Estradiol reduces anxiety- and depression-like behavior of aged female mice

Beneficial effects of the ovarian steroid, 17β-estradiol (E₂), for affective behavior have been reported in young individuals, but less is known about the effects of E₂ among older individuals, and the capacity of older individuals to respond to E₂ following its decline. In the present study, the effects of acute E₂ administration to aged mice for anxiety-like and depression-like behaviors were investigated. Intact female C57BL/6 mice (N = 18) that were approximately 24 months old were administered vehicle (sesame oil, n = 9) or E₂ (10 μg, n = 9) subcutaneously 1 h prior to behavioral testing. Mice were tested for anxiety-like behavior (open field, elevated plus maze, mirror chamber, light-dark transition task, Vogel conflict task) and depression-like behavior (forced swim task). To assess the role of general motor behavior and coordination in these aged mice, performance in an activity monitor and rotarod task, and total entries made in tasks (open field, elevated plus maze, light-dark transition task) were determined. Mice administered E₂, compared to vehicle, demonstrated anti-anxiety behavior in the open field, mirror chamber, and light-dark transition task, and anti-depressive-like behavior in the forced swim task. E₂ also tended to have anti-anxiety effects in the elevated plus maze and Vogel task compared to vehicle administration, but these effects did not reach statistical significance. E₂ did not alter motor behavior and/or coordination in the activity monitor, open field, or rotarod tasks. Thus, an acute E₂ regimen produced specific anti-anxiety and anti-depressant effects, independent of effects on motor behavior, when administered to aged female C57BL/6 mice.     

Brain activity in goal-directed movements in a real compared to a virtual environment using the Nintendo Wii

Low budget virtual environments like the Nintendo Wii increased in popularity and may play a role in motor learning related to sports and exercise. But nothing was known about the comparability of cortical activity of motor tasks in real and virtual environments. The aim of the study was to examine cortical differences between real and Wii based virtual sports performances using the golf putt as a model. Ten male golfers (26.0 ± 0.7 years; 81.8 ± 5.6 kg; 184.5 ± 6.0 cm; handicap 30.0 ± 10.0; 2.9 ± 1.0 years of golf experience) were asked to putt for 3 min in random order in the real and the virtual Wii condition. A rest in sitting position (3 min) followed each performance. The score and cortical activity (EEG) were recorded continuously. The participants performed with a significant better score in the real condition (p ≤ 0.01). Compared to virtual putting Theta spectral power showed a significant increase during real performance at F3 and F4 (p ≤ 0.05). Significantly increased Alpha-2 power was demonstrated during real putting compared to the virtual putting performance at P3 (p ≤ 0.05). The findings suggested that putting performance and brain activity was influenced by the choice of a real or virtual environment. The results were discussed based on the concept of the working memory where increased frontal Theta power indicated higher focused attention and higher Alpha-2 power was inversely related to the quantity of sensory information processing in the real putting compared to the virtual condition.     

The behavioral change of locomotor activity in a kaolin-induced hydrocephalus rat model: Evaluation of the effect on the dopaminergic system with progressive ventricle dilatation

Hydrocephalus is a pathological enlargement of the cerebral ventricle that results from an obstruction of the space containing cerebrospinal fluid (CSF) in the brain. Motor abnormalities, such as abnormal gait and posture, are frequently seen in patients with hydrocephalus. The present study was designed to investigate locomotor activity in the elevated plus maze behaviorally. Hydrocephalus was induced in Sprague–Dawley rats by injection of 0.1 ml of 20% kaolin solution into the cisterna magna (n = 14). Control rats received the same volume of saline (n = 12). The rats were sacrificed at 3 days and 4 weeks after the elevated plus maze test. Tyrosine hydroxlyase (TH) immunoreactivity in the substantia nigra was evaluated by immunohistological staining. Hydrocephalic rats showed decreased motor activity for entries of arms when compared to control rats (p < 0.05). Compared to control rats, the number of TH immunoreactive neurons was significantly decreased in hydrocephalic rats. These results suggest that decreased motor responses due to ventricle enlargement in hydrocephalic rats are associated with the functional impairment of the central dopamine system.     

EEG activity during the verbal-cognitive stage of motor skill acquisition

This study examined changes in EEG activity associated with motor performance during the verbal-cognitive stage of skill learning. Participants (n = 14) were required to practice a sequential finger tapping task. EEG activity was recorded both before and after short-term practice, during finger tapping and during two control conditions. EEG power (Fz, Cz, Pz, T3, T4) and coherence (T3-Fz, T4-Fz, Fz-Cz, Fz-Pz) were computed for the theta (4-8 Hz), slow alpha (8-10 Hz), fast alpha (10-12 Hz), slow beta (12-20 Hz), and fast beta (20-28 Hz) bandwidths. Changes in motor performance were rapid during the very early stages of practice and then slowed in accord with the law of practice. These changes were accompanied by increases of theta power at Fz and beta coherence at T4-Fz, suggesting that progression through the verbal-cognitive stage of a sequential finger tapping task is accompanied by more narrowed attention and improved mapping between the stimuli and the finger movements.     

