Applying fractal analysis to heart rate time series of sheep experiencing pain

The objective assessment of pain is difficult in animals and humans alike. Detrended fluctuation analysis (DFA) is a method which extracts “hidden” information from heart rate time series, and may offer a novel way of assessing the subjective experience associated with pain. The aim of this study was to investigate whether any fractal differences could be detected in heart rate time series of sheep due to the infliction of ischaemic pain. Heart rate variability (HRV) was recorded continuously in five ewes during treatment sequences of baseline, intervention and post-intervention for up to 60 min. Heart rate time series were subjected to a DFA, and the median of the scaling coefficients (α) was found to be α = 1.10 for the baseline sequences, 1.01 for the intervention sequences and 1.00 for the post-intervention sequences. The complexity in the regulation of heartbeats decreased between baseline and intervention (p ∼ 0.03) and baseline and post-intervention (p ∼ 0.01), indicating reperfusion pain and nociceptive sensitization in the post-intervention sequence. Random time series based on Gaussian white noise were generated, with similar mean and variance to the HRV sequences. No difference was found between these series (p ∼ 0.28), pointing to a true difference in complexity in the original data. We found no difference in the scaling coefficient α between the different treatments, possibly due to the small sample size or a fear induced sympathetic arousal during test day 1 confounding the results. The decrease in the scaling coefficient α may be due to sympathetic activation and vagal withdrawal. DFA of heart rate time series may be a useful method to evaluate the progressive shift of cardiac regulation toward sympathetic activation and vagal withdrawal produced by pain or negative emotional responses such as fear.     

Autonomic nervous system reactivity to positive and negative mood induction: the role of acute psychological responses and frontal electrocortical activity

The differential effects of positive versus negative emotions on autonomic nervous system activity are insufficiently understood. This study examined the role of acute mood responses and central nervous system activity on heart rate variability (HRV) using 5-min event recall tasks (happiness and anger recall) and a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25 ± 4 years, 55% female). HRV was measured in high frequency (HF) and low frequency (LF) domains, and frontal brain activity using electroencephalography (EEG) in the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF-HRV (p = 0.005) but not HF-HRV (p = 0.71). Anger Recall did not change HRV (p-values > 0.10). The SCWT produced decreases in HF-HRV (p = 0.001) as well as LF-HRV (p = 0.001). The magnitude of feeling “happy” during Happiness Recall was positively correlated with ΔHF-HRV (p = 0.050), whereas an incongruent mood state (“frustrated”) was associated with smaller ΔHF-HRV (p = 0.070). Associations between frontal EEG activation and HRV responses were mostly non-significant, except for increased right frontal activation during Happiness Recall which was associated with a decrease in LF/HF ratio (p = 0.009). It is concluded that positive and negative mood induction result in differential HRV responses, which is related to both task valence and the intensity of task-induced emotions.     

Behavioral evidence of thermal hyperalgesia and mechanical allodynia induced by intradermal cinnamaldehyde in rats

TRPA1 agonists cinnamaldehyde (CA) and mustard oil (allyl isothiocyanate = AITC) induce heat hyperalgesia and mechanical allodynia in human skin, and sensitize responses of spinal and trigeminal dorsal horn neurons to noxious skin heating in rats. TRPA1 is also implicated in cold nociception. We presently used behavioral methods to investigate if CA affects sensitivity to thermal and mechanical stimuli in rats. Unilateral intraplantar injection of CA (5–20%) induced a significant, concentration-dependent reduction in latency for ipsilateral paw withdrawal from a noxious heat stimulus, peaking (61.7% of pre-injection baseline) by 30 min with partial recovery at 120 min. The highest dose of CA also significantly reduced the contralateral paw withdrawal latency. CA significantly reduced mechanical withdrawal thresholds of the injected paw that peaked sooner (3 min) and was more profound (44.4% of baseline), with no effect contralaterally. Bilateral intraplantar injections of CA resulted in a significant cold hyperalgesia (cold plate test) and a weak enhancement of innocuous cold avoidance (thermal preference test). The data are consistent with roles for TRPA1 in thermal (hot and cold) hyperalgesia and mechanical allodynia.     

Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine

Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n = 6) and gilts (n = 4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1 h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex interaction, and day of injection, with mixed models and Tukey's post-hoc tests. The best-fit range for LF was 0.0-0.09 Hz, and HF was 0.09-2.0 Hz (r²: 0.41 and 0.43, respectively). Propranolol and saline injections led to a greater overall total power and overall higher inter-beat interval, HF and LF power. Atropine led to a dominant sympathovagal balance of the cardiac activity in pigs. In addition, atropine led to an increase in LF power of both systolic and diastolic blood pressures in gilts suggesting vagal tone mediation of BPV. The understanding of autonomic regulation of HRV and BPV in domestic swine facilitates our ability to detect and quantify stress responses, and broadens its application in assessing farm animal welfare.     

Fatiguing exercise attenuates pain-induced corticomotor excitability

The purpose of this study was to assess net corticomotor excitability during a painful stimulus before and after exercise. In the first study, 25 subjects participated in three sessions: one familiarization session and two experimental sessions. The two experimental sessions were randomized and involved measurement of pain perception before and after (1) a submaximal isometric fatiguing contraction with the left elbow flexor muscles and (2) 30 min of quiet rest. Pain perception was assessed using a pressure device applied to the right index finger for 2 min. Motor evoked potentials (MEPs) of the left brachioradialis muscle were measured following transcranial magnetic stimulation (TMS) which was delivered before, during, and after the 2 min pain test. In the second study, 12 subjects participated in one session which involved application of TMS to elicit MEPs at the same time points as in study one, before and after a submaximal fatiguing contraction, but in the absence of pain. In the absence of the mechanical noxious stimulus, MEP amplitude was reduced following the fatiguing contraction and unchanged over this time period. In study one, pain threshold increased and pain ratings decreased following the isometric contraction but not after 30 min of quiet rest. During application of the mechanical noxious stimulus to the right index finger, MEP amplitude of the left brachioradialis muscle increased indicating an increase in net corticomotor excitability. The pain-induced increase in MEPs was attenuated following the isometric fatiguing contraction and this occurred in parallel with the decrease in pain.     

Eye temperature and heart rate variability of calves disbudded with or without local anaesthetic

The possibility that pain can be detected from changes in eye temperature and heart rate variability (HRV) during disbudding was examined in thirty calves, randomly assigned to four treatments: 1) sham handling (control), 2) local anaesthetic (LA, cornual nerve injection) and sham disbudded, 3) sham LA and disbudded, 4) LA and disbudded. During a 40 min sampling period, maximum eye temperature, behavior and HRV parameters were recorded continuously. One week later, twelve disbudded calves were injected with adrenocorticotrophic hormone (ACTH) or saline and maximum eye temperature was recorded. There was a rapid drop in eye temperature during the 5 min following disbudding without LA (P<0.05). Eye temperature then increased and was higher than baseline over the remaining sampling period following both disbudding procedures (P<0.001), a response which could not be explained by increased physical activity LA increased eye temperature prior to disbudding (P<0.001). Heart rate increased (P<0.001) during the 5 min following disbudding with and without LA, however, LF/HF ratio only increased during this time (P<0.01) following disbudding without LA. Eye temperature did not change following ACTH, suggesting that hypothalamus-pituitary-adrenal axis (HPA) activity is not responsible for the changes in eye temperature following disbudding. The increase in LF/HF ratio following disbudding without LA suggests an acute sympathetic response to pain, which could be responsible for the drop in eye temperature via vasoconstriction. HRV and eye temperature together may be a useful non-invasive and more immediate index of pain than HPA activity alone.     

