Racial stereotypes impair flexibility of emotional learning

PubMed Central

Kubota, Jennifer T.; Li, Jian; Coelho, Cesar A.O.; Phelps, Elizabeth A.

2016-01-01

Flexibility of associative learning can be revealed by establishing and then reversing cue-outcome discriminations. Here, we used functional MRI to examine whether neurobehavioral correlates of reversal-learning are impaired in White and Asian volunteers when initial learning involves fear-conditioning to a racial out-group. For one group, the picture of a Black male was initially paired with shock (threat) and a White male was unpaired (safe). For another group, the White male was a threat and the Black male was safe. These associations reversed midway through the task. Both groups initially discriminated threat from safety, as expressed through skin conductance responses (SCR) and activity in the insula, thalamus, midbrain and striatum. After reversal, the group initially conditioned to a Black male exhibited impaired reversal of SCRs to the new threat stimulus (White male), and impaired reversals in the striatum, anterior cingulate cortex, midbrain and thalamus. In contrast, the group initially conditioned to a White male showed successful reversal of SCRs and successful reversal in these brain regions toward the new threat. These findings provide new evidence that an aversive experience with a racial out-group member impairs the ability to flexibly and appropriately adjust fear expression towards a new threat in the environment. PMID:27107298

[Effects of aluminum on neurobehavioral function and metabolism of monoamine neurotransmitter].

PubMed

Yang, H; Zheng, Y; Liang, Y

1998-03-01

To evaluate the effects of occupational exposure to aluminum on neurobahavioral function and metabolism of monoamine neurotransmitter. Thirty-three workers exposed to aluminum and 40 controls were studied. Air aluminum concentrations in workplace environment were detected with an atomic absorption spectrophotometer, homovanillic acid (HVA) and vanilylmandellic acid (VMA) in urine and aluminum in serum and urine were detected with high perfolmance liquid chromatography. Neurobehavioral function was tested with Neurobehavioral Core Test Battery recommended by WHO. Geometric time-weighted average of aluminum in workplace environment was 0.95 mg/m3, ranging from 0.31 to 4.12 mg/m3, and urine aluminum levels in workers exposed to aluminum averaged 12.25 micrograms/L, significantly higher than that in controls (5.78 micrograms/L). There was no significant difference in serum aluminum between the exposed and controls. Both urine VMA and HVA levels were higher in the workers exposed to aluminum, and urine VMA level in the exposed was significantly higher than that in controls. There was significant difference in neurobehavioral test, including Santa Ana, digit symbol and Benton tests between the exposed and control workers. It suggests that occupational exposure to low level of aluminum can affect the neurobehavioral function and metabolism of monoamine neurotransmitter.

Advancing Clinical Outcomes, Biomarkers and Treatments for Severe TBI

DTIC Science & Technology

2017-08-01

determining the neurobehavioral and neural effects of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive technique to stimulate the...examined to determine effectiveness in inducing structural and functional neural plasticity and improving neurobehavioral recovery after severe TBI...Specific Aims: Aim I will determine presence, direction and sustainability of rTMS-induced neurobehavioral effects measured with the Disability Rating

Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes.

PubMed

Chen, Yanxing; Dai, Chun-Ling; Wu, Zhe; Iqbal, Khalid; Liu, Fei; Zhang, Baorong; Gong, Cheng-Xin

2017-01-01

General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM) 2-6 days after anesthesia exposure, in aged (17-18 months old) wild-type (WT) mice and in adult (7-8 months old) 3xTg-AD mice (a triple transgenic mouse model of Alzheimer's disease (AD)), but not in adult WT mice. Anesthesia resulted in long-term neurobehavioral changes in the fear conditioning task carried out 65 days after exposure to anesthesia in 3xTg-AD mice. Importantly, daily intranasal administration of insulin (1.75 U/mouse/day) for only 3 days prior to anesthesia completely prevented the anesthesia-induced deficits in spatial learning and memory and the long-term neurobehavioral changes tested 65 days after exposure to anesthesia in 3xTg-AD mice. These results indicate that aging and AD-like brain pathology increase the vulnerability to cognitive impairment after anesthesia and that intranasal treatment with insulin can prevent anesthesia-induced cognitive impairment.

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2016-10-01

of rTMS-induced neurobehavioral effects measured with the Disability Rating Scale. Aim II will determine the presence, direction and sustainability...Aim IV addresses the need to confirm rTMS safety for severe TBI. 15. SUBJECT TERMS Disability Rating Scale (DRS), Neurobehavioral, Repetitive...rTMS sessions. The Disability Rating Scale (DRS) will be used at four time points to measure neurobehavioral recovery slopes. Net neural effects

Are there gender differences in cognitive function, chronic stress, and neurobehavioral symptoms after mild-to-moderate traumatic brain injury?

PubMed

Covassin, Tracey; Bay, Esther

2012-06-01

Research is inconclusive on whether gender differences exist in cognitive function in persons who sustain a mild-to-moderate traumatic brain injury (TBI). Furthermore, it is also unclear whether there is a relationship between chronic stress and cognitive function in these persons. The purpose of this integrative review is to determine whether gender differences exist in cognitive function, neurobehavioral symptoms, and chronic stress levels after a mild-to-moderate TBI. Participants (n = 72) were recruited from eight outpatient rehabilitation centers. Participants completed the demographic questions, the Immediate Postconcussion Assessment Cognitive Testing neurocognitive test battery, the Perceived Stress Scale-14, and the Neurobehavioral Functioning Inventory (NFI). Gender differences were present on verbal memory composite scores (p = .033), with women performing worse than men. There were no other between-gender differences on cognitive tasks, neurobehavioral symptoms, or chronic stress. Higher chronic stress levels result in a decrease in verbal memory (p = .015) and motor processing speed (p = .006) and slower reaction time (p = .007) for women. As male NFI cognition scores increased, motor processing speed scores decreased (p = .012) and reaction time got slower (p = .019), whereas women exhibited decreased verbal memory (p = .017) and slower reaction time (p = .034). As NFI motor symptoms increased, men exhibited decreased verbal memory (p = .005), visual memory (p = .002), and motor processing speed (p = .002) and slower reaction time (p = .002). Overall, this study only found gender differences on verbal memory composite scores, whereas the remaining cognitive tasks, neurobehavioral symptoms, and chronic stress did not indicate gender differences. Correlations between chronic stress, neurobehavioral symptoms, and cognitive function differed in both men and women with TBI. Persons in the chronic phase of recovery from a TBI may benefit from training in compensatory strategies for verbal memory deficits and stress management.

Sleep disturbance and neurobehavioral performance among postpartum women.

PubMed

Insana, Salvatore P; Williams, Kayla B; Montgomery-Downs, Hawley E

2013-01-01

Sleep disturbances cause neurobehavioral performance and daytime functioning impairments. Postpartum women experience high levels of sleep disturbance. Thus, the study objective was to describe and explore the relation between neurobehavioral performance and sleep among women during the early postpartum period. Longitudinal field-based study. There were 70 primiparous women and nine nulliparous women in a control group. None. During their first 12 postpartum weeks, 70 primiparous women wore continuous wrist actigraphy to objectively monitor their sleep. Each morning they self-administered the psychomotor vigilance test (PVT) to index their neurobehavioral performance. Nine nulliparous women in a control group underwent the same protocol for 12 continuous weeks. Postpartum PVT mean reciprocal (1/RT) reaction time did not differ from that of women in the control group at postpartum week 2, but then worsened over time. Postpartum slowest 10% 1/RT PVT reaction time was significantly worse than that of women in the control group at all weeks. Despite improvements in postpartum sleep, neurobehavioral performance continued to worsen from week 2 through the end of the study. Across the first 12 postpartum weeks, PVT measures were more frequently associated with percent sleep compared with total sleep time, highlighting the deleterious consequences of sleep disruption on maternal daytime functioning throughout the early postpartum period. Worsened maternal neurobehavioral performance across the first 12 postpartum weeks may have been influenced by the cumulative effects of sleep disturbance. These results can inform future work to identify the particular sleep profiles that could be primary intervention targets to improve daytime functioning among postpartum women, and indicate need for further research on the effectiveness of family leave policies. The time when postpartum women return to control-level daytime functioning is unknown.

The effect of occupational exposure to benzo[a]pyrene on neurobehavioral function in coke oven workers.

PubMed

Qiu, Chongying; Peng, Bin; Cheng, Shuqun; Xia, Yinyin; Tu, Baijie

2013-03-01

Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (B[a]P), known as an indicator species for PAH contamination, is a neurobehavioral toxicant. The purpose of the study was to evaluate the relationship between B[a]P exposure, a B[a]P-related urinary metabolite and neurobehavioral function among coke oven workers. Coke oven workers and oxygen factory workers participated in this study. B[a]P exposure was monitored by air sampling pump, and urinary 1-hydroxypyrene (1-OHP) level was detected with high performance liquid chromatography (HPLC). A questionnaire and the neurobehavioral core test battery (NCTB) were administered to all subjects. B[a]P-exposed workers were found to have higher urinary 1-OHP levels and worse NCTB performances on eight items than control workers. B[a]P concentrations were higher in the coke oven plant than that in the controls' workplace. The performances on simple reaction time, correct pursuit aiming, and error pursuit aiming decreased with increasing airborne B[a]P in coke oven workers. There were significant correlations between urinary 1-OHP level and six items of the NCTB. Occupational exposure to B[a]P is associated with neurobehavioral function impairment in coke oven workers. Copyright © 2012 Wiley Periodicals, Inc.

Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: Evidence from Neuroimaging Research

PubMed Central

Seymour, Karen E.; Reinblatt, Shauna P.; Benson, Leora; Carnell, Susan

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (e.g. obesity, binge / loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, e.g. functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing i) reward processing, ii) response inhibition, and iii) emotional processing and regulation, and outline three specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research. PMID:26098969

Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

PubMed

Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

2015-07-01

Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood. © 2014 Society for the Study of Addiction.

Developmental emergence of fear/threat learning: neurobiology, associations and timing

PubMed Central

Tallot, L.; Doyère, V.; Sullivan, R. M.

2016-01-01

Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups’ transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes. PMID:26534899

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2015-09-01

for public release; distribution unlimited Autism spectrum disorder (ASD); biomarker; early brain development; intrinsic functional brain networks...three large neuroimaging/neurobehavioral datasets to identify brain-imaging based biomarkers for Autism Spectrum Disorders (ASD). At Yale, we focus...neurobehavioral!datasets!in!order!to!identify! brainFimaging!based!biomarkers!for! Autism ! Spectrum ! Disorders !(ASD),!including!1)!BrainMap,! developed!and

[Psychological and neurobehavioral effects of aluminum on exposed workers].

PubMed

Guo, G; Ma, H; Wang, X

1998-09-01

To explore neurotoxicity and the changes in psychological and neurobehavioral functions in workers exposed to aluminum. Psychological status and neurobehavioral functions of 103 exposed workers and 64 controls were examined with Neurobehavioral Core Test Battery recommended by World Health Organization (WHO), and meanwhile, air concentrations of aluminum in the workplaces and urine levels of aluminum in the exposed workers were determined. Urine levels of aluminum in the exposed workers were markedly higher than those in non-exposed controls, with a statistical significance. Scores for tension, depression, anger, fatigue and confusion in the workers exposed to aluminum for more than ten years were significantly more than those in non-exposed controls. Scores of the performance of Santa Ana, digit symbol and pursuit aiming in the former were significantly lower, and no other changes in psychological and behavioral functions was found in workers exposed for less than ten years, except for their scores of pursuit aiming. Obvious changes in psychological status, neuromotor speed and their accuracy were observed in workers exposed to aluminum for a long term.

APPROACHES TO ASSESSING THE VALIDITY OF A FUNCTIONAL OBSERVATIONAL BATTERY

EPA Science Inventory

With the growing importance of neurobehavioral assessments at the preliminary stage of chemical testing, it is critical that the screening procedures utilized be valid indicators of neurobehavioral dysfunction in addition to being sensitive, specific, and reliable. fforts in this...

NEUROBEHAVIORAL TESTING IN ANIMALS AND THE APPLICATION TO RISK ASSESSMENT.

EPA Science Inventory

Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

Association among parental substance use disorder, p300 amplitude, and neurobehavioral disinhibition in preteen boys at high risk for substance use disorder.

PubMed

Habeych, Miguel E; Sclabassi, Robert J; Charles, Prophete J; Kirisci, Levent; Tarter, Ralph E

2005-06-01

The P300 amplitude of the event-related potential as a mediator of the association between parental substance use disorder (SUD) and child's neurobehavioral disinhibition was assessed. The P300 amplitude was recorded using an oddball task in sons of fathers having either lifetime SUD (n = 105) or no psychiatric disorder (n = 160). Neurobehavioral disinhibition was assessed using measures of affect regulation, behavior control, and executive cognitive function. Parental SUD and child's P300 amplitude accounted for, respectively, 16.6% and 16.8% of neurobehavioral disinhibition variance. Controlling for parental and child psychopathology, an association between parental SUD and child's P300 amplitude was not observed. It was concluded that the P300 amplitude does not mediate the association between parental SUD and child's neurobehavioral disinhibition. Copyright 2005 APA, all rights reserved.

Neurobehavioral Performance Impairment in Insomnia: Relationships with Self-Reported Sleep and Daytime Functioning

PubMed Central

Shekleton, Julia A.; Flynn-Evans, Erin E.; Miller, Belinda; Epstein, Lawrence J.; Kirsch, Douglas; Brogna, Lauren A.; Burke, Liza M.; Bremer, Erin; Murray, Jade M.; Gehrman, Philip; Lockley, Steven W.; Rajaratnam, Shantha M. W.

2014-01-01

Study Objectives: Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Design: Cross-sectional, multicenter study. Setting: Three sleep laboratories in the USA and Australia. Patients: Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). Interventions: N/A. Measurements and Results: Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. Conclusions: We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency. Citation: Shekleton JA; Flynn-Evans EE; Miller B; Epstein LJ; Kirsch D; Brogna LA; Burke LM; Cremer E; Murray JM; Gehrman P; Lockley SW; Rajaratnam SMW. Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning. SLEEP 2014;37(1):107-116. PMID:24470700

Prenatal Antecedents of Newborn Neurological Maturation

ERIC Educational Resources Information Center

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2010-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth…

[Interaction Between Occupational Vanadium Exposure and hsp70-hom on Neurobehavioral Function].

PubMed

Zhang, Qin; Liu, Yun-xing; Cui, Li; Li, Shun-pin; Gao, Wei; Hu, Gao-lin; Zhang, Zu-hui; Lan, Ya-jia

2016-01-01

In determine the effect of heat shock protein 70-hom gene (hsp70-hom) polymorphism on the neurobehavioral function of workers exposed to vanadium. Workers from the vanadium products and chemical industry were recruited by cluster sampling. Demographic data and exposure information were collected using a questionnaire. Neurobehavioral function was assessed by Neurobehavioral Core Test Battery. The hsp70-hom genotype was detected by restricted fragment length polymorphism-polymerase chain reaction (RFLP-PCR). A neurobehavioral index (NBI) was formulated through principal component analysis. Workers with a T/C genotype had worse performance in average reaction time, visual retention, digital span (backward), Santa Ana aiming (non-habitual hand), pursuit aiming (right points, total points), digit symbol and NBI score than others (P < 0.05). The relative risk of abnormal NBI score of the workers with a T/C genotype was 1.748 fold of those with a T/T genotype. The relative risk of abnormal.NBI score of the workers exposed to vanadium was 3.048 fold of controls (P < 0.05). But after adjustment with age and education, only vanadium exposure appeared with a significant effect on NBI score. When gene polymorphism and vanadium exposure coexisted, the effect of vanadium on neurobehavioral function was attenuated, but the influence of T/C genotype increased Codds ratio (OR = 4.577, P < 0.05). After adjustment with age and education, the OR of T/C genotype further increased to 7.777 (P < 0.05). Vanadium exposure and T/C genotype had.a bio-interaction effect on NBI score Crelative excess risk due to interaction (RERI) = 4.12, attributable proportion (AP) = 0.7, synergy index (S) = 6.45]. After adjustment with age and education, the RERI became 2.49 and the AP became 0.75, but no coefficient of interaction was produced. Priorities of occupational protection should be given to vanadium-exposed workers with a hsp70-hom T/C genotype and low education level.

Racial and ethnic disparities in functional, psychosocial, and neurobehavioral outcomes after brain injury.

PubMed

Arango-Lasprilla, Juan Carlos; Kreutzer, Jeffrey S

2010-01-01

Because of the growing minority population in the past 3 decades in the United States and the increasing numbers of individuals who sustain a traumatic brain injury (TBI), researchers and clinicians have started to pay more attention to the role of race and ethnicity in outcomes after TBI, with the goal of better serving this population. The aim of this article is to review the literature on the influence of race/ethnicity on functional, psychosocial, and neurobehavioral outcomes after TBI. Specifically, the following 8 areas of outcomes will be examined: (1) treatment outcomes, (2) neuropsychological outcomes, (3) employment/productivity, (4) functional outcomes, (5) community integration, (6) marital status, (7) quality of life/life satisfaction, and (8) emotional/neurobehavioral outcomes. To conclude this review, suggestions for improvements in professional competency, research, systems of care, and training are proposed.

Effects of onboard insecticide use on airline flight attendants.

PubMed

Kilburn, Kaye H

2004-06-01

Flight attendants (FAs) exposed to insecticide spray in an aircraft were compared with unexposed subjects for neurobehavioral function, pulmonary function, mood states, and symptoms. The 33 symptomatic FAs were self-selected, and 5 had retired for disability. Testing procedures included balance, reaction time, color discrimination, visual fields, grip strength, verbal recall, problem solving, attention and discrimination functions, and long-term memory functions. Measurements were expressed as a percentage of their predicted values (derived from unexposed controls), and the author compared the means of the percentage predicted values by analysis of variance. Symptom frequencies and Profile of Mood States (POMS) scores were assessed. FAs were significantly more impaired than controls with respect to balance with eyes closed, grip strength, and color discrimination. Nearly half had 3 or more abnormal neurobehavioral functions, after adjustment was made for age, sex, and education level. Neither elevated POMS scores nor frequencies of average symptoms correlated with their numbers of abnormal measurements. Occupational exposure to synthetic pyrethrin insecticides on airliners was associated with neurobehavioral impairment and disability retirement.

Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure

PubMed Central

Hagan, Joseph F.; Balachova, Tatiana; Bertrand, Jacquelyn; Chasnoff, Ira; Dang, Elizabeth; Fernandez-Baca, Daniel; Kable, Julie; Kosofsky, Barry; Senturias, Yasmin N.; Singh, Natasha; Sloane, Mark; Weitzman, Carol; Zubler, Jennifer

2017-01-01

Children and adolescents affected by prenatal exposure to alcohol who have brain damage that is manifested in functional impairments of neurocognition, self-regulation, and adaptive functioning may most appropriately be diagnosed with neurobehavioral disorder associated with prenatal exposure. This Special Article outlines clinical implications and guidelines for pediatric medical home clinicians to identify, diagnose, and refer children regarding neurobehavioral disorder associated with prenatal exposure. Emphasis is given to reported or observable behaviors that can be identified as part of care in pediatric medical homes, differential diagnosis, and potential comorbidities. In addition, brief guidance is provided on the management of affected children in the pediatric medical home. Finally, suggestions are given for obtaining prenatal history of in utero exposure to alcohol for the pediatric patient. PMID:27677572

Do all roads lead to Rome? The role of neuro-immune interactions before birth in the programming of offspring obesity

PubMed Central

Jasoni, Christine L.; Sanders, Tessa R.; Kim, Dong Won

2015-01-01

The functions of the nervous system can be powerfully modulated by the immune system. Although traditionally considered to be quite separate, neuro-immune interactions are increasingly recognized as critical for both normal and pathological nervous system function in the adult. However, a growing body of information supports a critical role for neuro-immune interactions before birth, particularly in the prenatal programming of later-life neurobehavioral disease risk. This review will focus on maternal obesity, as it represents an environment of pathological immune system function during pregnancy that elevates offspring neurobehavioral disease risk. We will first delineate the normal role of the immune system during pregnancy, including the role of the placenta as both a barrier and relayer of inflammatory information between the maternal and fetal environments. This will be followed by the current exciting findings of how immuno-modulatory molecules may elevate offspring risk of neurobehavioral disease by altering brain development and, consequently, later life function. Finally, by drawing parallels with pregnancy complications other than obesity, we will suggest that aberrant immune activation, irrespective of its origin, may lead to neuro-immune interactions that otherwise would not exist in the developing brain. These interactions could conceivably derail normal brain development and/or later life function, and thereby elevate risk for obesity and other neurobehavioral disorders later in the offspring's life. PMID:25691854

Neurobehavioral epidemiology: application in risk assessment.

PubMed Central

Grandjean, P; White, R F; Weihe, P

1996-01-01

Neurobehavioral epidemiology may contribute information to risk assessment in relation to a) characterization of neurotoxicity and its time course; b) the dose-effect relationship; c) the dose-response relationship; and d) predisposing factors. The quality of this information relies on the validity of the exposure data, the validity and sensitivity of neurobehavioral function tests, and the degree to which sources of bias are controlled. With epidemiologic studies of methylmercury-associated neurotoxicity as an example, the field of research involves numerous uncertainties that should be taken into account in the risk assessment process. PMID:9182047

Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Hilton, Sterling C.; Hawkins, Melissa; Costigan, Kathleen A.; Pressman, Eva K.

2002-01-01

Investigated associations between maternal psychological and fetal neurobehavioral functioning with data provided at 24, 30, and 36 weeks gestation. Found that fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more pregnancy-specific hassles were more active across gestation. Fetuses of women…

Pediatric Oncology Branch - Neurobehavioral Assessments | Center for Cancer Research

Cancer.gov

Neurobehavioral Research Assessments As part of the clinical trials investigating new treatments or natural history studies exploring the effects of diseases, such as cancer and neurofibromatosis type 1, we conduct comprehensive assessments of children, adolescents, and adults to identify strengths and weaknesses in neuropsychological functioning and to monitor changes in

Association of aryl hydrocarbon receptor gene polymorphism with the neurobehavioral function and autonomic nervous system function changes induced by benzo[a]pyrene exposure in coke oven workers.

PubMed

Zhang, Hongmei; Nie, Jisheng; Li, Xin; Niu, Qiao

2013-03-01

To analyze the association of aryl hydrocarbon receptor (AhR) gene polymorphism and the neurotoxicity induced by benzo[a]pyrene (B[a]P) in coke oven workers. Subjects, 214 coke oven workers and 81 controls, were detected for neurobehavioral function and autonomic nervous system (ANS) function. Airborne B[a]P concentration, urinary 1-hydroxypyrene level, and AhR gene polymorphisms were determined and analyzed for their association with B[a]P neurotoxicity. Neurobehavioral function and ANS function were significantly decreased and dependent on B[a]P dose. The AhR GG, GA, and AA genotypes in G1661A fitted the Hardy-Weinberg equation, whereas C1549T and G1708A gene mutants were not detected. Indices indicating neurotoxicity showed no significant difference among individuals with AA, GG, or GA genotype except for the confusion-bewilderment (P > 0.05). The AhR gene polymorphism is not thought to correlate with B[a]P neurotoxicity among coke oven workers.

Ecologically relevant neurobehavioral assessment of the development of threat learning

PubMed Central

Mouly, Anne-Marie

2016-01-01

As altricial infants gradually transition to adults, their proximate environment changes. In three short weeks, pups transition from a small world with the caregiver and siblings to a complex milieu rich in dangers as their environment expands. Such contrasting environments require different learning abilities and lead to distinct responses throughout development. Here, we will review some of the learned fear conditioned responses to threats in rats during their ontogeny, including behavioral and physiological measures that permit the assessment of learning and its supporting neurobiology from infancy through adulthood. In adulthood, odor–shock conditioning produces robust fear learning to the odor that depends upon the amygdala and related circuitry. Paradoxically, this conditioning in young pups fails to support fear learning and supports approach learning to the odor previously paired with shock. This approach learning is mediated by the infant attachment network that does not include the amygdala. During the age range when pups transition from the infant to the adult circuit (10–15 d old), pups have access to both networks: odor–shock conditioning in maternal presence uses the attachment circuit but the adult amygdala-dependent circuit when alone. However, throughout development (as young as 5 d old) the attachment associated learning can be overridden and amygdala-dependent fear learning supported, if the mother expresses fear in the presence of the pup. This social modulation of the fear permits the expression of defense reactions in life threatening situations informed by the caregiver but prevents the learning of the caregiver itself as a threat. PMID:27634146

Ecologically relevant neurobehavioral assessment of the development of threat learning.

PubMed

Boulanger Bertolus, Julie; Mouly, Anne-Marie; Sullivan, Regina M

2016-10-01

As altricial infants gradually transition to adults, their proximate environment changes. In three short weeks, pups transition from a small world with the caregiver and siblings to a complex milieu rich in dangers as their environment expands. Such contrasting environments require different learning abilities and lead to distinct responses throughout development. Here, we will review some of the learned fear conditioned responses to threats in rats during their ontogeny, including behavioral and physiological measures that permit the assessment of learning and its supporting neurobiology from infancy through adulthood. In adulthood, odor-shock conditioning produces robust fear learning to the odor that depends upon the amygdala and related circuitry. Paradoxically, this conditioning in young pups fails to support fear learning and supports approach learning to the odor previously paired with shock. This approach learning is mediated by the infant attachment network that does not include the amygdala. During the age range when pups transition from the infant to the adult circuit (10-15 d old), pups have access to both networks: odor-shock conditioning in maternal presence uses the attachment circuit but the adult amygdala-dependent circuit when alone. However, throughout development (as young as 5 d old) the attachment associated learning can be overridden and amygdala-dependent fear learning supported, if the mother expresses fear in the presence of the pup. This social modulation of the fear permits the expression of defense reactions in life threatening situations informed by the caregiver but prevents the learning of the caregiver itself as a threat. © 2016 Boulanger Bertolus et al.; Published by Cold Spring Harbor Laboratory Press.

Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan

1999-01-01

Total sleep deprivation leads to decrements in neurobehavioral performance and changes in electroencephalographic (EEG) oscillations as well as the incidence of slow eye movements ad detected in the electro-oculogram (EOG) during wakefulness. Although total sleep deprivation is a powerful tool to investigate the association of EEG/EOG and neurobehavioral decrements, sleep loss during space flight is usual only partial. Furthermore exposure to the microgravity environment leads to changes in sodium and volume homeostasis and associated renal and cardio-endocrine responses. Some of these changes can be induced in head down tilt bedrest studies. We integrate research tools and research projects to enhance the fidelity of the simulated conditions of space flight which are characterized by complexity and mutual interactions. The effectiveness of countermeasures and physiologic mechanisms underlying neurobehavioral changes and renal-cardio endocrine changes are investigated in Project 3 of the Human Performance Team and Project 3 of the Cardiovascular Alterations Team respectively. Although the. specific aims of these two projects are very different, they employ very similar research protocols. Thus, both projects investigate the effects of posture/bedrest and sleep deprivation (total or partial) on outcome measures relevant to their specific aims. The main aim of this enhancement grant is to exploit the similarities in research protocols by including the assessment of outcome variables relevant to the Renal-Cardio project in the research protocol of Project 3 of the Human Performance Team and by including the assessment of outcome variables relevant to the Quantitative EEG and Sleep Deprivation Project in the research protocols of Project 3 of the Cardiovascular Alterations team. In particular we will assess Neurobehavioral Function and Waking EEG in the research protocols of the renal-cardio endocrine project and renin-angiotensin and cardiac function in the research protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

Developmental emergence of fear/threat learning: neurobiology, associations and timing.

