Physiological blunting during pregnancy extends to induced relaxation

There is accumulating evidence that pregnancy is accompanied by hyporesponsivity to physical, cognitive, and psychological challenges. This study evaluates whether observed autonomic blunting extends to conditions designed to decrease arousal. Physiological and psychological responsivity to an 18-min guided imagery relaxation protocol in healthy pregnant women during the 32nd week of gestation (n = 54) and non-pregnant women (n = 28) was measured. Data collection included heart period (HP), respiratory sinus arrhythmia (RSA), tonic and phasic measures of skin conductance (SCL and NS-SCR), respiratory period (RP), and self-reported psychological relaxation. As expected, responses to the manipulation included increased HP, RSA, and RP and decreased SCL and NS-SCR, followed by post-manipulation recovery. However, responsivity was attenuated for all physiological measures except RP in pregnant women, despite no difference in self-reported psychological relaxation. Findings support non-specific blunting of physiological responsivity during pregnancy.     

Impaired emotional contagion following severe traumatic brain injury

Empathy deficits are widely-documented in individuals after severe traumatic brain injury (TBI). This study examined the relationship between empathy deficits and psychophysiological responsivity in adults with TBI to determine if impaired responsivity is ameliorated through repeated emotional stimulus presentations. Nineteen TBI participants (13 males; 41 years) and 25 control participants (14 males; 31 years) viewed five repetitions of six 2-min film clip segments containing pleasant, unpleasant, and neutral content. Facial muscle responses (zygomaticus and corrugator), tonic heart rate (HR) and skin conductance level (SCL) were recorded. Mean responses for each viewing period were compared to a pre-experiment 2-min resting baseline period. Self-reported emotional empathy was also assessed. TBI participants demonstrated identical EMG response patterns to controls, i.e. an initial large facial response to both pleasant and unpleasant films, followed by habituation over repetitions for pleasant films, and sustained response to unpleasant films. Additionally, an increase in both arousal and HR deceleration to stimulus repetitions was found, which was larger for TBI participants. Compared to controls, TBI participants self-reported lower emotional empathy, and had lower resting arousal, and these measures were positively correlated. Results are consistent with TBI producing impairments in emotional empathy and responsivity. While some normalisation of physiological arousal appeared with repeated stimulus presentations, this came at the cost of greater attentional effort.     

Autonomic arousal explains social cognitive abilities in high-functioning adults with autism spectrum disorder

Empirical research into behavioural profiles and autonomic responsivity in individuals with autism spectrum disorders (ASDs) is highly variable and inconsistent. Two preliminary studies of children with ASDs suggest that there may be subgroups of ASDs depending on their resting arousal levels, and that these subgroups show different profiles of autonomic responsivity. The aim of the present study was to determine whether (i) adults with high-functioning ASDs may be separated into subgroups according to variation in resting arousal; and (ii) these ASD arousal subgroups differ in their behavioural profiles for basic emotion recognition, judgements of trustworthiness, and cognitive and affective empathy. Thirty high-functioning adults with ASDs and 34 non-clinical controls participated. Resting arousal was determined as the average skin conductance (SCL) across a 2 min resting period. There was a subgroup of ASD adults with significantly lower resting SCL. These individuals demonstrated poorer emotion recognition, tended to judge faces more negatively, and had atypical relationships between SCL and affective empathy. In contrast, low cognitive empathy was a feature of all ASD adults. These findings have important implications for clinical interventions and future studies investigating autonomic functioning in ASDs.     

Timing of caffeine's impact on autonomic and central nervous system measures: clarification of arousal effects

The timing of caffeine effects on arousal levels was examined. From previous work in our laboratory, an increase in skin conductance level (SCL) was used as the marker of arousal increase, and we sought to identify the timing of this and related effects following caffeine ingestion. A single oral dose of caffeine (250 mg) was used in a randomised double-blind placebo-controlled repeated-measures cross-over study. Eyes-closed resting electroencephalogram (EEG) and autonomic data (SCL, heart rate, respiration rate, and systolic and diastolic blood pressure) during 2 min epochs that commenced every 4 min after ingestion, were analysed. The SCL placebo data were used to identify potential arousal measures prior to examining caffeine effects. Caffeine was associated with increased SCL, increased respiratory rate and a global reduction in alpha power. There were no significant cardiovascular effects of caffeine-induced arousal. These caffeine results are consistent with our recent electrodermal and EEG studies of arousal, and confirm the potential use of caffeine as a simple means of experimentally modifying arousal levels without task-related confounds.     