Pattern of biphasic response to various noxious stimuli in rats ingesting sucrose ad libitum

Sucrose ingestion is reported to produce an initial (20-30 min) analgesia and late (<5 h) hyperalgesia. However, the influence of the characteristics of noxious stimuli and sweet substances on the pattern of transition from analgesia to hyperalgesia is not known. Therefore, we investigated the effect of sucrose (20%, sucrose fed group), saccharin (0.1%, saccharin fed group) and water ingestion (control group) on pain responses to various noxious stimuli for 5 h. Latency of motor response of tail (TFL), paws to noxious thermal stimuli, threshold for elicitation of motor responses to electrical stimulation of tail nociceptive afferents in 5 sessions (0, 0.25, 1, 3 and 5 h) and pain-related behavior to tonic noxious stimulus in 3 sessions at 1, 3 and 5 h were recorded. In sucrose fed rats as compared to controls, the TFL sequentially increased (9.29 ± 0.47 s from 8.41 ± 0.25; p < 0.01), recovered to base-line and decreased (6.61 ± 0.61 sec; p < 0.0001) in sessions II, III and V indicating analgesia, eualgesia and hyperalgesia, respectively. In saccharin fed rats the initial analgesia extended until session III followed by eualgesia and hyperalgesia in sessions IV and V. Pain related behaviour to tonic noxious stimulus also indicated an initial analgesia (0-5 min), intermediate eualgesia and late hyperalgesia (3-5 h) in sucrose fed rats, whereas only analgesia in saccharin fed rats. The results of our study suggest that sucrose ingestion for 5 h leads to a bi-phasic response to both phasic and tonic noxious stimuli, albeit there are variations in their durations. Therefore, the temporal relationship of the nociceptive responses to palatable food is a function of the stimulus quality of both.     

Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells

This study examined whether rats can simultaneously learn to associate lithium chloride (LiCl)-induced nausea with both contextual and intravascular taste cues. During the conditioning phase (4 days, 72 h apart), 32 male Long Evans rats were injected intraperitoneally with either isotonic saline (NaCl), lithium chloride (LiCl, 127 mg/kg), saline plus 2% saccharin (NaCl + Saccharin), or lithium chloride plus 2% saccharin (LiCl + Saccharin) immediately prior to a 30 min exposure to a novel context. 72 h following the final conditioning day, each animal was re-exposed to the context on a drug-free test day. The next day, animals received a 24 h 2-bottle preference test with a choice between water and a palatable saccharin solution. Results showed that animals treated with LiCl during conditioning, with or without saccharin, displayed significantly higher levels of conditioned gaping responses, indicative of nausea, upon re-exposure to the context, relative to NaCl and NaCl + Saccharin controls. Animals administered LiCl + Saccharin during conditioning also displayed significant conditioned taste avoidance to the saccharin solution during the two bottle choice test. These results indicate that systemic administration (intraperitoneal) of a LiCl + Saccharin solution is effective in simultaneously conditioning toxin elicited nausea to both internal (taste) and external (context) cues.     

Decreased pain response in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1 subunit

Studies have shown that N-methyl-d-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. In this study, we used cortex-specific NR1 knockout mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in pain processes. On post-natal day 20, paw withdrawal latency (PWL) to a noxious thermal stimulus was measured in male and female knockout (KO), control (Ctrl), and C57BL/6 (C57) mice. Twenty-four hours later, the same mice were tested in the formalin-pain assay (20 μl of 5% formalin injected into one hind-paw). The results show that KO mice (both male and female) have significantly reduced pain responses during both early and late phases of formalin test, as compared with Ctrl and C57 mice (p < 0.01). By contrast, no differences among groups were found in PWL to a noxious thermal stimulus. Taken together, these results demonstrate dissociation in the role of cortical NMDA receptors in mediating different types of pain.     

Unconditioned and conditioned effects of intravenous insulin and glucose on heart rate variability in healthy men

