Forced swimming test (FST) is an animal model which evaluates behavioral despair and the effect of antidepressants such as the selective serotonin reuptake inhibitors; the FST modifies the expression of some receptors related to antidepressant response, but it is not known whether serotonin transporter (SERT), their main target, is affected by this test in animals of different ages. Antidepressant response has shown age-dependent variations which could be associated with SERT expression. The aim of the present study was to analyze changes in the SERT immunoreactivity (SERT-IR) in dorsal raphe and lateral septum of male rats from different age groups with or without behavioral despair induced by their exposure to the FST, since these two structures are related to the expression of this behavior.
Prepubertal (24 PN), pubertal (40 PN), young adult (3–5 months) and middle-aged (12 months) male rats were assigned to a control group (non-FST) or depressed group (FST, two sessions separated by 24 h). Changes in SERT-IR in dorsal raphe and lateral septum were determined with immunofluorescence.
Pubertal and middle-aged rats showed higher levels of immobility behavior compared to prepubertal rats on the FST. SERT-IR showed an age-dependent increase followed by a moderate decrease in middle-aged rats in both structures; a decreased in SERT-IR in lateral septum and dorsal raphe of pubertal rats was observed after the FST.
Age differences were observed in the SERT-IR of structures related to behavioral despair; SERT expression was modified by the FST in lateral septum and dorsal raphe of pubertal rats.
Despair; Forced swimming test; Rats; Serotonin transporter; Age differences
There is biological evidence that the brain opioidergic system plays a critical role in the addictive properties of nicotine. The purpose of the present study was to examine the associations of single nucleotide polymorphisms (SNPs) in the genes encoding mu-opioid receptor (MOR) and the MOR-interacting proteins (including OPRM1, ARRB2, and HINT1) with smoking behaviors in Chinese men.
A total of 284 subjects (including current and ex-smokers) were recruited. Special questionnaires were used to assess smoking behaviors including age of smoking initiation, daily cigarette consumption, and Fagerström test for nicotine dependence (FTND) score. Participant samples were genotyped for six SNPs in the opioid pathway genes: rs1799971 in OPRM1, rs1045280, rs2036657 and rs3786047 in ARRB2, rs3852209 and rs2278060 in HINT1. Linear and logistic regression models were used to determine single-locus and haplotype-based association analyses.
There was no significant association between any of SNPs analyzed and smoking behaviors. Logistic regression analyses under dominant, recessive, and additive models showed no significant associations of the six SNPs with smoking status (current vs. ex-smokers). After adjustment for age at enrollment and smoking initiation age, HINT1 rs3852209 was significantly associated with smoking status with an OR of 0.54 (95% CI, 0.31-0.95; P = 0.03) under dominant inheritance model. No haplotypes in ARRB2 or HINT1 were related to smoking status.
The present study indicates no significant association between common genetic variations in MOR and MOR-interacting proteins and smoking behaviors in Chinese men, and gives suggestive evidence that HINT1 rs3852209 may be related to smoking status. The findings require confirmation from further studies in additional larger samples.
Smoking; Polymorphisms; Mu-opioid receptor; ARRB2; HINT1
Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls.
SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure.
Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed.
Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD symptoms in genetically vulnerable individuals. In normal controls, exposure may not constitute an environmental risk factor for developing the full range of ADHD symptoms, but can produce specific behavioral changes.
ADHD; PCB; SHR; WKY; Behavior; Operant conditioning; Reinforcement
Attention-deficit/hyperactivity disorder (ADHD) is a common chronic neurodevelopmental disorder with a high heritability. Much evidence of hemisphere asymmetry has been found for ADHD probands from behavioral level, electrophysiological level and brain morphology. One previous research has reported possible association between BAIAP2, which is asymmetrically expressed in the two cerebral hemispheres, with ADHD in European population. The present study aimed to investigate the association between BAIAP2 and ADHD in Chinese Han subjects.
A total of 1,397 ADHD trios comprised of one ADHD proband and their parents were included for family-based association tests. Independent 569 ADHD cases and 957 normal controls were included for case-control studies. Diagnosis was performed according to the DSM-IV criteria. Nine single nucleotide polymorphisms (SNPs) of BAIAP2 were chosen and performed genotyping for both family-based and case-control association studies.