Caffeine effects on resting-state arousal in children

From previous work in our laboratory, increases in skin conductance level (SCL), together with global (across-scalp) decreases in electroencephalogram (EEG) alpha power and increases in alpha frequency, are useful indices of arousal increase, and here we sought to identify changes in these indices with caffeine ingestion in children. We explored the effects of a single oral dose of caffeine (80 mg) in a randomised double-blind placebo-controlled repeated-measures cross-over study. Thirty healthy children aged between 8 and 13 years (mean age 10.5 years; 11 females) participated in two sessions, 1 week apart. EEG and SCL from a 3 min eyes-closed epoch, commencing approximately 30 min after ingestion of caffeine or placebo, were examined. Caffeine was associated with increased SCL, and a global reduction in EEG power in the theta and alpha bands, as well as topographically-focused reductions in delta and beta power, and a focal increase in alpha frequency. Only global alpha level demonstrated the expected inverse relationship with SCL in both placebo and caffeine conditions. These results are generally consistent with recent electrodermal and EEG studies of arousal. Together with our previous adult data, they indicate that caffeine can be used to increase arousal in both adults and children, without the potential confounds associated with varying task demands. Caffeine appears useful as a simple tool for manipulating arousal in studies exploring its role in physiological and behavioural functioning. This may be helpful in determining the role of hypothetical arousal anomalies in syndromes such as attention-deficit/hyperactivity disorder.     

Excess beta activity in the EEG of children with attention-deficit/hyperactivity disorder: A disorder of arousal?

Past research has reported that a small proportion of children with attention-deficit/hyperactivity disorder (AD/HD) have excess beta activity in their EEG, rather than the excess theta typical of the syndrome. This atypical group has been tentatively labeled as hyperaroused. The aim of this study was to determine whether these children have a hyperaroused central nervous system. Participants included 104 boys aged 8 to 13 years old, with a diagnosis of either the Combined or Inattentive type of AD/HD (67 combined type), and 67 age-matched male controls. Ten and a half minutes of EEG and skin conductance (SCL) were simultaneously recorded during an eyes-closed resting condition. The EEG was Fourier transformed and estimates of total power, and relative power in the delta, theta, alpha, and beta bands, and the theta/beta ratio, were calculated. AD/HD patients were divided into an excess beta group and a typical excess theta group. Relative to controls, the typical excess theta group had significantly increased frontal total power, theta and theta/beta ratio, with reduced alpha and beta across the scalp. The excess beta group had significantly reduced posterior total power, increased centro-posterior delta, globally reduced alpha, globally increased beta activity, and globally reduced theta/beta ratio. Both AD/HD groups had significantly reduced SCL compared to the control group, but the two groups did not differ from each other on SCL. These results indicate that AD/HD children with excess beta activity are not hyperaroused, and confirm that the theta/beta ratio is not associated with arousal. This is the first study of arousal measures in AD/HD children with excess beta activity, and has implications for existing models of AD/HD.     

The influence of attention and arousal on emotion perception in adults with severe traumatic brain injury