Maternal care alterations induced by repeated ethanol leads to heightened consumption of the drug and motor impairment during adolescence: a dose-response analysis

Maternal ethanol exposure during lactation induces behavioral alterations in offspring, including disruptions in motor skills and heightened ethanol ingestion during adolescence. These behavioral outcomes appear to partially depend on ethanol-induced disruptions in maternal care. The present study assessed motor skills and ethanol intake in adolescent rats raised by dams that had been repeatedly given ethanol during lactation. Female rats (postpartum days [PDs] 3-13) were administered ethanol (0.5, 1.5, or 2.5 g/kg) or vehicle every other day and allowed to freely interact with their pups. During adolescence, the offspring were evaluated for motor coordination (accelerating rotarod test) and oral ethanol self administration. The lowest maternal ethanol dose (0.5 g/kg) mildly affected motor performance, whereas the higher doses (1.5 and 2.5 g/kg) resulted in motor coordination impairment and greater ethanol intake. Maternal care behavior was affected by ethanol in a dose-dependent fashion. These results indicate that early experience with ethanol during lactation, even when the drug dosage is kept relatively low, leads to long-term consequences in offspring. Dose-response effects on maternal care behavior (i.e., nest building, crouching) may underlie disruptions in motor development and greater ethanol intake resulting from these early ethanol experiences.     

Hypoxia-induced short-term potentiation of respiratory-modulated facial motor output in the rat

Respiratory-modulated facial (VII) nerve discharge includes pre-inspiratory (Pre-I) and inspiratory (I) components. Tonic VII bursting is also present across the respiratory cycle. We tested the hypothesis that hypoxia-induced plasticity of VII motor activity is differentially expressed in Pre-I, I and tonic bursting. Phrenic and VII neurograms were recorded in urethane-anesthetized, vagotomized and ventilated adult rats. A 3 min isocapnic hypoxic challenge (PaO₂ = 33 ± 2 mmHg) was used to evoke respiratory short-term potentiation (STP). Pre-I, I and tonic VII activity increased immediately at the initial stage of hypoxia (i.e. acute response) and then progressively increased as hypoxia was maintained. Following hypoxia, I VII activity remained elevated (i.e. post-hypoxia STP) but both Pre-I and tonic activity immediately returned to baseline values. We conclude that STP following hypoxia is preferentially expressed in I compared to Pre-I and tonic VII activity.     

Influence of 5 Hz repetitive transcranial magnetic stimulation on motor learning

The aim of our study was to assess a possible improvement in motor learning induced by 5 Hz repetitive transcranial magnetic stimulation (rTMS) of human motor cortex. The same stimulation protocol previously enhanced perceptual learning as assessed by tactile discrimination performance when applied to the human primary somatosensory cortex. We applied 1250 pulses of 5 Hz “real” rTMS at 90% of resting motor threshold to the motor hotspot of the abductor pollicis brevis (APB) muscle in 15 healthy subjects before 1 h of motor training. Furthermore, 15 subjects received 5 Hz “sham” rTMS and served as control group. The motor task consisted of a synchronized co-contraction of the right APB and deltoid muscle. The latency between the onsets of muscle contractions was measured during training and served as a parameter for motor learning. MEP amplitudes were assessed in a subgroup of 10 subjects before and after rTMS as a parameter of corticospinal excitability. We found a significant learning effect in both groups as indicated by a reduction of latencies between the onsets of muscle contractions in the course of the training. Corticospinal excitability increased after “real”, but not after “sham” rTMS. However, “real” rTMS did not significantly influence motor learning as compared to “sham” rTMS. We conclude that 5 Hz rTMS of human primary motor cortex is not able to improve motor learning in healthy subjects, which might be due to the higher complexity of motor learning as compared to perceptual learning in the tactile domain.     

Anxiety-like behavior in weanling and young adult male and female malnourished rats

The present study determined whether protein-calorie malnutrition alters anxiety-like behavior in weanling and young adult, male and female malnourished rats. On the day of birth, litters of Wistar rats were divided into Control (C) and Malnutrition (M) groups. In the C group, litters were fed by dams receiving ad libitum lab chow, whereas in the M group, litters were fed by dams receiving 40% of the total amount of the diet offered to dams in the C group. After weaning (PND21) until PND50, animals received the same food as theirs mothers (i.e., ad libitum access in the C group and 40% of the C group food in the M group). On PND21 and PND50, independent C (male [CM] and female [CF]) and M (male [MM] and female [MF]) groups were exposed to the elevated T-maze. The time taken to withdraw four paws from this arm was recorded (baseline latency [BL]). The same measurement was repeated twice at 30 s intervals (avoidance trial 1 [AT1] and avoidance 2 [AT2]). The cutoff time in each trial was 300 s. ANOVA indicated a four-way age × diet × sex × trials interaction. Post hoc comparisons revealed that PND50 rats had a lower BL and AT1 latency compared with PND21 rats. Training increased both AT1 and AT2 latencies compared with BL in both the CM and CF groups. Weanling malnourished rats exhibited reduced anxiety-like behavior and young adult male rats presented less anxiety-like behavior than young adult female rats in this experimental model.     