We examined whether an injection of intravenous insulin and intravenous glucose would affect frequency-domain measures of heart rate variability (HRV), i.e., the high-frequency (HF-) band and the ratio of the low frequency (LF-) to the HF-band in healthy humans. Using a classical conditioning protocol, we also assessed whether the measures of HRV are subject to classical conditioning. Thirty healthy men were divided into three groups, given a conditioned stimulus (CS) and an intravenous injection of either insulin (0.05 IU/kg) in Group 1, glucose (15%, 0.5 g/kg) in Group 2, or placebo (physiological saline [0.9%]) in Group 3 during the 4-day acquisition phase. All subjects were given an olfactory CS (rosewood-peppermint smell) and placebo injection on day 5 (test). Due to their high inter-individual variability, HF and LF/HF-ratio were analysed by intragroup comparisons, using a pre-injection baseline interval (min -15 to -5), and three functional post-injection intervals: a) the interval to the maximum insulin level, i. e. insulin peak (min 0-5) in Groups 1 and 2, b) the interval to the maximum of insulin-induced hypoglycaemia (min 20-25) in Group 1, and c) the end of the session (min 70-75). On days 1 to 4, we found significant increases of the HF-band from baseline to interval min 0-5 in Group 1, and an even more pronounced increase in the glucose-treated Group 2. At the test (Day 5), both experimental groups responded with an HF-increase in the interval of the former insulin peak, and also at the other measurement intervals, reflecting some general increase of vagal activity remaining as a conditioned response. On days 1 to 4, the HF-band was positively correlated with the change of peripheral insulin levels in Group 1, reaching statistical significance on days 3 and 4. This pattern only emerged in tendency on Day 4 in Group 2. In conclusion, insulin triggers an increase in parasympathetic tone at maximum hyperinsulinaemia, and our data support the notion that this response pattern can become classically conditioned.     

Dorsal root ganglion neurons respond with prolonged extracellular signal-regulated protein kinase phosphorylation following noxious heat and cold stimulation

In the present study the time course of extracellular signal-regulated protein kinase phosphorylation (pERK1/2 appearance) in lumbar sensory dorsal root ganglia (DRG) was determined following a 5-min noxious heat or a noxious cold stimulus to the hind paw of the rat. The thermal stimuli were chosen to activate transient receptor potential (TRP) channels, but not to induce tissue damage. A quantitative analysis of phospho-ERK1/2 was performed by protein extraction and Western blot analysis. Western blot analysis showed that following the heat stimulus, phosphorylation of ERK1/2 increased 2–3-fold between 10 and 30 min in the DRG on the ipsilateral side. High levels were maintained from 30 min up to 16 h. Following the cold stimulus to the paw, pERK1/2 immediately increased 2-fold within 2 min in the DRG on the ipsilateral side, it declined within 2 h and reached a second peak at 4 h. In the DRGs on the contralateral side of the paw's heat or cold immersion the pERK1/2 remained low at all time points investigated. Fluorescence immunohistochemistry of the DRG following the thermal stimuli revealed an increased cytoplasmic staining for pERK1/2 in neurons. The present results show that following a 5-min nociceptive thermal stimulus sensory neurons respond with a characteristic long-lasting phosphorylation of ERK1/2.     

Slower eating rate is independent to gastric emptying in obese minipigs

The aim of our study was to investigate whether the altered eating behavior observed in the context of a diet-induced metabolic syndrome is related to changes of the gastric emptying and autonomic balance. Eight adult male Göttingen minipigs were subjected during 5 months to ad libitum Western diet (WD). Several factors were compared between the lean (before WD) and obese conditions: general activity and eating behavior, gastric emptying, adiposity, glycemia and insulinemia during IVGTT, and heart rate variability (HRV). In our model, obesity did not alter the gastric emptying (258 ± 26 vs. 256 ± 14 min, P > 0.10) but induced insulin resistance: increased basal insulinemia (12.6 ± 0.8 to 36.6 ± 6.1 mU/l, P < 0.02) and reduced insulin sensitivity (4.5E−4 ± 0.7E−4 to 2.5E−4 ± 0.2E−4 min⁻¹ per mU.l⁻¹ of insulin, P < 0.05). The HRV and sympathovagal balance were not significantly modified (P > 0.10). Fed ad libitum with WD, animals overate durably (P < 0.001). During a 30-min meal test though, the ingestion speed, the food ingested (1076 ± 48 vs. 520 ± 52 g) and energy intake decreased in the obese condition (P < 0.05), which can be explained by the fragmentation of the daily caloric intake. These data suggest that the slower eating rate and increased number of meals observed in obese minipigs without neuropathy is independent to gastric emptying. The explanation may be sought rather in central modifications induced by obesity that might modify the food perception and/or motivation.     

Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age = 39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention.     