Many people with traumatic brain injury (TBI) have poor emotion recognition, with negative emotions more frequently impaired. They can also display abnormal affective responses to emotionally charged material, however, the mechanisms underpinning such deficits are unclear. This study examined whether affective responsivity can be improved by focusing attention and whether responsivity is associated with perception accuracy. Eighteen adults with moderate-to-severe TBI and 18 control participants viewed facial expressions while skin conductance (SCR) and evoked cardiac deceleration (ECD) (used as indices of orientation) and skin conductance levels (SCL) (used as an index of phasic arousal) were monitored. They viewed two blocks of faces (8 angry and 8 happy per block), passively in the first block and with the instruction to identify the emotional expression in the second. No differences between conditions, emotions or groups were found using SCR. Both groups demonstrated increasing ECD for the attend condition relative to the passive condition. For the passive task the control group showed increasing SCL (sensitisation) over trials when viewing angry faces and decreasing SCL (habituation) to happy faces. No differences between emotions were shown for the TBI group who rapidly habituated to both expressions. For the attend task, there was no evidence of habituation for either expression for either the control or TBI participants. Physiological measures did not correlate to accuracy in recognising emotions. The results suggest that increasing attentional demands improves orientation and emotional engagement (arousal) to emotional faces following TBI. However, the relationship to this and emotion perception accuracy remains unclear.     

The role of arousal in the preparation for voluntary movement

Planning and readiness for action are associated with pre-movement brain activity reflected in the readiness potential (RP). Previous research suggests that RP is affected by higher-order cognitive functions. The present study investigated the relationship between arousal and RP. Twenty participants performed a RP paradigm in which they executed self-paced movements approximately every 4-5 s. Participants’ arousal level was directly manipulated through interaction with the experimenter during the rest breaks preceding the movement task. Skin conductance level (SCL) differed between arousal conditions, indicating that the arousal manipulation was effective. RP was significantly higher under the low arousal than the high arousal condition. This arousal effect also changed depending on whether RP was measured at overall high or low levels of arousal. Our data indicate that arousal does not directly activate structures underlying action preparation. We suggest that the arousal effect may be mediated by the attentional resources allocated to the movement.     

Psychophysiological investigations in depersonalization disorder and effects of electrodermal biofeedback

Previous studies investigating depersonalization disorder (DPD) report a lower baseline skin conductance level (SCL) and attenuated skin conductance response (SCR) to emotive stimuli. We hypothesized that increasing physiological arousal levels via electrodermal biofeedback may ameliorate disembodiment and emotional numbing symptomatology. Real-time versus sham biofeedback yielded a significant SCL increase after just 3 real-time biofeedback sessions in healthy volunteers. Subsequently, a randomized controlled biofeedback trial was administered with DPD patients. Findings were not replicated as SCL tended to fall, curiously more substantially in the real-time condition, concomitant with increased low- and high-frequency heart rate variability. To further investigate abnormal autonomic regulation in DPD, we compared basal autonomic activity between patients and healthy volunteers and found the former to be significantly more labile, indexed by greater nonspecific SCRs and higher resting SCLs. Rather than low sympathetic arousal, DPD might be better characterized by abnormal autonomic regulation affecting emotional and physiological responsivity.     

SSVEP and ERP measurement of cognitive fatigue caused by stereoscopic 3D

Characteristically within the resting brain there are slow fluctuations (around 0.1 Hz) of EEG and NIRS-(de)oxyhemoglobin ([deoxy-Hb], [oxy-Hb]) signals. An interesting question is whether such slow oscillations can be related to the intention to perform a motor act. To obtain an answer we analyzed continuous blood pressure (BP), heart rate (HR), prefrontal [oxy-Hb], [deoxy-Hb] and EEG signals over sensorimotor areas in 10 healthy subjects during 5 min of rest and during 10 min of voluntary finger movements. Analyses of prefrontal [oxy-Hb]/[deoxy-Hb] oscillations around 0.1 Hz and central EEG band power changes in the beta (alpha) band revealed that the positive [oxy-Hb] peaks preceded the central EEG beta (alpha) power peak by 3.6 ± 0.9 s in the majority of subjects. A similar relationship between prefrontal [oxy-Hb] and central EEG beta power was found during voluntary movements whereby the post movement beta power increase (beta rebound) is known to coexist with a decreased excitability of cortico-spinal neurons. Therefore, we speculate that the beta power increase ∼3 s after slow fluctuating [oxy-Hb] peaks during rest is indicative for a slow excitability change of central motor cortex neurons. This work provides the first evidence that initiation of finger movements at free will in relatively constant intervals around 10 s could be temporally related to slow oscillations of prefrontal [oxy-Hb] and autonomic blood pressure in the resting brain.     

