Influence of Depth of Hypnosis on Pupillary Reactivity to a Standardized Tetanic Stimulus in Patients Under Propofol-Remifentanil Target-Controlled Infusion: A Crossover Randomized Pilot Study.

BACKGROUND: Pupillometry allows the measurement of pupillary diameter variations in response to nociceptive stimuli. This technique has been used to monitor the balance between analgesia and nociception. Under general anesthesia, the amplitude of pupillary dilation is related to the amount of administered opioids. The objective of this study was to determine whether at a constant infusion rate of opioids, the pupillary response was influenced by depth of hypnosis assessed by the bispectral index (BIS). METHODS: Twelve patients (14-20 years) anesthetized for orthopedic surgery were included. Under propofol-remifentanil target-controlled infusion, remifentanil effect site target concentration was fixed at 1 ng/mL. Two measures of pupillary reflex dilation were performed on each patient in a randomized order: one at BIS 55 and one at BIS 25. These levels of BIS were obtained by adjusting propofol target concentration and maintained for 10 minutes before each measure. For each measure, we applied a standardized tetanic stimulation on the patient's forearm (60 mA, 100 Hz, 5 seconds). All measures were performed before the beginning of surgery. RESULTS: Pupillary dilation was significantly greater at BIS 55 than at BIS 25: 32.1% ± 5.3% vs 10.4% ± 2.5% (mean difference estimate [95% confidence interval]: 21.8% [12.9-30.6], P < .001), without carryover effect (P = .30) nor period effect (P = .52). Hemodynamic parameters and BIS were not modified by the stimulation. CONCLUSIONS: In patients receiving a constant infusion of remifentanil at a target concentration of 1 ng/mL, pupillary dilation after a standardized tetanic stimulation was influenced by depth of hypnosis assessed by the BIS.

Change in flash visual evoked potentials in New Zealand albino rabbits after sub-tenon's anesthesia.

CONTEXT: The occurrence of amaurosis during ophthalmic anesthesia is well known. The reason for this manifestation has not been studied. PURPOSE: To investigate the effect of sub-tenon's anesthesia on visual conduction in rabbit eyes. METHODS: Fifteen right eyes of 15 New Zealand albino rabbits were included. 2% lidocaine hydrochloride and 0.75% bupivacaine hydrochloride (1 ml, 1:1 mixture) was injected in the sub-tenon's space of 8 eyes while the control group (n = 7) was injected with 1 ml physiological saline. Flash visual evoked potentials (FVEP) were performed with Roland reti-scan system before and, 5 min, 15 min, and 5 days after injection. The natural pupillary diameter and minimal pupillary diameter with light reflex were recorded. RESULTS: In the anesthesia group, N1 latency, P1 latency, and P1 amplitude were 17.13 ± 1.13 ms, 28.25 ± 1.83 ms, 13.45 ± 4.36 µv respectively before injection; 21.75 ± 3.06 ms, 29.63 ± 2.67 ms, 7.24 ± 4.64 µv at 5 min after injection; 22.25 ± 1.39 ms, 29.50 ± 2.51 ms, 7.54 ± 4.47 µv at 15 min after injection, and, 17.75 ± 0.71 ms, 28.13 ± 2.42 ms, 13.17 ± 4.08 µv 5 days after injection. When compared with baseline, N1 latency at 5 min and 15 min after injection showed prolongation (p = 0.019 and p = 0.001, respectively). Likewise, P1 amplitude decreased at 5 min and 15 min after injection (p < 0.001, p < 0.001, respectively). Both N1 latency and P1 amplitude recovered 5 days after the injection. Pupillary light reflex (PLR) constriction amplitude was 35.42% and 0.00% before and at 5 min after injection (p = 0.012). After 5 days it recovered to 33.33%. The FVEP and PLR constriction amplitude did not change significantly after injection in the control group. DISCUSSION: Sub-tenon's anesthesia was associated with changes in the FVEP and pupullary light reflex in rabbit eyes in our study. CONCLUSIONS: The data from this study suggested that sub-tenon's anesthesia could reversibly block visual conduction in rabbit's eyes.

Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study.

Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate's diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system.

SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences.

PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.

Pupillary changes among Nigerian adults following the instillation of Garcinia kola nut extracts: multicentric studies.

