experience based learning.

The aim was to establish how ICT could apply feedback principles to experience based learning. Based on a survey of student and staff requirements, we developed a personalized educational technology ('iSUS') that: (1) Made students clear what they should learn; (2) Helped them meet appropriate real patients; (3) Encouraged reflective feedback; (4) Calculated benchmarks from accumulated feedback; (5) Compared individual students' feedback against those benchmarks; (6) Matched clinical activities to curriculum objectives; (7) Gave feedback to teachers and course leads. Bench testing proved the system usable. During seven weeks of real time use, a whole year group of 111 students feedback on 1183 learning episodes. Five hundred and forty-one (46%) of feedback episodes were self initiated. We have successfully prototyped an application of feedback principles to experience based learning that students seem to find useful.

Computer-Assisted Instruction↗

The effects of augmented feedback on students' perceptions and performance.

The effects of augmented feedback on perceptions of ability (SPA), practice behaviors, and performance during motor skill instruction of a novel task were investigated. Fourth-grade students (N = 103) were randomly assigned to one of four conditions: (a) no feedback; (b) motivational feedback; (c) task feedback; or (d) motivation and task feedback. They then practiced simple and complex cupstacking skills. On a relatively simple task, the type of feedback did not have a significant effect on children's SPA, practice behaviors, or performance; but on a more complex task, differential effects of feedback were evident. Results indicate that informational feedback is an important factor in facilitating student engagement, fostering positive perceptions of ability, and ultimately improving performance on a challenging task.

Analysis of Variance↗

Feedback control of coronal plane hip angle in paraplegic subjects using functional neuromuscular stimulation.

This paper reports on an investigation of feedback control of coronal plane posture in paraplegic subjects who stand using functional neuromuscular stimulation (FNS). A feedback control system directed at regulating coronal plane hip angle in neutral position was designed, implemented, and evaluated in two paraplegic subjects. The control system included sensor mounting and signal processing techniques, a two-stage feedback controller, stimulation hardware, and a set of percutaneous intramuscular electrodes. The feedback controller consisted of two-stages in cascade: a modified discrete-time proportional-integral-derivative (PID) stage and a nonlinear single-input, multiple-output stage to determine the stimulation to be sent to several muscles. The focus of this work was on evaluating the performance of the feedback controller by comparing the response of the feedback-controlled system to that of an open-loop stimulation system. In an evaluation based on temporal response characteristics the controlled system exhibited a 41% reduction in root-mean-squared (rms) error (where error is defined as the deviation from the desired angle), a 52% reduction in steady-state error, and a 22% reduction in hip compliance. In addition, the feedback-controlled system exhibited significant reductions in variability of these measures on several days. These results demonstrate the ability of the feedback controller to improve the temporal response characteristics of the FNS control system.

Diagnosis, Computer-Assisted↗

Evidence for force-feedback inhibition in chronic stroke.

The presence of force-feedback inhibition was explored during reflex responses in five subjects with known incidence of stroke. Using constant velocity stretches, it was previously found that after movement onset, active reflex force progressively increases with increasing joint angle, at a rate proportional to a fractional exponent of the speed of stretch. However, after the reflex force magnitude exceeds a particular level, it begins rolling off until maintaining a steady-state value. The magnitudes of these force plateaus are correlated with the speed of stretch, such that higher movement speeds result in higher steady-state forces. Based upon these previous studies, we hypothesized that force plateau behavior could be explained by a force-feedback inhibitory pathway. To help facilitate an understanding of this stretch reflex force roll off, a simple model representing the elbow reflex pathways was developed. This model contained two separate feedback pathways, one representing the monosynaptic stretch reflex originating from muscle spindle excitation, and another representing force-feedback inhibition arising from force sensitive receptors. It was found that force-feedback inhibition altered the stretch reflex response, resulting in a force response that followed a sigmoidal shape similar to that observed experimentally. Furthermore, simulated reflex responses were highly dependent on force-feedback gain, where predicted reflex force began plateauing at decreasing levels with increases in this force-feedback gain. The parameters from the model fits indicate that the force threshold for force-sensitive receptors is relatively high, suggesting that the inhibition may arise from muscle free nerve endings rather than Golgi tendon organs. The experimental results coupled with the simulations of elbow reflex responses suggest the possibility that after stroke, the effectiveness of force-feedback inhibition may increase to a level that has functional significance. Practical implications of these findings are discussed in relation to muscle weakness commonly associated with stroke.

Chronic Disease↗

Feedback and the mini clinical evaluation exercise.