Differential effects of background noise of various intensities on neuronal activation associated with arousal and stress response in a maze task

Background noise (BGN) can affect performance of various tasks as a function of its intensity. Such effects may involve modulation of arousal level during task performance, though the neural mechanisms responsible for the intensity-dependence of effects of BGN are still unclear in detail. We examined the effects of BGN (white noise) of various intensities (control, < 40 dB without BGN; 70 dB; 100 dB) during maze task on neuronal activity related to arousal and stress responses using c-Fos immunohistochemistry in rats. Performance (number of errors, time to goal, and number of rearings) during the maze task under 70 dB-BGN, but not 100 dB-BGN, was improved compared with the control condition. In addition, 70 dB-BGN increased c-Fos expression in brain areas responsible for arousal, including mesopontine tegmentum, basal forebrain (BF), locus coeruleus (LC), and cortex, whereas 100 dB-BGN markedly activated neurons in stress-related nuclei, such as the hypothalamic paraventricular nucleus, central nucleus and basolateral nucleus of the amygdala, as well as BF cholinergic neurons, LC neurons, and cortex. These findings suggest that BGN during maze task can induce differential neuronal activation depending on the intensity of BGN in the brain areas relating to arousal and stress responses, which might be involved in maze performance.     

Sympathetic arousal during the processing of dysphoric affect by youths at high and low familial risk for depression

Youths at high risk for depression have been shown to have problems in repairing their own sad mood. Given that sympathetic arousal has been implicated both in the experience and regulation of affect, an atypical pattern of arousal may be one of the factors that contribute to mood repair problems. In the current study, we measured sympathetic arousal of never-depressed youths at high (n = 56) and low (n = 67) familial risk for depression during sad mood induction and instructed mood repair. Sympathetic arousal was indexed by skin conductance level (SCL) and cardiac pre-ejection period (PEP); mood repair outcome was indexed by self-rated affect. High-risk youths demonstrated increased SCL during sadness induction, which persisted during mood repair; low-risk youths evidenced increased SCL only during mood repair. Shortened PEP was evident only among high-risk youths and only during mood repair. Furthermore, shortened PEP during mood induction predicted less successful mood repair in the low-risk but not in the high-risk group. The findings suggest that: (a) depression-prone youths differ from control peers in patterns of sympathetic responses to emotional stimuli, which may impair their ability to relieve sadness, and (b) activation patterns differ across subsystems (SCL vs. PEP) of sympathetic activity, in conjunction with depression risk status.     

Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates arousal response accompanied by yawning behavior in rats

We have reported that an arousal response accompanied by yawning behavior can be evoked by electrical and chemical stimulation of the hypothalamic paraventricular nucleus (PVN) in rats, although the mechanism responsible for the arousal response accompanied by yawning evoked by PVN stimulation is still unknown. In the present study, we examined the involvement of corticotropin-releasing factor (CRF) in the arousal response during yawning induced by electrical stimulation of the PVN in anesthetized, spontaneous breathing rats using intracerebroventricular (icv) injection of alpha-helical CRF, a CRF antagonist (4.2 microg, lateral ventricle). The electrocorticogram (ECoG) was recorded to evaluate arousal responses during yawning. Fast Fourier transform was used to obtain the power spectrum in delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-20 Hz) bands. We also recorded the intercostal electromyogram as an index of inspiratory activity and blood pressure (BP) as an index of autonomic function to evaluate yawning response. PVN stimulation induced significant increases in relative powers of theta, alpha, and beta bands, but not delta band, concurrent with yawning events regardless of icv injection, though the relative powers after icv injection of alpha-helical CRF were significantly lower than those after saline injection. These findings suggest that CRF neurons in the PVN are primarily responsible for the arousal response accompanied by yawning behavior.     