BACKGROUND: A multi-centre, open, within-patient controlled study was performed on 106 adult volunteers to investigate the effects of Garcinia kolanut extracts on the pupillary sizes. STUDY DESIGN: 106 participants in three Nigerian Ophthalmic Centres with no pupillary defects and associated ocular or systemic co-morbidities had their pupillary diameters measured at 0, 15, 30 and 45 minutes respectively with a pupillometer (Neuroptics model # 586009). Using the left eyes as control, Garcinia kolanut extract was instilled into the right eyes at 15 minutes intervals. RESULTS: There were 63 females and 43 males ranging in age from 18 to 58 years with the mean age of 34.9 years. Average pupillary diameter measured among participants was 4.1 - 8.4 mm with the mean value of 6.0 mm prior to garcinia kola nut extract instillation. There was a gradual reduction in the baseline pupillary size with age in years at 0.2mm per decade without garcinia extract instillation. There was a significant higher baseline pupillary diameter in males than females with males and females mean values of 6.29mm (6.00 - 6.56mm) and 5.85mm (5.60 - 6.11mm) in the right eye (p=0.026) and mean pupillary diameters 6.16mm (5.90 - 6.42mm) and 5.80mm (5.56 - 6.04mm) in the left eyes (p=0.05) respectively. There were consistent significant miosis in the right eyes with instilled Garcinia kola nut extract compared to the left eyes at 15, 30 and 45 minutes (p=0.0000). CONCLUSION: 4% Garcinia kola nut extract drop has a transient miotic effect on human pupils not sustainable for more than 45 minutes.

Effects of goshuyuto on lateralization of pupillary dynamics in headache.

Autonomic nervous imbalance is implicated in chronic headache. We investigated the effects of goshuyuto-a representative Kampo medicine for headache-on the lateralization of the pupillary autonomic nervous system by using binocular infrared video pupillography. Patients with chronic headache were administered goshuyuto extract for 1 month (1st stage). Goshuyuto was discontinued for 1 month, following which the patients were randomly divided into 2 groups: placebo and goshuyuto. In the 2nd stage, the respective groups were administered placebo or goshuyuto for 3 months. The average laterality of the pupillary dynamics decreased significantly in the goshuyuto group. These results suggest that the reduction of the difference in pupillary autonomic balance between the left and right eyes might be one of the action mechanisms of goshuyuto to relieve chronic headache.

The effects of lorazepam on skin conductance responses to aversive stimuli in healthy subjects.

BACKGROUND: Autonomic responses to aversive stimuli are widely used to model anxiolytic drug effects in healthy humans. Benzodiazepine anxiolytics dose dependently attenuate autonomic responses to aversive stimuli by their anxiolytic as well as sedative action. The present study aimed to examine the effects of non-sedative doses of lorazepam on skin cutaneous responses to aversive stimuli and subjective mood. METHODS: A randomized, double blind, cross over study of 12 healthy male volunteers aged 24 years (23-32; median; range) was carried out. Subjects received single oral doses of 0.5 and 1.0 mg lorazepam as well as placebo on three different occasions with at least 5 days in-between. Skin conductance responses (SCRs) to unpleasant pictures and noises, pupillary unrest index as well as subjective levels of anxiety were measured repeatedly before and after drug administration. RESULTS: SCRs were found significantly lower 2 hours following ingestion of 0.5 mg lorazepam as well as 1, 2 and 3 hours after 1.0 mg lorazepam were given as compared to baseline conditions. By contrast, administration of placebo did not influence SCRs to a significant extent. Both doses of lorazepam did not change pupillary unrest index nor subjective mood. CONCLUSIONS: Lorazepam may attenuate SCRs to aversive stimuli without affecting vigilance nor subjective mood. Attenuation of autonomic responses to aversive stimuli may not be specific for an anxiolytic effect.

Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors.

Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

Preliminary investigation of the effect of peppermint oil on an objective measure of daytime sleepiness.

The assertion, often quoted in the popular literature, that peppermint has invigorating properties has been investigated through objective assessment of daytime sleepiness. Pupillary fatigue oscillations have been used to give an index of pupillary unrest that can be used as a reliable measure of daytime sleepiness. When compared with a no-odour condition, the presence of peppermint oil limited the increase in sleepiness during 11 min spent in a darkened room. This significant difference in sleepiness between the peppermint oil and the no-odour conditions was shown not to be related to differences in subjective ratings of initial sleepiness, from the Stanford Sleepiness Scale (SSS). Neither was it related to differences in initial pupillary unrest or mean pupil size. It seems that in conditions that favour an increase in daytime sleepiness, peppermint oil can indeed reduce sleepiness. However, the mechanisms by which peppermint oil has its effect and the applicability of these findings to situations in everyday life will require further empirical investigation.

Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women.