PubMed

Tallot, L; Doyère, V; Sullivan, R M

2016-01-01

Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation Through Mathematical Modeling

DTIC Science & Technology

2007-06-01

the effects of rest -activity-work schedules and interventions on neurobehavioral function. In a symposium titled “Modeling Human Neurobehavioral...physio- logic basis of Process S. The mutually inhibitory neu- ronal populations, together with the surrogate Process S, have the potential to serve...as a function of both ta and φ (Czeisler et al., 1999). Briefly, by imposing a cyclic pattern of bed rest and wake time at a period, T, sufficiently

The Effect of One Night's Sleep Deprivation on Adolescent Neurobehavioral Performance

PubMed Central

Louca, Mia; Short, Michelle A.

2014-01-01

Study Objectives: To investigate the effects of one night's sleep deprivation on neurobehavioral functioning in adolescents. Design: Participants completed a neurobehavioral test battery measuring sustained attention, reaction speed, cognitive processing speed, sleepiness, and fatigue every 2 h during wakefulness. Baseline performance (defined as those test bouts between 09:00 and 19:00 on days 2 and 3, following two 10-h sleep opportunities) were compared to performance at the same clock time the day following total sleep deprivation. Setting: The sleep laboratory at the Centre for Sleep Research. Participants: Twelve healthy adolescents (6 male), aged 14-18 years (mean = 16.17, standard deviation = 0.83). Measurements and Results: Sustained attention, reaction speed, cognitive processing speed, and subjective sleepiness were all significantly worse following one night without sleep than following 10-h sleep opportunities (all main effects of day, P < 0.05). Sleep deprivation led to increased variability on objective performance measures. There were between-subjects differences in response to sleep loss that were task-specific, suggesting that adolescents may not only vary in terms of the degree to which they are affected by sleep loss but also the domains in which they are affected. Conclusions: These findings suggest that one night of total sleep deprivation has significant deleterious effects upon neurobehavioral performance and subjective sleepiness. These factors impair daytime functioning in adolescents, leaving them at greater risk of poor academic and social functioning and accidents and injuries. Citation: Louca M, Short MA. The effect of one night's sleep deprivation on adolescent neurobehavioral performance. SLEEP 2014;37(11):1799-1807. PMID:25364075

Influence of Dopamine-Related Genes on Neurobehavioral Recovery after Traumatic Brain Injury during Early Childhood.

PubMed

Treble-Barna, Amery; Wade, Shari L; Martin, Lisa J; Pilipenko, Valentina; Yeates, Keith Owen; Taylor, H Gerry; Kurowski, Brad G

2017-06-01

The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3.5 and 7 years after injury. Thirty-two single nucleotide polymorphisms (SNPs) in dopamine-related genes (dopamine receptor D2 [DRD2], solute carrier family 6 member 3 [SLC6A3], solute carrier family 18 member A2 [SLC18A2], catechol-o-methyltransferase [COMT], and ankyrin repeat and kinase domain containing 1 [ANKK1]) were examined in association with short- and long-term executive function and behavioral adjustment, as well as their trajectories over time. After controlling for premorbid child functioning, genetic variation within the SLC6A3 (rs464049 and rs460000) gene was differentially associated with neurobehavioral recovery trajectories over time following TBI relative to OI, with rs464049 surviving multiple testing corrections. In addition, genetic variation within the ANKK1 (rs1800497 and rs2734849) and SLC6A3 (rs464049, rs460000, and rs1042098) genes was differentially associated with short- and long-term neurobehavioral recovery following TBI, with rs460000 and rs464049 surviving multiple testing corrections. The findings provide preliminary evidence that genetic variation in genes involved in DRD2 expression and density (ANKK1) and dopamine transport (SLC6A3) plays a role in neurobehavioral recovery following pediatric TBI.

Behavioral and Physiological Consequences of Sleep Restriction

PubMed Central

Banks, Siobhan; Dinges, David F.

2007-01-01

Adequate sleep is essential for general healthy functioning. This paper reviews recent research on the effects of chronic sleep restriction on neurobehavioral and physiological functioning and discusses implications for health and lifestyle. Restricting sleep below an individual's optimal time in bed (TIB) can cause a range of neurobehavioral deficits, including lapses of attention, slowed working memory, reduced cognitive throughput, depressed mood, and perseveration of thought. Neurobehavioral deficits accumulate across days of partial sleep loss to levels equivalent to those found after 1 to 3 nights of total sleep loss. Recent experiments reveal that following days of chronic restriction of sleep duration below 7 hours per night, significant daytime cognitive dysfunction accumulates to levels comparable to that found after severe acute total sleep deprivation. Additionally, individual variability in neurobehavioral responses to sleep restriction appears to be stable, suggesting a traitlike (possibly genetic) differential vulnerability or compensatory changes in the neurobiological systems involved in cognition. A causal role for reduced sleep duration in adverse health outcomes remains unclear, but laboratory studies of healthy adults subjected to sleep restriction have found adverse effects on endocrine functions, metabolic and inflammatory responses, suggesting that sleep restriction produces physiological consequences that may be unhealthy. Citation: Banks S; Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med 2007;3(5):519-528. PMID:17803017

Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum electrolytic workers.

PubMed

He, S C; Qiao, N; Sheng, W

2003-01-01

The purpose of our study is to determine the alteration of neurobehavioral parameters, autonomic nervous function and lymphocyte subsets in aluminum electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/- 2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/- 6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was measured by means of graphite furnace atomic absorption spectrophotometer. Normal reference group were selected from a flour plant. Neurobehavioral core test battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to measure the lymphocyte subsets of peripheral blood. The mean air aluminum level in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral results showed that the scores of DSY, PAC and PA in Al electrolytic workers were significantly lower than those of control group, The score of POMSC, POMSF and SRT among Al exposed workers were significantly augmented in relation to those of control group. Autonomic nervous function test results showed that R-R interval variability of maximum ratio of immediately standing up in Al electrolytic workers were decreased compare with the control group, while the BP-IS, HR-V, HR-DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This study suggests that Al exposure exerts adverse effects on neurobehavioral performance, especially movement coordination and negative mood, and parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte subsets.

Organophosphorus pesticide exposure and neurobehavioral performance in Latino children living in an orchard community.

PubMed

Butler-Dawson, Jaime; Galvin, Kit; Thorne, Peter S; Rohlman, Diane S

2016-03-01

Children living in agricultural communities have a greater risk from pesticides due to para-occupational pathways. The goal of this study was to assess the impact of exposure to organophosphorus pesticides on the neurobehavioral performance of school-aged Latino children over time. Two exposure measures were used to estimate children's pesticide exposure: parent's occupation (agricultural or non-agricultural) and organophosphate residues in home carpet dust samples. During 2008-2011, 206 school-aged children completed a battery of neurobehavioral tests two times, approximately one year apart. The associations between both exposure measures and neurobehavioral performance were examined. Pesticide residues were detected in dust samples from both agricultural and non-agricultural homes, however, pesticides were detected more frequently and in higher concentrations in agricultural homes compared to non-agricultural homes. Although few differences were found between agricultural and non-agricultural children at both visits, deficits in learning from the first visit to the second visit, or less improvement, was found in agricultural children relative to non-agricultural children. These differences were significant for the Divided Attention and Purdue Pegboard tests. These findings are consistent with previous research showing deficits in motor function. A summary measure of organophosphate residues was not associated with neurobehavioral performance. Results from this study indicate that children in agricultural communities are at increased risk from pesticides as a result of a parent working in agricultural. Our findings suggest that organophosphate exposure may be associated with deficits in learning on neurobehavioral performance, particularly in tests of with motor function. In spite of regulatory phasing out of organophosphates in the U.S., we still see elevated levels and higher detection rates of several organophosphates in agricultural households than non-agricultural households, albeit lower levels than prior studies. Copyright © 2016. Published by Elsevier B.V.

Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: a cross-sectional study.

PubMed

Kiciński, Michał; Viaene, Mineke K; Den Hond, Elly; Schoeters, Greet; Covaci, Adrian; Dirtu, Alin C; Nelen, Vera; Bruckers, Liesbeth; Croes, Kim; Sioen, Isabelle; Baeyens, Willy; Van Larebeke, Nicolas; Nawrot, Tim S

2012-11-14

Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. A two-fold increase of the sum of serum PBDE's was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE's on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.

Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: a cross-sectional study

PubMed Central

2012-01-01

Background Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. Methods As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. Results A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. Conclusions This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones. PMID:23151181

Neurobehavioral Functioning and Survival Following Lung Transplantation

PubMed Central

Blumenthal, James A.; Carney, Robert M.; Freedland, Kenneth E.; O’Hayer, C. Virginia F.; Trulock, Elbert P.; Martinu, Tereza; Schwartz, Todd A.; Hoffman, Benson M.; Koch, Gary G.; Davis, R. Duane; Palmer, Scott M.

2014-01-01

Background: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. Methods: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. Results: One hundred eleven patients died over a mean follow-up of 10.8 years (SD = 0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR] = 1.09, P = .012) and memory performance (HR = 1.11, P = .030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored > 13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR = 1.85 [95% CI, 1.04, 3.28], P = .036). Conclusions: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. Trial registry: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov PMID:24233282

Psychopathology in children of schizophrenics

PubMed Central

Shah, Sharita; Kamat, Sanjeev; Sawant, Urmila; Dhavale, H.S.

2003-01-01

The higher prevalence of schizophrenia in children of schizophrenics than in the general population has generated an interest in pinpointing those behaviors that may precede the disorder and serve as an index of vulnerability to the disorder. Signs of neurobehavioral dysfunction in areas of neurocognitive functioning and social behavior have been found in school-age children of schizophrenic parents. This study assessed the neurobehavioral functioning, social behavior, cognitive functioning, attention and intelligence in children with a schizophrenic parent and compared the same parameters with children of mentally healthy parents. The children aged 12-15 years, were assessed with a battery of neurobehavioral tests. The children with a schizophrenic parent performed more poorly on the tests as compared to the children of mentally healthy parents. The children with a schizophrenic parent were seen to have more behavioral problems, especially withdrawn behavior and more social problems when compared to the other children in the study. Poor attention, disordered thoughts and lower intelligence were also observed to be more in the children of the schizophrenic parent PMID:21206831

Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results

PubMed Central

Himes, Sarah K.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Smith, Lynne M.; Arria, Amelia M.; Grotta, Sheri A. Della; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.; Huestis, Marilyn A.

2014-01-01

Background The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Methods Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results. Results A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure. Conclusions Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years. PMID:24518561

Risk of neurobehavioral disinhibition in prenatal methamphetamine-exposed young children with positive hair toxicology results.

PubMed

Himes, Sarah K; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Smith, Lynne M; Arria, Amelia M; Della Grotta, Sheri A; Dansereau, Lynne M; Abar, Beau; Neal, Charles R; Lester, Barry M; Huestis, Marilyn A

2014-08-01

The objective was to evaluate the effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa, and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child's neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared with child hair results. A total of 264 children were evaluated. Significantly more PME children (n = 133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n = 131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared with PME children without postnatal exposure. Child hair testing offered a noninvasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years.

Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring.

PubMed

Huizink, Anja C; Mulder, Eduard J H

2006-01-01

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

Distal 10q monosomy: new evidence for a neurobehavioral condition?

PubMed

Plaisancié, Julie; Bouneau, Laurence; Cances, Claude; Garnier, Christelle; Benesteau, Jacques; Leonard, Samantha; Bourrouillou, Georges; Calvas, Patrick; Vigouroux, Adeline; Julia, Sophie; Bieth, Eric

2014-01-01

Pure distal monosomy of the long arm of chromosome 10 is a rare cytogenetic abnormality. The location and size of the deletions described in this region are variable. Nevertheless, the patients share characteristic facial appearance, variable cognitive impairment and neurobehavioral manifestations. A Minimal Critical Region corresponding to a 600 kb Smallest Region of deletion Overlap (SRO) has been proposed. In this report, we describe four patients with a distal 10q26 deletion, who displayed attention-deficit/hyperactivity disorders (ADHD). One of them had a marked behavioral profile and relatively preserved cognitive functions. Interestingly, the SRO was not included in the deleted segment of this patient suggesting that this deletion could contain candidate genes involved in the control of neurobehavioral functions. One of these candidates was the CALY gene, known for its association with ADHD patients and whose expression level was shown to be correlated with neurobehavioral disturbances in varying animal models. This report emphasizes the importance of the behavioral problems as a cardinal feature of the 10q microdeletion syndrome. Haploinsufficiency of CALY could play a crucial role in the development of the behavioral troubles within these patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning.

PubMed

Shekleton, Julia A; Flynn-Evans, Erin E; Miller, Belinda; Epstein, Lawrence J; Kirsch, Douglas; Brogna, Lauren A; Burke, Liza M; Bremer, Erin; Murray, Jade M; Gehrman, Philip; Lockley, Steven W; Rajaratnam, Shantha M W

2014-01-01

Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Cross-sectional, multicenter study. Three sleep laboratories in the USA and Australia. Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). N/A. Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency.

The effect of one night's sleep deprivation on adolescent neurobehavioral performance.

PubMed

Louca, Mia; Short, Michelle A

2014-11-01

To investigate the effects of one night's sleep deprivation on neurobehavioral functioning in adolescents. Participants completed a neurobehavioral test battery measuring sustained attention, reaction speed, cognitive processing speed, sleepiness, and fatigue every 2 h during wakefulness. Baseline performance (defined as those test bouts between 09:00 and 19:00 on days 2 and 3, following two 10-h sleep opportunities) were compared to performance at the same clock time the day following total sleep deprivation. The sleep laboratory at the Centre for Sleep Research. Twelve healthy adolescents (6 male), aged 14-18 years (mean = 16.17, standard deviation = 0.83). Sustained attention, reaction speed, cognitive processing speed, and subjective sleepiness were all significantly worse following one night without sleep than following 10-h sleep opportunities (all main effects of day, P < 0.05). Sleep deprivation led to increased variability on objective performance measures. There were between-subjects differences in response to sleep loss that were task-specific, suggesting that adolescents may not only vary in terms of the degree to which they are affected by sleep loss but also the domains in which they are affected. These findings suggest that one night of total sleep deprivation has significant deleterious effects upon neurobehavioral performance and subjective sleepiness. These factors impair daytime functioning in adolescents, leaving them at greater risk of poor academic and social functioning and accidents and injuries.

Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

PubMed

Zhu, Yan; Deng, Li; Tang, Huajun; Gao, Xiaoqing; Wang, Youhua; Guo, Kan; Kong, Jiming; Yang, Chaoxian

2017-05-01

Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

CE Neuropsychological and neurobehavioral outcome following childhood arterial ischemic stroke: Attention deficits, emotional dysregulation, and executive dysfunction

PubMed Central

Liégeois, Frédérique; Eve, Megan; Ganesan, Vijeya; King, John; Murphy, Tara

2013-01-01

Objectives To investigate neuropsychological and neurobehavioral outcome in children with arterial ischemic stroke (AIS). Background Childhood stroke can have consequences on motor, cognitive, and behavioral development. We present a cross-sectional study of neuropsychological and neurobehavioral outcome at least one year poststroke in a uniquely homogeneous sample of children who had experienced AIS. Method Forty-nine children with AIS aged 6 to 18 years were recruited from a specialist clinic. Neuropsychological measures of intelligence, reading comprehension, attention, and executive function were administered. A triangulation of data collection included questionnaires completed by the children, their parents, and teachers, rating behavior, executive functions, and emotions. Key Findings Focal neuropsychological vulnerabilities in attention (response inhibition and dual attention) and executive function were found, beyond general intellectual functioning, irrespective of hemispheric side of stroke. Difficulties with emotional and behavioral regulation were also found. Consistent with an “early plasticity” hypothesis, earlier age of stroke was associated with better performance on measures of executive function. Conclusions A significant proportion of children poststroke are at long-term risk of difficulties with emotional regulation, executive function, and attention. Data also suggest that executive functions are represented in widespread networks in the developing brain and are vulnerable to unilateral injury. PMID:24028185

Vanadium Exposure-Induced Neurobehavioral Alterations among Chinese Workers

PubMed Central

Li, Hong; Zhou, Dinglun; Zhang, Qin; Feng, Chengyong; Zheng, Wei; He, Keping; Lan, Yajia

2014-01-01

Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China. A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects. A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders. The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests. The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p<0.05). Performances in the Simple Reaction Time, Digit Span, Benton Visual Retention and Pursuit Aiming were also poorer among exposed workers as compared to unexposed control workers(p<0.05). Some of these poor performances in tests were also significantly related to workers’ exposure duration. P300 latencies were longer in the exposed group than in the control (p<0.05). Longer mean reaction times and more counting errors were also found in the exposed workers (p<0.05). Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium. PMID:23500660

Patterned feeding experience for preterm infants: study protocol for a randomized controlled trial.

PubMed

Pickler, Rita H; Wetzel, Paul A; Meinzen-Derr, Jareen; Tubbs-Cooley, Heather L; Moore, Margo

2015-06-04

Neurobehavioral disabilities occur in 5-15% of preterm infants with an estimated 50-70% of very low birth weight preterm infants experiencing later dysfunction, including cognitive, behavioral, and social delays that often persist into adulthood. Factors implicated in poor neurobehavioral and developmental outcomes are hospitalization in the neonatal intensive care unit (NICU) and inconsistent caregiving patterns. Although much underlying brain damage occurs in utero or shortly after birth, neuroprotective strategies can stop lesions from progressing, particularly when these strategies are used during the most sensitive periods of neural plasticity occurring months before term age. The purpose of this randomized trial is to test the effect of a patterned feeding experience on preterm infants' neurobehavioral organization and development, cognitive function, and clinical outcomes. This trial uses an experimental, longitudinal, 2-group design with 120 preterm infants. Infants are enrolled within the first week of life and randomized to an experimental group receiving a patterned feeding experience from the first gavage feeding through discharge or to a control group receiving usual feeding care experience. The intervention involves a continuity of tactile experiences associated with feeding to train and build neuronal networks supportive of normal infant feeding experience. Primary outcomes are neurobehavioral organization as measured by Neurobehavioral Assessment of the Preterm Infant at 3 time points: the transition to oral feedings, NICU discharge, and 2 months corrected age. Secondary aims are cognitive function measured using the Bayley Scales of Infant and Toddler Development, Third Edition at 6 months corrected age, neurobehavioral development (sucking organization, feeding performance, and heart rate variability), and clinical outcomes (length of NICU stay and time to full oral feeding). The potential effects of demographic and biobehavioral factors (perinatal events and conditions of maternal or fetal/newborn origin and immunologic and genetic biomarkers) on the outcome variables will also be considered. Theoretically, the intervention provided at a critical time in neurologic system development and associated with a recurring event (feeding) should enhance neural connections that may be important for later development, particularly language and other cognitive and neurobehavioral organization skills. NCT01577615 11 April 2012.

Reliability of Neurobehavioral Assessments from Birth to Term Equivalent Age in Preterm and Term Born Infants.

PubMed

Eeles, Abbey L; Olsen, Joy E; Walsh, Jennifer M; McInnes, Emma K; Molesworth, Charlotte M L; Cheong, Jeanie L Y; Doyle, Lex W; Spittle, Alicia J

2017-02-01

Neurobehavioral assessments provide insight into the functional integrity of the developing brain and help guide early intervention for preterm (<37 weeks' gestation) infants. In the context of shorter hospital stays, clinicians often need to assess preterm infants prior to term equivalent age. Few neurobehavioral assessments used in the preterm period have established interrater reliability. To evaluate the interrater reliability of the Hammersmith Neonatal Neurological Examination (HNNE) and the NICU Network Neurobehavioral Scale (NNNS), when used both preterm and at term (>36 weeks). Thirty-five preterm infants and 11 term controls were recruited. Five assessors double-scored the HNNE and NNNS administered either preterm or at term. A one-way random effects, absolute, single-measures interclass correlation coefficient (ICC) was calculated to determine interrater reliability. Interrater reliability for the HNNE was excellent (ICC > 0.74) for optimality scores, and good (ICC 0.60-0.74) to excellent for subtotal scores, except for 'Tone Patterns' (ICC 0.54). On the NNNS, interrater reliability was predominantly excellent for all items. Interrater agreement was generally excellent at both time points. Overall, the HNNE and NNNS neurobehavioral assessments demonstrated mostly excellent interrater reliability when used prior to term and at term.

Neurobehavioral Impairments Caused by Developmental Imidacloprid Exposure in Zebrafish

PubMed Central

Crosby, Emily B.; Bailey, Jordan M.; Oliveri, Anthony N.; Levin, Edward D.

2015-01-01

BACKGROUND Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. METHODS Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4 h to 5 d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. RESULTS In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strain of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. DISCUSSION Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. PMID:25944383

Neurobehavioral Assessment from Fetus to Infant: The NICU Network Neurobehavioral Scale and the Fetal Neurobehavior Coding Scale

ERIC Educational Resources Information Center

Salisbury, Amy L.; Fallone, Melissa Duncan; Lester, Barry

2005-01-01

This review provides an overview and definition of the concept of neurobehavior in human development. Two neurobehavioral assessments used by the authors in current fetal and infant research are discussed: the NICU Network Neurobehavioral Assessment Scale and the Fetal Neurobehavior Coding System. This review will present how the two assessments…

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 (ALAD2) and Peptide Transporter 2*2 Haplotype (hPEPT2*2) Differently Influence Neurobehavior in Low-Level Lead Exposed Children

PubMed Central

Sobin, Christina; Gisel Flores-Montoya, Mayra; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2014-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1 to 11.8 years. Ninety-six percent of children had BLLs < 5.0 µg/dL. After adjusting for covariates (sex, age and mother’s level of education) and sibling exclusion (N = 252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. PMID:25514583

δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children.

PubMed

Sobin, Christina; Flores-Montoya, Mayra Gisel; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2015-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1-11.8years. Ninety-six percent of children had BLLs<5.0μg/dl. After adjusting for covariates (sex, age and mother's level of education) and sibling exclusion (N=252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Circadian Rhythms, Sleep Deprivation, and Human Performance

PubMed Central

Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

2014-01-01

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month.

PubMed

Salisbury, Amy L; O'Grady, Kevin E; Battle, Cynthia L; Wisner, Katherine L; Anderson, George M; Stroud, Laura R; Miller-Loncar, Cynthia L; Young, Marion E; Lester, Barry M

2016-02-01

The purpose of this article was to systematically compare the developmental trajectory of neurobehavior over the first postnatal month for infants with prenatal exposure to pharmacologically untreated maternal depression, selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors (collectively: SSRIs), SSRIs with concomitant benzodiazepines (SSRI plus benzodiazepine), and no maternal depression or drug treatment (no exposure). Women (N=184) were assessed at two prenatal time points to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined with a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at multiple time points across the first postnatal month. SSRI exposure was confirmed in a subset of participants with plasma SSRI levels. General linear-mixed models were used to examine group differences in neurobehavioral scores over time with adjustment for demographic variables and depression severity. Infants in the SSRI and SSRI plus benzodiazepine groups had lower motor scores and more CNS stress signs across the first postnatal month, as well as lower self-regulation and higher arousal at day 14. Infants in the depression group had low arousal throughout the newborn period. Infants in all three clinical groups had a widening gap in scores from the no-exposure group at day 30 in their response to visual and auditory stimuli while asleep and awake. Infants in the SSRI plus benzodiazepine group had the least favorable scores on the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Neonatal adaptation syndrome was not limited to the first 2 weeks postbirth. The profile of neurobehavioral development was different for SSRI exposure than depression alone. Concomitant benzodiazepine use may exacerbate adverse behavioral effects.

Neurobehavioral performance in adolescents is inversely associated with traffic exposure.

PubMed

Kicinski, Michal; Vermeir, Griet; Van Larebeke, Nicolas; Den Hond, Elly; Schoeters, Greet; Bruckers, Liesbeth; Sioen, Isabelle; Bijnens, Esmée; Roels, Harry A; Baeyens, Willy; Viaene, Mineke K; Nawrot, Tim S

2015-02-01

On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: -0.02 to -0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sleep Deprivation and Neurobehavioral Dynamics

PubMed Central

Basner, Mathias; Rao, Hengyi; Goel, Namni; Dinges, David F.

2013-01-01

Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neuromodulatory changes in brain physiology that could explain why recovery from it may require more time than from acute sleep loss. High intraclass correlations in neurobehavioral responses to sleep loss suggest that these trait-like differences are phenotypic and may include genetic components. Sleep deprivation induces changes in brain metabolism and neural activation that involve distributed networks and connectivity. PMID:23523374

Quantitative EEG Monitoring of Vigilance: Effects of Sleep Deprivation, Circadian Phase and Sympathetic Activation

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan

1999-01-01

Shuttle astronauts typically sleep only 6 to 6.5 hours per day while in orbit. This sleep loss is related to recurrent sleep cycle shifting--due to mission-dependent orbital mechanics and mission duration requirements-- and associated circadian displacement of sleep, the operational demands of space flight, noise and space motion sickness. Such sleep schedules are known to produce poor subjective sleep quality, daytime sleepiness, reduced attention, negative mood, slower reaction times, and impaired daytime alertness. Countermeasures to allow crew members to obtain an adequate amount of sleep and maintain adequate levels of neurobehavioral performance are being developed and investigated. However, it is necessary to develop methods that allow effective and attainable in-flight monitoring of vigilance to evaluate the effectiveness of these countermeasures and to detect and predict online critical decrements in alertness/performance. There is growing evidence to indicate that sleep loss and associated decrements in neurobehavioral function are reflected in the spectral composition of the electroencephalogram (EEG) during wakefulness as well as in the incidence of slow eye movements recorded by the electro-oculogram (EOG). Further-more, our preliminary data indicated that these changes in the EEG during wakefulness are more pronounced when subjects are in a supine posture, which mimics some of the physiologic effects of microgravity. Therefore, we evaluate the following hypotheses: (1) that during a 40-hour period of wakefulness (i.e., one night of total sleep deprivation) neurobehavioral function deteriorates, the incidence of slow eye-movements and EEG power density in the theta frequencies increases especially in frontal areas of the brain; (2) that the sleep deprivation induced deterioration of neurobehavioral function and changes in the incidence of slow eye movements and the spectral composition of the EEG are more pronounced when subjects are in a supine position; and (3) that based on assessment of slow-eye movements and quantitative on-line topographical analyses of EEG during wakefulness an EEG and or EOG parameter can be derived/constructed which accurately predicts changes in neurobehavioral function.

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents

PubMed Central

Lo, June C.; Lee, Su Mei; Teo, Lydia M.; Lim, Julian; Gooley, Joshua J.

2017-01-01

Abstract Study Objectives: To characterize adolescents’ neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction. Methods: Fifty-seven healthy adolescents (aged 15–19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00–06:00) and recovery (9-hr TIB for two nights per cycle; 23:00–08:00) intended to simulate the weekday sleep loss and weekend attempt to “catch up” on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day. Results: Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study. Conclusions: Adolescents’ neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend “catch-up sleep,” even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night. PMID:28364507

Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

PubMed

Crosby, Emily B; Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

2015-01-01

Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strains of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents.

PubMed

Lo, June C; Lee, Su Mei; Teo, Lydia M; Lim, Julian; Gooley, Joshua J; Chee, Michael W L

2017-02-01

To characterize adolescents' neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction. Fifty-seven healthy adolescents (aged 15-19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00-06:00) and recovery (9-hr TIB for two nights per cycle; 23:00-08:00) intended to simulate the weekday sleep loss and weekend attempt to "catch up" on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day. Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study. Adolescents' neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend "catch-up sleep," even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night. © Sleep Research Society 2016. Published by Oxford University Press [on behalf of the Sleep Research Society].

Indoor mold exposure associated with neurobehavioral and pulmonary impairment: a preliminary report.