Non-invasive measurement of stress in dairy cows using infrared thermography

The possibility that changes in eye temperature, measured using infrared thermography (IRT), can detect stress in dairy cattle was examined by six different stimulations of the stress axis. Six cows were given six treatments in a random Latin-square design: 1) Control (saline) 2) ACTH (0.05 mg Synacthen) 3) bCRH (20 mug) 4) bCRH (40 mug) 5) epinephrine (1.4 mug /kg liveweight) and 6) social isolation. Treatments were administered at time 0 and blood samples were taken at -30, -15, 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 180 and 240 min except for epinephrine which was sampled at -30, -15, -10, -5, 0, 2, 5, 10, 15, 20, 30, 45, 60, 90 and 120 min. Core body temperature was recorded every 10 min and eye images collected every 2 min. Eye temperature and cortisol increased following catheterization (P<0.05). ACTH increased following bCRH, cortisol increased following ACTH and bCRH (P<0.001) and NEFA increased following epinephrine (P<0.001). Core body temperature was unaffected by treatments. Eye temperature was unaffected by CRH and epinephrine but was higher 30 and 60 min following control and ACTH (P<0.001). Our results provide evidence that exogenous HPA stimulation does not increase eye temperature. The increases in eye temperature following catheterization however raise the possibility that a cognitive component may be required for an eye temperature response to occur.     

Exercise-induced energy expenditure: Implications for exercise prescription and obesity

Objective

Walking is commonly recommended to help with weight management. We measured total energy expenditure (TEE) and its components to quantify the impact of increasing exercise-induced energy expenditure (ExEE) on other components of TEE.

Methods

Thirteen obese women underwent an 8-week walking group intervention. TEE was quantified using doubly labeled water, ExEE was quantified using heart rate monitors, daily movement was assessed by accelerometry and resting metabolic rate was measured using indirect calorimetry.

Results

Four of the 13 participants achieved the target of 1500 kcal wk⁻¹ of ExEE and all achieved 1000 kcal wk⁻¹. The average ExEE achieved by the group across the 8 weeks was 1434 ± 237 kcal wk⁻¹. Vigorous physical activity, as assessed by accelerometry, increased during the intervention by an average of 30 min per day. Non-exercise activity thermogenesis (NEAT) decreased, on average, by 175 kcal d⁻¹ (−22%) from baseline to the intervention and baseline fitness was correlated with change in NEAT.

Conclusions

Potential alterations in non-exercise activity should be considered when exercise is prescribed. The provision of appropriate education on how to self-monitor daily activity levels may improve intervention outcomes in groups who are new to exercise.

Practice implications

Strategies to sustain incidental and light physical activity should be offered to help empower individuals as they develop and maintain healthy and long-lasting lifestyle habits.     

Entry of a heparan sulphate-binding HRV8 variant strictly depends on dynamin but not on clathrin, caveolin, and flotillin

The major group human rhinovirus type 8 can enter cells via heparan sulphate. When internalized into ICAM-1 negative rhabdomyosarcoma (RD) cells, HRV8 accumulated in the cells but caused CPE only after 3 days when used at high MOI. Adaptation by three blind passages alternating between RD and HeLa cells resulted in variant HRV8v with decreased stability at acidic pH allowing for productive infection in the absence of ICAM-1. HRV8v produced CPE at 10 times lower MOI within 1 day. Confocal fluorescence microscopy colocalization and the use of pharmacological and dominant negative inhibitors revealed that viral uptake is clathrin, caveolin, and flotillin independent. However, it is blocked by dynasore, amiloride, and EIPA. Furthermore, HRV8v induced FITC-dextran uptake and colocalized with this fluid phase marker. Except for the complete inhibition by dynasore, the entry pathway of HRV8v via HS is similar to that of HRV14 in RD cells that overexpress ICAM-1.     