Zinc supplementation provides behavioral resiliency in a rat model of traumatic brain injury

Depression, anxiety, and impairments in learning and memory are all associated with traumatic brain injury (TBI). Because of the strong link between zinc deficiency, depression, and anxiety, in both humans and rodent models, we hypothesized that dietary zinc supplementation prior to injury could provide behavioral resiliency to lessen the severity of these outcomes after TBI. Rats were fed a marginal zinc deficient (5 ppm), zinc adequate (30 ppm), or zinc supplemented (180 ppm) diet for 4 weeks followed by a moderately-severe TBI using the well-established model of controlled cortical impact (CCI). Following CCI, rats displayed depression-like behaviors as measured by the 2-bottle saccharin preference test for anhedonia. Injury also resulted in evidence of stress and impairments in Morris water maze (MWM) performance compared to sham-injured controls. While moderate zinc deficiency did not worsen outcomes following TBI, rats that were fed the zinc supplemented diet for 4 weeks showed significantly attenuated increases in adrenal weight (p < 0.05) as well as reduced depression-like behaviors (p < 0.001). Supplementation prior to injury improved resilience such that there was not only significant improvements in cognitive behavior compared to injured rats fed an adequate diet (p < 0.01), there were no significant differences between supplemented and sham-operated rats in MWM performance at any point in the 10-day trial. These data suggest a role for supplemental zinc in preventing cognitive and behavioral deficits associated with TBI.     

The anatomical characteristics of the stria terminalis in the human brain: a diffusion tensor tractography study

The role played by spinal adrenergic and cholinergic receptors in the antinociceptive effects of intrathecal sildenafil in formalin-induced nociception was examined. Intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats, and nociception was assessed using the formalin test, consisting of a subcutaneous injection of 50 μL of 5% formalin solution into the hind paw. We examined the effects of an alpha 1 adrenergic receptor antagonist (prazosin), an alpha 2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) on sildenafil-induced antinociception. Intrathecal sildenafil (3, 10, and 30 μg) suppressed, in a dose-dependent manner, formalin-induced flinching during phases 1 and 2 of the test. Intrathecal sildenafil (30 μg) could not show any effects against intrathecal prazosin (3 μg), yohimbine (10 μg), atropine (10 μg), and mecamylamine (10 μg) pretreatment during both phases of the formalin test. These results suggest that intrathecal sildenafil effectively attenuated the pain evoked by formalin injection. Additionally, spinal alpha 1, alpha 2, muscarinic and nicotinic receptors might play a role in sildenafil-induced antinociception.     

Alpha power is influenced by performance errors

Error commission evokes changes in event-related potentials, autonomic nervous system activity, and behavior, presumably reflecting the operation of a cognitive control network. Here we test the hypothesis that errors lead to increased cortical arousal, measurable as changes in electroencephalogram (EEG) alpha band power. Participants performed a Stroop task while EEG was recorded. Following correct responses, alpha power increased and then decreased in a quadratic pattern, implying transient mental disengagement during the intertrial interval. This trend was absent following errors, which elicited significantly less alpha power than correct trials. Moreover, post-error alpha power was a better predictor of individual differences in post-error slowing than the error-related negativity (ERN), whereas the ERN was a better predictor of post-error accuracy than alpha power. These findings imply that changes in cortical arousal play a unique role in modulating post-error behavior.     

Reliability of psychophysiological assessment within temperament-groups

Four groups of 16 people selected for their relatively extreme scores (greater or equal to 1 S.D. from the mean) on both the E and N scales of the Eysenck Personality Inventory visited the laboratory for four separate but identical testing sessions. Three physiological indices were recorded at each session: heart rate (HR), basal skin conductance level (SCL), and the number of spontaneous skin conductance responses (SCR). Test-retest correlation coefficients were calculated within E x N groups across days. HR and SCR showed moderate to good reliabilities across all groups. The most interesting finding was that SCL was a consistently reliable index for extraverts but not for introverts. Correlations between days were statistically significant for extraverts but not for introverts. A speculative explanation for these results is that SCL is affected by cognitive activity rather than autonomic arousal per se. This study suggests that there are systematic effects of temperament on physiological measures that are important and should not be relegated to error variance.     

Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury

Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n = 6; CCI-Veh, n = 7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n = 7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p < 0.01) and from CCI-SP scores on days 4, 9 and 14 (p < 0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.