PubMed

Kilburn, Kaye H

2003-07-01

Recently, patients who have been exposed indoors to mixed molds, spores, and mycotoxins have reported asthma, airway irritation and bleeding, dizziness, and impaired memory and concentration, all of which suggest the presence of pulmonary and neurobehavioral problems. The author evaluated whether such patients had measurable pulmonary and neurobehavioral impairments by comparing consecutive cases in a series vs. a referent group. Sixty-five consecutive outpatients exposed to mold in their respective homes in Arizona, California, and Texas were compared with 202 community subjects who had no known mold or chemical exposures. Balance, choice reaction time, color discrimination, blink reflex, visual fields, grip, hearing, problem-solving, verbal recall, perceptual motor speed, and memory were measured. Medical histories, mood states, and symptom frequencies were recorded with checklists, and spirometry was used to measure various pulmonary volumes and flows. Neurobehavioral comparisons were made after individual measurements were adjusted for age, educational attainment, and sex. Significant differences between groups were assessed by analysis of variance; a p value of less than 0.05 was used for all statistical tests. The mold-exposed group exhibited decreased function for balance, reaction time, blink-reflex latency, color discrimination, visual fields, and grip, compared with referents. The exposed group's scores were reduced for the following tests: digit-symbol substitution, peg placement, trail making, verbal recall, and picture completion. Twenty-one of 26 functions tested were abnormal. Airway obstructions were found, and vital capacities were reduced. Mood state scores and symptom frequencies were elevated. The author concluded that indoor mold exposures were associated with neurobehavioral and pulmonary impairments that likely resulted from the presence of mycotoxins, such as trichothecenes.

Assessment and evaluation of the high risk neonate: the NICU Network Neurobehavioral Scale.

PubMed

Lester, Barry M; Andreozzi-Fontaine, Lynne; Tronick, Edward; Bigsby, Rosemarie

2014-08-25

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

Placebo-Controlled Trial of Familiar Auditory Sensory Training for Acute Severe Traumatic Brain Injury: A Preliminary Report.

PubMed

Pape, Theresa Louise-Bender; Rosenow, Joshua M; Steiner, Monica; Parrish, Todd; Guernon, Ann; Harton, Brett; Patil, Vijaya; Bhaumik, Dulal K; McNamee, Shane; Walker, Matthew; Froehlich, Kathleen; Burress, Catherine; Odle, Cheryl; Wang, Xue; Herrold, Amy A; Zhao, Weihan; Reda, Domenic; Mallinson, Trudy; Conneely, Mark; Nemeth, Alexander J

2015-07-01

Sensory stimulation is often provided to persons incurring severe traumatic brain injury (TBI), but therapeutic effects are unclear. This preliminary study investigated neurobehavioral and neurophysiological effects related to sensory stimulation on global neurobehavioral functioning, arousal, and awareness. A double-blind randomized placebo-controlled trial where 15 participants in states of disordered consciousness (DOC), an average of 70 days after TBI, were provided either the Familiar Auditory Sensory Training (FAST) or Placebo of silence. Global neurobehavioral functioning was measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was measured using functional magnetic resonance imaging (fMRI). FAST (n = 8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but FAST patients had significantly (P = .049; 95% confidence interval [CI] = -1.51, -.005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed-effects models confirm CNC findings (P = .002). Treatment effect, based on CNC, is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST patients had more fMRI activation in language regions and whole brain (P values <.05) resembling healthy controls' activation. For persons with DOC 29 to 170 days after TBI, FAST resulted in CNC gains and increased neural responsivity to vocal stimuli in language regions. Clinicians should consider providing the FAST to support patient engagement in neurorehabilitation. © The Author(s) 2015.

Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.

PubMed

Eluvathingal, Thomas J; Behen, Michael E; Chugani, Harry T; Janisse, James; Bernardi, Bruno; Chakraborty, Pulak; Juhasz, Csaba; Muzik, Otto; Chugani, Diane C

2006-10-01

We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.

Perinatal supplementation with omega-3 polyunsaturated fatty acids improves sevoflurane-induced neurodegeneration and memory impairment in neonatal rats.

PubMed

Lei, Xi; Zhang, Wenting; Liu, Tengyuan; Xiao, Hongyan; Liang, Weimin; Xia, Weiliang; Zhang, Jun

2013-01-01

To investigate if perinatal Omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation can improve sevoflurane-induced neurotoxicity and cognitive impairment in neonatal rats. Female Sprague-Dawley rats (n = 3 each group) were treated with or without an n-3 PUFAs (fish oil) enriched diet from the second day of pregnancy to 14 days after parturition. The offspring rats (P7) were treated with six hours sevoflurane administration (one group without sevoflurane/prenatal n-3 PUFAs supplement as control). The 5-bromodeoxyuridine (Brdu) was injected intraperitoneally during and after sevoflurane anesthesia to assess dentate gyrus (DG) progenitor proliferation. Brain tissues were harvested and subjected to Western blot and immunohistochemistry respectively. Morris water maze spatial reference memory, fear conditioning, and Morris water maze memory consolidation were tested at P35, P63 and P70 (n = 9), respectively. Six hours 3% sevoflurane administration increased the cleaved caspase-3 in the thalamus, parietal cortex but not hippocampus of neonatal rat brain. Sevoflurane anesthesia also decreased the neuronal precursor proliferation of DG in rat hippocampus. However, perinatal n-3 PUFAs supplement could decrease the cleaved caspase-3 in the cerebral cortex of neonatal rats, and mitigate the decrease in neuronal proliferation in their hippocampus. In neurobehavioral studies, compared with control and n-3 PUFAs supplement groups, we did not find significant spatial cognitive deficit and early long-term memory impairment in sevoflurane anesthetized neonatal rats at their adulthood. However, sevoflurane could impair the immediate fear response and working memory and short-term memory. And n-3 PUFAs could improve neurocognitive function in later life after neonatal sevoflurane exposure. Our study demonstrated that neonatal exposure to prolonged sevoflurane could impair the immediate fear response, working memory and short-term memory of rats at their adulthood, which may through inducing neuronal apoptosis and decreasing neurogenesis. However, these sevoflurane-induced unfavorable neuronal effects can be mitigated by perinatal n-3 PUFAs supplementation.

The efficacy of a restart break for recycling with optimal performance depends critically on circadian timing.

PubMed

Van Dongen, Hans P A; Belenky, Gregory; Vila, Bryan J

2011-07-01

Under simulated shift-work conditions, we investigated the efficacy of a restart break for maintaining neurobehavioral functioning across consecutive duty cycles, as a function of the circadian timing of the duty periods. As part of a 14-day experiment, subjects underwent two cycles of five simulated daytime or nighttime duty days, separated by a 34-hour restart break. Cognitive functioning and high-fidelity driving simulator performance were tested 4 times per day during the two duty cycles. Lapses on a psychomotor vigilance test (PVT) served as the primary outcome variable. Selected sleep periods were recorded polysomnographically. The experiment was conducted under standardized, controlled laboratory conditions with continuous monitoring. Twenty-seven healthy adults (13 men, 14 women; aged 22-39 years) participated in the study. Subjects were randomly assigned to a nighttime duty (experimental) condition or a daytime duty (control) condition. The efficacy of the 34-hour restart break for maintaining neurobehavioral functioning from the pre-restart duty cycle to the post-restart duty cycle was compared between these two conditions. Relative to the daytime duty condition, the nighttime duty condition was associated with reduced amounts of sleep, whereas sleep latencies were shortened and slow-wave sleep appeared to be conserved. Neurobehavioral performance measures ranging from lapses of attention on the PVT to calculated fuel consumption on the driving simulators remained optimal across time of day in the daytime duty schedule, but degraded across time of night in the nighttime duty schedule. The 34-hour restart break was efficacious for maintaining PVT performance and other objective neurobehavioral functioning profiles from one duty cycle to the next in the daytime duty condition, but not in the nighttime duty condition. Subjective sleepiness did not reliably track objective neurobehavioral deficits. The 34-hour restart break was adequate for maintaining performance in the case of optimal circadian placement of sleep and duty periods (control condition) but was inadequate (and perhaps even detrimental) for maintaining performance in a simulated nighttime duty schedule (experimental condition). Current US transportation hours-of-service regulations mandate time off duty but do not consider the circadian aspects of shift scheduling. Reinforcing a recent trend of applying sleep science to inform policymaking for duty and rest times, our findings indicate that restart provisions in hours-of-service regulations could be improved by taking the circadian timing of the duty schedules into account.

Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations in coke oven workers.

PubMed

Niu, Qiao; Zhang, Hongmei; Li, Xin; Li, Meiqin

2010-07-01

To study alterations in neurobehavioral function and neurotransmitter levels in coke oven workers occupationally exposed to benzo[a]pyrene (B[a]P) and explore possible biomarkers of B[a]P neurotoxicity. 176 coke oven workers occupationally exposed to B[a]P and 48 warehouse workers (controls) were investigated by questionnaire. Emotional and cognitive function was investigated using the WHO/NCTB. B[a]P concentrations in the working environment, concentrations of monoamine and amino acid neurotransmitters, and levels of urinary 1-hydroxypyrene (1-OH-Py) were assayed by HPLC. Spectrophotometry was used to determine choline neurotransmitter concentrations. Airborne B[a]P concentrations were higher in the coke oven plant than in the controls' workplace, and 1-OH-Py levels were significantly increased in coke workers compared to controls (p=0.000). Digital span and order digital span scores indicated that learning and memory were significantly decreased in coke oven workers (p=0.006). Concentrations of norepinephrine (NE), dopamine, 5-hydroxytryptamine and homovanillic acid were lower, while levels of 5-hydroxyindoleacetic acid were higher in the exposed group compared to controls; the difference in NE was significant (p=0.000). Aspartic acid and gamma-aminobutyric acid levels were significantly decreased in coke oven workers compared to controls (p=0.004 and p=0.004). Acetylcholine (Ach) concentration was four- to fivefold greater in coke oven workers than in controls, while acetylcholine esterase (AchE) activity was significantly decreased (p=0.000 and p=0.012). Statistical analysis showed that digital span and order digital span scores were negatively correlated to Ach and positively correlated to AchE. Occupational B[a]P exposure may reduce coke oven workers' neurobehavioral function and monoamine, amino acid and choline neurotransmitter levels. Moreover, Ach and AchE correlated with neurobehavioral function; AchE has poor specificity, but Ach is a potential biomarker of B[a]P neurotoxicity in coke oven workers.

Modification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in children.

PubMed

Woods, James S; Heyer, Nicholas J; Russo, Joan E; Martin, Michael D; Pillai, Pradeep B; Farin, Federico M

2013-01-01

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that genetic variants of metallothionein (MT) that are reported to affect Hg toxicokinetics in adults would modify the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the completion of the clinical trial, we performed genotyping assays for variants of MT isoforms MT1M (rs2270837) and MT2A (rs10636) on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant interactions or independent main effects for Hg exposure and either of the MT gene variants were observed. In contrast, among boys, numerous significant interaction effects between variants of MT1M and MT2A, alone and combined, with Hg exposure were observed spanning multiple domains of neurobehavioral function. All dose-response associations between Hg exposure and test performance were restricted to boys and were in the direction of impaired performance. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with relatively common genetic variants of MT, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure. We note that because urinary Hg reflects a composite exposure index that cannot be attributed to a specific source, these findings do not support an association between Hg in dental amalgams specifically and the adverse neurobehavioral outcomes observed. © 2013.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed Central

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C.

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance. PMID:28620347

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age.

PubMed

Boucher, Olivier; Burden, Matthew J; Muckle, Gina; Saint-Amour, Dave; Ayotte, Pierre; Dewailly, Eric; Nelson, Charles A; Jacobson, Sandra W; Jacobson, Joseph L

2011-05-01

The beneficial effects of prenatal and early postnatal intakes of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. The aim of this study was to examine the relation of n-3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test-Children's Version. Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n-3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA-related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n-3 PUFA intake in utero on memory function in school-age children.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age123

PubMed Central

Boucher, Olivier; Burden, Matthew J; Muckle, Gina; Saint-Amour, Dave; Ayotte, Pierre; Dewailly, Eric; Nelson, Charles A; Jacobson, Sandra W

2011-01-01

Background: The beneficial effects of prenatal and early postnatal intakes of omega-3 (n−3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. Objective: The aim of this study was to examine the relation of n−3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. Design: In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test–Children's Version. Results: Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n−3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA–related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. Conclusion: To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n−3 PUFA intake in utero on memory function in school-age children. PMID:21389181

Impact of hospital-based environmental exposures on neurodevelopmental outcomes of preterm infants.

PubMed

Santos, Janelle; Pearce, Sarah E; Stroustrup, Annemarie

2015-04-01

Over 300,000 infants are hospitalized in a neonatal intensive care unit (NICU) in the United States annually during a developmental period critical to later neurobehavioral function. Environmental exposures during the fetal period and infancy have been shown to impact long-term neurobehavioral outcomes. This review summarizes evidence linking NICU-based environmental exposures to neurodevelopmental outcomes of children born preterm. Preterm infants experience multiple exposures important to neurodevelopment during the NICU hospitalization. The physical layout of the NICU, management of light and sound, social interactions with parents and NICU staff, and chemical exposures via medical equipment are important to long-term neurobehavioral outcomes in this highly vulnerable population. Existing research documents NICU-based exposure to neurotoxic chemicals, aberrant light, excess sound, and restricted social interaction. In total, this creates an environment of co-existing excesses (chemicals, light, sound) and deprivation (touch, speech). The full impact of these co-exposures on the long-term neurodevelopment of preterm infants has not been adequately elucidated. Research into the importance of the NICU from an environmental health perspective is in its infancy, but could provide understanding about critical modifiable factors impacting the neurobehavioral health of hundreds of thousands of children each year.

Neurobehavioral Function in School-Age Children Exposed to Manganese in Drinking Water

PubMed Central

Oulhote, Youssef; Mergler, Donna; Barbeau, Benoit; Bellinger, David C.; Bouffard, Thérèse; Brodeur, Marie-Ève; Saint-Amour, Dave; Legrand, Melissa; Sauvé, Sébastien

2014-01-01

Background: Manganese neurotoxicity is well documented in individuals occupationally exposed to airborne particulates, but few data are available on risks from drinking-water exposure. Objective: We examined associations of exposure from concentrations of manganese in water and hair with memory, attention, motor function, and parent- and teacher-reported hyperactive behaviors. Methods: We recruited 375 children and measured manganese in home tap water (MnW) and hair (MnH). We estimated manganese intake from water ingestion. Using structural equation modeling, we estimated associations between neurobehavioral functions and MnH, MnW, and manganese intake from water. We evaluated exposure–response relationships using generalized additive models. Results: After adjusting for potential confounders, a 1-SD increase in log10 MnH was associated with a significant difference of –24% (95% CI: –36, –12%) SD in memory and –25% (95% CI: –41, –9%) SD in attention. The relations between log10 MnH and poorer memory and attention were linear. A 1-SD increase in log10 MnW was associated with a significant difference of –14% (95% CI: –24, –4%) SD in memory, and this relation was nonlinear, with a steeper decline in performance at MnW > 100 μg/L. A 1-SD increase in log10 manganese intake from water was associated with a significant difference of –11% (95% CI: –21, –0.4%) SD in motor function. The relation between log10 manganese intake and poorer motor function was linear. There was no significant association between manganese exposure and hyperactivity. Conclusion: Exposure to manganese in water was associated with poorer neurobehavioral performances in children, even at low levels commonly encountered in North America. Citation: Oulhote Y, Mergler D, Barbeau B, Bellinger DC, Bouffard T, Brodeur ME, Saint-Amour D, Legrand M, Sauvé S, Bouchard MF. 2014. Neurobehavioral function in school-age children exposed to manganese in drinking water. Environ Health Perspect 122:1343–1350; http://dx.doi.org/10.1289/ehp.1307918 PMID:25260096

COMPARISON OF SCREENING APPROACHES

EPA Science Inventory

Neurobehavioral techniques have been used extensively n an ma toxicology studies because, in many Gases, such procedures are designed to evaluate neurobiological functions thought to be affected in chemical-exposed humans, e.g., changes in sensorimotor function. procedures used t...

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

PubMed Central

Kilburn, Kaye H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

Neurobehavior related to epigenetic differences in preterm infants

PubMed Central

Lester, Barry M; Marsit, Carmen J; Giarraputo, James; Hawes, Katheleen; LaGasse, Linda L; Padbury, James F

2015-01-01

Preterm birth is associated with medical problems affecting the neuroendocrine system, altering cortisol levels resulting in negative effects on newborn neurobehavior. Newborn neurobehavior is regulated by DNA methylation of NR3C1 and HSD11B2. Aim: Determine if methylation of HSD11B2 and NR3C1 is associated with neurobehavioral profiles in preterm infants. Patients & methods: Neurobehavior was measured before discharge from the hospital in 67 preterm infants. Cheek swabs were collected for DNA extraction. Results: Infants with the high-risk neurobehavioral profile showed more methylation than infants with the low-risk neurobehavioral profile at CpG3 for NR3C1 and less methylation of CpG3 for HSD11B2. Infants with these profiles were more likely to have increased methylation of NR3C1 and decreased methylation of HSD11B2 at these CpG sites. Conclusion: Preterm birth is associated with epigenetic differences in genes that regulate cortisol levels related to high-risk neurobehavioral profiles. PMID:26585459

The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

PubMed

Tsai, Song-Yen; Chou, Hung-Yi; The, Hee-Wen; Chen, Chao-Meei; Chen, Chien-Jen

2003-08-01

This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

Managing temptation in obesity treatment: a neurobehavioral model of intervention strategies

PubMed Central

Appelhans, Bradley M; French, Simone A; Pagoto, Sherry L; Sherwood, Nancy E

2015-01-01

Weight loss outcomes in lifestyle interventions for obesity are primarily a function of sustained adherence to a reduced-energy diet, and most lapses in diet adherence are precipitated by temptation from palatable food. The high nonresponse and relapse rates of lifestyle interventions suggest that current temptation management approaches may be insufficient for most participants. In this conceptual review, we discuss three neurobehavioral processes (attentional bias, temporal discounting, and the cold-hot empathy gap) that emerge during temptation and contribute to lapses in diet adherence. Characterizing the neurobehavioral profile of temptation highlights an important distinction between temptation resistance strategies aimed at overcoming temptation while it is experienced, and temptation prevention strategies that seek to avoid or minimize exposure to tempting stimuli. Many temptation resistance and temptation prevention strategies heavily rely on executive functions mediated by prefrontal systems that are prone to disruption by common occurrences such as stress, insufficient sleep, and even exposure to tempting stimuli. In contrast, commitment strategies are a set of devices that enable individuals to manage temptation by constraining their future choices, without placing heavy demands on executive functions. These concepts are synthesized in a conceptual model that categorizes temptation management approaches based on their intended effects on reward processing and degree of reliance on executive functions. We conclude by discussing the implications of our model for strengthening temptation management approaches in future lifestyle interventions, tailoring these approaches based on key individual difference variables, and suggesting high-priority topics for future research. PMID:26431681

Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI

PubMed Central

Feng, Pan; Zheng, Yong; Feng, Tingyong

2015-01-01

Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory. PMID:26576733

Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI.

PubMed

Feng, Pan; Zheng, Yong; Feng, Tingyong

2015-11-18

Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory.

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

PubMed Central

Mahadevan, Sangeetha K.; Fiorotto, Marta L.; Van den Veyver, Ignatia B.

2017-01-01

Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8–12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces food intake and energy expenditure, increases anxiety like behavior and disturbs sleep patterns but not circadian rhythm in adult male offspring. PMID:28099477

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction

PubMed Central

Feng, Pan; Zheng, Yong

2016-01-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. PMID:27013104

The Efficacy of a Restart Break for Recycling with Optimal Performance Depends Critically on Circadian Timing

PubMed Central

Van Dongen, Hans P.A.; Belenky, Gregory; Vila, Bryan J.

2011-01-01

Objectives: Under simulated shift-work conditions, we investigated the efficacy of a restart break for maintaining neurobehavioral functioning across consecutive duty cycles, as a function of the circadian timing of the duty periods. Design: As part of a 14-day experiment, subjects underwent two cycles of five simulated daytime or nighttime duty days, separated by a 34-hour restart break. Cognitive functioning and high-fidelity driving simulator performance were tested 4 times per day during the two duty cycles. Lapses on a psychomotor vigilance test (PVT) served as the primary outcome variable. Selected sleep periods were recorded polysomnographically. Setting: The experiment was conducted under standardized, controlled laboratory conditions with continuous monitoring. Participants: Twenty-seven healthy adults (13 men, 14 women; aged 22–39 years) participated in the study. Interventions: Subjects were randomly assigned to a nighttime duty (experimental) condition or a daytime duty (control) condition. The efficacy of the 34-hour restart break for maintaining neurobehavioral functioning from the pre-restart duty cycle to the post-restart duty cycle was compared between these two conditions. Results: Relative to the daytime duty condition, the nighttime duty condition was associated with reduced amounts of sleep, whereas sleep latencies were shortened and slow-wave sleep appeared to be conserved. Neurobehavioral performance measures ranging from lapses of attention on the PVT to calculated fuel consumption on the driving simulators remained optimal across time of day in the daytime duty schedule, but degraded across time of night in the nighttime duty schedule. The 34-hour restart break was efficacious for maintaining PVT performance and other objective neurobehavioral functioning profiles from one duty cycle to the next in the daytime duty condition, but not in the nighttime duty condition. Subjective sleepiness did not reliably track objective neurobehavioral deficits. Conclusions: The 34-hour restart break was adequate for maintaining performance in the case of optimal circadian placement of sleep and duty periods (control condition) but was inadequate (and perhaps even detrimental) for maintaining performance in a simulated nighttime duty schedule (experimental condition). Current US transportation hours-of-service regulations mandate time off duty but do not consider the circadian aspects of shift scheduling. Reinforcing a recent trend of applying sleep science to inform policymaking for duty and rest times, our findings indicate that restart provisions in hours-of-service regulations could be improved by taking the circadian timing of the duty schedules into account. Citation: Van Dongen HPA; Belenky G; Vila BJ. The efficacy of a restart break for recycling with optimal performance depends critically on circadian timing. SLEEP 2011;34(7):917-929. PMID:21731142

Brain imaging and behavioral outcome in traumatic brain injury.

PubMed

Bigler, E D

1996-09-01

Brain imaging studies have become an essential diagnostic assessment procedure in evaluating the effects of traumatic brain injury (TBI). Such imaging studies provide a wealth of information about structural and functional deficits following TBI. But how pathologic changes identified by brain imaging methods relate to neurobehavioral outcome is not as well known. Thus, the focus of this article is on brain imaging findings and outcome following TBI. The article starts with an overview of current research dealing with the cellular pathology associated with TBI. Understanding the cellular elements of pathology permits extrapolation to what is observed with brain imaging. Next, this article reviews the relationship of brain imaging findings to underlying pathology and how that pathology relates to neurobehavioral outcome. The brain imaging techniques of magnetic resonance imaging, computerized tomography, and single photon emission computed tomography are reviewed. Various image analysis procedures, and how such findings relate to neuropsychological testing, are discussed. The importance of brain imaging in evaluating neurobehavioral deficits following brain injury is stressed.

Familiar auditory sensory training in chronic traumatic brain injury: a case study.

PubMed

Sullivan, Emily Galassi; Guernon, Ann; Blabas, Brett; Herrold, Amy A; Pape, Theresa L-B

2018-04-01

The evaluation and treatment for patients with prolonged periods of seriously impaired consciousness following traumatic brain injury (TBI), such as a vegetative or minimally conscious state, poses considerable challenges, particularly in the chronic phases of recovery. This blinded crossover study explored the effects of familiar auditory sensory training (FAST) compared with a sham stimulation in a patient seven years post severe TBI. Baseline data were collected over 4 weeks to account for variability in status with neurobehavioral measures, including the Disorders of Consciousness scale (DOCS), Coma Near Coma scale (CNC), and Consciousness Screening Algorithm. Pre-stimulation neurophysiological assessments were completed as well, namely Brainstem Auditory Evoked Potentials (BAEP) and Somatosensory Evoked Potentials (SSEP). Results revealed that a significant improvement in the DOCS neurobehavioral findings after FAST, which was not maintained during the sham. BAEP findings also improved with maintenance of these improvements following sham stimulation as evidenced by repeat testing. The results emphasize the importance for continued evaluation and treatment of individuals in chronic states of seriously impaired consciousness with a variety of tools. Further study of auditory stimulation as a passive treatment paradigm for this population is warranted. Implications for Rehabilitation Clinicians should be equipped with treatment options to enhance neurobehavioral improvements when traditional treatment methods fail to deliver or maintain functional behavioral changes. Routine assessment is crucial to detect subtle changes in neurobehavioral function even in chronic states of disordered consciousness and determine potential preserved cognitive abilities that may not be evident due to unreliable motor responses given motoric impairments. Familiar Auditory Stimulation Training (FAST) is an ideal passive stimulation that can be supplied by families, allied health clinicians and nursing staff of all levels.

The effect of claustrum lesions on human consciousness and recovery of function.

PubMed

Chau, Aileen; Salazar, Andres M; Krueger, Frank; Cristofori, Irene; Grafman, Jordan

2015-11-01

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of methanol vapor on human neurobehavioral measures. Research report, Jul 88-Oct 90

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, M.R.; Bergman, F.J.; Cohen, H.D.

1991-01-01

Methanol may become an important alternative fuel for vehicles in the near future. The objective of the preliminary study was to determine if inhalation exposure to methanol, near the maximum concentration allowed for an eight-hour average exposure in the workplace (200 ppm), would have adverse effects on human neurobehavioral functions. Twelve healthy young men were exposed twice to filtered air and twice to 192 ppm methanol vapors for 75 minutes on different days under double-blind conditions. Twenty-two neurobehavioral and neurophysiological tests were administered before, during, and after exposure to measure visual, behavioral, reasoning, and hearing functions. Exposure to methanol producedmore » significant increases in blood and urine methanol concentration at the end of the exposure period. As expected, no changes in plasma formate were observed. Methanol exposure had no effect on the subjects' performance on most of the tests. However, some methanol-exposed subjects reported more fatigue and lack of concentration. Performance was also slightly impaired on the Sternberg memory task. There were also changes in the latency of the P200 component of the visual- and auditory-event related potential. These effects were small and did not exceed the range of results measured in filtered air-exposed subjects.« less

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction.

PubMed

Feng, Pan; Zheng, Yong; Feng, Tingyong

2016-06-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Diet-induced obesity: dopamine transporter function, impulsivity and motivation.

PubMed

Narayanaswami, V; Thompson, A C; Cassis, L A; Bardo, M T; Dwoskin, L P

2013-08-01

A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity.

Diet-induced obesity: dopamine transporter function, impulsivity and motivation

PubMed Central

Narayanaswami, V; Thompson, AC; Cassis, LA; Bardo, MT; Dwoskin, LP

2013-01-01

OBJECTIVE A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. DESIGN To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. METHODS Striatal D2-receptor density was determined by in vitro kinetic analysis of [3H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [3H]dopamine uptake, methamphetamine-evoked [3H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. RESULTS Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [3H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. CONCLUSION Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity. PMID:23164701

Functional Assays for Neurotoxicity Testing

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Functional Assays for Neurotoxicity Testing*

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Needleman, H.L.; Schell, A.; Bellinger, D.

To determine whether the effects of low-level lead exposure persist, we reexamined 132 of 270 young adults who had initially been studied as primary school-children in 1975 through 1978. In the earlier study, neurobehavioral functioning was found to be inversely related to dentin lead levels. As compared with those we restudied, the other 138 subjects had had somewhat higher lead levels on earlier analysis, as well as significantly lower IQ scores and poorer teachers' ratings of classroom behavior. When the 132 subjects were reexamined in 1988, impairment in neurobehavioral function was still found to be related to the lead contentmore » of teeth shed at the ages of six and seven. The young people with dentin lead levels greater than 20 ppm had a markedly higher risk of dropping out of high school (adjusted odds ratio, 7.4; 95 percent confidence interval, 1.4 to 40.7) and of having a reading disability (odds ratio, 5.8; 95 percent confidence interval, 1.7 to 19.7) as compared with those with dentin lead levels less than 10 ppm. Higher lead levels in childhood were also significantly associated with lower class standing in high school, increased absenteeism, lower vocabulary and grammatical-reasoning scores, poorer hand-eye coordination, longer reaction times, and slower finger tapping. No significant associations were found with the results of 10 other tests of neurobehavioral functioning. Lead levels were inversely related to self-reports of minor delinquent activity. We conclude that exposure to lead in childhood is associated with deficits in central nervous system functioning that persist into young adulthood.« less

Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV.