We studied the nature of feedback given after a miniCEX. We investigated whether the feedback was interactive; specifically, did the faculty allow the trainee to react to the feedback, enable self-assessment, and help trainees to develop an action plan for improvement. Finally, we investigated the number of types of recommendations given by faculty. One hundred and seven miniCEX feedback sessions were audiotaped. The faculty provided at least 1 recommendation for improvement in 80% of the feedback sessions. The majority of the sessions (61%) involved learner reaction, but in only 34% of the sessions did faculty ask for self-assessment from the intern and only 8% involved an action plan from the faculty member. Faculty are using the miniCEX to provide recommendations and often encourage learner reaction, but are underutilizing other interactive feedback methods of self-assessment and action plans. Programs should consider both specific training in feedback and changes to the miniCEX form to facilitate interactive feedback.

Clinical Competence↗

Influence of water-diuresis or saline volume expansion on deep nephron tubuloglomerular feedback.

We have recently demonstrated the existence of a tubuloglomerular feedback mechanism in juxtamedullary nephrons in rat kidneys during antidiuresis. In the present experiments, we have investigated the influence of water-diuresis on Munich Wistar rats and in homozygote Brattleboro rats. We have also observed the effect of saline volume expansion on the tubuloglomerular feedback of juxtamedullary nephrons in Munich Wistar rats. For comparison, the feedback mechanism was also studied in surface nephrons during water-diuresis in Munich Wistar rats. Measurements of flow rate in the descending limb of Henle and single nephron glomerular filtration rate (GFR) using micropuncture at the renal papilla were performed, while the ascending limb was microperfused at varying perfusion rates with a modified Ringer solution. In surface nephrons early proximal flow rate, single nephron GFR and stop-flow pressure was measured during microperfusion of the end-proximal loop. No significant changes were measured in surface nephrons during water-diuresis: the tubular flow rates, feedback responses, stop-flow pressure and stop-flow pressure changes were similar to those during anti-diuresis. In juxtamedullary nephrons, Henle loop flow rate increases during water-diuresis but the feedback-mediated flow and single nephron GFR response curves obtained during microperfusion were unaltered compared to controls. Together, these results indicate that the feedback could be more activated during water-diuresis than during control conditions. On the other hand, during saline volume expansion, reduced tubuloglomerular feedback sensitivity was found as shown earlier for surface nephrons. The reduction of tubuloglomerular feedback sensitivity therefore seems to be important in maintaining salt-, but not water-balance.

Animals↗

Derepression and repression of the histidine operon: role of the feedback site of the first enzyme.

Thiazolealanine, a false feedback inhibitor, causes transient repression of the his operon previously derepressed by a severe histidine limitation in strains with a wild-type or feedback-hypersensitive first enzyme but not in feedback-resistant mutants. Since experiments reported here clearly demonstrate that thiazolealanine is not transferred to tRNAHis, it is proposed that this "transient repression" is effected through the interaction of thiazolealanine with the feedback site of the enzyme. Experiments in the presence of rifampin indicate that this thiazolealanine-mediated effect is exerted at the level of translation. We conclude that histidine (free), in addition to forming co-repressor, also represses the operon at the level of translation through feedback interaction with the first enzyme of the pathway (adenosine 5'-triphosphate phosphoribosyltransferase). Rates of derepression in feedback-resistant strains are roughly half of those observed in controls, suggesting a positive role played by a first enzyme with a normal but unoccupied feedback site. Some feedback-resistant mutants, in contrast to the wild type, were unable to exhibit derepression under histidine limitation caused by aminotriazole.

ATP Phosphoribosyltransferase↗

The effect of audit and feedback on data recording in the accident and emergency department.

Thirteen newly appointed senior house officers (SHOs) at two hospitals were assessed in the recording of two variables: Glasgow Coma Scale (GCS) and diagnostic coding at Hospital A, and GCS at Hospital B. At Hospitals A and B baseline recordings of these variables were established. Active feedback (in the form of data presentation and discussion) was given at 6 and 11 weeks and a final 4-week audit was performed on GCS recordings at 20 weeks. Analysis of GCS recordings of head injuries at Hospitals A and B showed an increase from baseline values of 162/401 (40%) to 336/420 (80%) after feedback 1, and after feedback 2 recordings increased to 379/429 (88%). This was maintained in the last 4-week audit which showed recordings of 220/244 (90%). Further analysis of Hospital A's data showed the SHOs recorded diagnostic coding in 1335/4406 (30%) of cases. After feedback 1, recordings increased to 2550/3327 (77%). After feedback 2 there was no change in recording 2712/3530 (77%). Active feedback improves data recording. The first feedback has a greater impact than the second. Two feedbacks produce a sustained effect in 6 months.