Integration of cortical areas during performance of a catching ball task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop; specifically through quantitative electroencephalography (qEEG) alpha absolute power changes. Our hypothesis is that during the preparation of motor action (i.e., 2 s before ball’s drop) occurred integration among left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. This hypothesis supports a lateralization of motor function. Although we contend that in right-handers the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy subjects (13 male and 10 female), right handed, with ages varying between 25 and 40 years old (32.5 ± 7.5), absence of mental and physical illness, right handed, and do not make use of any psychoactive or psychotropic substance at the time of the study. The experiment consisted of a task of catching balls in free drop. The three-way ANOVA analysis demonstrated an interaction between moment and position in left medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode; p < 0.001). Summarizing, through experimental task employed, it was possible to observe integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation. In this way, it established an absolute predominance of this mechanism under the left hemisphere.     

Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 ± 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p = 0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p = 0.001). Additionally, main effects were observed for condition (p = 0.001), period (p = 0.001) and electrodes (p = 0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli.     

Respiratory pattern in awake rats: Effects of motor activity and of alerting stimuli

Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n = 5) and Hooded Wistar (HW, n = 5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336 ± 19 and 532 ± 80 ms for HW and SD, p < 0.05; modes for fast peak 128 ± 6 and 132 ± 7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R² ranging 0.96-0.99 (n = 10, p < 0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117 ± 7 to 430 ± 15 cpm; sudden side move — from 134 ± 13 to 487 ± 16 cpm, and turning on lights — from 136 ± 12 to 507 ± 14 cpm (n = 10; p < 0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity.     

l-DOPA treatment reverses the motor alterations induced by manganese exposure as a Parkinson disease experimental model

This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl₂) and manganese acetate (Mn(OAc)₃), 1 h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5 mg/kg l-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with l-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl₂/Mn(OAc)₃ are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.     

Inhibition of motor cortex excitability with 15 Hz transcranial alternating current stimulation (tACS)

There remains a lack of solid evidence showing whether transcranial stimulation with weak alternating current (transcranial alternating current stimulation, tACS) can in fact induce significant neurophysiological effects. Previously, a study in which tACS was applied for 2 and 5 min with current density = 0.16–0.25 A/m² was unable to show robust effects on cortical excitability. Here we applied tACS at a significantly higher current density (0.80 A/m²) for a considerably longer duration (20 min) and were indeed able to demonstrate measurable changes to cortical excitability. Our results show that active 15 Hz tACS of the motor cortex (electrodes placed at C3 and C4) significantly diminished the amplitude of motor evoked potentials and decreased intracortical facilitation (ICF) as compared to baseline and sham stimulation. In addition, we show that our method of sham tACS is a reliable control condition. These results support the notion that AC stimulation with weak currents can induce significant changes in brain excitability; in this case, 15 Hz tACS led to a pattern of inhibition of cortical excitability. We propose that tACS may have a dampening effect on cortical networks and perhaps interfere with the temporal and spatial summation of weak subthreshold electric potentials.     

Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet

Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a ‘Western’ diet, enriched with saturated fat and cholesterol. Socially-housed adult female cynomolgus monkeys (n = 36) were fed the Western diet for 27 months and depressive behavior was recorded weekly. Body weight, body mass index and circulating cholesterol profiles were measured in all animals, and fatty acids (FA) and FA-based signaling molecules were measured in the 6 least and 6 most depressed monkeys. Monkeys consuming the Western diet exhibited a broad range of percent time spent in depressive behavior. The percent time spent depressed was positively correlated with total plasma and LDL cholesterol and negatively correlated with HDL cholesterol. Despite being leaner, depressed monkeys had higher concentrations of monounsaturated fats (C16:1 and C17:1), a higher ω6/ω3 polyunsaturated fatty acid (PUFA) ratio and higher concentrations of omega-6 (ω6) PUFAs, particularly C18:2ω6 and C20:3ω6. FA ratios suggest that stearoyl CoA desaturase 1 activity was increased in depressed monkeys. Depressed female cynomolgus monkeys had elevated concentrations of serum lipids and lipid signaling molecules that are typically associated with obesity, insulin resistance and cardiovascular disease, which may account in part for the comorbidity of depression and CHD.     