PubMed

Chiò, A; Ilardi, A; Cammarosano, S; Moglia, C; Montuschi, A; Calvo, A

2012-04-03

To assess the effect of neurobehavioral dysfunction on amyotrophic lateral sclerosis (ALS) survival and on the use of life-prolonging therapies in a population-based setting. Of the 132 patients diagnosed with ALS in the province of Torino, Italy, between January 1, 2007, and June 30, 2008, 128 participated in the study. Neurobehavioral dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), using the Family Rating forms, administered within 4 months from diagnosis. The 128 patients included 71 men and 57 women, with a mean age at onset of 64.7 (SD 11) years. Forty-one patients (32.0%) had a neurobehavioral dysfunction and 9 (7.0%) an isolated dysexecutive behavior. Enteral nutrition (EN) and noninvasive ventilation (NIV) were performed with similar frequencies in patients with and without neurobehavioral dysfunction. Patients with neurobehavioral dysfunction had a significantly shorter survival than those with a normal FrSBe score (median survival, 3.3 vs 4.3 years; p = 0.02). Patients with isolated dysexecutive behavior had a shorter survival than those without neurobehavioral dysfunction (median survival, 2.5 vs 4.5 years; p = 0.03). Patients with neurobehavioral dysfunction had a shorter survival after EN and NIV, while patients with isolated dysexecutive behavior had a shorter survival after NIV but not after EN. The negative effect of comorbid neurobehavioral dysfunction and of isolated dysexecutive behavior on survival persisted under the Cox multivariate model. The presence of neurobehavioral dysfunction or of isolate dysexecutive behavior in ALS at diagnosis is a strong predictor of a poor outcome, partially related to a reduced efficacy of life-prolonging therapies.

Environmental enrichment synergistically improves functional recovery by transplanted adipose stem cells in chronic hypoxic-ischemic brain injury.

PubMed

Seo, Jung Hwa; Kim, Hyongbum; Park, Eun Sook; Lee, Jong Eun; Kim, Dong Wook; Kim, Hyun Ok; Im, Sang Hee; Yu, Ji Hea; Kim, Ji Yeon; Lee, Min-Young; Kim, Chul Hoon; Cho, Sung-Rae

2013-01-01

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.

Neurobehavioral function in school-age children exposed to manganese in drinking water.

PubMed

Oulhote, Youssef; Mergler, Donna; Barbeau, Benoit; Bellinger, David C; Bouffard, Thérèse; Brodeur, Marie-Ève; Saint-Amour, Dave; Legrand, Melissa; Sauvé, Sébastien; Bouchard, Maryse F

2014-12-01

Manganese neurotoxicity is well documented in individuals occupationally exposed to airborne particulates, but few data are available on risks from drinking-water exposure. We examined associations of exposure from concentrations of manganese in water and hair with memory, attention, motor function, and parent- and teacher-reported hyperactive behaviors. We recruited 375 children and measured manganese in home tap water (MnW) and hair (MnH). We estimated manganese intake from water ingestion. Using structural equation modeling, we estimated associations between neurobehavioral functions and MnH, MnW, and manganese intake from water. We evaluated exposure-response relationships using generalized additive models. After adjusting for potential confounders, a 1-SD increase in log10 MnH was associated with a significant difference of -24% (95% CI: -36, -12%) SD in memory and -25% (95% CI: -41, -9%) SD in attention. The relations between log10 MnH and poorer memory and attention were linear. A 1-SD increase in log10 MnW was associated with a significant difference of -14% (95% CI: -24, -4%) SD in memory, and this relation was nonlinear, with a steeper decline in performance at MnW > 100 μg/L. A 1-SD increase in log10 manganese intake from water was associated with a significant difference of -11% (95% CI: -21, -0.4%) SD in motor function. The relation between log10 manganese intake and poorer motor function was linear. There was no significant association between manganese exposure and hyperactivity. Exposure to manganese in water was associated with poorer neurobehavioral performances in children, even at low levels commonly encountered in North America.

The relational neurobehavioral approach: can a non-aversive program manage adults with brain injury-related aggression without seclusion/restraint?

PubMed

Kalapatapu, Raj K; Giles, Gordon M

2017-11-01

The Relational Neurobehavioral Approach (RNA) is a set of non-aversive intervention methods to manage individuals with brain injury-related aggression. New data on interventions used in the RNA and on how the RNA interventions can be used with patients with acquired brain injury (ABI) who have differing levels of functional impairment are provided in this paper. The study was conducted over a 6-week period in a secure 65-bed program for individuals with ABI that is housed in two units of a skilled nursing facility (SNF). Implementation of the RNA was compared between two units that housed patients with differing levels of functional impairment (n = 65 adults). Since this was a hierarchical clustered dataset, Generalized Estimating Equations regression was used in the analyses. RNA interventions used to manage the 495 aggressive incidents included the following: Aggression ignored, Closer observation, Talking to patient, Reassurance, Physical distraction, Isolation without seclusion, Immediate medication by mouth, Holding patient. Different interventions were implemented differentially by staff based on level of functional impairment and without use of seclusion or mechanical restraint. The RNA can be used to non-aversively manage aggression in patients with brain injury and with differing levels of functional impairment. Programs adopting the RNA can potentially manage brain injury-related aggression without seclusion or mechanical restraint. Implications for Rehabilitation The Relational Neurobehavioral Approach (RNA) is a set of non-aversive intervention methods to manage individuals with brain injury-related aggression. RNA methods can be used to manage aggression in patients with brain injury who have differing levels of functional impairment. Successful implementation of the RNA may allow for the management of brain injury-related aggression without seclusion or mechanical restraint.

Infant Neurobehavioral Development

PubMed Central

Lester, Barry M.; Miller, Robin J.; Hawes, Katheleen; Salisbury, Amy; Bigsby, Rosemarie; Sullivan, Mary C.; Padbury, James F.

2011-01-01

The trend toward single-room neonatal intensive care units (NICUs) is increasing; however scientific evidence is, at this point, mostly anecdotal. This is a critical time to assess the impact of the single-room NICU on improving medical and neurobehavioral outcomes of the preterm infant. We have developed a theoretical model that may be useful in studying how the change from an open-bay NICU to a single-room NICU could affect infant medical and neurobehavioral outcome. The model identifies mediating factors that are likely to accompany the change to a single-room NICU. These mediating factors include family centered care, developmental care, parenting and family factors, staff behavior and attitudes, and medical practices. Medical outcomes that plan to be measured are sepsis, length of stay, gestational age at discharge, weight gain, illness severity, gestational age at enteral feeding, and necrotizing enterocolitis (NEC). Neurobehavioral outcomes include the NICU Network Neurobehavioral Scale (NNNS) scores, sleep state organization and sleep physiology, infant mother feeding interaction scores, and pain scores. Preliminary findings on the sample of 150 patients in the open-bay NICU showed a “baseline” of effects of family centered care, developmental care, parent satisfaction, maternal depression, and parenting stress on the neurobehavioral outcomes of the newborn. The single-room NICU has the potential to improve the neurobehavioral status of the infant at discharge. Neurobehavioral assessment can assist with early detection and therefore preventative intervention to maximize developmental outcome. We also present an epigenetic model of the potential effects of maternal care on improving infant neurobehavioral status. PMID:21255702

Relationship of Temporal Lobe Volumes to Neuropsychological Test Performance in Healthy Children

ERIC Educational Resources Information Center

Wells, Carolyn T.; Mahone, E. Mark; Matson, Melissa A.; Kates, Wendy R.; Hay, Trisha; Horska, Alena

2008-01-01

Ecological validity of neuropsychological assessment includes the ability of tests to predict real-world functioning and/or covary with brain structures. Studies have examined the relationship between adaptive skills and test performance, with less focus on the association between regional brain volumes and neurobehavioral function in healthy…

Neurobehavior disinhibition, parental substance use disorder, neighborhood quality and development of cannabis use disorder in boys☆

PubMed Central

Ridenour, Ty A.; Tarter, Ralph E.; Reynolds, Maureen; Mezzich, Ada; Kirisci, Levent; Vanyukov, Michael

2009-01-01

This prospective investigation examined the contribution of neighborhood context and neurobehavior disinhibition to the association between substance use disorder (SUD) in parents and cannabis use disorder in their sons. It was hypothesized that both neighborhood context and son’s neurobehavior disinhibition mediate this association. Two hundred and sixteen boys were tracked from ages 10–12 to age 22. The extent to which neighborhood context and neurobehavior disinhibition mediate the association between parental SUD and son’s cannabis use disorder was evaluated using structural equation modeling. The best fitting model positioned neighborhood context and neurobehavior disinhibition as mediators of the association between parental SUD and cannabis use disorder in sons. Neurobehavior disinhibition also was a mediator of the association between neighborhood context and son’s cannabis use. The implications of this pattern of association between parental SUD, neighborhood context and individual risk for SUD for improving prevention are discussed. PMID:19268495

Tourette Syndrome

MedlinePlus

... and arranging. People with TS have also reported problems with depression or anxiety disorders, as well as other difficulties ... possible that neurobehavioral disorders such as ADHD, OCD, depression, generalized ... with TS? Although students with TS often function well in the regular ...

No effects of power line frequency extremely low frequency electromagnetic field exposure on selected neurobehavior tests of workers inspecting transformers and distribution line stations versus controls.

PubMed

Li, Li; Xiong, De-fu; Liu, Jia-wen; Li, Zi-xin; Zeng, Guang-cheng; Li, Hua-liang

2014-03-01

We aimed to evaluate the interference of 50 Hz extremely low frequency electromagnetic field (ELF-EMF) occupational exposure on the neurobehavior tests of workers performing tour-inspection close to transformers and distribution power lines. Occupational short-term "spot" measurements were carried out. 310 inspection workers and 300 logistics staff were selected as exposure and control. The neurobehavior tests were performed through computer-based neurobehavior evaluation system, including mental arithmetic, curve coincide, simple visual reaction time, visual retention, auditory digit span and pursuit aiming. In 500 kV areas electric field intensity at 71.98% of total measured 590 spots were above 5 kV/m (national occupational standard), while in 220 kV areas electric field intensity at 15.69% of total 701 spots were above 5 kV/m. Magnetic field flux density at all the spots was below 1,000 μT (ICNIRP occupational standard). The neurobehavior score changes showed no statistical significance. Results of neurobehavior tests among different age, seniority groups showed no significant changes. Neurobehavior changes caused by daily repeated ELF-EMF exposure were not observed in the current study.

Celebrating the 125th anniversary of the American Psychological Association: A quarter century of neuropsychology.

PubMed

Brown, Gregory G; Anderson, Vicki; Bigler, Erin D; Chan, Agnes S; Fama, Rosemary; Grabowski, Thomas J; Zakzanis, Konstantine K

2017-11-01

The American Psychological Association (APA) celebrated its 125th anniversary in 2017. As part of this celebration, the APA journal Neuropsychology has published in its November 2017 issue 11 papers describing some of the advances in the field of neuropsychology over the past 25 years. The papers address three broad topics: assessment and intervention, brain imaging, and theory and methods. The papers describe the rise of new assessment and intervention technologies, the impact of evidence for neuroplasticity on neurorehabilitation. Examples of the use of mathematical models of cognition to investigate latent neurobehavioral processes, the development of the field of neuropsychology in select international countries, the increasing sophistication of brain imaging methods, the recent evidence for localizationist and connectionist accounts of neurobehavioral functioning, the advances in neurobehavioral genomics, and descriptions of newly developed statistical models of longitudinal change. Together the papers convey evidence of the vibrant growth in the field of neuropsychology over the quarter century since APA's 100th anniversary in 1992. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

PubMed

Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

2015-10-01

The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The Differential Effects of Regular Shift Work and Obstructive Sleep Apnea on Sleepiness, Mood and Neurocognitive Function.

PubMed

Cori, Jennifer M; Jackson, Melinda L; Barnes, Maree; Westlake, Justine; Emerson, Paul; Lee, Jacen; Galante, Rosa; Hayley, Amie; Wilsmore, Nicholas; Kennedy, Gerard A; Howard, Mark

2018-06-15

To assess whether poor sleep quality experienced by regular shift workers and individuals with obstructive sleep apnea (OSA) affects neurobehavioral function similarly, or whether the different etiologies have distinct patterns of impairment. Thirty-seven shift workers (> 24 hours after their last shift), 36 untreated patients with OSA, and 39 healthy controls underwent assessment of sleepiness (Epworth Sleepiness Scale [ESS]), mood (Beck Depression Index, State Trait Anxiety Inventory [STAI], Profile of Mood States), vigilance (Psychomotor Vigilance Task [PVT], Oxford Sleep Resistance Test [OSLER], driving simulation), neurocognitive function (Logical Memory, Trails Making Task, Digit Span Task, Victoria Stroop Test) and polysomnography. Sleepiness (ESS score; median, interquartile range) did not differ between the OSA (10.5, 6.3-14) and shift work (7, 5-11.5) groups, but both had significantly elevated scores relative to the control group (5, 3-6). State anxiety (STAI-S) was the only mood variable that differed significantly between the OSA (35, 29-43) and shift work (30, 24-33.5) groups, however both demonstrated several mood deficits relative to the control group. The shift work and control groups performed similarly on neurobehavioral tasks (simulated driving, PVT, OSLER and neurocognitive tests), whereas the OSA group performed worse. On the PVT, lapses were significantly greater for the OSA group (3, 2-6) than both the shift work (2, 0-3.5) and control (1, 0-4) groups. Shift workers and patients with OSA had similar sleepiness and mood deficits relative to healthy individuals. However, only the patients with OSA showed deficits on vigilance and neurocognitive function relative to healthy individuals. These findings suggest that distinct causes of sleep disturbance likely result in different patterns of neurobehavioral dysfunction. © 2018 American Academy of Sleep Medicine.

Exposure to bisphenol A affects GABAergic neuron differentiation in neurosphere cultures.

PubMed

Fukushima, Nobuyuki; Nagao, Tetsuji

2018-06-13

Endocrine-disrupting chemicals (EDCs) influence not only endocrine functions but also neuronal development and functions. In-vivo studies have suggested the relationship of EDC-induced neurobehavioral disorders with dysfunctions of neurotransmitter mechanisms including γ-aminobutyric acid (GABA)ergic mechanisms. However, whether EDCs affect GABAergic neuron differentiation remains unclear. In the present study, we show that a representative EDC, bisphenol A (BPA), affects GABAergic neuron differentiation. Cortical neurospheres prepared from embryonic mice were exposed to BPA for 7 days, and then neuronal differentiation was induced. We found that BPA exposure resulted in a decrease in the ratio of GABAergic neurons to total neurons. However, the same exposure stimulated the differentiation of neurons expressing calbindin, a calcium-binding protein observed in a subpopulation of GABAergic neurons. These findings suggested that BPA might influence the formation of an inhibitory neuronal network in developing cerebral cortex involved in the occurrence of neurobehavioral disorders.

Fetal alcohol spectrum disorders--a case-control study from India.

PubMed

Nayak, Raghavendra; Murthy, Pratima; Girimaji, Satish; Navaneetham, Jamuna

2012-02-01

Maternal alcohol abuse during pregnancy can lead to fetal neurotoxicity and fetal alcohol spectrum disorder (FASD). To compare the clinical features and neurobehavioral profiles of children exposed to alcohol during pregnancy with controls. Children exposed to alcohol in utero (n = 26) and 27-years age- and sex-matched controls were compared on FAS facial features, minor physical anomalies (MPAs), anthropometric measures, behavioral problems and intellectual functioning. MPAs were more common in cases (p = 0.001). Among FAS facial features, only philtrum smoothness varied significantly between the groups (p = 0.001). Behavioral problems (on Childhood Behavior Check List) were more pronounced (p = 0.001) and intellectual functioning significantly poorer in cases (p = 0.001) compared to controls. Children prenatally exposed to alcohol manifest several neurobehavioral problems compared to controls. Underlying malnutrition may have altered some of the clinical findings.

Potential short-term neurobehavioral alterations in children associated with a peak pesticide spray season: The Mother's Day flower harvest in Ecuador

PubMed Central

Suarez-Lopez, Jose R.; Checkoway, Harvey; Jacobs, David R.; Al-Delaimy, Wael K.; Gahagan, Sheila

2017-01-01

Background Exposures to cholinesterase inhibitor pesticides (e.g. organophosphates) have been associated with children's neurobehavioral alterations, including attention deficit and impulsivity. Animal studies have observed transient alterations in neurobehavioral performance in relation to cholinesterase inhibitor pesticide exposures; however, limited evidence exists regarding transient effects in humans. Methods We estimated the associations between neurobehavioral performance and time after Mother's Day flower harvest (the end of a heightened pesticide usage period) among 308 4-to 9-year-old children living in floricultural communities in Ecuador in 2008 who participated in the ESPINA study. Children's neurobehavior was examined once (NEPSY-II: 11 subtests covering 5 domains), between 63-100 days (SD: 10.8 days) after Mother's Day harvest (blood acetylcholinesterase activity levels can take 82 days to normalize after irreversible inhibition with organophosphates). Results The mean (SD) neurobehavioral scaled scores across domains ranged from 6.6 (2.4) to 9.9 (3.3); higher values reflect greater performance. Children examined sooner after Mother's Day had lower neurobehavioral scores than children examined later, in the domains of (score difference per 10.8 days, 95%CI): Attention/Inhibitory Control (0.38, 0.10-0.65), Visuospatial Processing (0.60, 0.25-0.95) and Sensorimotor (0.43, 0.10-0.77). Scores were higher with longer time post-harvest among girls (vs. boys) in Attention/Inhibitory Control. Conclusions Our findings, although cross-sectional, are among the first in non-worker children to suggest that a peak pesticide use period may transiently affect neurobehavioral performance, as children examined sooner after the flower harvest had lower neurobehavioral performance than children examined later. Studies assessing pre- and post-exposure measures are needed. PMID:28188819

NICU Network Neurobehavioral Profiles Predict Developmental Outcomes in a Low Risk Sample

PubMed Central

Sucharew, Heidi; Khoury, Jane C.; Xu, Yingying; Succop, Paul; Yolton, Kimberly

2012-01-01

Summary Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. In conclusion, three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations. PMID:22686386

Impact of Sleep Restriction on Neurobehavioral Functioning of Children with Attention Deficit Hyperactivity Disorder

PubMed Central

Gruber, Reut; Wiebe, Sabrina; Montecalvo, Lisa; Brunetti, Bianca; Amsel, Rhonda; Carrier, Julie

2011-01-01

Study Objectives: The objective of this study was to assess the cumulative impact of 1 hour of nightly sleep restriction over the course of 6 nights on the neurobehavioral functioning (NBF) of children with attention deficit hyperactivity disorder (ADHD) and healthy controls. Design: Following 6 nights of actigraphic monitoring of sleep to determine baseline sleep duration, children were asked to restrict sleep duration by 1 hour for 6 consecutive nights. NBF was assessed at baseline (Day 6) and following sleep manipulation (Day 12). Setting: A quiet location within their home environments. Participants: Forty-three children (11 ADHD, 32 Controls, mean age = 8.7 years, SD = 1.3) between the ages of 7 and 11 years. Interventions: NA Measurements: Sleep was monitored using actigraphy. In addition, parents were asked to complete nightly sleep logs. Sleepiness was evaluated using a questionnaire. The Conners' Continuous Performance Test (CPT) was used to assess NBF. Results: Restricted sleep led to poorer CPT scores on two-thirds of CPT outcome measures in both healthy controls and children with ADHD. The performance of children with ADHD following sleep restriction deteriorated from subclinical levels to the clinical range of inattention on two-thirds of CPT outcome measures. Conclusions: Moderate sleep restriction leads to a detectable negative impact on the NBF of children with ADHD and healthy controls, leading to a clinical level of impairment in children with ADHD. Citation: Gruber R; Wiebe S; Montecalvo L; Brunetti B; Amsel R; Carrier J. Impact of sleep restriction on neurobehavioral functioning of children with attention deficit hyperactivity disorder. SLEEP 2011;34(3):315-323. PMID:21358848

Prospective Study of Insufficient Sleep and Neurobehavioral Functioning Among School-Age Children.

PubMed

Taveras, Elsie M; Rifas-Shiman, Sheryl L; Bub, Kristen L; Gillman, Matthew W; Oken, Emily

2017-08-01

To examine associations between insufficient sleep and neurobehavioral functioning in childhood as reported by mothers and teachers. Participants were 1046 children in a prebirth cohort study. Main exposures were insufficient sleep durations at 3 time points: 6 months to 2 years, defined as sleep <11 h/d, 11 to <12 h/d (vs ≥12); 3 to 4 years, defined as sleep <10 h/d, 10 to <11 h/d (vs ≥11); and 5 to 7 years, sleep <9 h/d, 9 to <10 h/d (vs ≥10). Outcomes at age 7 years were executive function, behavior, and social-emotional functioning, assessed using the Behavioral Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ). Higher scores indicate poorer functioning. Mothers and teachers completed both instruments independently. At age 7 years, mean (SD) mother and teacher report of the BRIEF global executive composite scale were 48.3 (7.9) and 50.7 (9.4) points, respectively, and of the SDQ total difficulties score was 6.5 (4.7) and 6.2 (5.7). In multivariable models, children who slept <10 h/d at 3 to 4 years had worse maternal-reported scores for the BRIEF (2.11 points; 95% confidence interval, 0.17-4.05) and SDQ (1.91 points; 95% confidence interval, 0.78-3.05) than those with age-appropriate sleep. Children who slept <9 h/d at 5 to 7 years also had worse scores. At both ages, associations with teacher-reported results were consistent with those of mothers. Infants who slept 11 to <12 h/d had higher teacher- but not mother-reported scores. Insufficient sleep in the preschool and early school years is associated with poorer mother- and teacher-reported neurobehavioral processes in midchildhood. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Tobacco as a Reproductive and Developmental Toxicant

EPA Science Inventory

Maternal cigarette smoking has long been known to result in effects on offspring including lower birthweight and neurobehavioral effects. Continuing studies have expanded the list of adverse outcomes in offspring to include Sudden Infant Death Syndrome, impaired lung function, an...

[Assessment for effect of low level lead-exposure on neurobehavior in workers of printing house].

PubMed

Niu, Q; Dai, F; Chen, Y

1998-11-30

WHO Neurobehavioral Core Test Battery (NCTB) was conducted among 28 lead-exposed workers (mean age 24.84, SD2.85) in printing house and 46 controls (mean age 22.78, SD1.45), in order to assess whether low level lead exposure may be related to neurobehavioral dysfunction. The items of test were: 1. Profile of mood state(POMS), (2) Simple reaction time, (3) Digit span, (4) Santa Anna manual dexterity, (5) Digit simbol, (6) Benton visual retention; and Prusuit aiming test. In all the NCTB test values, there was no significant difference between two groups. Multiple stepwise regression analysis shows that exposure duration is related to neurobehavior scores. Mild lead exposure may affect neurobehavior in some degree but not significant.

Neurobehavioral effects of ambient air pollution on cognitive performance in US adults.

PubMed

Chen, Jiu-Chiuan; Schwartz, Joel

2009-03-01

In vivo animal experiments demonstrate neurotoxicity of exposures to particulate matter (PM) and ozone, but only one small epidemiological study had linked ambient air pollution with central nervous system (CNS) functions in children. To examine the neurobehavioral effects associated with long-term exposure to ambient PM and ozone in adults. We conducted a secondary analysis of the Neurobehavioral Evaluation System-2 (NES2) data (including a simple reaction time test [SRTT] measuring motor response speed to a visual stimulus; a symbol-digit substitution test [SDST] for coding ability; and a serial-digit learning test [SDLT] for attention and short-term memory) from 1764 adult participants (aged 37.5+/-10.9 years) of the Third National Health and Nutrition Examination Survey in 1988-1991. Based on ambient PM(10) (PM with aerodynamic diameter <10microm) and ozone data from the EPA Aerometric Information Retrieval System database, estimated annual exposure prior to the examination were aggregated at the centroid of each census-block group of geocoded residences, using distance-weighted averages from all monitors in the residing and adjoining counties. Generalized linear models were constructed to examine the associations, adjusting for potential confounders. In age- and sex-adjusted models, PM(10) predicted reduced CNS functions, but the association disappeared after adjustment for sociodemographic factors. There were consistent associations between ozone and reduced performance in NES2. In models adjusting for demographics, socioeconomic status, lifestyle, household and neighborhood characteristics, and cardiovascular risk factors, ozone predicted high scores in SDST and SDLT, but not in SRTT. Each 10-ppb increase in annual ozone was associated with increased SDST and SDLT scores by 0.16 (95%CI: 0.01, 0.23) and 0.56 (95%CI: 0.07, 1.05), equivalent to 3.5 and 5.3 years of aging-related decline in cognitive performance. Our study provides the first epidemiological data supporting the adverse neurobehavioral effects of ambient air pollutants in adults.

Nicotine increases fear responses and brain acetylcholinesterase activity in a context-dependent manner in zebrafish.

PubMed

Ziani, Paola R; Müller, Talise E; Stefanello, Flavia V; Fontana, Barbara D; Duarte, Tâmie; Canzian, Julia; Rosemberg, Denis B

2018-07-01

Nicotine is an alkaloid with positive effects on learning and memory processes. Exposure to conspecific alarm substance (CAS) elicits fear responses in zebrafish, but the effects of nicotine on aversive behaviors and associative learning in this species remain unclear. Here, we evaluated whether nicotine enhances contextual fear responses in zebrafish and investigated a putative involvement of brain acetylcholinesterase (AChE) in associative learning. Fish were exposed to 1 mg/L nicotine for 3 min and then kept in non-chlorinated water for 20 min. Later, animals were transferred to experimental tanks in the absence or presence of 3.5 mL/L CAS for 5 min (training session). After 24 h, fish were tested in tanks with similar or altered context in the absence of CAS (post-training session) and brain AChE activity was further assessed. At training, CAS increased freezing, erratic movements, and decreased the time spent in top area, while nicotine abolished the effects of CAS on erratic movements. Nicotine/CAS group tested in a similar context showed exacerbated freezing and reduced transitions to top area. Moreover, a decrease in distance traveled was observed in control, nicotine, and nicotine/CAS groups at post-training. Nicotine also stimulated brain AChE activity in CAS-exposed animals reintroduced in tanks with similar context. Although freezing bouts and time spent in top could serve as behavioral endpoints that reflect CAS-induced sensitization, the effects of nicotine occurred in a context-dependent manner. Collectively, our data suggest an involvement of cholinergic signaling in aversive learning, reinforcing the growing utility of zebrafish models to explore the neurobehavioral effects of nicotine in vertebrates. Copyright © 2018 Elsevier Inc. All rights reserved.

Level of NICU Quality of Developmental Care and Neurobehavioral Performance in Very Preterm Infants

PubMed Central

Del Prete, Alberto; Bellù, Roberto; Tronick, Ed; Borgatti, Renato

2012-01-01

OBJECTIVE: To examine the relation between the neurobehavior of very preterm infants and the level of NICU quality of developmental care. METHODS: The neurobehavior of 178 very preterm infants (gestational age ≤29 weeks and/or birth weight ≤1500 g) from 25 NICUs participating in a large multicenter, longitudinal study (Neonatal Adequate Care for Quality of Life, NEO-ACQUA) was examined with a standardized neurobehavioral assessment, the NICU Network Neurobehavioral Scale (NNNS). A questionnaire, the NEO-ACQUA Quality of Care Checklist was used to evaluate the level of developmental care in each of the NICUs. A factor analyses applied to NEO-ACQUA Quality of Care Checklist produced 2 main factors: (1) the infant-centered care (ICC) index, which measures parents’ involvement in the care of their infant and other developmentally oriented care interventions, and (2) the infant pain management (IPM) index, which measures the NICU approach to and the procedures used for reducing infant pain. The relations between NNNS neurobehavioral scores and the 2 indexes were evaluated. RESULTS: Infants from NICUs with high scores on the ICC evidenced higher attention and regulation, less excitability and hypotonicity, and lower stress/abstinence NNNS scores than infants from low-care units. Infants from NICUs with high scores on the IPM evidenced higher attention and arousal, lower lethargy and nonoptimal reflexes NNNS scores than preterm infants from low-scoring NICUs. CONCLUSIONS: Very preterm infant neurobehavior was associated with higher levels of developmental care both in ICC and in IPM, suggesting that these practices support better neurobehavioral stability. PMID:22492762

CORRELATIONS OF PESTICIDE-INDUCED CHOLINESTERASE INHIBITION AND MOTOR ACTIVITY CHANGES IN ADULT RATS.