Craniocerebral Trauma↗

Enhanced tubuloglomerular feedback in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension.

The present study was performed to evaluate tubuloglomerular feedback responses in transgenic rats [TGR(Cypa1a1Ren2)] with inducible malignant hypertension and to determine the degree to which feedback responsiveness is modulated by ANG II in these rats. Male Cyp1a1-Ren2 rats were fed a normal diet containing the aryl hydrocarbon indole-3-carbinol (I3C; 0.3%), for 5-6 days to stimulate expression of the Cyp1a1-Ren2 transgene and, thereby, to induce malignant hypertension. Stop-flow pressure (SFP) feedback responses to a late proximal perfusion rate of 40 nl/min were assessed in pentobarbital sodium-anesthetized rats during control conditions and after administration of the AT(1) receptor antagonist candesartan (0.1 mg/kg iv). Rats induced with I3C (n = 6) exhibited elevated mean arterial pressure and increased maximal SFP feedback responses compared with noninduced rats (n = 4; 163 +/- 4 vs. 130 +/- 2 mmHg, P < 0.01 and 16.3 +/- 1.4 vs. 11.7 +/- 0.5 mmHg, P < 0.05, respectively). Systemic candesartan decreased arterial pressure (to 98 +/- 7 and to 101 +/- 5 mmHg, respectively, P < 0.001) and attenuated SFP feedback responses (to 2.0 +/- 0.4 and to 3.3 +/- 0.9 mmHg, respectively, P < 0.01) in both hypertensive and normotensive rats. In additional experiments, peritubular capillary infusion of 10(-3) M candesartan did not alter arterial pressure but attenuated feedback responses in both hypertensive (19.3 +/- 1.4 to 8.8 +/- 0.9 mmHg, P < 0.01, n = 9) and normotensive Cyp1a1-Ren2 rats (9.0 +/- 0.8 to 4.7 +/- 0.6 mmHg, P < 0.01, n = 7). The present findings indicate that Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension exhibit augmented tubuloglomerular feedback responses. The data also show that AT(1) receptor activation by ANG II contributes to the enhanced feedback responsiveness in Cyp1a1-Ren2 rats with malignant hypertension.

Angiotensin II↗

Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism.

To evaluate further the role of adenosine in the transmission of tubuloglomerular feedback signals, we studied the effects of an adenosine receptor antagonist and an adenosine A1-receptor agonist on feedback-mediated changes in stop-flow pressure (SFP). In orthograde perfusion experiments conducted in anesthetized rats, systemic administration of the adenosine receptor blocker 1,3-dipropyl-8-sulfophenylxanthine (PSPX) did not inhibit feedback responses. Control SFP feedback responses averaged 9.7 +/- 0.65 before and 8.6 +/- 0.55 mmHg during systemic infusion of the receptor blocker. In retrograde perfusion experiments, intratubular administration of the A1 agonist (360 nM) N6-cyclopentyladenosine (CPA), added to a hypotonic solution, markedly enhanced feedback responses. This effect was completely prevented by coinfusion of PSPX. Addition of 10 mM of the antagonist to the CPA-containing solution attenuated SFP feedback responses to less than 1 mmHg (delta = 0.44 +/- 0.50). Furthermore, PSPX also inhibited feedback responses obtained with an isotonic solution alone. Furosemide, which has been shown to block normal SFP responses obtained with isotonic solutions, failed to block CPA-induced decreases in SFP. These data demonstrate that intraluminal administration of an adenosine A1 analogue causes feedback-mediated decreases in SFP and therefore support a role for adenosine receptors in the signal transmission pathway.

Adenosine↗

Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat.

In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.

Animals↗

Formative feedback in teaching undergraduate psychiatry.

OBJECTIVE: This paper describes the introduction of formative feedback into a psychiatry attachment at an Australian university and evaluates students' responses to that initiative. METHOD: Students were provided with formative feedback sessions employing a standardized instrument, also used at the end of the attachment for summative assessment. They were asked to both define formative feedback and rate its usefulness on a questionnaire, providing open-ended written comments where appropriate. RESULTS: The concept and purpose of formative feedback were understood by 91.9% of the students who completed a questionnaire. The vast majority considered it to be useful, but some identified the need for constructive criticism and structured feedback as important characteristics of formative sessions. CONCLUSIONS: Rigorous research is needed to establish whether formative feedback impacts summative assessments. However, it is clear that such feedback is desirable, in that it increases student confidence and direction. We encourage our colleagues to consider introducing and evaluating formative feedback into psychiatry curricula.

Attitude↗