Gamma band oscillations under influence of bromazepam during a sensorimotor integration task: An EEG coherence study

The goal of the present study was to explore the dynamics of the gamma band using the coherence of the quantitative electroencephalography (qEEG) in a sensorimotor integration task and the influence of the neuromodulator bromazepam on the band behavior. Our hypothesis is that the needs of the typewriting task will demand the coupling of different brain areas, and that the gamma band will promote the binding of information. It is also expected that the neuromodulator will modify this coupling. The sample was composed of 39 healthy subjects. We used a randomized double-blind design and divided subjects into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). The two-way ANOVA analysis demonstrated a main effect for the factors condition (i.e., C4–CZ electrode pair) and moment (i.e., C3–CZ, C3–C4 and C4–CZ pairs of electrodes). We propose that the gamma band plays an important role in the binding among several brain areas in complex motor tasks and that each hemisphere is influenced in a different manner by the neuromodulator.     

Cerebral cortical dynamics and the quality of motor behavior during social evaluative challenge

To determine the influence of arousal on cerebral cortical dynamics and motor behavior, 58 channels of EEG were recorded in 13 college‐age men (n=6) and women during an aiming task performed alone and in a social evaluation condition. Moderate arousal, as measured by heart rate, skin conductance, and self‐reported mood, was induced during the social evaluation. In accord with the Yerkes–Dodson Hypothesis, which posits optimal performance during moderate arousal, improved performance (i.e., quality of the aiming trajectories) was observed. During social evaluation, changes in electroencephalogram dynamics included decreased coherence between the motor planning (Fz) and right temporal region (T4), increased coherence in the sensorimotor networks subserving the task, and increased local processing (gamma, 30–44 Hz) in the temporal regions. The results imply that moderate arousal promotes specific alterations in cortical dynamics that facilitate motor performance.     

Parietal and temporal activity during a multimodal dance video game: an fNIRS study

Using functional near infrared spectroscopy (fNIRS) we studied how playing a dance video game employs coordinated activation of sensory-motor integration centers of the superior parietal lobe (SPL) and superior temporal gyrus (STG). Subjects played a dance video game, in a block design with 30 s of activity alternating with 30 s of rest, while changes in oxy-hemoglobin (oxy-Hb) levels were continuously measured. The game was modified to compare difficult (4-arrow), simple (2-arrow), and stepping conditions. Oxy-Hb levels were greatest with increased task difficulty. The quick-onset, trapezoidal time-course increase in SPL oxy-Hb levels reflected the on-off neuronal response of spatial orienting and rhythmic motor timing that were required during the activity. Slow-onset, bell-shaped increases in oxy-Hb levels observed in STG suggested the gradually increasing load of directing multisensory information to downstream processing centers associated with motor behavior and control. Differences in temporal relationships of SPL and STG oxy-Hb concentration levels may reflect the functional roles of these brain structures during the task period. NIRS permits insights into temporal relationships of cortical hemodynamics during real motor tasks.     

Developmental effects of dietary n− 3 fatty acids on activity and response to novelty

Insufficient availability of n− 3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n− 3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing α-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in α-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n− 3 PUFA content, likely underlies these effects.     

Hypocretinergic neurons are activated in conjunction with goal-oriented survival-related motor behaviors

Hypocretinergic neurons are located in the area of the lateral hypothalamus which is responsible for mediating goal-directed, survival-related behaviors. Consequently, we hypothesize that the hypocretinergic system functions to promote these behaviors including those patterns of somatomotor activation upon which they are based. Further, we hypothesize that the hypocretinergic system is not involved with repetitive motor activities unless they occur in conjunction with the goal-oriented behaviors that are governed by the lateral hypothalamus. In order to determine the veracity of these hypotheses, we examined Fos immunoreactivity (as a marker of neuronal activity) in hypocretinergic neurons in the cat during: a) Exploratory Motor Activity; b) Locomotion without Reward; c) Locomotion with Reward; and d) Wakefulness without Motor Activity. Significantly greater numbers of hypocretinergic neurons expressed c-fos when the animals were exploring an unknown environment during Exploratory Motor Activity compared with all other paradigms. In addition, a larger number of Hcrt + Fos + neurons were activated during Locomotion with Reward than during Wakefulness without Motor Activity. Finally, very few hypocretinergic neurons were activated during Locomotion without Reward and Wakefulness without Motor Activity, wherein there was an absence of goal-directed activities. We conclude that the hypocretinergic system does not promote wakefulness per se or motor activity per se but is responsible for mediating specific goal-oriented behaviors that take place during wakefulness. Accordingly, we suggest that the hypocretinergic system is responsible for controlling the somatomotor system and coordinating its activity with other systems in order to produce successful goal-oriented survival-related behaviors that are controlled by the lateral hypothalamus.