EPA Science Inventory

The acute neurobehavioral effects of acetylcholinesterase-inhibiting pesticides are primarily due to overstimulation of the cholinergic system. Lowered motor activity levels represent a sensitive endpoint with which to monitor functional changes in laboratory animals exposed to ...

ANALYSES OF NEUROBEHAVIORAL SCREENING DATA: BENCHMARK DOSE ESTIMATION.

EPA Science Inventory

Analysis of neurotoxicological screening data such as those of the functional observational battery (FOB) traditionally relies on analysis of variance (ANOVA) with repeated measurements, followed by determination of a no-adverse-effect level (NOAEL). The US EPA has proposed the ...

Zebrafish larvae require specific strains of bacteria for neurobehavioral development

EPA Science Inventory

There is an increasing appreciation of the relationship between gut microbiota and nervous system development and function. We previously showed that axenic (microbe-free) larvae are hyperactive at 10 days post fertilization (dpf) relative to colonized zebrafish larvae. Interesti...

Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.

PubMed

Meyers, C A; Weitzner, M A; Valentine, A D; Levin, V A

1998-07-01

Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy. We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylphenidate. Ability to function in activities of daily living and magnetic resonance imaging (MRI) findings were also documented. Patients were assessed on 10, 20, and 30 mg of methylphenidate twice daily. Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.

The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

NASA Technical Reports Server (NTRS)

Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

2003-01-01

OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.

Prenatal Antecedents of Newborn Neurological Maturation

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2009-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24- to -38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the 1st weeks after birth were examined. Prenatal measures included fetal heart rate variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity; fetal heart rate variability and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation. PMID:20331657

CORRELATING NEUROBEHAVIORAL PERFORMANCE WITH BIOMARKERS OF ORGANOPHOSPHOROUS PESTICIDE EXPOSURE

PubMed Central

Rohlman, Diane S.; Anger, W Kent; Lein, Pamela J

2011-01-01

There is compelling evidence that adverse neurobehavioral effects are associated with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral studies of pesticide applicators, greenhouse workers, agricultural workers and farm residents exposed repeatedly over months or years to low levels of OPs reveal a relatively consistent pattern of neurobehavioral deficits. However, only two studies have demonstrated a link between neurobehavioral performance and current biomarkers of OP exposure including blood cholinesterase (ChE) activity and urinary levels of OP metabolites. A variety of reasons may explain why so few studies have reported such correlations, including differing individual and group exposure histories, differing methodologies for assessing behavior and exposure, and lack of a reliable index of exposure. Alternatively, these data may suggest that current biomarkers (ChE, urine metabolites) are neither predictive nor diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This review focuses on the evidence that neurobehavioral performance deficits are associated with occupational OP pesticide exposure and concludes that research needs to return to the basics and rigorously test the relationships between neurobehavioral performance and both current (ChE and urine metabolites) and novel (eg, inflammation and oxidative stress) biomarkers using human and animal models. The results of such studies are critically important because OP pesticides are widely and extensively used throughout the world, including situations where exposure controls and personal protective equipment are not routinely used. PMID:21182866

The role of fear-avoidance and helplessness in explaining functional disability in chronic pain: a prospective study.

PubMed

Samwel, Han J A; Kraaimaat, Floris W; Crul, Ben J P; Evers, Andrea W M

2007-01-01

Based on the fear-avoidance and helplessness models, the relative contribution of fear of pain, avoidance behavior, worrying, and helplessness were examined in relation to fluctuations in functional disability in chronic-pain patients. A cohort of 181 chronic-pain patients first completed various questionnaires and kept a 7-day pain journal during a standard 3-month waiting-list period prior to their scheduled treatment at an Interdisciplinary Pain Centre and did so again immediately preceding the intervention. At baseline, fear of pain, avoidance behavior, and helplessness all predicted functional disability after 3 months. Stepwise regression analyses showed avoidance behavior to be the strongest predictor of change in functional disability followed by helplessness, thus both ahead of fear of pain. The current findings support the roles of both fear-avoidance factors and helplessness in the functional disability in chronic-pain patients awaiting treatment but revealed a central role for avoidance behavior.

[Short- and long-term consequences of prenatal exposure to cannabis].

PubMed

Karila, L; Cazas, O; Danel, T; Reynaud, M

2006-02-01

Cannabis is one of the most commonly used drugs by pregnant women. The objective of this review of literature was to examine the association between cannabis use during pregnancy and effects upon growth, cognitive development (memory, attention, executive functions...) and behavior of newborns, children and teenagers. We searched for articles indexed in the medline database from 1970 to 2005. The following terms were used in the literature search: cannabis/marijuana, pregnancy, fetal development, newborn, prenatal exposure, neurobehavioral deficits, cognitive deficits, executive functions, cannabinoids, reproduction. Most of the articles were published in English. Cannabis use during pregnancy is related to diverse neurobehavioral and cognitive outcomes, including symptoms of inattention, impulsivity, deficits in learning and memory, and a deficiency in aspects of executive functions. It seems difficult to identify complications, such as lower birth weight, only attributable to cannabis as opposed to the multiple perinatal complications associated with tobacco smoking. In addition to alcohol and cigarettes, information should be given to women about the potentially harmful effects on fetal development, newborns, children and teenagers of smoking cannabis. Therefore, it seems necessary to develop prevention programs on this subject.

Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

PubMed

Komanapalli, Esther S; Sherchan, Prativa; Rolland, William; Khatibi, Nikan; Martin, Robert D; Applegate, Richard L; Tang, Jiping; Zhang, John H

2016-01-01

Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models.

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

PubMed

Turan, Nefize; Miller, Brandon A; Huie, J Russell; Heider, Robert A; Wang, Jun; Wali, Bushra; Yousuf, Seema; Ferguson, Adam R; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2018-02-01

Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

PubMed

Kiesswetter, Ernst; Schäper, M; Buchta, M; Schaller, K H; Rossbach, B; Kraus, T; Letzel, S

2009-11-01

This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene

PubMed Central

Vengeliene, Valentina; Bespalov, Anton; Roßmanith, Martin; Horschitz, Sandra; Berger, Stefan; Relo, Ana L.; Noori, Hamid R.; Schneider, Peggy; Enkel, Thomas; Bartsch, Dusan; Schneider, Miriam; Behl, Berthold; Hansson, Anita C.; Schloss, Patrick

2017-01-01

ABSTRACT The research domain criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity. PMID:28167616

Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene.

PubMed

Vengeliene, Valentina; Bespalov, Anton; Roßmanith, Martin; Horschitz, Sandra; Berger, Stefan; Relo, Ana L; Noori, Hamid R; Schneider, Peggy; Enkel, Thomas; Bartsch, Dusan; Schneider, Miriam; Behl, Berthold; Hansson, Anita C; Schloss, Patrick; Spanagel, Rainer

2017-04-01

The research domain criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT) gene ( Slc6a3 _N157K) to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3 _N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity. © 2017. Published by The Company of Biologists Ltd.

Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.

PubMed

Bruining, Hilgo; Matsui, Asuka; Oguro-Ando, Asami; Kahn, René S; Van't Spijker, Heleen M; Akkermans, Guus; Stiedl, Oliver; van Engeland, Herman; Koopmans, Bastijn; van Lith, Hein A; Oppelaar, Hugo; Tieland, Liselotte; Nonkes, Lourens J; Yagi, Takeshi; Kaneko, Ryosuke; Burbach, J Peter H; Yamamoto, Nobuhiko; Kas, Martien J

2015-10-01

Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development. Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology. Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed. This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

PubMed

Mink, Pamela J; Goodman, Michael; Barraj, Leila M; Imrey, Harriet; Kelsh, Michael A; Yager, Janice

2004-07-01

Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Relatively small differences (0.5 standard deviations) in confounding variables between "exposed" and "unexposed" groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3-10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables. Copyright 2004 Lippincott Williams and Wilkins

Neurobehavioral Outcomes 11 Years After Neonatal Caffeine Therapy for Apnea of Prematurity.

PubMed

Mürner-Lavanchy, Ines M; Doyle, Lex W; Schmidt, Barbara; Roberts, Robin S; Asztalos, Elizabeth V; Costantini, Lorrie; Davis, Peter G; Dewey, Deborah; D'Ilario, Judy; Grunau, Ruth E; Moddemann, Diane; Nelson, Harvey; Ohlsson, Arne; Solimano, Alfonso; Tin, Win; Anderson, Peter J

2018-05-01

Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial. Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models. Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine motor coordination (mean difference [MD] = 2.9; 95% confidence interval [CI]: 0.7 to 5.1; P = .01), visuomotor integration (MD = 1.8; 95% CI: 0.0 to 3.7; P < .05), visual perception (MD = 2.0; 95% CI: 0.3 to 3.8; P = .02), and visuospatial organization (MD = 1.2; 95% CI: 0.4 to 2.0; P = .003). Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the long-term safety of caffeine therapy for apnea of prematurity in very low birth weight neonates. Copyright © 2018 by the American Academy of Pediatrics.

Placental epigenetic patterning of glucocorticoid response genes is associated with infant neurodevelopment

PubMed Central

Paquette, Alison G; Lester, Barry M; Lesseur, Corina; Armstrong, David A; Guerin, Dylan J; Appleton, Allison A; Marsit, Carmen J

2015-01-01

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes. Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales. Using exploratory factor analysis, the relationships between methylation factor scores and neurobehavioral profiles were examined. Results: Increased scores of the factor characterized by NR3C1 methylation were associated with membership in a reactive, poorly regulated profile (odds ratio: 1.47; 95% CI: 1.00–2.18), while increased scores of the factor characterized by HSD11B2 methylation reduced this risk. Conclusion: These results suggest that coordinated regulation of these genes influences neurobehavior and demonstrates the importance of examining these alterations in a harmonized fashion. PMID:26343289

What Can Ethobehavioral Studies Tell Us About The Brain’s Fear System?

PubMed Central

Pellman, Blake A.; Kim, Jeansok J.

2016-01-01

Foraging-associated predation risk is a natural problem all prey must face. Fear evolved due to its protective functions, guiding and shaping behaviors that help animals adapt to various ecological challenges. Despite the breadth of risky situations in nature that demand diversity in fear behaviors, contemporary neurobiological models of fear stem largely from Pavlovian fear conditioning studies that focus on how a particular cue becomes capable of eliciting learned fear responses, thus oversimplifying the brain’s fear system. Here we review fear from functional, mechanistic, and phylogenetic perspectives where environmental threats cause animals to alter their foraging strategies in terms of spatial and temporal navigation, and discuss whether the inferences we draw from fear conditioning studies operate in the natural world. PMID:27130660

Symptoms of posttraumatic stress disorder and exposure to traumatic stressors are related to brain structural volumes and behavioral measures of affective stimulus processing in police officers.

PubMed

Shucard, Janet Louise; Cox, Jennifer; Shucard, David William; Fetter, Holly; Chung, Charles; Ramasamy, Deepa; Violanti, John

2012-10-30

Traumatic experiences and subsequent symptoms of posttraumatic stress disorder (PTSD) have been shown to affect brain structure and function. Although police officers are routinely exposed to traumatic events, the neurobehavioral effects of trauma in this population have rarely been studied. In this study, police officers with exposure to trauma-related stressors underwent structural magnetic resonance imaging (MRI). They also provided valence and arousal ratings of neutral and negative (trauma-related) picture stimuli. Relationships were examined among PTSD symptom scores (avoidance, reexperiencing, and hyperarousal), picture ratings, structural MRI measures, and number of trauma exposures. We hypothesized that greater PTSD symptomatology would be related to higher valence and arousal ratings of trauma-related stimuli and to decreased volume of limbic and Basal ganglia structures. Results revealed that officers with higher reexperiencing scores tended to have higher arousal ratings of negative pictures and reduced amygdala, thalamus, and globus pallidus volumes. There was a trend toward higher reexperiencing and reduced hippocampal volume. The frequency of traumatic exposures was also related to MRI measures of atrophy and to increased PTSD symptomatology. These findings suggest that chronic reexperiencing of traumatic events may result in volumetric reductions in brain structures associated with autonomic arousal and the acquisition of conditioned fear. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; And Others

1996-01-01

Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

Relationship between alertness, performance, and body temperature in humans.

PubMed

Wright, Kenneth P; Hull, Joseph T; Czeisler, Charles A

2002-12-01

Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.

Relationship between alertness, performance, and body temperature in humans

NASA Technical Reports Server (NTRS)

Wright, Kenneth P Jr; Hull, Joseph T.; Czeisler, Charles A.

2002-01-01

Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.

What is the relation between fear of falling and physical activity in older adults?

PubMed

Hornyak, Victoria; Brach, Jennifer S; Wert, David M; Hile, Elizabeth; Studenski, Stephanie; Vanswearingen, Jessie M

2013-12-01

To describe the association between fear of falling (FOF) and total daily activity in older adults. Cross-sectional observational study. Ambulatory clinical research training center. Community-dwelling older adults aged ≥64 years (N=78), who were independent in ambulation with or without an assistive device. Not applicable. FOF was defined by self-reported fear ratings using the Survey of Activities and Fear of Falling in the Elderly and self-reported fear status determined by response to the following question: Are you afraid of falling? Physical function was assessed using the Late Life Function and Disability Instrument. Physical activity was recorded using an accelerometer worn on the waist for 7 consecutive days, and mean daily counts of activity per minute were averaged over the 7-day period. Fear ratings were related to total daily activity (r=-.26, P=.02). The relation was not as strong as the relation of function and physical activity (r=.45, P<.001). When stratified by exercise status or functional status, fear was no longer related to total daily activity. Physical function explained 19% of the variance in physical activity, whereas the addition of fear status did not add to the explained variance in physical activity. FOF is related to total daily physical activity; however, FOF was not independently associated with physical activity when accounting for physical function. Some FOF may be reported as a limitation in function. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Fear and decision-making in narcissistic personality disorder-a link between psychoanalysis and neuroscience.

PubMed

Ronningstam, Elsa; Baskin-Sommers, Arielle R

2013-06-01

Linking psychoanalytic studies with neuroscience has proven increasingly productive for identifying and understanding personality functioning. This article focuses on pathological narcissism and narcissistic personality disorder (NPD), with the aim of exploring two clinically relevant aspects of narcissistic functioning also recognized in psychoanalysis: fear and decision-making. Evidence from neuroscientific studies of related conditions, such as psychopathy, suggests links between affective and cognitive functioning that can influence the sense of self-agency and narcissistic self-regulation. Attention can play a crucial role in moderating fear and self-regulatory deficits, and the interaction between experience and emotion can be central for decision-making. In this review we will explore fear as a motivating factor in narcissistic personality functioning, and the impact fear may have on decision-making in people with pathological narcissism and NPD. Understanding the processes and neurological underpinnings of fear and decision-making can potentially influence both the diagnosis and treatment of NPD.

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

PubMed Central

Panczakiewicz, Amy L.; Glass, Leila; Coles, Claire D.; Kable, Julie A.; Sowell, Elizabeth R.; Wozniak, Jeffrey R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

2016-01-01

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented, however the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure (n=192) and controls (n=215). Two age groups [child (5–7y) or adolescent (10–16y)] and both sexes were included. All subjects completed standardized neuropsychological testing and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) MANOVAs. Significant effects were followed by univariate analyses. Results No three-way or two-way interactions were significant. The main effect of group was significant in all three MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on three measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual-spatial scores and fewer somatic complaints than females. Conclusion Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for non-exposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the two age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. PMID:27430360

The neurobehavioral teratology of retinoids: a 50-year history.

PubMed

Adams, Jane

2010-10-01

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vibol, Sao; Faculty of Agricultural Technology and Management, Royal University of Agriculture, Phnom Penh; Hashim, Jamal Hisham, E-mail: jamalhas@hotmail.com

The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300–500 μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50–300 μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samplesmore » were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93 μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22 μg/g, and the control site (n=214) had a median hair As level of 0.08 μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57–4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93 µg/g among those from the highly contaminated study site, showed clear evidence of neurobehavioral effects. - Highlights: • We measured the level of arsenic concentration in school secondary school children's hair. • As contamination in groundwater is the major source effect on the neurobehavioral performance of school children. • School children in highly and moderately contaminated sites are at risk of As exposure.« less

Pediatric Out-of-Hospital Cardiac Arrest Characteristics and Their Association With Survival and Neurobehavioral Outcome.

PubMed

Meert, Kathleen L; Telford, Russell; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Dean, J Michael; Moler, Frank W

2016-12-01

To investigate relationships between cardiac arrest characteristics and survival and neurobehavioral outcome among children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial. Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data. Thirty-six PICUs in the United States and Canada. All children (n = 295) had chest compressions for greater than or equal to 2 minutes, were comatose, and required mechanical ventilation after return of circulation. Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting prearrest status) and 12 months postarrest. U.S. norms for Vineland Adaptive Behavior Scales, Second Edition scores are 100 (mean) ± 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Cardiac etiology of arrest, initial arrest rhythm of ventricular fibrillation/tachycardia, shorter duration of chest compressions, compressions not required at hospital arrival, fewer epinephrine doses, and witnessed arrest were associated with greater 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Weekend arrest was associated with lower 12-month survival. Body habitus was associated with 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70; underweight children had better outcomes, and obese children had worse outcomes. On multivariate analysis, acute life threatening event/sudden unexpected infant death, chest compressions more than 30 minutes, and weekend arrest were associated with lower 12-month survival; witnessed arrest was associated with greater 12-month survival. Acute life threatening event/sudden unexpected infant death, other respiratory causes of arrest except drowning, other/unknown causes of arrest, and compressions more than 30 minutes were associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Many factors are associated with survival and neurobehavioral outcome among children who are comatose and require mechanical ventilation after out-of-hospital cardiac arrest. These factors may be useful for identifying children at risk for poor outcomes, and for improving prevention and resuscitation strategies.

Low-level hydrogen sulfide and central nervous system dysfunction.

PubMed

Kilburn, Kaye H; Thrasher, Jack D; Gray, Michael R

2010-08-01

Forty-nine adults living in Lovington, Tatum, and Artesia, the sour gas/oil sector of Southeastern New Mexico, were tested for neurobehavioral impairment. Contributing hydrogen sulfide were (1) an anaerobic sewage plant; (2) two oil refineries; (3) natural gas/oil wells and (4) a cheese-manufacturing plant and its waste lagoons. Comparisons were to unexposed Wickenburg, Arizona, adults. Neurobehavioral functions were measured in 26 Lovington adults including 23 people from Tatum and Artesia, New Mexico, and 42 unexposed Arizona people. Participants completed questionnaires including chemical exposures, symptom frequencies and the Profile of Mood States. Measurements included balance, reaction time, color discrimination, blink reflex, visual fields, grip strength, hearing, vibration, problem solving, verbal recall, long-term memory, peg placement, trail making and fingertip number writing errors (FTNWE). Average numbers of abnormalities and test scores were adjusted for age, gender, educational level, height and weight, expressed as percent predicted (% pred) and compared by analysis of variance (ANOVA). Ages and educational attainment of the three groups were not statistically significantly different (ssd). Mean values of Lovington residents were ssd from the unexposed Arizona people for simple and choice reaction times, balance with eyes open and closed, visual field score, hearing and grip strength. Culture Fair, digit symbol substitution, vocabulary, verbal recall, peg placement, trail making A and B, FTNWE, information, picture completion and similarities were also ssd. The Lovington adults who averaged 11.8 abnormalities were ssd from, Tatum-Artesia adults who had 3.6 and from unexposed subjects with 2.0. Multiple source community hydrogen sulfide exposures impaired neurobehavioral functions.

Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice

PubMed Central

Yu, Tian; Taussig, Matthew D.; DiPatrizio, Nicholas V.; Astarita, Giuseppe; Piomelli, Daniele; Bergman, Bryan C.; Dell’Acqua, Mark L.; Eckel, Robert H.; Wang, Hong

2015-01-01

Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer’s disease. Lipoprotein lipase (LPL) hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS). Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/-) and 10 mo in heterozygous mice (NEXLPL+/-). In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid β accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n-3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation. PMID:26263173

COMPARISON OF ACUTE NEUROBEHAVIORAL AND CHOLINESTERASE INHIBITORY EFFECTS OF N-METHYL CARBAMATES IN RAT

EPA Science Inventory

There are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (R...

NEUROBEHAVIORAL ASSESSMENT USING A FUNCTIONAL OBSERVATIONAL BATTERY AND MOTOR ACTIVITY IN RATS PERINATALLY EXPOSED TO DE-71.

EPA Science Inventory

Polybrominated Diphenyl ethers (PBDEs) have been widely used as flame retardants in a variety of commercial products. Their persistence in the environment and detection in populations throughout the world has raised concern about their toxic effects. Developmental Neurotoxic ef...

Executive functions deficits impair extinction of generalization of fear of movement-related pain.

PubMed

Niederstrasser, N G; Meulders, A; Meulders, M; Struyf, D; Vlaeyen, J W

2017-05-01

Generalization of fear of movement-related pain across novel but similar movements can lead to fear responses to movements that are actually not associated with pain. The peak-shift effect describes a phenomenon whereby particular novel movements elicit even greater fear responses than the original pain-provoking movement (CS+), because they represent a more extreme version of the CS+. There is great variance in the propensity to generalize as well as the speed of extinction learning when these novel movements are not followed by pain. It can be argued that this variance may be associated with executive function capacity, as individuals may be unable to intentionally inhibit fear responses. This study examined whether executive function capacity contributes to generalization and extinction of generalization as well as peak-shift of conditioned fear of movement-related pain and expectancy. Healthy participants performed a proprioceptive fear conditioning task. Executive function tests assessing updating, switching, and inhibition were used to predict changes in (extinction of) fear of movement-related pain and pain expectancy generalization. Low inhibitory capacity was associated with slower extinction of generalized fear of movement-related pain and pain expectancy. Evidence was found in favor of an area-shift, rather than a peak-shift effect, which implies that the peak conditioned fear response extended to, but did not shift to a novel stimulus. Participants with low inhibitory capacity may have difficulties withholding fear responses, leading to a slower decrease of generalized fear over time. The findings may be relevant to inform treatments. Low inhibitory capacity is not associated with slower generalization, but extinction of fear generalization. Fear elicited by a novel safe movement, situated outside the CS+/- continuum on the CS+ side, can be as strong as to the original stimulus predicting the pain-onset. © 2017 European Pain Federation - EFIC®.

Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance.

PubMed

Gonzalez, Raul

2007-09-01

Cannabis has an ancient history of human use and is currently one of the most commonly used drugs worldwide. Understanding its impact on neurobehavioral functioning is of significant public health concern. In recent decades, substantial progress has been made in understanding the impact of cannabis use on neurobehavioral functioning. This has been fueled, in part, by characterization of an endocannabinoid signaling system in the brain through which cannabis exerts its psychoactive effects. Acute intoxication with cannabis causes marked changes in subjective mental status, brain functioning, and neuropsychological performance. Some of these changes are consistently detected and well characterized, yet others are not. Changes in brain functioning and neuropsychological performance are also reported after abstinence, but appear to be mild, circumscribed, and transient. On the other hand, functional neuroimaging often reveals subtle differences in the brain functioning of abstinent cannabis users compared with controls. The persistence and clinical significance of these differences, however, remains to be determined. Neuropsychological deficits and differences in brain functioning are most consistently observed only among frequent, heavy users, who are those most likely addicted to cannabis. The dire impact of drug addiction on a person's life and everyday functioning suggests that the large number of individuals addicted to cannabis experience substantial negative effects from its use. This manuscript reviews the scientific literature on the aforementioned topics in detail, providing evidence for converging findings, and highlighting areas in need of further investigation.

Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Melloni N.; Dunning, Jonathan P; Wiley, Ronald G

2007-01-01

We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsivenessmore » to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.« less

Current status of the scientific study of the personality disorders: an overview of epidemiological, longitudinal, experimental psychopathology, and neurobehavioral perspectives.

PubMed

Lenzenweger, Mark F

2010-08-01

Research on the nature and development of personality disorders has grown immensely over the past thirty years. A selective summary overview is given of the current status of the scientific study of the personality disorders from several perspectives, including the epidemiological, longitudinal, experimental psychopathology, and neurobehavioral perspectives. From this research, we now know that approximately 10 percent of the general population suffer from a diagnosable personality disorder. Moreover, contrary to nearly a century of theory and clinical pedagogy, modern longitudinal studies clearly suggest that personality disorders decrease in severity over time. The mechanisms by which this change occurs are not understood at present, though it is not likely that change in underlying normal personality systems drives the change in personality disorder. The methods of the experimental psychopathology laboratory, including neuroimaging approaches, are being brought to bear on the nature of personality disorders in efforts to relate neurobiological and neurocognitive functions to personality disorder symptomatology. A model that links personality disorder feature development to underlying, interacting brain-based neurobehavioral systems is reviewed in brief. Current issues and findings illustrative of these developments are given using borderline personality disorder as an exemplar. Finally, areas of intersection between psychoanalytic treatment approaches and the growing science of personality disorder are highlighted.

Reciprocal relationship between fear of falling and depression in elderly Chinese primary care patients.

PubMed

Chou, Kee-Lee; Chi, Iris

2008-09-01

The objective of the current study is to investigate the link between depression and fear of falling in Hong Kong Chinese older adults in primary are settings. Using longitudinal data collected on 321 Chinese primary care patients 65 years of age and older, the authors investigated the reciprocal relationship between fear of falling and depression and examined whether functional disability and social functioning mediated the link between fear of falling and depression. Participants were recruited from three primary care units in Hong Kong. Subjects were assessed in Cantonese by two trained assessors with Minimum Data Set-Home Care twice over a period of one year. Findings revealed that fear of falling at baseline significantly predicted depression at 12 month follow-up assessment after age, gender, marital status, education and depression at baseline were adjusted, but depression at baseline did not predict fear of falling at 12 months after fear of falling at baseline was adjusted. Moreover, social functioning mediated the impact of fear of falling on depression. The findings presented here indicate that fear of falling potentially increases the risk of depression in Chinese older adults in primary care settings.

Magnesium supplement promotes sciatic nerve regeneration and down-regulates inflammatory response.

PubMed

Pan, Hung-Chuan; Sheu, Meei-Ling; Su, Hong-Lin; Chen, Ying-Ju; Chen, Chun-Jung; Yang, Dar-Yu; Chiu, Wen-Ta; Cheng, Fu-Chou

2011-06-01

Magnesium (Mg) supplements have been shown to significantly improve functional recovery in various neurological disorders. The essential benefits of Mg supplementation in peripheral nerve disorders have not been elucidated yet. The effect and mechanism of Mg supplementation on a sciatic nerve crush injury model was investigated. Sciatic nerve injury was induced in mice by crushing the left sciatic nerve. Mice were randomly divided into three groups with low-, basal- or high-Mg diets (corresponding to 10, 100 or 200% Mg of the basal diet). Neurobehavioral, electrophysiological and regeneration marker studies were conducted to explore nerve regeneration. First, a high Mg diet significantly increased plasma and nerve tissue Mg concentrations. In addition, Mg supplementation improved neurobehavioral, electrophysiological functions, enhanced regeneration marker, and reduced deposits of inflammatory cells as well as expression of inflammatory cytokines. Furthermore, reduced Schwann cell apoptosis was in line with the significant expression of bcl-2, bcl-X(L) and down-regulated expression of active caspase-3 and cytochrome C. In summary, improved neurological function recovery and enhanced nerve regeneration were found in mice with a sciatic nerve injury that were fed a high- Mg diet, and Schwann cells may have been rescued from apoptosis by the suppression of inflammatory responses.

Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation.

PubMed

Holst, Sebastian C; Müller, Thomas; Valomon, Amandine; Seebauer, Britta; Berger, Wolfgang; Landolt, Hans-Peter

2017-04-10

Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D 2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.

Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests

NASA Astrophysics Data System (ADS)

Hienz, Robert; Davis, Catherine; Weed, Michael; Guida, Peter; Gooden, Virginia; Brady, Joseph; Roma, Peter

Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests INTRODUCTION Risk assessment of the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA radiation research. Of critical importance is the need for a risk assessment of damage to the central nervous system (CNS) leading to functional cognitive/behavioral changes during long-term space missions, and the development of effective shielding or biological countermeasures to such risks. The present research focuses on the use of an animal model that employs neurobehavioral tests identical or homologous to those currently in use in human models of risk assessment by U.S. agencies such as the Depart-ment of Defense and Federal Aviation and Federal Railroad Administrations for monitoring performance and estimating accident risks associated with such variables as fatigue and/or alcohol or drug abuse. As a first approximation for establishing human risk assessments due to exposure to space radiation, the present work provides animal performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT that is currently employed for human risk assessments via quantification of sustained attention (e.g., 'vigilance' or 'readiness to perform' tasks). Ground-based studies indicate that radiation can induce neurobehavioral changes in rodents, including impaired performance on motor tasks and deficits in spatial learning and memory. The present study is testing the hypothesis that radiation exposure impairs motor function, performance accuracy, vigilance, motivation, and memory in adult male rats. METHODS The psychomotor vigilance test (PVT) was originally developed as a human cognitive neurobe-havioral assay for tracking the temporally dynamic changes in sustained attention, and has also been used to track changes in circadian rhythm. In humans the test requires responding to a small, bright-red-light stimulus (LED-digital counter) as soon as the stimulus appears, which stops the stimulus counter and displays the reaction time for each trial in milliseconds for a 1-sec period. Simple to perform, the PVT has only very minor learning effects, is widely used in human risk assessments in operational environments, and has been recently developed and adopted for use on the ISS for astronauts as a "self test" to provide performance feedback, detect changes in alertness, prevent errors, and manage fatigue from sleep loss, circadian dis-ruption, and high workload requirements. A rodent version of the PVT, the rPVT, has been developed and demonstrated to track the same types of performance variables as the human PVT -i.e., general motor function and speed, fine motor control, inhibitory control ("impul-sivity"), timing, selective attention, motivation, and basic sensory function. Five cohorts of 16 rats each (total N = 80) were trained on the rPVT, exported to BNL for head-only radiation exposure (0, 25, 50, 100, and 200 cGy protons @ 150 MeV/n), then returned to Johns Hopkins for follow-up testing. RESULTS The rPVT was readily learned by all rats and required as little as 5-7 days of training to acquire baseline performance levels. Following irradiation, performances in the rPVT were disrupted at exposure levels of 50, 100, and 200 cGy, showing a consistent, significant increase (i.e., slowing) in reaction times and increased lapses in responding, both indicative of a decrease in sustained attention. Additionally, premature responses showed consistent increases at the higher radiation levels. None of these changes were observed in the non-exposed control animals. Over this same time period, no significant changes were observed in discrimination accuracy, motivation (as indicated by trials completed), or food intake. SUMMARY AND CONCLUSIONS The results of these experiments demonstrate the sensitivity of tests such as the rPVT for assessing the effects of head-only space radiation on cognitive neurobehavioral function. Expo-sure to protons at as little as 50 cGy produce highly specific effects on vigilance that include impaired attention and motor function (i.e., slowed reaction times, increased lapses in atten-tion, and increased premature responding). Such deficits could significantly impact routine performances in operational environments during lunar and Mars missions, and also negatively affect post-mission adjustment upon return to Earth.

Fear and decision-making in narcissistic personality disorder—a link between psychoanalysis and neuroscience

PubMed Central

Ronningstam, Elsa; Baskin-Sommers, Arielle R.

2013-01-01

Linking psychoanalytic studies with neuroscience has proven increasingly productive for identifying and understanding personality functioning. This article focuses on pathological narcissism and narcissistic personality disorder (NPD), with the aim of exploring two clinically relevant aspects of narcissistic functioning also recognized in psychoanalysis: fear and decision-making. Evidence from neuroscientific studies of related conditions, such as psychopathy, suggests links between affective and cognitive functioning that can influence the sense of self-agency and narcissistic self-regulation. Attention can play a crucial role in moderating fear and self-regulatory deficits, and the interaction between experience and emotion can be central for decision-making. In this review we will explore fear as a motivating factor in narcissistic personality functioning, and the impact fear may have on decision-making in people with pathological narcissism and NPD. Understanding the processes and neurological underpinnings of fear and decision-making can potentially influence both the diagnosis and treatment of NPD. PMID:24174893

Excitatory strength of expressive faces: effects of happy and fear expressions and context on the extinction of a conditioned fear response.

PubMed

Lanzetta, J T; Orr, S P

1986-01-01

In a recent study, Orr and Lanzetta (1984) showed that the excitatory properties of fear facial expressions previously described (Lanzetta & Orr, 1981; Orr & Lanzetta, 1980) do not depend on associative mechanisms; even in the absence of reinforcement, fear faces intensify the emotional reaction to a previously conditioned stimulus and disrupt extinction of an acquired fear response. In conjunction with the findings on acquisition, the failure to obtain extinction suggests that fear faces have some of the functional properties of "prepared" (fear-relevant) stimuli. In the present study we compared the magnitude of conditioned fear responses to happy and fear faces when a potent danger signal, the shock electrodes, are attached or unattached. If fear faces are functionally analogous to prepared stimuli, then, even in the absence of veridical support for an expectation of shock, they should retain excitatory strength, whereas happy faces should not. The results are consistent with this view of fear expressions. In the absence of reinforcement, and with shock electrodes removed, conditioned fear responses and basal levels of arousal were of greater magnitude for the fear-face condition than for the happy-face condition.

Fear of pain in the context of intensive pain rehabilitation among children and adolescents with neuropathic pain: associations with treatment response.

PubMed

Simons, Laura E; Kaczynski, Karen J; Conroy, Caitlin; Logan, Deirdre E

2012-12-01

Recent research has implicated pain-related fear in relation to functional outcomes in children with chronic pain. The current study examined fear of pain, disability, and depression within the context of an intensive pain rehabilitation program. One hundred forty-five children and adolescents who participated in an intensive interdisciplinary pediatric pain rehabilitation day program were assessed in this study. Patients completed measures of pain intensity, pain-related fears, functional disability, and depressive symptoms at admission, discharge, and on average, 2 months postdischarge. After controlling for pain intensity, pain-related fear was significantly related to disability and depressive symptoms at all time points. As predicted, a decline in pain-related fear was significantly associated with a decrease in disability and depressive symptoms. Interestingly, high levels of pain-related fears at admission predicted less reduction in functional disability and depression at discharge, suggesting that high levels of pain-related fear may be a risk factor in relation to treatment outcomes. Overall, results indicate that the relationship between fear of pain and changes in disability and depressive symptoms are closely linked, with fear of pain playing an important role in treatment. This paper presents results underscoring the importance of pain-related fear in relation to treatment response for children and adolescents with chronic pain. These findings support the need to develop and implement interventions that target reductions in pain-related fear. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

Prevalence of Neurobehavioral, Social, and Emotional Dysfunction in Patients Treated for Childhood Craniopharyngioma: A Systematic Literature Review

PubMed Central

Zada, Gabriel; Kintz, Natalie; Pulido, Mario; Amezcua, Lilyana

2013-01-01

Background Craniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas. Materials and Methods A systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in ≥10 patients were included. Results Of the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts. Conclusions Neurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders. PMID:24223703

Comparison of physical impairment, functional, and psychosocial measures based on fear of reinjury/lack of confidence and return-to-sport status after ACL reconstruction.

PubMed

Lentz, Trevor A; Zeppieri, Giorgio; George, Steven Z; Tillman, Susan M; Moser, Michael W; Farmer, Kevin W; Chmielewski, Terese L

2015-02-01

Fear of reinjury and lack of confidence influence return-to-sport outcomes after anterior cruciate ligament (ACL) reconstruction. The physical, psychosocial, and functional recovery of patients reporting fear of reinjury or lack of confidence as their primary barrier to resuming sports participation is unknown. To compare physical impairment, functional, and psychosocial measures between subgroups based on return-to-sport status and fear of reinjury/lack of confidence in the return-to-sport stage and to determine the association of physical impairment and psychosocial measures with function for each subgroup at 6 months and 1 year after surgery. Case-control study; Level of evidence, 3. Physical impairment (quadriceps index [QI], quadriceps strength/body weight [QSBW], hamstring:quadriceps strength ratio [HQ ratio], pain intensity), self-report of function (International Knee Documentation Committee [IKDC]), and psychosocial (Tampa Scale for Kinesiophobia-shortened form [TSK-11]) measures were collected at 6 months and 1 year after surgery in 73 patients with ACL reconstruction. At 1 year, subjects were divided into "return-to-sport" (YRTS) or "not return-to-sport" (NRTS) subgroups based on their self-reported return to preinjury sport status. Patients in the NRTS subgroup were subcategorized as NRTS-Fear/Confidence if fear of reinjury/lack of confidence was the primary reason for not returning to sports, and all others were categorized as NRTS-Other. A total of 46 subjects were assigned to YRTS, 13 to NRTS-Other, and 14 to NRTS-Fear/Confidence. Compared with the YRTS subgroup, the NRTS-Fear/Confidence subgroup was older and had lower QSBW, lower IKDC score, and higher TSK-11 score at 6 months and 1 year; however, they had similar pain levels. In the NRTS-Fear/Confidence subgroup, the IKDC score was associated with QSBW and pain at 6 months and QSBW, QI, pain, and TSK-11 scores at 1 year. Elevated pain-related fear of movement/reinjury, quadriceps weakness, and reduced IKDC score distinguish patients who are unable to return to preinjury sports participation because of fear of reinjury/lack of confidence. Despite low average pain ratings, fear of pain may influence function in this subgroup. Assessment of fear of reinjury, quadriceps strength, and self-reported function at 6 months may help identify patients at risk for not returning to sports at 1 year and should be considered for inclusion in return-to-sport guidelines. © 2014 The Author(s).

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

PubMed Central

Morey, R A; Dunsmoor, J E; Haswell, C C; Brown, V M; Vora, A; Weiner, J; Stjepanovic, D; Wagner, H R; Brancu, Mira; Marx, Christine E; Naylor, Jennifer C; Van Voorhees, Elizabeth; Taber, Katherine H; Beckham, Jean C; Calhoun, Patrick S; Fairbank, John A; Szabo, Steven T; LaBar, K S

2015-01-01

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma. PMID:26670285

Extinction during reconsolidation eliminates recovery of fear conditioned to fear-irrelevant and fear-relevant stimuli.

PubMed

Thompson, Alina; Lipp, Ottmar V

2017-05-01

Extant literature suggests that extinction training delivered during the memory reconsolidation period is superior to traditional extinction training in the reduction of fear recovery, as it targets the original fear memory trace. At present it is debated whether different types of fear memories are differentially sensitive to behavioral manipulations of reconsolidation. Here, we examined post-reconsolidation recovery of fear as a function of conditioned stimulus (CS) fear-relevance, using the unconditioned stimulus (US) to reactivate and destabilize conditioned fear memories. Participants (N = 56; 25 male; M = 24.39 years, SD = 7.71) in the US-reactivation and control group underwent differential fear conditioning to fear-relevant (spiders/snakes) and fear-irrelevant (geometric shapes) CSs on Day 1. On Day 2, participants received either reminded (US-reactivation) or non-reminded extinction training. Tests of fear recovery, conducted 24 h later, revealed recovery of differential electrodermal responding to both classes of CSs in the control group, but not in the US-reactivation group. These findings indicate that the US reactivation-extinction procedure eliminated recovery of extinguished responding not only to fear-irrelevant, but also to fear-relevant CSs. Contrasting previous reports, our findings show that post-reconsolidation recovery of conditioned responding is not a function of CS fear-relevance and that persistent reduction of fear, conditioned to fear-relevant CSs, can be achieved through behavioral manipulations of reconsolidation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age

PubMed Central

Graham, Alice M.; Buss, Claudia; Rasmussen, Jerod M.; Rudolph, Marc D.; Demeter, Damion V.; Gilmore, John H.; Styner, Martin; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.

2015-01-01

The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health. PMID:26499255

Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

PubMed

Mukherjee, Prerona; Whalley, Heather C; McKirdy, James W; McIntosh, Andrew M; Johnstone, Eve C; Lawrie, Stephen M; Hall, Jeremy

2011-03-31

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Effects of Maternal Alcohol Consumption and Cigarette Smoking during Pregnancy on Acoustic Cry Analysis.

ERIC Educational Resources Information Center

Nugent, J. Kevin; And Others

1996-01-01

Measured the neurobehavioral integrity of Irish infants and maternal alcohol consumption and cigarette smoking. Subjects were 127 primiparous mothers. Results demonstrated significant cry effects on infants of heavily drinking mothers, supporting the conclusion that newborn infants show functional disturbances in the nervous system resulting from…

Neurobehavioral and Neurophysiological Assessment of Healthy and "At-Risk" Full-Term Infants.

ERIC Educational Resources Information Center

Eldredge, Lynnette; Salamy, Alan

1988-01-01

Study evaluates the functioning of the central nervous system (CNS) of 15 neonates born at-risk for neurological sequelae and 15 healthy controls. CNS information was generated through the use of two measures: (1) the Neurological and Adaptive Capacity Score (NACS) and the auditory brainstem response (ABR). (Author/RWB)

Biologic and plastic effects of experimental traumatic brain injury treatment paradigms and their relevance to clinical rehabilitation

PubMed Central

Garcia, Alexandra N.; Shah, Mansi A.; Dixon, C. Edward; Wagner, Amy K.; Kline, Anthony E.

2011-01-01

Neuroplastic changes, whether induced by traumatic brain injury (TBI) or therapeutic interventions, alter neurobehavioral outcome. Here we present several treatment strategies that have been evaluated using experimental TBI models and discuss potential mechanisms of action (i.e., plasticity) and how such changes affect function. PMID:21703575

Sensory Motor and Functional Skills of Dizygotic Twins: One with Smith-Magenis Syndrome and a Twin Control

ERIC Educational Resources Information Center

Smith, Michaele R.; Hildenbrand, Hanna; Smith, Ann C. M.

2009-01-01

Smith-Magenis syndrome (SMS), the result of an interstitial deletion within chromosome 17p11.2, is a disorder that may include minor dysmorphic features, brachydactyly, short stature, hypotonia, speech delays, cognitive deficits, signs of peripheral neuropathy, scoliosis, and neurobehavioral problems including sleep disturbances and maladaptive…

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

PubMed Central

Oscar-Berman, Marlene

2013-01-01

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff’s syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking — the types of information and abilities tapped by intelligence tests — remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

Interleukin-4 Ameliorates the Functional Recovery of Intracerebral Hemorrhage Through the Alternative Activation of Microglia/Macrophage.

PubMed

Yang, Jianjing; Ding, Saidan; Huang, Weilong; Hu, Jiangnan; Huang, Shengwei; Zhang, Yu; Zhuge, Qichuan

2016-01-01

Neuro-inflammation plays an important role in the recovery of brain injury after stroke. Microglia/macrophage is the major executor in the neuro-inflammation, which can be polarized into two distinct phenotypes: injurious/toxic classical activation (M1 phenotype) and protective alternative activation (M2 phenotype). Here, we investigated whether intracerebral administration of interleukin-4 (IL-4) at an early stage could affect the activation of microglia/macrophage and the corresponding outcome after intracerebral hemorrhage (ICH). The neuro-behavior was recorded between different groups in the rat ICH model. The M1 and M2 markers were then determined by qRT-PCR, western blotting, ELISA, and immunofluorescence, respectively. We observed aberrant activation of microglia/macrophage after ICH. After intracerebral injection of IL-4, M1 activation was greatly inhibited while M2 activation was enhanced, along with improving neurobehavioral recovery from deficits after ICH. Our study showed that early intracerebral injection of IL-4 potentially promotes neuro-functional recovery, probably through enhancing the alternative activation of microglia/macrophage.

Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury

PubMed Central

Hellmich, Helen L.; Eidson, Kristine; Cowart, Jeremy; Crookshanks, Jeanna; Boone, Deborah K.; Shah, Syed; Uchida, Tatsuo; DeWitt, Douglas S.; Prough, Donald S.

2008-01-01

Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade- positive neurons in the rat hippocampus 24 hours after injury but does not improve neurobehavioral outcome (spatial memory deficits) two weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory. PMID:18556117

The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

PubMed

Yarnell, Angela M; Barry, Erin S; Mountney, Andrea; Shear, Deborah; Tortella, Frank; Grunberg, Neil E

2016-04-08

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models. Copyright © 2016 John Wiley & Sons, Inc.

Sex differences in brain and behavior in adolescence: Findings from the Philadelphia Neurodevelopmental Cohort.

PubMed

Gur, Raquel E; Gur, Ruben C

2016-11-01

Sex differences in brain and behavior were investigated across the lifespan. Parameters include neurobehavioral measures linkable to neuroanatomic and neurophysiologic indicators of brain structure and function. Sexual differentiation of behavior has been related to organizational factors during sensitive periods of development, with adolescence and puberty gaining increased attention. Adolescence is a critical developmental period where transition to adulthood is impacted by multiple factors that can enhance vulnerability to brain dysfunction. Here we highlight sex differences in neurobehavioral measures in adolescence that are linked to brain function. We summarize neuroimaging studies examining brain structure, connectivity and perfusion, underscoring the relationship to sex differences in behavioral measures and commenting on hormonal findings. We focus on relevant data from the Philadelphia Neurodevelopmental Cohort (PNC), a community-based sample of nearly 10,000 clinically and neurocognitively phenotyped youths age 8-21 of whom 1600 have received multimodal neuroimaging. These data indicate early and pervasive sexual differentiation in neurocognitive measures that is linkable to brain parameters. We conclude by describing possible clinical implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) effective for preterm infants with intrauterine growth restriction?

PubMed Central

Als, H; Duffy, FH; McAnulty, GB; Fischer, CB; Kosta, S; Butler, SC; Parad, RB; Blickman, JG; Zurakowski, D; Ringer, SA

2014-01-01

Objective This study investigates the effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) on neurobehavioral and electrophysiological functioning of preterm infants with severe intrauterine growth restriction (IUGR). Study Design Thirty IUGR infants, 28 to 33 weeks gestational age, randomized to standard care (control/C = 18), or NIDCAP (experimental/E = 12), were assessed at 2 weeks corrected age (2wCA) and 9 months corrected age (9mCA) in regard to health, anthropometrics, and neurobehavior, and additionally at 2wCA in regard to electrophysiology (EEG). Result The two groups were comparable in health and anthropometrics at 2wCA and 9mCA. The E-group at 2wCA showed significantly better autonomic, motor, and self-regulation functioning, improved motility, intensity and response thresholds, and reduced EEG connectivity among several adjacent brain regions. At 9mCA, the E-group showed significantly better mental performance. Conclusion This is the first study to show NIDCAP effectiveness for IUGR preterm infants. PMID:20651694

Sex differences in brain and behavior in adolescence: Findings from the Philadelphia Neurodevelopmental Cohort

PubMed Central

Gur, Raquel E.; Gur, Ruben C.

2016-01-01

Sex differences in brain and behavior were investigated across the lifespan. Parameters include neurobehavioral measures linkable to neuroanatomic and neurophysiologic indicators of brain structure and function. Sexual differentiation of behavior has been related to organizational factors during sensitive periods of development, with adolescence and puberty gaining increased attention. Adolescence is a critical developmental period where transition to adulthood is impacted by multiple factors that can enhance vulnerability to brain dysfunction. Here we highlight sex differences in neurobehavioral measures in adolescence that are linked to brain function. We summarize neuroimaging studies examining brain structure, connectivity and perfusion, underscoring the relationship to sex differences in behavioral measures and commenting on hormonal findings. We focus on relevant data from the Philadelphia Neurodevelopmental Cohort (PNC), a community-based sample of nearly 10,000 clinically and neurocognitively phenotyped youths age 8–21 of whom 1600 have received multimodal neuroimaging. These data indicate early and pervasive sexual differentiation in neurocognitive measures that is linkable to brain parameters. We conclude by describing possible clinical implications. PMID:27498084

Attentional Control and Fear Extinction in Subclinical Fear: An Exploratory Study

PubMed Central

Forcadell, Eduard; Torrents-Rodas, David; Treen, Devi; Fullana, Miquel A.; Tortella-Feliu, Miquel

2017-01-01

Attentional control (AC) and fear extinction learning are known to be involved in pathological anxiety. In this study we explored whether individual differences in non-emotional AC were associated with individual differences in the magnitude and gradient of fear extinction (learning and recall). In 50 individuals with fear of spiders, we collected measures of non-emotional AC by means of self-report and by assessing the functioning of the major attention networks (executive control, orienting, and alerting). The participants then underwent a paradigm assessing fear extinction learning and extinction recall. The two components of the orienting network functioning (costs and benefits) were significantly associated with fear extinction gradient over and above the effects of trait anxiety. Specifically, participants with enhanced orienting costs (i.e., difficulties in disengaging attention from cues not relevant for the task) showed faster extinction learning, while those with enhanced orienting benefits (i.e., attention facilitated by valid cues) exhibited faster extinction recall as measured by fear-potentiated startle and Unconditioned Stimulus expectancies, respectively. Our findings suggest that, in non-emotional conditions, the orienting component of attention may be predictive of fear extinction. They also show that the use of fear extinction gradients and the exploration of individual differences in non-emotional AC (using performance-based measures of attentional network functioning) can provide a better understanding of individual differences in fear learning. Our findings also may help to understand differences in exposure therapy outcomes. PMID:29018384

Genetic variation in serotonin transporter function affects human fear expression indexed by fear-potentiated startle.

PubMed

Klumpers, Floris; Heitland, Ivo; Oosting, Ronald S; Kenemans, J Leon; Baas, Johanna M P

2012-02-01

The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N=82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation. Copyright © 2011 Elsevier B.V. All rights reserved.

Hypervigilance for fear after basolateral amygdala damage in humans

PubMed Central

Terburg, D; Morgan, B E; Montoya, E R; Hooge, I T; Thornton, H B; Hariri, A R; Panksepp, J; Stein, D J; van Honk, J

2012-01-01

Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach–Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brain's threat vigilance system, which has important implications for the understanding of the amygdala's role in the disorders of fear and anxiety. PMID:22832959

Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior.

PubMed

Eppolito, Amy K; Bachus, Susan E; McDonald, Craig G; Meador-Woodruff, James H; Smith, Robert F

2010-01-01

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

PubMed

Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

2015-02-01

The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort.

PubMed

Julvez, J; Torrent, M; Guxens, M; Antó, J M; Guerra, S; Sunyer, J

2009-09-01

Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy. To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later. A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used. Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30-7.24) was associated with the lowest tertile (scorings < or =90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4. Neuropsychologic functioning and later atopy are negatively associated in preschool age children.

The relationships between pesticide metabolites and neurobehavioral test performance in the third National Health and Nutrition Examination Survey.

PubMed

Krieg, Edward F

2013-01-01

Regression analysis was used to estimate and test for relationships between urinary pesticide metabolites and neurobehavioral test performance in adults, 20 to 59 years old, participating in the third National Health and Nutrition Examination Survey. The 12 pesticide metabolites included 2 naphthols, 8 phenols, a phenoxyacetic acid, and a pyridinol. The 3 neurobehavioral tests included in the survey were simple reaction time, symbol-digit substitution, and serial digit learning. As the 2,4-dichlorophenol, 2,5-dichlorophenol, and the pentachlorophenol concentrations increased, performance on the serial digit learning test improved. As the 2,5-dichlorophenol concentration increased, performance on the symbol-digit substitution test improved. At low concentrations, the parent compounds of these metabolites may act at acetylcholine and γ-aminobutyric acid synapses in the central nervous system to improve neurobehavioral test performance.

Principal components analysis of the Neurobehavioral Symptom Inventory in a nonclinical civilian sample.

PubMed

Sullivan, Karen A; Lurie, Janine K

2017-01-01

The study examined the component structure of the Neurobehavioral Symptom Inventory (NSI) under five different models. The evaluated models comprised the full NSI (NSI-22) and the NSI-20 (NSI minus two orphan items). A civilian nonclinical sample was used. The 575 volunteers were predominantly university students who screened negative for mild TBI. The study design was cross-sectional, with questionnaires administered online. The main measure was the Neurobehavioral Symptom Inventory. Subscale, total and embedded validity scores were derived (the Validity-10, the LOW6, and the NIM5). In both models, the principal components analysis yielded two intercorrelated components (psychological and somatic/sensory) with acceptable internal consistency (alphas > 0.80). In this civilian nonclinical sample, the NSI had two underlying components. These components represent psychological and somatic/sensory neurobehavioral symptoms.

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders.

PubMed

Chang, Yongmin; Kim, Yangho; Woo, Seung-Tae; Song, Hui-Jin; Kim, Suk Hwan; Lee, Hun; Kwon, Young Joo; Ahn, Joon-Ho; Park, Sin-Jae; Chung, In-Sung; Jeong, Kyoung Sook

2009-07-01

The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.

Effects of neurobehavioral assessment on feeding and weight gain in preterm neonates.

PubMed

Senn, Theresa E; Espy, Kimberly Andrews

2003-04-01

Neonatal intensive care unit personnel and parents often are concerned that developmental assessment will tire preterm neonates and impair their feeding ability and subsequent weight gain. Therefore, the amount of fluid consumed by 108 preterm neonates (

Neurobehavioral presentations of brain neoplasms.

PubMed Central

Filley, C M; Kleinschmidt-DeMasters, B K

1995-01-01

We studied 8 patients with frontal or temporolimbic neoplasms who had psychiatric presentations to clarify diagnostic criteria for distinguishing psychiatric disease from structural brain lesions and to examine brain-behavior relationships associated with cerebral neoplasms using modern neuroimaging techniques. Medical records were retrospectively reviewed for evidence of neurobehavioral and neurologic manifestations, tumor histologic features, and the results of treatment. Clinical presentations were correlated with tumor location as determined by computed tomography and magnetic resonance imaging. Patients with frontal lobe tumors presented with abulia, personality change, or depression, whereas those with temporolimbic tumors had auditory and visual hallucinations, mania, panic attacks, or amnesia. After treatment, neurobehavioral syndromes abated or resolved in 7 of 8 patients. We recommend that any patient 40 years of age or older with a change in mental state, cognitive or emotional, should have neuroimaging of the brain. Any patient with a psychiatric presentation who has specific neurobehavioral or neurologic findings or an unexpectedly poor response to psychopharmacologic treatment should also have brain imaging. These case reports extend and update observations on the importance of frontal and temporolimbic systems in the pathogenesis of neurobehavioral disorders. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. PMID:7667978

SPIDER OR NO SPIDER? NEURAL CORRELATES OF SUSTAINED AND PHASIC FEAR IN SPIDER PHOBIA.