Transmission disequilibrium tests (TDTs) for family-based association studies showed significant association between the CA haplotype comprised by rs3934492 and rs9901648 with predominantly inattentive type (ADHD-I). For case-control study, chi-square tests provided evidence for the contribution of SNP rs4969239, rs3934492 and rs4969385 to ADHD and its two clinical subtypes, ADHD-I and ADHD-C. However, only the associations for ADHD and ADHD-I retained significant after corrections for multiplicity or logistic regression analyses adjusting the potential confounding effect of gender and age.
These above results indicated the possible involvement of BAIAP2 in the etiology of ADHD, especially ADHD-I.
Attention-deficit/hyperactivity disorder (ADHD); BAIAP2; Hemispheric asymmetry; Subtype
Interoception refers to the conscious perception of body signals. Mindfulness is a meditation practice that encourages individuals to focus on their internal experiences such as bodily sensations, thoughts, and emotions. In this study, we selected a behavioral measure of interoceptive sensitivity (heartbeat detection task, HBD) to compare the effect of meditation practice on interoceptive sensitivity among long term practitioners (LTP), short term meditators (STM, subjects that completed a Mindfulness-Based Stress Reduction (MBSR) program) and controls (non-meditators). All participants were examined with a battery of different tasks including mood state, executive function and social cognition tests (emotion recognition, empathy and theory of mind).
Compared to controls, both meditators’ groups showed lower levels of anxiety and depression, but no improvement in executive function or social cognition performance was observed (except for lower scores compared to controls only in the personal distress dimension of empathy). More importantly, meditators’ performance did not differ from that of nonmeditators regarding cardiac interoceptive sensitivity.
Results suggest no influence of meditation practice in cardiac interoception and in most related social cognition measures. These negative results could be partially due to the fact that awareness of heartbeat sensations is not emphasized during mindfulness/vipassana meditation and may not be the best index of the awareness supported by the practice of meditation.
Interoception; Meditation; Mindfulness; Social cognition; Heartbeat detection task
Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling.
Gastrointestinal-brain axis; Iodoacetamide-induced gastritis; Anxiety; Depression; Gender difference
Poor sleep is common in heart failure (HF), though mechanisms of sleep difficulties are not well understood. Adverse brain changes among regions important for sleep have been demonstrated in patients with HF. Cerebral hypoperfusion, a correlate of sleep quality, is also prevalent in HF and a likely contributor to white matter hyperintensities (WMH). However, no study to date has examined the effects of cerebral blood flow, WMH, and brain volume on sleep quality in HF.
Fifty-three HF patients completed the Pittsburgh Sleep Quality Index and underwent brain magnetic resonance imaging to quantify brain and WMH volume. Transcranial Doppler ultrasonography assessed cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA).
75.5% of HF patients reported impaired sleep. Regression analyses adjusting for medical and demographic factors showed decreased CBF-V of the MCA and greater WMH volume were associated with poor sleep quality. No such pattern emerged on total brain or regional volume indices.
Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF. Future studies are needed to confirm these findings and clarify the effects of cerebral blood flow and WMH on sleep in healthy and patient samples.
Sleep quality; Heart failure; MRI; Brain perfusion; White matter hyperintensity
In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism.
Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain.
The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively).
We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions.
Bruxism; Orofacial pain; Temporomandibular disorders; Dystonia; Oro facial dystonia; Trigeminal electrophysiology; Bilateral Root-MEPs
Genome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear.
After performing quality control for minor-allele frequency > 5% using a JPT HapMap sample and our sample, a genotyping call rate > 95% and Hardy-Weinberg equilibrium testing (p > 0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n = 173) and healthy subjects (n = 449).
The rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T = 4.96, p = 0.0088, left T = 4.66, p = 0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE-correction for multiple tests (p > 0.05).
Our findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri.
Schizophrenia; Genome-wide association study; Voxel-based morphometry; Cyclin M2 (CNNM2); Inferior frontal gyrus
Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance.
Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls.
Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control.
The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.
Adolescence; Stress; Social defeat; Spatial working memory; Dopamine; Prefrontal cortex
The lateral entorhinal cortex receives inputs from ventral tegmental area dopamine neurons that are activated by exposure to food-related cues, and exogenously applied dopamine is known to modulate excitatory synaptic responses within the entorhinal cortex.