Glutamate receptor blockade in the rostral ventromedial medulla reduces the force of multisegmental motor responses to supramaximal noxious stimuli

The rostral ventromedial medulla (RVM) has been established as part of a descending pain-modulatory pathway. While the RVM has been shown to modulate homosegmental nociceptive reflexes such as tail flick or hindpaw withdrawal, it is not known what role the RVM plays in modulating the magnitude of multisegmental, organized motor responses elicited by noxious stimuli. Using local blockade of glutamate receptors with the non-specific glutamate receptor antagonist kynurenate (known to selectively block nociceptive facilitatory ON-cells), we tested the hypothesis that the RVM facilitates the magnitude of multi-limb movements elicited by intense noxious stimuli. In male Sprague–Dawley rats, we determined the minimum alveolar concentration (MAC) of isoflurane necessary to block multi-limb motor responses to noxious tail clamp. MAC was determined so that all animals were anesthetized at an equipotent isoflurane concentration (0.7 MAC). Supramaximal mechanical stimulation of the hindpaw or electrical stimulation of the tail elicited synchronous, repetitive movements in all four limbs that ceased upon, or shortly after (<5 s) termination of the stimulus. Kynurenate microinjection (2 nmol) into the RVM significantly attenuated, by 40–60%, the peak and integrated limb forces elicited by noxious mechanical stimulation of the hindpaw (p < 0.001; two-way ANOVA; n = 8) or electrical stimulation of the tail (peak force: p < 0.011, two-way ANOVA; n = 8), with significant recovery 40–60 min following injection. The results suggest that glutamatergic excitation of RVM neurons, presumably ON-cells, facilitates organized, multi-limb escape responses to intense noxious stimuli.     

Maintenance of Wakefulness Test scores and driving performance in sleep disorder patients and controls

Objective

Sleepiness at the wheel is a risk factor for traffic accidents. Past studies have demonstrated the validity of the Maintenance of Wakefulness Test (MWT) scores as a predictor of driving impairment in untreated patients with obstructive sleep apnea syndrome (OSAS), but there is limited information on the validity of the maintenance of wakefulness test by MWT in predicting driving impairment in patients with hypersomnias of central origin (narcolepsy or idiopathic hypersomnia). The aim of this study was to compare the MWT scores with driving performance in sleep disorder patients and controls.

Methods

19 patients suffering from hypersomnias of central origin (9 narcoleptics and 10 idiopathic hypersomnia), 17 OSAS patients and 14 healthy controls performed a MWT (4 × 40-minute trials) and a 40-minute driving session on a real car driving simulator. Participants were divided into 4 groups defined by their MWT sleep latency scores. The groups were pathological (sleep latency 0–19 min), intermediate (20–33 min), alert (34–40 min) and control (> 34 min). The main driving performance outcome was the number of inappropriate line crossings (ILCs) during the 40 minute drive test.

Results

Patients with pathological MWT sleep latency scores (0–19 min) displayed statistically significantly more ILC than patients from the intermediate, alert and control groups (F (3, 46) = 7.47, p < 0.001).

Interpretation

Pathological sleep latencies on the MWT predicted driving impairment in patients suffering from hypersomnias of central origin as well as in OSAS patients. MWT is an objective measure of daytime sleepiness that appears to be useful in estimating the driving performance in sleepy patients.     

Parietal and frontal object areas underlie perception of object orientation in depth

Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder of cognition. Behavioral symptoms of ADHD are inattention, hyperactivity, and impulsivity. We investigated the effects of treadmill exercise and methylphenidate (MPH) on activity and spatial learning memory in relation to dopamine synthesis and brain-derived neurotrophic factor (BDNF) expression using spontaneously hypertensive adult male rats. The rats in the MPH-treated group received 1 mg/kg MPH orally once a day for 28 days. The rats in the treadmill exercise group were made to run on a treadmill for 30 min once a day, five times a week, for 28 days. Activity was determined by an open-field test and spatial learning memory was evaluated by an 8-arm maze test. Immunohistochemistry and Western blotting were conducted to examine the levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, and BDNF. The rats in the ADHD group showed hyperactivity and spatial learning memory deficit. Reduction of TH in the striatum and substantia nigra and BDNF in the hippocampus was observed of the rats in the ADHD group. Treadmill exercise and MPH alleviated the ADHD-induced hyperactivity and spatial learning memory impairment. Expressions of TH and BDNF in the ADHD rats were also increased by both treadmill exercise and MPH. These findings provide a possibility that exercise may be used as an effective therapeutic intervention for ADHD patients as MPH treatment.