PubMed

Münsterkötter, Anna Luisa; Notzon, Swantje; Redlich, Ronny; Grotegerd, Dominik; Dohm, Katharina; Arolt, Volker; Kugel, Harald; Zwanzger, Peter; Dannlowski, Udo

2015-09-01

Processes of phasic fear responses to threatening stimuli are thought to be distinct from sustained, anticipatory anxiety toward an unpredicted, potential threat. There is evidence for dissociable neural correlates of phasic fear and sustained anxiety. Whereas increased amygdala activity has been associated with phasic fear, sustained anxiety has been linked with activation of the bed nucleus of stria terminalis (BNST), anterior cingulate cortex (ACC), and the insula. So far, only a few studies have focused on the dissociation of neural processes related to both phasic and sustained fear in specific phobia. We suggested that first, conditions of phasic and sustained fear would involve different neural networks and, second, that overall neural activity would be enhanced in a sample of phobic compared to nonphobic participants. Pictures of spiders and neutral stimuli under conditions of either predicted (phasic) or unpredicted (sustained) fear were presented to 28 subjects with spider phobia and 28 nonphobic control subjects during functional magnetic resonance imaging (fMRI) scanning. Phobic patients revealed significantly higher amygdala activation than controls under conditions of phasic fear. Sustained fear processing was significantly related to activation in the insula and ACC, and phobic patients showed a stronger activation than controls of the BNST and the right ACC under conditions of sustained fear. Functional connectivity analysis revealed enhanced connectivity of the BNST and the amygdala in phobic subjects. Our findings support the idea of distinct neural correlates of phasic and sustained fear processes. Increased neural activity and functional connectivity in these networks might be crucial for the development and maintenance of anxiety disorders. © 2015 Wiley Periodicals, Inc.

Fear extinction, persistent disruptive behavior and psychopathic traits: fMRI in late adolescence.

PubMed

Cohn, Moran D; van Lith, Koen; Kindt, Merel; Pape, Louise E; Doreleijers, Theo A H; van den Brink, Wim; Veltman, Dick J; Popma, Arne

2016-07-01

Children diagnosed with a Disruptive Behavior Disorder (DBD, i.e. Oppositional Defiant Disorder or Conduct Disorder), especially those with psychopathic traits, are at risk of developing persistent and severe antisocial behavior. Reduced fear conditioning has been proposed to underlie persistent antisocial development. However, we have recently shown that both DBD persisters and desisters are characterized by increased fear conditioning compared with healthy controls (HCs). In this study, we investigated whether brain function during fear extinction is associated with DBD subgroup-membership and psychopathic traits. Adolescents from a childhood arrestee cohort (mean age 17.6 years, s.d. 1.4) who met criteria for a DBD diagnosis during previous assessments were re-assessed and categorized as persistent DBD (n = 25) or desistent DBD (n = 25). Functional MRI during the extinction phase of a classical fear-conditioning task was used to compare regional brain function between these subgroups and 25 matched controls. Both DBD persisters and desisters showed hyperreactivity during fear extinction, when compared with HCs. Impulsive-irresponsible psychopathic traits were positively associated with responses in the fear neurocircuitry and mediated the association between neural activation and group membership. These results suggest that fear acquisition and fear extinction deficits may provide an endophenotype for an emotionally hyperreactive subtype of antisocial development. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Fear and disgust in women: Differentiation of cardiovascular regulation patterns.

PubMed

Comtesse, Hannah; Stemmler, Gerhard

2017-02-01

Both fear and disgust facilitate avoidance of threat. From a functional view, however, cardiovascular responses to fear and disgust should differ as they prepare for appropriate behavior to protect from injury and infection, respectively. Therefore, we examined the cardiovascular responses to fear and contamination-related disgust in comparison to an emotionally neutral state induced with auditory scripts and film clips in female participants. Ten emotion and motivation self-reports and ninecardiovascular response factors derived from 23 cardiovascular variables served as dependent variables. Self-reports confirmed the specific induction of fear and disgust. In addition, fear and disgust differed in their cardiovascular response patterning. For fear, we observed specific increases in factors indicating vasoconstriction and cardiac pump function. For disgust, we found specific increases in vagal cardiac control and decreases in myocardial contractility. These findings provide support for the cardiovascular specificity of fear and disgust and are discussed in terms of a basic emotions approach. Copyright © 2016. Published by Elsevier B.V.

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure.

PubMed

Panczakiewicz, Amy L; Glass, Leila; Coles, Claire D; Kable, Julie A; Sowell, Elizabeth R; Wozniak, Jeffrey R; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2016-09-01

Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Subjects were 407 youth with prenatal alcohol exposure (n = 192) and controls (n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. Copyright © 2016 by the Research Society on Alcoholism.

Exercise training improves selected aspects of daytime functioning in adults with obstructive sleep apnea.

PubMed

Kline, Christopher E; Ewing, Gary B; Burch, James B; Blair, Steven N; Durstine, J Larry; Davis, J Mark; Youngstedt, Shawn D

2012-08-15

To explore the utility of exercise training for improving daytime functioning in adults with obstructive sleep apnea (OSA). Forty-three sedentary and overweight/obese adults aged 18-55 years with at least moderate-severity untreated OSA (apnea-hypopnea index ≥ 15) were randomized to 12 weeks of moderate-intensity aerobic and resistance exercise training (n = 27) or low-intensity stretching control treatment (n = 16). As part of a trial investigating the efficacy of exercise training on OSA severity, daytime functioning was assessed before and following the intervention. Sleepiness, functional impairment due to sleepiness, depressive symptoms, mood, and quality of life (QOL) were evaluated with validated questionnaires, and cognitive function was assessed with a neurobehavioral performance battery. OSA severity was measured with one night of laboratory polysomnography before and following the intervention. Compared with stretching control, exercise training resulted in significant improvements in depressive symptoms, fatigue and vigor, and aspects of QOL (p < 0.05). Sleepiness and functional impairment due to sleepiness also were improved following exercise versus control to a similar degree in terms of effect sizes (d > 0.5), though these changes were not statistically significant. No neurobehavioral performance improvements were found. Reduced fatigue following exercise training was mediated by a reduction in OSA severity, but changes in OSA severity did not significantly mediate improvement in any other measure of daytime functioning. These data provide preliminary evidence that exercise training may be helpful for improving aspects of daytime functioning of adults with OSA. Larger trials are needed to further verify the observed improvements.

Parent-rated emotional-behavioral and executive functioning in childhood epilepsy.

PubMed

Kavanaugh, Brian C; Scarborough, Vanessa Ramos; Salorio, Cynthia F

2015-01-01

The present study examined clinical and demographic risk factors associated with parent-rated emotional-behavioral and executive functioning in children and adolescents with epilepsy. The medical records of 152 children and adolescents with epilepsy referred for neuropsychological evaluation were reviewed. Results indicated that the sample displayed significantly elevated symptoms across the emotional-behavioral and executive domains assessed. Executive functioning and behavioral symptoms had the highest rates of clinically elevated scores, with lowest rates of elevated scores in internalizing and externalizing emotional problems. Only 34% of those participants with clinically significant emotional-behavioral or executive functioning difficulties had a history of psychological or counseling services, highlighting the underserved mental health needs of this population. In regard to clinical factors, the majority of seizure-related variables were not associated with emotional-behavioral or executive functioning. However, the frequency of seizures (i.e., seizure status) was associated with behavioral regulation aspects of executive functioning, and the age at evaluation was associated with externalizing problems and behavioral symptoms. Family psychiatric history (with the exception of ADHD) was associated with all domains of executive and emotional-behavioral functioning. In summary, emotional-behavioral and executive functioning difficulties frequently co-occur with seizures in childhood epilepsy, with both seizure-related and demographic factors contributing to the presentation of such neurobehavioral comorbidities. The present findings provide treatment providers of childhood epilepsy with important information to assist in better identifying children and adolescents who may be at risk for neurobehavioral comorbidities and may benefit from intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significantmore » changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.« less

Cerebral oxygenation in patients undergoing shoulder surgery in beach chair position: comparing general to regional anesthesia and the impact on neurobehavioral outcome.

PubMed

Aguirre, J; Borgeat, A; Trachsel, T; Cobo Del Prado, I; De Andrés, J; Bühler, P

2014-02-01

Ischemic brain damage has been reported in healthy patients after beach chair position for surgery due to cerebral hypoperfusion. Near-infrared spectroscopy has been described as a non-invasive, continuous method to monitor cerebral oxygen saturation. However, its impact on neurobehavioral outcome comparing different anesthesia regimens has been poorly described. In this prospective, assessor-blinded study, 90 patients undergoing shoulder surgery in beach chair position following general (G-group, n=45) or regional anesthesia (R-group; n=45) were enrolled to assess the prevalence of cerebral desaturation events comparing anesthesia regimens and their impact on neurobehavioral and neurological outcome. Anesthesiologists were blinded to regional cerebral oxygen saturation values. Baseline data assessed the day before surgery included neurological and neurobehavioral tests, which were repeated the day after surgery. The baseline data for regional cerebral oxygen saturation/bispectral index and invasive blood pressure both at heart and auditory meatus levels were taken prior to anesthesia, 5 min after induction of anesthesia, 5 min after beach chair positioning, after skin incision and thereafter all 20 min until discharge. Patients in the R-group showed significantly less cerebral desaturation events (p<0.001), drops in regional cerebral oxygen saturation values (p<0.001), significantly better neurobehavioral test results the day after surgery (p<0.001) and showed a greater hemodynamic stability in the beach chair position compared to patients in the G-group. The incidence of regional cerebral oxygen desaturations seems to influence the neurobehavioral outcome. Regional anesthesia offers more stable cardiovascular conditions for shoulder surgery in beach chair position influencing neurobehavioral test results at 24h. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Modification of neurobehavioral effects of mercury by a genetic polymorphism of coproporphyrinogen oxidase in children.

PubMed

Woods, James S; Heyer, Nicholas J; Echeverria, Diana; Russo, Joan E; Martin, Michael D; Bernardo, Mario F; Luis, Henrique S; Vaz, Lurdes; Farin, Federico M

2012-01-01

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

A population-based study on phobic fears and DSM-IV specific phobia in 70-year olds.

PubMed

Sigström, Robert; Östling, Svante; Karlsson, Björn; Waern, Margda; Gustafson, Deborah; Skoog, Ingmar

2011-01-01

This population-based study reports on the prevalence and characteristics of specific phobia (SP) and phobic fears in an elderly population. A representative population sample of Swedish 70-year-olds without dementia (N = 558) was examined using semi-structured interviews. Phobic fears included fear of animals, natural environment, specific situations, blood-injection-injury and 'other'. Mental disorders, including SP, were diagnosed according to DSM-IV. Phobic fears (71.0% vs. 37.9%) and SP (13.8% vs. 4.5%) were more common in women than in men. Among those with phobic fears, more than 80% reported onset before age 21. Of those with SP, 35.7% had another DSM-IV diagnosis compared to 8.5% of those reporting no fear. Fear of specific situations and 'other' fears were related to SP and other anxiety disorders. SP was related to lower global functioning. We conclude that specific phobia in the elderly should receive attention from health professionals as it is common and associated with a decrease in global functioning. Copyright © 2010 Elsevier Ltd. All rights reserved.

Branched-chain amino acids alter neurobehavioral function in rats

PubMed Central

Coppola, Anna; Wenner, Brett R.; Ilkayeva, Olga; Stevens, Robert D.; Maggioni, Mauro; Slotkin, Theodore A.; Levin, Edward D.

2013-01-01

Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders. PMID:23249694

Estimation of health effects of prenatal methylmercury exposure using structural equation models.

PubMed

Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe; Weihe, Pal

2002-10-14

Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity. Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker. The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets.

Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement.

PubMed

Filley, C M; Price, B H; Nell, V; Antoinette, T; Morgan, A S; Bresnahan, J F; Pincus, J H; Gelbort, M M; Weissberg, M; Kelly, J P

2001-01-01

Violence is a global problem that poses a major challenge to individuals and society. This document is a consensus statement on neurobehavioral aspects of violence as one approach to its understanding and control. This consensus group was convened under the auspices of the Aspen Neurobehavioral Conference, an annual consensus conference devoted to the understanding of issues related to mind and brain. The conference is supported by the Brain Injury Association and by individual philanthropic contributions. Participants were selected by conference organizers to represent leading opinion in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary psychology, medical ethics, and law. A literature review of the role of the brain in violent behavior was conducted and combined with expert opinion from the group. The major goal was to survey this field so as to identify major areas of interest that could be targeted for further research. Additional review was secured from the other attendees at the Aspen Neurobehavioral Conference. The group met in the spring of 1998 and 1999 for two 5-day sessions, between which individual assignments were carried out. The consensus statement was prepared after the second meeting, and agreement on the statement was reached by participants after final review of the document. Violence can result from brain dysfunction, although social and evolutionary factors also contribute. Study of the neurobehavioral aspects of violence, particularly frontal lobe dysfunction, altered serotonin metabolism, and the influence of heredity, promises to lead to a deeper understanding of the causes and solution of this urgent problem.

Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups.

PubMed

Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih

2015-07-01

Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values. Eighty-five patients with AD underwent neurobehavioral assessments including the minimental state examination (MMSE) and 12-item neuropsychiatric inventory twice with a 1.5-year interval to represent major outcome factors. In the cross-sectional data, total cholesterol, low-density lipoprotein, vitamin B12, and homocysteine levels correlated variably with WM FA values. After entering the biomarkers and WM FA into a regression model to predict neurobehavioral outcomes, only fiber tract FA or homocysteine level predicted the MMSE score, and fiber tract FA or age predicted the neuropsychiatric inventory total scores and subdomains of apathy, disinhibition, and aberrant motor behavior. In the follow-up neurobehavioral data, the mean global FA value predicted the MMSE and aberrant motor behavior subdomain, while age predicted the anxiety and elation subdomains. Cerebrovascular risk biomarkers may modify WM microstructural organization, while the association with fiber integrity showed greater clinical significance to the prediction of neurobehavioral outcomes both cross-sectionally and longitudinally.

Sex Differences in the Generalization of Fear as a Function of Retention Intervals

ERIC Educational Resources Information Center

Lynch, Joseph, III; Cullen, Patrick K.; Jasnow, Aaron M.; Riccio, David C.

2013-01-01

In previous studies using male rodents, context change disrupted a fear response at a short, but not a long, retention interval. Here, we examined the effects of context changes on fear responses as a function of time in male and female rats. Males displayed context discrimination at all intervals, whereas females exhibited generalization by 5 d.…

Microbial colonization is required for normal neurobehavioral development in zebrafish..

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

APPLICATIONS OF A NEUROBEHAVIORAL SCREENING BATTERY

EPA Science Inventory

With the growing awareness of the neurological effects of many environmental chemicals there is considerable emphasis being placed on the detection of neurotoxic potential at the screening, or first-tier, level of testing. e have developed a neurobehavioral screening battery cons...

Microbial colonization is required for normal neurobehavioral development in zebrafish.

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

The interaction between manganese exposure and alcohol on neurobehavioral outcomes in welders.

PubMed

Ellingsen, Dag G; Kusraeva, Zarina; Bast-Pettersen, Rita; Zibarev, Evgenij; Chashchin, Maxim; Thomassen, Yngvar; Chashchin, Valery

2014-01-01

Neurobehavioral functions were studied in 137 welders exposed to the geometric mean (GM) air concentration of 214 μg/m(3) (range 1-3230) of manganese (Mn) based on the individual mean from two days of air sampling. Only 22 μg/m(3) (GM) was soluble in the artificial lung fluid Hatch solution. The welders were compared to 137 referents (turner/fitters) recruited from the same plants. The GM concentrations of Mn in whole blood (B-Mn) and urine (U-Mn) were 12.8 μg/L and 0.36 μg/g creatinine versus 8.0 μg/L and 0.07 μg/g creatinine in the referents. Alcohol consumption was assessed by measuring carbohydrate deficient transferrin in serum (sCDT). The welders had poorer performance than the referents on the Grooved Pegboard, Finger Tapping, Simple Reaction Time (SRT) and possibly the Maximum Frequency tests. They also reported more subjective symptoms. Welders with sCDT above the upper reference limit had substantially poorer performances on the Grooved Pegboard test, Finger Tapping test and SRT than welders with sCDT below this level. No effect of high sCDT was observed in the referents, indicating an interaction between high sCDT and exposure to Mn for these tests. Self-reported alcohol consumption had no impact on these neurobehavioral test results. A statistically significant difference in the SRT and Grooved Pegboard test results remained after excluding all subjects with sCDT above the normal level, but the difference in test scores between the groups was smaller. These welders also reported more subjective symptoms than the referents. The results suggest that sCDT should be measured in neurobehavioral studies of occupationally Mn exposed populations for a more precise estimation of high alcohol consumption. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal Exposure to DEHP Induces Neuronal Degeneration and Neurobehavioral Abnormalities in Adult Male Mice.

PubMed

Barakat, Radwa; Lin, Po-Ching; Park, Chan Jin; Best-Popescu, Catherine; Bakery, Hatem H; Abosalum, Mohamed E; Abdelaleem, Nabila M; Flaws, Jodi A; Ko, CheMyong

2018-04-23

Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus. Pregnant CD-1 female mice were orally administered 200μg, 500mg, or 750mg/kg/day DEHP or vehicle from gestational day 11 until birth. The neurobehavioral impact of the prenatal DEHP exposure was assessed at the ages of 16 to 22 months. Elevated plus maze and open field tests were used to measure anxiety levels. Y-maze and novel object recognition tests were employed to measure memory function. The oxidative damage in the hippocampus was measured by the levels of oxidative DNA damage and by SLIM microscopic counting of hippocampal neurons. Adult male mice that were prenatally exposed to DEHP exhibited anxious behaviors and impaired spatial and short-term recognition memory. The number of hippocampal pyramidal neurons was significantly decreased in the DEHP mice. Furthermore, DEHP mice expressed remarkably high levels of cyclooxygenase-2, 8-hydroxyguanine, and thymidine glycol in their hippocampal neurons. DEHP mice also had lower circulating testosterone concentrations and displayed a weaker immunoreactivity than the control mice to androgen receptor expression in the brain. This study found that prenatal exposure to DEHP caused elevated anxiety behavior and impaired recognition memory. These behavioral changes may originate from neurodegeneration caused by oxidative damage and inflammation in the hippocampus. Decreased circulating testosterone concentrations and decreased expression of androgen receptor in the brain also may be factors contributing to the impaired neurobehavior in the DEHP mice.

Persistence of Amygdala-Hippocampal Connectivity and Multi-Voxel Correlation Structures During Awake Rest After Fear Learning Predicts Long-Term Expression of Fear.

PubMed

Hermans, Erno J; Kanen, Jonathan W; Tambini, Arielle; Fernández, Guillén; Davachi, Lila; Phelps, Elizabeth A

2017-05-01

After encoding, memories undergo a process of consolidation that determines long-term retention. For conditioned fear, animal models postulate that consolidation involves reactivations of neuronal assemblies supporting fear learning during postlearning "offline" periods. However, no human studies to date have investigated such processes, particularly in relation to long-term expression of fear. We tested 24 participants using functional MRI on 2 consecutive days in a fear conditioning paradigm involving 1 habituation block, 2 acquisition blocks, and 2 extinction blocks on day 1, and 2 re-extinction blocks on day 2. Conditioning blocks were preceded and followed by 4.5-min rest blocks. Strength of spontaneous recovery of fear on day 2 served as a measure of long-term expression of fear. Amygdala connectivity primarily with hippocampus increased progressively during postacquisition and postextinction rest on day 1. Intraregional multi-voxel correlation structures within amygdala and hippocampus sampled during a block of differential fear conditioning furthermore persisted after fear learning. Critically, both these main findings were stronger in participants who exhibited spontaneous recovery 24 h later. Our findings indicate that neural circuits activated during fear conditioning exhibit persistent postlearning activity that may be functionally relevant in promoting consolidation of the fear memory. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism.

PubMed

Marsh, Abigail A

2016-06-01

Because the face is the central focus of human social interactions, emotional facial expressions provide a unique window into the emotional lives of others. They play a particularly important role in fostering empathy, which entails understanding and responding to others' emotions, especially distress-related emotions such as fear. This Review considers how fearful facial as well as vocal and postural expressions are interpreted, with an emphasis on the role of the amygdala. The amygdala may be best known for its role in the acquisition and expression of conditioned fear, but it also supports the perception and recognition of others' fear. Various explanations have been supplied for the amygdala's role in interpreting and responding to fearful expressions. They include theories that amygdala responses to fearful expressions 1) reflect heightened vigilance in response to uncertain danger, 2) promote heightened attention to the eye region of faces, 3) represent a response to an unconditioned aversive stimulus, or 4) reflect the generation of an empathic fear response. Among these, only empathic fear explains why amygdala lesions would impair fear recognition across modalities. Supporting the possibility of a link between fundamental empathic processes and amygdala responses to fear is evidence that impaired fear recognition in psychopathic individuals results from amygdala dysfunction, whereas enhanced fear recognition in altruistic individuals results from enhanced amygdala function. Empathic concern and caring behaviors may be fostered by sensitivity to signs of acute distress in others, which relies on intact functioning of the amygdala. © 2015 Wiley Periodicals, Inc.

COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

EPA Science Inventory

The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

COMPUTERIZED ASSESSMENT OF HUMAN NEUROTOXICITY: SENSITIVITY TO NITROUS OXIDE EXPOSURE

EPA Science Inventory

The authors recently developed a flexible, portable, computer based neurobehavioral evaluation system (NES) to standardize data collection in epidemiologic field studies of individuals at risk for neurobehavioral toxicity. The current study was performed to examine the system's s...

Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grebe, E.; Schaeffer, D.J.

1991-05-01

The authors are developing bioassays which use planarians (free-living platyhelminthes) for the rapid determination of various types of toxicity, including acute mortality, tumorigenicity, and short-term neurobehavioral responses. Their motivation for using these animals is due to their importance as components of the aquatic ecology of unpolluted streams their sensitivity to low concentrations of environmental toxicants and the presence of a sensitive neurological system with a true brain which allows for complex social behavior. A previous paper described the results of a neurobehavioral bioassay using phenol in a crossover study. This paper reports a similar crossover study using cadmium sulfate.

Relationship between fear of falling and outcomes of an inpatient geriatric rehabilitation population--fear of the fear of falling.

PubMed

Denkinger, Michael D; Igl, Wilmar; Lukas, Albert; Bader, Anne; Bailer, Stefanie; Franke, Sebastian; Denkinger, Claudia M; Nikolaus, Thorsten; Jamour, Michael

2010-04-01

To examine the effects of various risk factors on three functional outcomes during rehabilitation. Geriatric inpatient rehabilitation unit. Observational longitudinal study. One hundred sixty-one geriatric rehabilitation inpatients (men, women), mean age 82, who were capable of walking at baseline. Functional status was assessed weekly between admission and discharge and at a follow-up 4 months later at home using the function component of the Short Form-Late Life Function and Disability Instrument, the Barthel Index, and Habitual Gait Speed. Various risk factors, such as falls-related self-efficacy (Falls Efficacy Scale-International), were measured. Associations between predictors and functional status at discharge and follow-up were analyzed using linear regression models and bivariate plots. Fear of falling predicted functioning across all outcomes except for habitual gait speed at discharge and follow-up. Visual comparison of functional trajectories between subgroups confirmed these findings, with different levels of fear of falling across time in linear plots. Thus, superior ability of this measure to discriminate between functional status at baseline across all outcomes and to discriminate between functional change especially with regard to the performance-based outcome was demonstrated. Falls-related self-efficacy is the only parameter that significantly predicts rehabilitation outcome at discharge and follow-up across all outcomes. Therefore, it should be routinely assessed in future studies in (geriatric) rehabilitation and considered to be an important treatment goal.

Medial prefrontal cortex neuronal circuits in fear behavior.

PubMed

Courtin, J; Bienvenu, T C M; Einarsson, E Ö; Herry, C

2013-06-14

The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The Effects of Sleep Restriction and Extension on School-Age Children: What a Difference an Hour Makes.

ERIC Educational Resources Information Center

Sadeh, Avi; Gruber, Reut; Raviv, Amiram

2003-01-01

Assessed effects of sleep restriction and extension on 9- to 12-year-olds' neurobehavioral functioning. Found that modest sleep restriction led to improved sleep quality but to reduced reported alertness. Children who extended sleep improved significantly from baseline their performance on the digit forward memory test and reaction time on the…

Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

DTIC Science & Technology

2012-11-01

testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging ( DTI )] to gain a comprehensive understanding of... DTI fiber tracking) and neurobehavioral testing (computerized assessment and standard neuropsychological testing) on 60 chronic trauma patients: 15...data analysis. 15. SUBJECT TERMS Blast-related traumatic brain injury (TBI), fMRI, DTI , cognition 16. SECURITY CLASSIFICATION OF: 17. LIMITATION

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

NASA Technical Reports Server (NTRS)

Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

1999-01-01

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

PubMed

Wang, Yan; Fu, Wei; Liu, Jing

2016-01-01

Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

Developmental Exposure to a Commercial PBDE mixture, DE·71: Neurobehavioral, Hormonal, and Reproductive Effects

EPA Science Inventory

Developmental effects of PBDEs have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial m...

Neurobehavioral, Hormonal, and Reproductive Effects following Developmental Exposure to a Commercial PBDE Mixture, DE-71

EPA Science Inventory

Developmental effects caused by PBDEs have been suspected due to their chemically structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabromi...

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

PubMed

Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

2016-10-01

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maladaptive cognitive appraisals in children with high-functioning autism: associations with fear, anxiety and theory of mind.

PubMed

Sharma, Shilpi; Woolfson, Lisa M; Hunter, Simon C

2014-04-01

Despite the well-documented success of cognitive restructuring techniques in the treatment of anxiety disorders, there is still little clarity on which cognitions underpin fear and anxiety in children with high-functioning autism spectrum disorder. This study examined whether certain cognitive appraisals, known to be associated with fear and anxiety in typically developing groups, may help explain these emotions in children with high-functioning autism spectrum disorder. It also investigated relations between these cognitive appraisals and theory of mind. Appraisals, fear and anxiety were assessed using a vignette approach in 22 children with high-functioning autism spectrum disorders and 22 typically developing children. The two groups differed significantly on all four appraisal types. Anxiety was negatively correlated with future expectancy and positively with problem-focused coping potential in the high-functioning autism spectrum disorder group but was not correlated with appraisals in the typically developing group. The two appraisals associated with fear were emotion-focused coping potential (in the high-functioning autism spectrum disorder group only) and self-accountability (in the typically developing group only). Linear regression analysis found that appraisals of emotion-focused coping potential, problem-focused coping potential and future expectancy were significant predictors of theory-of-mind ability in the high-functioning autism spectrum disorders group. These findings indicate that specific, problematic patterns of appraisal may characterise children with high-functioning autism spectrum disorders.

The Impact of Multiple Concussions on Emotional Distress, Post-Concussive Symptoms, and Neurocognitive Functioning in Active Duty United States Marines Independent of Combat Exposure or Emotional Distress

PubMed Central

Lathan, Corinna E.; Bleiberg, Joseph; Tsao, Jack W.

2014-01-01

Abstract Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms, emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post-concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat. PMID:25003552

Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

PubMed

Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

2015-10-01

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy. © The Author(s) 2015.

Risk and Resilience in Pediatric Chronic Pain: Exploring the Protective Role of Optimism.

PubMed

Cousins, Laura A; Cohen, Lindsey L; Venable, Claudia

2015-10-01

Fear of pain and pain catastrophizing are prominent risk factors for pediatric chronic pain-related maladjustment. Although resilience has largely been ignored in the pediatric pain literature, prior research suggests that optimism might benefit youth and can be learned. We applied an adult chronic pain risk-resilience model to examine the interplay of risk factors and optimism on functioning outcomes in youth with chronic pain. Participants included 58 children and adolescents (8-17 years) attending a chronic pain clinic and their parents. Participants completed measures of fear of pain, pain catastrophizing, optimism, disability, and quality of life. Consistent with the literature, pain intensity, fear of pain, and catastrophizing predicted functioning. Optimism was a unique predictor of quality of life, and optimism contributed to better functioning by minimizing pain-related fear and catastrophizing. Optimism might be protective and offset the negative influence of fear of pain and catastrophizing on pain-related functioning. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The structural and functional correlates of the efficiency in fearful face detection.