The present study used in vivo synaptic field potential recording techniques to determine how exposure to cues associated with food reward modulates synaptic responses in the entorhinal cortex of the awake rat. Chronically implanted electrodes were used to monitor synaptic potentials in the entorhinal cortex evoked by stimulation of the piriform (olfactory) cortex, and to determine how synaptic responses are modulated by food-related cues.
The amplitudes of evoked synaptic responses were reduced during exposure to cues associated with delivery of chocolate, and during delivery of chocolate for consumption at unpredictable intervals. Reductions in synaptic responses were not well predicted by changes in behavioural mobility, and were not fully blocked by systemic injection of either the D1-like receptor antagonist SCH23390, or the muscarinic receptor antagonist scopolamine. However, the reduction in synaptic responses was blocked by injection of the D2-like receptor antagonist eticlopride.
Exposure to cues associated with palatable food results in a suppression of synaptic responses in olfactory inputs to the entorhinal cortex that is mediated in part by activation of dopamine D2 receptors.
Entorhinal cortex; Piriform cortex; Reward; Dopamine; Acetylcholine
Astragalus is a widely used traditional Chinese medicine and has been proven beneficial for many aspects of human health. It is important to explore the neuroprotective effect and mechanism of astragalus injection in cerebral ischemia reperfusion injury.
The focal cerebral ischemic model with middle cerebral artery occlusion (MCAO) reperfusion was established by Longa’s method in healthy adult male Wistar rats, and treated by injecting intraperitoneally astragalus injection (3 ml/kg). The neurobehavioral function of rats was evaluated by Longa’s test. The cerebral blood flow (CBF) was measured by laser Doppler flowmetry and the cerebral infarct volume was calculated by tetrazolium chloride (TTC) stain. The shape and structure of neurons in parahippocampal area was observed by HE stain and the neuronal apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and flow cytometry. The expressions of c-jun N-terminal kinase 3 (JNK3) mRNA and protein were determined by RT-PCR and immunohistochemical assay and Western blotting respectively.
After treatment with astragalus injection, the expressions of JNK3 mRNA and protein reduced significantly, the number of neuronal apoptosis minus, the cerebral infarct volume shrink, the neuronal shape-structure and animal neurobehavioral function improved significantly than those in model rats.
It is suggested that astragalus injection could inhibit neuronal apoptosis, reduce infarct volume and improve neurobehavioral function by down-regulating the expression of JNK3 gene after cerebral ischemia reperfusion injury in rats.
Astragalus injection; Cerebral ischemia; Reperfusion injury; Apoptosis; JNK3; Rats
There is significant interest in the generation of improved assays to clearly identify experimental mice possessing functional vision, a property that could qualify mice for inclusion in behavioral and neuroscience studies. Widely employed current methods rely on mouse responses to visual cues in assays of reflexes, depth perception, or cognitive memory. However, commonly assessed mouse reflexes can sometimes be ambiguous in their expression, while depth perception assays are sometimes confounded by variation in anxiety responses and exploratory conduct. Furthermore, in situations where experimental groups vary in their cognitive memory capacity, memory assays may not be ideal for assessing differences in vision.
We have optimized a non-invasive behavioral assay that relies on an untrained, innate response to identify individual experimental mice possessing functional vision: slow angled-descent forepaw grasping (SLAG). First, we verified that SLAG performance depends on vision and not olfaction. Next, all members of an age-ranged cohort of 158 C57BL/6 mice (57 wild-type, 101 knockout, age range 44–241 days) were assessed for functional vision using the SLAG test without training or conditioning. Subjecting the population to a second innate behavioral test, Dark Chamber preference, corroborated that the functional vision assessment of SLAG was valid.
We propose that the SLAG assay is immediately useful to quickly and clearly identify experimental mice possessing functional vision. SLAG is based on a behavioral readout with a significant innate component with no requirement for training. This will facilitate the selection of mice of known sighted status in vision-dependent experiments that focus on other types of behavior, neuroscience, and/or cognitive memory.
Vision; Innate behavior; SLAG; Dark chamber; C57BL/6; Mouse; Behavioral assay
Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a high prevalence of major depression and low levels of BDNF. We therefore explored whether the BDNF Val66Met polymorphism is associated with co-morbid depression and whether depression affects the serum levels of BDNF in a Han Chinese subjects with T2DM.
A Total of 296 T2DM patients and 70 healthy volunteers (Health control, HC group) were recruited in this study. T2DM patients were divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non-depressive diabetes group (NDDM group, n = 232), according to the presence or the absence of depression assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit.