BACKGROUND: Zinc deficiency may result in abnormal dark adaptation or night blindness, a symptom primarily of vitamin A deficiency. During a placebo-controlled trial in Nepal, weekly vitamin A supplementation of women reduced but failed to eliminate the incidence of night blindness during pregnancy, suggesting a role for zinc. OBJECTIVE: The study examined the efficacy of daily zinc supplementation in restoring night vision of pregnant women who developed night blindness while routinely receiving either vitamin A, beta-carotene, or placebo in a field trial. DESIGN: Women (n = 202) who reported to be night blind during pregnancy were randomly assigned in a double-blind manner, stratified on vitamin A, beta-carotene, or placebo receipt, to receive 25 mg Zn or placebo daily for 3 wk. Thus, the 6 groups studied were as follows: beta-carotene + zinc, beta-carotene alone, vitamin A + zinc, vitamin A alone (vitamin A + placebo), zinc alone (zinc + placebo), and placebo (2 placebos: one for the vitamin A or beta-carotene study and one for the zinc study). Women underwent a clinic-based assessment that included pupillary threshold testing and phlebotomy before and after supplementation. Supplement use and daily history of night blindness were obtained at home twice every week. RESULTS: Zinc treatment increased serum zinc concentrations, but alone (zinc alone group), failed to restore night vision or to improve dark adaptation. However, women in the vitamin A + zinc group who had baseline serum zinc concentrations <9.9 micromol/L were 4 times more likely to have their night vision restored (95% CI: 1.1, 17.3) than were women in the placebo group and tended to have a small improvement in pupillary threshold scores (by 0.21 log candela/m2; P = 0.09). CONCLUSION: These data suggest that zinc potentiated the effect of vitamin A in restoring night vision among night-blind pregnant women with low initial serum zinc concentrations.

Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man.

It has been shown previously that the amplitude of the acoustic startle reflex is enhanced, and the amplitude of the light reflex reduced, when subjects anticipate an aversive event, compared to periods when subjects are resting ('fear-potentiated startle reflex' and 'fear-inhibited light reflex'). We examined whether the anxiolytic diazepam would reverse the effects of threat on the startle and pupillary reflexes. Twelve male volunteers participated in three weekly sessions in which they received oral treatment with placebo, diazepam 5 mg and diazepam 10 mg, according to a balanced crossover double-blind design. One hour after ingestion of the treatments, miotic responses to light pulses and electromyographic responses of the orbicularis oculi muscle to sound pulses were elicited during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with a significant increase in the amplitude of the electromyographic (EMG) response, a significant reduction of the miotic response amplitude, and an increase in self-rated anxiety. Diazepam attenuated all these effects of THREAT. Diazepam did not affect the amplitude of the miotic response under the SAFE condition, but did suppress the EMG response under this condition. These results confirm the validity of the fear-potentiated startle reflex and fear-inhibited light reflex as laboratory models of human anxiety, and reveal some differences between the effects of diazepam on the two reflexes.

Pupillometric changes during gradual opiate detoxification correlate with changes in symptoms of opiate withdrawal as measured by the Weak Opiate Withdrawal Scale.

The relationship between pupil size and subjective symptoms of opiate withdrawal during gradual opiate agonist detoxification has not yet been studied. In the current study, the authors sought to determine the relationship between pupil size and intensity of opiate withdrawal symptoms. To accomplish this, they examined 19 subjects meeting DSM-IV criteria for opiate dependence (304.00) on agonist therapy. All subjects were undergoing opiate detoxification with either methadone or the longer-acting 1-alpha acetylmethadol (LAMM). During two separate visits, subjects' pupil sizes were assessed in the dark using a pupillometer. At each visit, subjects completed two standardized assessment tools (the Subjective Opiate Withdrawal Scale [SOWS] and the Weak Opiate Withdrawal Scale [WOWS]) for measuring subjective symptoms of opiate withdrawal. It was found that changes in pupil size significantly correlated with WOWS, but not with SOWS, scores. Larger pupil sizes were associated with less withdrawal distress. The sensitivity of the pupillometric test to detect increases in opiate craving during opiate agonist medication reduction was 92%, with a specificity of 57%. The predictive value of a positive test was 79%, whereas the predictive value of a negative test was 80%. Pupillometry may provide an objective measure of the intensity of opiate withdrawal in subjects during gradual methadone detoxification.

Transcutaneous electrical stimulation applied to the infratrochlear nerve induces a homatropine-resistant miosis in humans.

1. Both high- and low-intensity transcutaneous electrical stimuli were applied to the emergence of the infratrochlear nerve in 18 healthy subjects. The effect on the size of the homolateral pupil was investigated. The width of the pupil was also measured when high-intensity transcutaneous electrical stimulation was applied to the contralateral side. 2. The high-intensity pulse resulted in constriction of the pupil when the stimulation was homolateral. The miosis was slow in onset (120 s latency) and long-lasting (80 s). No pupillary changes were detected after either ipsilateral low-intensity or contralateral high-intensity stimuli. 3. In 11 healthy subjects, the pupillary response to transcutaneous electrical stimulation was evaluated during iris parasympathetic blockade induced by homatropine eyedrops. The disappearance of the light reflex due to homatropine was considered an index of the parasympathetic blockade. Afterwards, a high-intensity pulse was transcutaneously delivered to the emergence of the infratrochlear nerve and the ipsilateral pupil size was measured. 4. A reduction in the pupillary size followed the electrical stimulation, still under the effect of homatropine which abolished the light reflex. The time course of this pupillary constriction was similar to that seen without the influence of homatropine. 5. The findings suggest that homolateral miosis, observed after unilateral high-intensity stimulation of the infratrochlear nerve, does not stem from cholinergic activation. It has been suggested that miosis induced by transcutaneous electrical stimulation may be due to an antidromic activation of the iris sensory fibres.