In this study, 21.6% (64/296) patients with T2DM had depression. The BDNF Val66Met genotype distributions were statistically different among the three groups (χ2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met allele (53.9%) compared to HC group (39.3%) and NDDM group (38.8%). Subjects with Met/Met had lowest serum BDNF levels (76.59 ± 5.12 pg/ml, F = 7.39, p < 0.05) compared to subjects with Val/Met (79.04 ± 5.19 pg/ml) and Val/Val (83.83 ± 3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels in DDM group were significantly lower than those in NDDM group (76.67 ± 5.35 vs. 79.84 ± 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum levels were significant correlations with genotypes (r = −0.346, p < 0.01), depression scores (r = −0.486, p < 0.01) and HbA1c (r = −0.168, p < 0.05). After adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR = 0.835, p < 0.01) were independently associated with depression in T2DM.
The BDNF Val66Met polymorphism might be implicated in the pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese Subjects.
Type 2 diabetes (T2DM); Depression; Brain-derived neurotrophic factor (BDNF); Polymorphism
Although recent studies have clearly demonstrated functional and structural abnormalities in adolescents with internet gaming addiction (IGA), less is known about how IGA affects perfusion in the human brain. We used pseudocontinuous arterial spin-labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to measure the effects of IGA on resting brain functions by comparing resting cerebral blood flow in adolescents with IGA and normal subjects.
Fifteen adolescents with IGA and 18 matched normal adolescents underwent structural and perfusion fMRI in the resting state. Direct subtraction, voxel-wise general linear modeling was performed to compare resting cerebral blood flow (CBF) between the 2 groups. Correlations were calculated between the mean CBF value in all clusters that survived AlphaSim correction and the Chen Internet Addiction Scale (CIAS) scores, Barratt Impulsiveness Scale-11 (BIS-11) scores, or hours of Internet use per week (hours) in the 15 subjects with IGA.
Compared with control subjects, adolescents with IGA showed significantly higher global CBF in the left inferior temporal lobe/fusiform gyrus, left parahippocampal gyrus/amygdala, right medial frontal lobe/anterior cingulate cortex, left insula, right insula, right middle temporal gyrus, right precentral gyrus, left supplementary motor area, left cingulate gyrus, and right inferior parietal lobe. Lower CBF was found in the left middle temporal gyrus, left middle occipital gyrus, and right cingulate gyrus. There were no significant correlations between mean CBF values in all clusters that survived AlphaSim correction and CIAS or BIS-11 scores or hours of Internet use per week.
In this study, we used ASL perfusion fMRI and noninvasively quantified resting CBF to demonstrate that IGA alters the CBF distribution in the adolescent brain. The results support the hypothesis that IGA is a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.
Internet addiction; Internet gaming addiction; Arterial spin-labeling perfusion; fMRI; Cerebral blood flow
Ramadan fasting and its attendant lifestyle changes induce changes in the circadian rhythm and in associated physiological and metabolic functions. Previous studies that have assessed psychomotor performance during Ramadan fasting have reported conflicting results. Therefore, we designed this study to objectively assess the effects of intermittent fasting during and outside Ramadan (to control for lifestyle changes) on drowsiness, blink total duration and mean reaction time (MRT) test while controlling for potential confounders.
Eight healthy volunteers with a mean age of 25.3 ± 2.9 years and a mean body mass index (BMI) of 23.4 ± 3.2 kg/m2 reported to the sleep laboratory on four occasions for polysomnography (PSG) and drowsiness and psychomotor assessments as follows: 1) adaptation; 2) 4 weeks before Ramadan while performing the Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting (Ramadan). OPTALERT™ was used to objectively assess daytime drowsiness using the Johns Drowsiness Scale (JDS), and blink total duration and a visual reaction time test were used to assess MRT.
Rapid eye movement (REM) sleep percentage was significantly lower at BLF (17.7 ± 8.1%) and at Ramadan (18.6 ± 10.7%) compared with BL (25.6 ± 4.8%) (p < 0.05). There were no significant differences between JDS scores and blink total duration during the two test periods in BL, BLF and Ramadan. There were no significant changes in MRT during BL, BLF and Ramadan.
Under controlled conditions of fixed light/dark exposure, caloric intake, sleep/wake schedule and sleep quality, the Islamic intermittent fasting has no impact on drowsiness and vigilance as measured by the JDS, total blink duration and MRT.
Ramadan; Fasting; REM sleep; Vigilance; Mean reaction time; Blink duration; Optalert; Johns Drowsiness Scale
Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population.
Subjects were 599 healthy adults (166 males and 433 females; mean age 43.8 ± 15.5 years). The Wechsler Memory Scale-Revised (WMS-R) was administered to all participants to assess memory performance. Genotyping was performed for 6 selected tagging SNPs of PAH (rs1722387, rs3817446, rs1718301, rs2037639, rs10860936 and rs11111419).
Analyses of covariance controlling for sex and education years, indicated a significant association between a SNP (rs2037639) and age-corrected verbal memory index of WMS-R (nominal p = 0.0013) which remained significant after correction for multiple testing ( p = 0.0013 < 0.0017 = 0.05/30tests). Individuals with the GG genotype showed a significantly lower mean verbal memory score, compared with those individuals carrying the AA/AG genotype (106.0 ± 16.0 vs. 111.7 ± 13.4; p = 0.00099). A haplotype block containing two markers of rs2037639 and rs10860936 was associated with verbal memory index (permutation global p = 0.0091).
Our findings suggest that common genetic variations in PAH are associated with verbal memory in healthy adults. Unknown functional polymorphisms in PAH or those in other genes nearby might affect memory performance.
Genetic polymorphism; Phenylalanine hydroxylase; Verbal memory; Wechsler Memory Scale-Revised (WMS-R); Association study
To analyze the correlation between the pharmacotherapy response and the characteristics of the pre-treatment regional cerebral blood flow (rCBF) in patients with obsessive-compulsive disorder (OCD).
Single-photon emission-computed tomography (SPECT) was used to determine the pre-treatment rCBF in 30 OCD patients and 30 normal controls. Based on their clinical remission response, the subjects were divided into two groups: selective serotonin reuptake inhibitors (SSRIs) and SSRIs plus quetiapine. The subjects with clinical remission response were identified after treatment for a period of 24 weeks, and the rCBF imaging data were processed using statistical parametric mapping (SPM) software with two-sample Z-tests.
Nineteen OCD patients who achieved clinical remission were included in the study. Increased rCBF in forebrain regions, including the frontal lobe, cingulate gyrus, hypothalamus, and basal ganglia, was found in 11 responders to SSRIs compared to normal control patients. The eight SSRI plus quetiapine responders exhibited a decrease in rCBF within posterior brain regions, including the parietal lobe, cerebellar vermis, and occipital lobe, and an increase in rCBF in the frontal lobe, thalamus, basal ganglia, and cerebellum tonsil compared to normal control patients.
The characteristics of increased rCBF in forebrain regions and decreased rCBF in posterior brain regions before treatment of OCD patients was a potentially predictor of treatment response to guide treatment options.
Obsessive-compulsive disorder; Regional cerebral blood flow; SSRI; Quetiapine; Therapy response
It has been established that the overall performance of associative memory was disproportionately impaired in contrast to item memory in aMCI (Amnestic mild cognitive impairment) patients, but little is known about the specific aspects of the memory process that show differences between aMCI and healthy controls. By comparing an item-item associative learning test with an individual item learning test, the present study investigated whether the rate of learning was slower in associative memory than in item memory in aMCI. Furthermore, we examined whether deficits in intertrial acquisition and consolidation contributed to the potential disproportionate impairments in the learning rate of associative memory for aMCI patients. In addition, we further explored whether the aMCI-discriminative power of the associative memory test increases more than that of the item memory test when the number of learning-test trials increases.
A group of 40 aMCI patients and 40 matched control participants were administered a standardized item memory test (Auditory Verbal Learning Test, AVLT) and a standardized associative memory test (Paired Associative Learning Test, PALT), as well as other neuropsychological tests and clinical assessments.
The results indicated that the learning rate deficits in aMCI patients were more obvious for associative memory than for item memory and that the deficits resulted from impairments in both intertrial acquisition and consolidation. In addition, the receiver operating characteristic curve and logistical regression analysis revealed that the discriminative power of the associative memory test for aMCI was larger than that of the item memory test, especially with more than one learning-test trials.
Due to more deficits in learning rate of associative memory than that of item memory, the discriminative power for aMCI tended to be larger in associative memory than in item memory when the number of learning-test trials increased. It is suggested that associative memory tests with multiple trials may be particularly useful for early detection of aMCI.