Static and dynamic pupillometry for determination of the course of gradual detoxification of opiate-addicted patients.

In order to assess the course of methadone (Heptadone) substitution therapy, 29 inpatients at the Vienna Psychiatric University Clinic (21 males, mean age = 27 years, SD 4 years; 8 females, mean age 29.75 years, SD 5.28 years) who were addicted to opium tea or to a mixture of opium and heroin were investigated by means of computer-assisted "static"- and "light-evoked dynamic" pupillometry. Pupillary measurements were carried out before the start of withdrawal, on the 2nd day 48 h after the administration of 10 mg methadone, and again after the maximum and half of the maximum dose of methadone had been administered. The constricted pupils (the effect of opiate) showed dilatation after the withdrawal syndrome appeared, but immediately after the start of the detoxification treatment, as well as 1 day after administration of the maximum methadone dose a decrease of pupillary diameter was observed. The narrowing of the pupil was followed by an increase in pupillary diameter, which peaked 48 h after the last minimal dose of methadone and nearly reached the normal level. The widening of the pupil reflects an increase of noradrenergic activity under conditions of opiate withdrawal. An increase of spontaneous fluctuations was observed during withdrawal and was only inhibited by the maximum dose of methadone. Finally, pupillary dynamics (shortening of latency time and increase of relative changes) improved during therapy. The pupillary measurement corresponded with clinical observations as well as with self-evaluation during treatment. Thus pupillometry seems to be a useful instrument for assessment of treatment of opiate-addicted patients.

A subchronic toxicity study of two inhaled aerosolized atropine sulfate formulations in rats and dogs.

The potential subchronic (21 days) toxicity of inhaled metered aerosol formulations (solution and suspension) of atropine sulfate was investigated in rats and dogs. The doses administered to rats were 0.78 and 2.5 mg/kg/day (solution) or 1.4 and 3.2 mg/kg/day (suspension). In the dog, the daily doses achieved were 0.5 and 1.3 mg/kg/day, regardless of formulation. In both species, sham control animals inhaled air only and vehicle control animals inhaled either placebo solution or placebo suspension. There was no mortality or other evidence of a toxic effect of atropine sulfate. The expected mydriatic effect of atropine sulfate was seen in both species and, similarly, the pupillary light reflex was impaired in rats and dogs receiving either formulation of atropine sulfate at both dose levels. Reduced salivation was also noted and ophthalmologic examinations in both species were unremarkable. In dogs, atropine sulfate (high-dose) caused tachycardia but there was no evidence of an adverse effect on the electrocardiogram or on systolic blood pressure. In both species, atropine sulfate did not alter body weight, food consumption or clinical pathology parameters. Necropsy observations and histopathological findings revealed no effect of atropine sulfate in either species although, in the rat, adrenal gland hypertrophy in both sexes followed inhalation of the suspension at both dose levels. With this possible exception, nothing but the expected pharmacological effects of atropine sulfate were seen in either rats or dogs.

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.

[Effects of tofisopam on the physiological changes induced by stress loading and hypothalamic stimulation (author's transl)].

Effects of tofisopam on the gastric ulceration induced by immobilization stress in olfactory-bulbectomized rats, propulsion of the small intestine caused by water immersion-stress in rats and autonomic responses to electrical stimulation of the hypothalamus in rabbits were investigated. Immobilization stress loading of 16.5 hours each for 10 days caused the augmentation of incidence and average index of gastric ulceration in olfactory-bulbectomized rats, compared with non-treated rats. Tofisopam 100 mg/kg, p.o. significantly inhibited the gastric ulceration in olfactory-bulbectomized rats. Water immersion-stress loading for 2 hours caused a significant increase in propulsion of the small intestine in rats. This increase was reversed to control levels after the oral administration of tofisopam in a dose of 100 mg/kg. Tofisopam at dose of 1 mg/kg i.v. inhibited the contraction of ear microvessels, the decrease in earlobe temperature and the mydriasis induced by electrical stimulation of the medial hypothalamic area in rabbits, Moreover, these inhibitions were also shown by the intra-cerebrospinal injection of tofisopam at a dose of 0.1 mg/kg. From these results, it is concluded that tofisopam could restore the autonomic abnormality induced by stress-loading and exerts such effects by acting on the hypothalamus, an area of the brain, which regulates autonomic nervous functions.