Mild cognitive impairment; Associative memory; Item memory; Learning rate
With the present functional magnetic resonance imaging (fMRI) study at 3 T, we investigated the neural correlates of visualization and verbalization during arithmetic word problem solving. In the domain of arithmetic, visualization might mean to visualize numbers and (intermediate) results while calculating, and verbalization might mean that numbers and (intermediate) results are verbally repeated during calculation. If the brain areas involved in number processing are domain-specific as assumed, that is, that the left angular gyrus (AG) shows an affinity to the verbal domain, and that the left and right intraparietal sulcus (IPS) shows an affinity to the visual domain, the activation of these areas should show a dependency on an individual’s cognitive style.
36 healthy young adults participated in the fMRI study. The participants habitual use of visualization and verbalization during solving arithmetic word problems was assessed with a short self-report assessment. During the fMRI measurement, arithmetic word problems that had to be solved by the participants were presented in an event-related design.
We found that visualizers showed greater brain activation in brain areas involved in visual processing, and that verbalizers showed greater brain activation within the left angular gyrus.
Our results indicate that cognitive styles or preferences play an important role in understanding brain activation. Our results confirm, that strong visualizers use mental imagery more strongly than weak visualizers during calculation. Moreover, our results suggest that the left AG shows a specific affinity to the verbal domain and subserves number processing in a modality-specific way.
fMRI; Cognitive styles; Number processing; Visual cortex; Angular gyrus
In contrast to olanzapine, ziprasidone has been reported to cause minimal or no weight gain. This study aimed to compare the effects of ziprasidone and olanzapine on weight, body composition, appetite, resting energy expenditure, substrate oxidation, and metabolic parameters in adults with schizophrenia or other psychotic disorders.
Twenty adults with schizophrenia or other psychotic disorders were randomized 1:1 to ziprasidone 20–160 mg/day or olanzapine 5–20 mg/day for 12 weeks. The mean doses during the 12-week study period were 109(range: 65–140) mg/day for ziprasidone and 11.6(range: 8.2–15.5) mg/day for olanzapine. Body weight, appetite, body composition, resting energy expenditure, and metabolic parameters were measured before and after drug treatment. Outcome measurements before and after medication were compared, and ziprasidone- and olanzapine-treated patients were compared.
After 12 weeks, olanzapine-treated patients showed significant weight gain, particularly fat gain, with increased low density lipoprotein-cholesterol and decreased high density lipoprotein-cholesterol concentrations. In contrast, ziprasidone-treated patients showed no significant weight gain with increased high density lipoprotein-cholesterol concentration.
Ziprasidone was associated with a lower propensity for weight gain and central fat deposition than olanzapine. Studies in larger patient samples are required to confirm these results.
Ziprasidone; Olanzapine; Weight gain; Resting energy expenditure; Body composition
A significant debate surrounds the nature of the cognitive mechanisms involved in non-symbolic number estimation. Several studies have suggested the existence of the same cognitive system for estimation of time, space, and number, called “a theory of magnitude” (ATOM). In addition, researchers have proposed the theory that non-symbolic number abilities might support our mathematical skills. Despite the large number of studies carried out, no firm conclusions can be drawn on either topic.
In the present study, we correlated the performance of adults on non-symbolic magnitude estimations and symbolic numerical tasks. Non-symbolic magnitude abilities were assessed by asking participants to estimate which auditory tone lasted longer (time), which line was longer (space), and which group of dots was more numerous (number). To assess symbolic numerical abilities, participants were required to perform mental calculations and mathematical reasoning.
We found a positive correlation between non-symbolic and symbolic numerical abilities. On the other hand, no correlation was found among non-symbolic estimations of time, space, and number.
Our study supports the idea that mathematical abilities rely on rudimentary numerical skills that predate verbal language. By contrast, the lack of correlation among non-symbolic estimations of time, space, and number is incompatible with the idea that these magnitudes are entirely processed by the same cognitive system.
Subitizing; ANS; OTS; Mathematical achievement; ATOM
Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague–Dawley rats were randomly assigned to three experimental groups: 1) Control, 2) Vehicle, animals supplemented with water, and 3) ω-3, rats supplemented with ω-3 (100 mg of DHA+25 mg of EPA). Each experimental group was divided into two subgroups: one of which was not subjected to stress while the other was subjected to a restraint stress paradigm. Afterwards, learning was analyzed by avoidance conditioning. As well, plasma corticosterone levels and anxiety were evaluated as stress markers, respectively by ELISA and the plus-maze test. Restraint stress impaired learning and increased both corticosterone levels and the number of entries into the open-arm (elevated plus-maze). These alterations were prevented by ω-3 supplementation. Thus, our results demonstrate that ω-3 supplementation had two beneficial effects on the stressed rats, a strong anti-stress effect and improved learning.
Stress; ω-3 polyunsaturated fatty acid; Anxiety; Learning
It has been proposed that an inappropriately conditioned fatigue sensation could be one cause of chronic fatigue. Although classical conditioning of the fatigue sensation has been reported in rats, there have been no reports in humans. Our aim was to examine whether classical conditioning of the mental fatigue sensation can take place in humans and to clarify the neural mechanisms of fatigue sensation using magnetoencephalography (MEG).
Ten and 9 healthy volunteers participated in a conditioning and a control experiment, respectively. In the conditioning experiment, we used metronome sounds as conditioned stimuli and two-back task trials as unconditioned stimuli to cause fatigue sensation. Participants underwent MEG measurement while listening to the metronome sounds for 6 min. Thereafter, fatigue-inducing mental task trials (two-back task trials), which are demanding working-memory task trials, were performed for 60 min; metronome sounds were started 30 min after the start of the task trials (conditioning session). The next day, neural activities while listening to the metronome for 6 min were measured. Levels of fatigue sensation were also assessed using a visual analogue scale. In the control experiment, participants listened to the metronome on the first and second days, but they did not perform conditioning session. MEG was not recorded in the control experiment.
The level of fatigue sensation caused by listening to the metronome on the second day was significantly higher relative to that on the first day only when participants performed the conditioning session on the first day. Equivalent current dipoles (ECDs) in the insular cortex, with mean latencies of approximately 190 ms, were observed in six of eight participants after the conditioning session, although ECDs were not identified in any participant before the conditioning session.
We demonstrated that the metronome sounds can cause mental fatigue sensation as a result of repeated pairings of the sounds with mental fatigue and that the insular cortex is involved in the neural substrates of this phenomenon.
Fatigue sensation; Chronic fatigue syndrome; Classical conditioning; Magnetoencephalography (MEG); Equivalent current dipole (ECD)
In animal models, the impact of social and environmental manipulations on chronic pain have been investigated in short term studies where enrichment was implemented prior to or concurrently with the injury. The focus of this study was to evaluate the impact of environmental enrichment or impoverishment in mice three months after induction of chronic neuropathic pain.
Thirty-four CD-1 seven to eight week-old male mice were used. Mice underwent surgery on the left leg under isoflurane anesthesia to induce the spared nerve injury model of neuropathic pain or sham condition. Mice were then randomly assigned to one of four groups: nerve injury with enriched environment (n = 9), nerve injury with impoverished environment (n = 8), sham surgery with enriched environment (n = 9), or sham surgery with impoverished environment (n = 8). The effects of environmental manipulations on mechanical (von Frey filaments) heat (hot plate) and cold (acetone test) cutaneous hypersensitivities, motor impairment (Rotarod), spontaneous exploratory behavior (open field test), anxiety-like behavior (elevated plus maze) and depression-like phenotype (tail suspension test) were assessed in neuropathic and control mice 1 and 2 months post-environmental change. Finally, the effect of the environment on spinal expression of the pro-nociceptive neuropeptides substance P and CGRP form the lumbar spinal cord collected at the end of the study was evaluated by tandem liquid chromatography mass spectrometry.
Environmental enrichment attenuated nerve injury-induced hypersensitivity to mechanical and cold stimuli. In contrast, an impoverished environment exacerbated mechanical hypersensitivity. No antidepressant effects of enrichment were observed in animals with chronic neuropathic pain. Finally, environmental enrichment resulted lower SP and CGRP concentrations in neuropathic animals compared to impoverishment. These effects were all observed in animals that had been neuropathic for several months prior to intervention.
These results suggest that environmental factors could play an important role in the rehabilitation of chronic pain patients well after the establishment of chronic pain. Enrichment is a potentially inexpensive, safe and easily implemented non-pharmacological intervention for the treatment of chronic pain.
Chronic neuropathic pain; Environmental enrichment; Environmental impoverishment; Animal model; Spared nerve injury