PubMed

Wang, Yongchao; Guo, Nana; Zhao, Li; Huang, Hui; Yao, Xiaonan; Sang, Na; Hou, Xin; Mao, Yu; Bi, Taiyong; Qiu, Jiang

2017-06-01

Human visual system is found to be much efficient in searching for a fearful face. Some individuals are more sensitive to this threat-related stimulus. However, we still know little about the neural correlates of such variability. In the current study, we exploited a visual search paradigm, and asked the subjects to search for a fearful face or a target gender. Every subject showed a shallower search function for fearful face search than face gender search, indicating a stable fearful face advantage. We then used voxel-based morphometry (VBM) analysis and correlated this advantage to the gray matter volume (GMV) of some presumably face related cortical areas. The result revealed that only the left fusiform gyrus showed a significant positive correlation. Next, we defined the left fusiform gyrus as the seed region and calculated its resting state functional connectivity to the whole brain. Correlations were also calculated between fearful face advantage and these connectivities. In this analysis, we found positive correlations in the inferior parietal lobe and the ventral medial prefrontal cortex. These results suggested that the anatomical structure of the left fusiform gyrus might determine the search efficiency of fearful face, and frontoparietal attention network involved in this process through top-down attentional modulation. Copyright © 2017. Published by Elsevier Ltd.

Postural control is associated with cognition and fear of falling in patients with multiple sclerosis.

PubMed

Perrochon, A; Holtzer, R; Laidet, M; Armand, S; Assal, F; Lalive, P H; Allali, G

2017-04-01

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting various neurological domains, such as postural control, cognition, fear of falling, depression-anxiety, and fatigue. This study examined the associations of cognitive functions, fear of falling, depression-anxiety, and fatigue with postural control in patients with MS. Postural control (sway velocity) of 63 patients with MS (age 39.0 ± 8.9 years; %female 57%; Expanded Disability Status Scale score median (interquartile range) 2.0 (1.5)) was recorded on two platforms at stable and unstable conditions. Cognition, fear of falling, depression-anxiety, and fatigue were evaluated by a comprehensive neuropsychological assessment. The associations between these domains and postural control have been measured by multivariable linear regression (adjusted for age, gender, disability, and education). In stable condition, only working memory was associated with postural control (p < 0.05). In unstable condition, working memory, executive functions, attention/processing speed, and fear of falling were associated with postural control (p < 0.05). Specific cognitive domains and fear of falling were associated with postural control in MS patients, particularly in unstable condition. These findings highlight the association of cognitive functions and fear of falling with postural control in MS.

Medial prefrontal cortex activity during the extinction of conditioned fear: an investigation using functional near-infrared spectroscopy.

PubMed

Guhn, Anne; Dresler, Thomas; Hahn, Tim; Mühlberger, Andreas; Ströhle, Andreas; Deckert, Jürgen; Herrmann, Martin J

2012-06-01

The majority of fear conditioning studies in humans have focused on fear acquisition rather than fear extinction. For this reason only a few functional imaging studies on fear extinction are available. A large number of animal studies indicate the medial prefrontal cortex (mPFC) as neuronal substrate of extinction. We therefore determined mPFC contribution during extinction learning after a discriminative fear conditioning in 34 healthy human subjects by using functional near-infrared spectroscopy. During the extinction training, a previously conditioned neutral face (conditioned stimulus, CS+) no longer predicted an aversive scream (unconditioned stimulus, UCS). Considering differential valence and arousal ratings as well as skin conductance responses during the acquisition phase, we found a CS+ related increase in oxygenated haemoglobin concentration changes within the mPFC over the time course of extinction. Late CS+ trials further revealed higher activation than CS- trials in a cluster of probe set channels covering the mPFC. These results are in line with previous findings on extinction and further emphasize the mPFC as significant for associative learning processes. During extinction, the diminished fear association between a former CS+ and a UCS is inversely correlated with mPFC activity--a process presumably dysfunctional in anxiety disorders. Copyright © 2012 S. Karger AG, Basel.

Long-Term Cognitive and Neuropsychiatric Consequences of Repetitive Concussion and Head-Impact Exposure.

PubMed

McAllister, Thomas; McCrea, Michael

2017-03-01

Initially, interest in sport-related concussion arose from the premise that the study of athletes engaged in sports associated with high rates of concussion could provide insight into the mechanisms, phenomenology, and recovery from mild traumatic brain injury. Over the last decade, concerns have focused on the possibility that, for some athletes, repetitive concussions may raise the long-term risk for cognitive decline, neurobehavioral changes, and neurodegenerative disease. First conceptualized as a discrete event with variable recovery trajectories, concussion is now viewed by some as a trigger of neurobiological events that may influence neurobehavioral function over the course of the life span. Furthermore, advances in technology now permit us to gain a detailed understanding of the frequency and intensity of repetitive head impacts associated with contact sports (eg, football, ice hockey). Helmet-based sensors can be used to characterize the kinematic features of concussive impacts, as well as the profiles of typical head-impact exposures experienced by athletes in routine sport participation. Many large-magnitude impacts are not associated with diagnosed concussions, whereas many diagnosed concussions are associated with more modest impacts. Therefore, a full understanding of this topic requires attention to not only the effects of repetitive concussions but also overall exposure to repetitive head impacts. This article is a review of the current state of the science on the long-term neurocognitive and neurobehavioral effects of repetitive concussion and head-impact exposure in contact sports.

Long-Term Cognitive and Neuropsychiatric Consequences of Repetitive Concussion and Head-Impact Exposure

PubMed Central

McAllister, Thomas; McCrea, Michael

2017-01-01

Initially, interest in sport-related concussion arose from the premise that the study of athletes engaged in sports associated with high rates of concussion could provide insight into the mechanisms, phenomenology, and recovery from mild traumatic brain injury. Over the last decade, concerns have focused on the possibility that, for some athletes, repetitive concussions may raise the long-term risk for cognitive decline, neurobehavioral changes, and neurodegenerative disease. First conceptualized as a discrete event with variable recovery trajectories, concussion is now viewed by some as a trigger of neurobiological events that may influence neurobehavioral function over the course of the life span. Furthermore, advances in technology now permit us to gain a detailed understanding of the frequency and intensity of repetitive head impacts associated with contact sports (eg, football, ice hockey). Helmet-based sensors can be used to characterize the kinematic features of concussive impacts, as well as the profiles of typical head-impact exposures experienced by athletes in routine sport participation. Many large-magnitude impacts are not associated with diagnosed concussions, whereas many diagnosed concussions are associated with more modest impacts. Therefore, a full understanding of this topic requires attention to not only the effects of repetitive concussions but also overall exposure to repetitive head impacts. This article is a review of the current state of the science on the long-term neurocognitive and neurobehavioral effects of repetitive concussion and head-impact exposure in contact sports. PMID:28387556

Appraisal of neurobehavioral methods in environmental health research: the developing brain as a target for neurotoxic chemicals.

PubMed

Winneke, Gerhard

2007-10-01

Psychological tests as developed and validated in the field of differential psychology have a longstanding tradition as tools to study individual differences. In clinical neuropsychology, global or more specific tests are used as neuropsychological tools in the differential diagnosis of various forms of brain damage or neurobehavioral dysfunction following chemical insults, such as mental sequelae of prenatal alcohol consumption by pregnant mothers (fetal alcohol syndrome) or of maternal thyroid deficiency during pregnancy. Psychometric tests are constructed to fulfill basic quality criteria, namely objectivity, reliability and validity. For strictly diagnostic purposes in individual cases they must also possess normative values based on representative reference groups. Intelligence tests or their developmental variants are often used as endpoints in environmental health research for studying neurodevelopmental adversity due to early exposure to neurotoxic chemicals in the environment. Intelligence as treated in psychology is a complex construct made up of specific cognitive functions which usually cover verbal, numerical and spatial skills, as well as perceptual speed, memory and reasoning. In this paper, case studies covering neurodevelopmental adversity of inorganic lead, of methylmercury and of polychlorinated biphenyls (PCBs) are reviewed, and the issue of postnatal behavioral sequelae of prenatal exposure is covered. In such observational studies precautions must be taken in order to avoid pitfalls of causative interpretation of associations between exposure and neurobehavioral outcome. This requires consideration of co-exposure and confounding. Important confounders considered in most modern developmental cohort studies are maternal intelligence and quality of the home environment.

Neonatal morphine exposure in very preterm infants-cerebral development and outcomes.

PubMed

Steinhorn, Rachel; McPherson, Christopher; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

2015-05-01

To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. Copyright © 2015 Elsevier Inc. All rights reserved.

Blast overpressure in rats: recreating a battlefield injury in the laboratory.

PubMed

Long, Joseph B; Bentley, Timothy L; Wessner, Keith A; Cerone, Carolyn; Sweeney, Sheena; Bauman, Richard A

2009-06-01

Blast injury to the brain is the predominant cause of neurotrauma in current military conflicts, and its etiology is largely undefined. Using a compression-driven shock tube to simulate blast effects, we assessed the physiological, neuropathological, and neurobehavioral consequences of airblast exposure, and also evaluated the effect of a Kevlar protective vest on acute mortality in rats and on the occurrence of traumatic brain injury (TBI) in those that survived. This approach provides survivable blast conditions under which TBI can be studied. Striking neuropathological changes were caused by both 126- and 147-kPa airblast exposures. The Kevlar vest, which encased the thorax and part of the abdomen, greatly reduced airblast mortality, and also ameliorated the widespread fiber degeneration that was prominent in brains of rats not protected by a vest during exposure to a 126-kPa airblast. This finding points to a significant contribution of the systemic effects of airblast to its brain injury pathophysiology. Airblast of this intensity also disrupted neurologic and neurobehavioral performance (e.g., beam walking and spatial navigation acquisition in the Morris water maze). When immediately followed by hemorrhagic hypotension, with MAP maintained at 30 mm Hg, airblast disrupted cardiocompensatory resilience, as reflected by reduced peak shed blood volume, time to peak shed blood volume, and time to death. These findings demonstrate that shock tube-generated airblast can cause TBI in rats, in part through systemic mediation, and that the resulting brain injury significantly impacts acute cardiovascular homeostatic mechanisms as well as neurobehavioral function.

Seeing the world through non rose-colored glasses: anxiety and the amygdala response to blended expressions

PubMed Central

Bishop, Sonia J.; Aguirre, Geoffrey K.; Nunez-Elizalde, Anwar O.; Toker, Daniel

2015-01-01

Anxious individuals have a greater tendency to categorize faces with ambiguous emotional expressions as fearful (Richards et al., 2002). These behavioral findings might reflect anxiety-related biases in stimulus representation within the human amygdala. Here, we used functional magnetic resonance imaging (fMRI) together with a continuous adaptation design to investigate the representation of faces from three expression continua (surprise-fear, sadness-fear, and surprise-sadness) within the amygdala and other brain regions implicated in face processing. Fifty-four healthy adult participants completed a face expression categorization task. Nineteen of these participants also viewed the same expressions presented using type 1 index 1 sequences while fMRI data were acquired. Behavioral analyses revealed an anxiety-related categorization bias in the surprise-fear continuum alone. Here, elevated anxiety was associated with a more rapid transition from surprise to fear responses as a function of percentage fear in the face presented, leading to increased fear categorizations for faces with a mid-way blend of surprise and fear. fMRI analyses revealed that high trait anxious participants also showed greater representational similarity, as indexed by greater adaptation of the Blood Oxygenation Level Dependent (BOLD) signal, between 50/50 surprise/fear expression blends and faces from the fear end of the surprise-fear continuum in both the right amygdala and right fusiform face area (FFA). No equivalent biases were observed for the other expression continua. These findings suggest that anxiety-related biases in the processing of expressions intermediate between surprise and fear may be linked to differential representation of these stimuli in the amygdala and FFA. The absence of anxiety-related biases for the sad-fear continuum might reflect intermediate expressions from the surprise-fear continuum being most ambiguous in threat-relevance. PMID:25870551

Screening for elevated levels of fear-avoidance beliefs regarding work or physical activities in people receiving outpatient therapy.

PubMed

Hart, Dennis L; Werneke, Mark W; George, Steven Z; Matheson, James W; Wang, Ying-Chih; Cook, Karon F; Mioduski, Jerome E; Choi, Seung W

2009-08-01

Screening people for elevated levels of fear-avoidance beliefs is uncommon, but elevated levels of fear could worsen outcomes. Developing short screening tools might reduce the data collection burden and facilitate screening, which could prompt further testing or management strategy modifications to improve outcomes. The purpose of this study was to develop efficient yet accurate screening methods for identifying elevated levels of fear-avoidance beliefs regarding work or physical activities in people receiving outpatient rehabilitation. A secondary analysis of data collected prospectively from people with a variety of common neuromusculoskeletal diagnoses was conducted. Intake Fear-Avoidance Beliefs Questionnaire (FABQ) data were collected from 17,804 people who had common neuromusculoskeletal conditions and were receiving outpatient rehabilitation in 121 clinics in 26 states (in the United States). Item response theory (IRT) methods were used to analyze the FABQ data, with particular emphasis on differential item functioning among clinically logical groups of subjects, and to identify screening items. The accuracy of screening items for identifying subjects with elevated levels of fear was assessed with receiver operating characteristic analyses. Three items for fear of physical activities and 10 items for fear of work activities represented unidimensional scales with adequate IRT model fit. Differential item functioning was negligible for variables known to affect functional status outcomes: sex, age, symptom acuity, surgical history, pain intensity, condition severity, and impairment. Items that provided maximum information at the median for the FABQ scales were selected as screening items to dichotomize subjects by high versus low levels of fear. The accuracy of the screening items was supported for both scales. This study represents a retrospective analysis, which should be replicated using prospective designs. Future prospective studies should assess the reliability and validity of using one FABQ item to screen people for high levels of fear-avoidance beliefs. The lack of differential item functioning in the FABQ scales in the sample tested in this study suggested that FABQ screening could be useful in routine clinical practice and allowed the development of single-item screening for fear-avoidance beliefs that accurately identified subjects with elevated levels of fear. Because screening was accurate and efficient, single IRT-based FABQ screening items are recommended to facilitate improved evaluation and care of heterogeneous populations of people receiving outpatient rehabilitation.

A Brief History of INA and ICOH SCNP: International Neurotoxicology Association and International Congress on Occupational Health Scientific Committee on Neurotoxicology and Psychophysiology

EPA Science Inventory

Two international scientific societies dedicated to research in neurotoxicology and neurobehavioral toxicology are the International Neurotoxicology Association (INA) and the International Congress on Occupational Health International Symposium on Neurobehavioral Methods and Effe...

NEUROBEHAVIORAL EFFECTS OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS IN CZECH CHILDREN

EPA Science Inventory

Ambient levels of SO2, NOx, PAHs and heavy metals are elevated in Northern Bohemia as a result of intensive mining and combustion of brown coal. To assess the neurotoxicological effects of exposure to these chemicals, tests from the Neurobehavioral Evaluation System (NES2) we...

Neurobehavioral Integrity of Chimpanzee Newborns: Comparisons across groups and across species reveal gene-environment interaction effects

PubMed Central

Bard, Kim A.; Brent, Linda; Lester, Barry; Worobey, John; Suomi, Stephen J.

2014-01-01

The aims of this article are to describe the neurobehavioral integrity of chimpanzee newborns, to investigate how early experiences affect the neurobehavioral organization of chimpanzees, and to explore species differences by comparing chimpanzee newborns to a group of typically developing human newborns. Neurobehavioral integrity related to orientation, motor performance, arousal, and state regulation of 55 chimpanzee (raised in four different settings) and 42 human newborns was measured with the Neonatal Behavioral Assessment Scale (NBAS) a semi-structured 25-minute interactive assessment. Thirty-eight chimpanzees were tested every other day from birth, and analyses revealed significant developmental changes in 19 of 27 NBAS scores. The cross-group and cross-species comparisons were conducted at 2 and 30 days of age. Among the 4 chimpanzee groups, significant differences were found in 23 of 24 NBAS scores. Surprisingly, the cross-species comparisons revealed that the human group was distinct in only 1 of 25 NBAS scores (the human group had significantly less muscle tone than all the chimpanzee groups). The human group was indistinguishable from at least one of the chimpanzee groups in the remaining 24 of 25 NBAS scores. The results of this study support the conclusion that the interplay between genes and environment, rather than genes alone or environment alone, accounts for phenotypic expressions of newborn neurobehavioral integrity in hominids. PMID:25110465

NICU Network Neurobehavioral Scale: 1-month normative data and variation from birth to 1 month.

PubMed

Provenzi, Livio; Olson, Karen; Giusti, Lorenzo; Montirosso, Rosario; DeSantis, Andrea; Tronick, Ed

2018-06-01

BackgroundThe Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized method for infant neurobehavioral assessment. Normative values are available for newborns, but the NNNS is not always feasible at birth. Unfortunately, 1-month NNNS normative data are lacking.AimsTo provide normative data for the NNNS examination at 1 month and to assess birth-to-one-month changes in NNNS summary scores.Study designThe NNNS was administered at birth and at 1 month within a longitudinal prospective study design.SubjectsA cohort of 99 clinically healthy full-term infants were recruited from a well-child nursery.Outcome measuresBirth-to-1-month NNNS variations were evaluated and the association of neonatal and sociodemographic variables with the rate of change of NNNS summary scores were investigated.Results and conclusionsNNNS scores from the 10th to the 90th percentile represent a range of normative performance at 1 month. A complex pattern of stability and change emerged comparing NNNS summary scores from birth to 1 month. Orienting, Regulation, and Quality of movements significantly increased, whereas Lethargy and Hypotonicity significantly decreased. Birth-to-1-month changes in NNNS performance suggest improvements in neurobehavioral organization. These data are useful for research purposes and for clinical evaluation of neurobehavioral performance in both healthy and at-risk 1-month-old infants.

Absence of fear renewal and functional connections between prefrontal cortex and hippocampus in infant mice.

PubMed

Li, Liyu; Gao, Xiaoli; Zhou, Qiang

2018-04-20

Impairment in fear extinction is widely viewed as a major contributor to, or even an underlying mechanism of, the pathogenesis of anxiety disorders and PTSD. Children with traumatic experience have a higher risk for developing anxiety disorders and PTSD in the adult. Little is known about the nature of fear memory extinction and its underlying mechanism during this period. Here we showed that while renewal of fear memory is context-specific in adult mice, it is absent in infant mice (P17). Using local injection of GABAa receptor antagonist picrotoxin, we found that there is no functional connectivity between infralimbic prefrontal cortex and hippocampus in P17 mice, while prefrontal cortex projection to amygdala is functioning. Hence, the lack of fear renewal is likely caused by the lack of connections between hippocampus and prefrontal cortex which are known to be involved in the regulation of extinction memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Executive Function and Temperamental Fear Concurrently Predict Deception in School-Aged Children.

PubMed

Babkirk, Sarah; Saunders, Lauren V; Solomon, Beylul; Kessel, Ellen M; Crossman, Angela; Gokhan, Nurper; Dennis, Tracy A

The decision to intentionally withhold truthful information, or deception, is a key component of moral development and may be a precursor to more serious anti-social tendencies. Two factors, executive function and temperamental fear are each thought to influence childhood deception. Few studies, however, have explored deception in relation to both of these factors simultaneously. This was the goal of the present study. Executive function, as measured by a working memory task, and temperamental fear, as measured via maternal report were assessed in relation to observed deceptive behavior among 6 - 9-year-old children ( N = 43). Results showed that children displaying high working memory capacity and high temperamental fear were more likely to exhibit deceptive behavior. Implications for predictors of childhood deception and applications for moral education are discussed.

Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

PubMed

Dinges, D F; Douglas, S D; Zaugg, L; Campbell, D E; McMann, J M; Whitehouse, W G; Orne, E C; Kapoor, S C; Icaza, E; Orne, M T

1994-05-01

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.

Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

PubMed Central

Dinges, D F; Douglas, S D; Zaugg, L; Campbell, D E; McMann, J M; Whitehouse, W G; Orne, E C; Kapoor, S C; Icaza, E; Orne, M T

1994-01-01

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep. PMID:7910171

Association of Psychosocial Factors With Physical Activity and Function After Total Knee Replacement: An Exploratory Study.

PubMed

Dominick, Gregory M; Zeni, Joseph A; White, Daniel K

2016-09-01

To examine the association between self-efficacy, social support, and fear of movement with physical activity and function at baseline and after 12 weeks of physical therapy. Nonrandomized cohort study, repeated-measures design. Outpatient rehabilitation clinic within the general community. Adults (N=49) undergoing outpatient physical therapy for total knee replacement (TKR). Not applicable. Self-efficacy for exercise (SEE), fear of movement, leisure-time physical activity (LTPA), 6-minute walk test (6MWT), and Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) were assessed at baseline and 12 weeks. Mean functional change scores significantly increased at 12 weeks for the 6MWT (95% confidence interval [CI], 42.3-106.2), KOS-ADLS (95% CI, 12.7-23.3), and LTPA (95% CI, 6.5-26.1). Self-efficacy and fear of movement were not significantly associated with function at baseline or 12 weeks. Participants with lower SEE had 6 fewer metabolic equivalents per week of improvement in LTPA than those with high self-efficacy (95% CI, -27.9 to 14.8), and those with high fear of movement had 26.1m less improvement in the 6MWT than those with low fear of movement (95% CI, -42.2 to 94.5). Most participants reported having no family or peer support for exercise. Physical therapy for TKR improves physical function and self-reported physical activity. High fear of movement and low SEE may be associated with less improvement in physical activity and function over time. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Parent observed neuro-behavioral and pro-social improvements with oxytocin following surgical resection of craniopharyngioma.

PubMed

Cook, Naomi; Miller, Jennifer; Hart, John

2016-08-01

Social and emotional impairment, school dysfunction, and neurobehavioral impairment are highly prevalent in survivors of childhood craniopharyngioma and negatively affect quality of life. As surgical resection of craniopharyngioma typically impairs hypothalamic/pituitary function, it has been postulated that perhaps post-operative deficiency of the hormone oxytocin may be the etiology of social/emotional impairment. Research on the benefits of oxytocin treatment as a hormone facilitating social interaction is well established. However, no research has yet been conducted on patients with known pituitary/hypothalamic dysfunction due to structural lesions or surgery. This case report investigates the effects of oxytocin therapy on a youngster with pituitary/hypothalamic dysfunction after craniopharyngioma removal. In this individual, treatment with low dose intranasal oxytocin resulted in increased desire for socialization and improvement in affection towards family. In light of these findings, the authors believe that further research into the potential benefits of intranasal oxytocin therapy for patients with panhypopituitarism is necessary to determine whether a broader population may also benefit from intranasal oxytocin therapy.

Add a picture for suspense: neural correlates of the interaction between language and visual information in the perception of fear.

PubMed

Willems, Roel M; Clevis, Krien; Hagoort, Peter

2011-09-01

We investigated how visual and linguistic information interact in the perception of emotion. We borrowed a phenomenon from film theory which states that presentation of an as such neutral visual scene intensifies the percept of fear or suspense induced by a different channel of information, such as language. Our main aim was to investigate how neutral visual scenes can enhance responses to fearful language content in parts of the brain involved in the perception of emotion. Healthy participants' brain activity was measured (using functional magnetic resonance imaging) while they read fearful and less fearful sentences presented with or without a neutral visual scene. The main idea is that the visual scenes intensify the fearful content of the language by subtly implying and concretizing what is described in the sentence. Activation levels in the right anterior temporal pole were selectively increased when a neutral visual scene was paired with a fearful sentence, compared to reading the sentence alone, as well as to reading of non-fearful sentences presented with the same neutral scene. We conclude that the right anterior temporal pole serves a binding function of emotional information across domains such as visual and linguistic information.

Fearfulness moderates the link between childhood social withdrawal and adolescent reward response

PubMed Central

Shaw, Daniel S.; Forbes, Erika E.

2015-01-01

Withdrawal from peers during childhood may reflect disruptions in reward functioning that heighten vulnerability to affective disorders during adolescence. The association between socially withdrawn behavior and reward functioning may depend on traits that influence this withdrawal, such as fearfulness or unsociability. In a study of 129 boys, we evaluated how boys’ fearfulness and sociability at age 5 and social withdrawal at school at ages 6 to 10 and during a summer camp at age 9/10 were associated with their neural response to reward at age 20. Greater social withdrawal during childhood was associated with heightened striatal and mPFC activation when anticipating rewards at age 20. Fearfulness moderated this effect to indicate that social withdrawal was associated with heightened reward-related response in the striatum for boys high on fearfulness. Altered striatal response associated with social withdrawal and fearfulness predicted greater likelihood to have a lifetime history of depression and social phobia at age 20. These findings add greater specificity to previous findings that children high in traits related to fear of novelty show altered reward responses, by identifying fearfulness (but not low levels of sociability) as a potential underlying mechanism that contributes to reward alterations in withdrawn children. PMID:25193948

Prospective Assessment of Neurocognition in Future Gulf-deployed and Gulf-nondeployed Military Personnel: A Pilot Study

DTIC Science & Technology

2007-02-01

increased emotional distress but with advantaged simple reactiontime. Unit cohesion buffers the adverse effects of early life events on PTSD prior to...motor speed), and emotional (e.g., mood) behaviors thought to reflect neural integrity. Unresolved issues include whether subjective...including neurobehavioral and emotional functioning, (b) examine the impact of deployment-related stress and environmental exposures on

Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

DTIC Science & Technology

2012-09-01

fMRI, DTI , cognition 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a...techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging ( DTI )] to gain a comprehensive understanding of the neural changes...orthopedic injuries. We accomplished this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2015-10-01

characterization of the mouse model of repeated blast also found no cumula- tive effect of repeated blast on cortical levels of reactive oxygen species [39]. C...overpressure in rats to investigate the cumulative effects of multiple blast exposures on neurologic status, neurobehavioral function, and brain...preclinical model of blast overpressure in rats to investigate the cumulative effects of multiple blast exposures using neurological, neurochemical

Fetal Neurobehavioral Development and the Role of Maternal Nutrient Intake and Psychological Health

ERIC Educational Resources Information Center

Spann, Marisa; Smerling, Jennifer; Gustafsson, Hanna C.; Foss, Sophie; Monk, Catherine

2014-01-01

Measuring and understanding fetal neurodevelopment provides insight regarding the developing brain. Maternal nutrient intake and psychological stress during pregnancy each impact fetal neurodevelopment and influence childhood outcomes and are thus important factors to consider when studying fetal neurobehavioral development. The authors provide an…

DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.

EPA Science Inventory

The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up t...

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Prenatal drug exposure: infant and toddler outcomes.

PubMed

Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

2010-04-01

This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may herald more significant learning and behavioral problems during school-age and adolescence when the child is inevitably confronted with increasing social and academic challenges is the subject of ongoing longitudinal research.

Functional cliques in the amygdala and related brain networks driven by fear assessment acquired during movie viewing.

PubMed

Kinreich, Sivan; Intrator, Nathan; Hendler, Talma

2011-01-01

One of the greatest challenges involved in studying the brain mechanisms of fear is capturing the individual's unique instantaneous experience. Brain imaging studies to date commonly sacrifice valuable information regarding the individual real-time conscious experience, especially when focusing on elucidating the amygdala's activity. Here, we assumed that by using a minimally intrusive cue along with applying a robust clustering approach to probe the amygdala, it would be possible to rate fear in real time and to derive the related network of activation. During functional magnetic resonance imaging scanning, healthy volunteers viewed two excerpts from horror movies and were periodically auditory cued to rate their instantaneous experience of "I'm scared." Using graph theory and community mathematical concepts, data-driven clustering of the fear-related functional cliques in the amygdala was performed guided by the individually marked periods of heightened fear. Individually tailored functions derived from these amygdala activation cliques were subsequently applied as general linear model predictors to a whole-brain analysis to reveal the correlated networks. Our results suggest that by using a localized robust clustering approach, it is possible to probe activation in the right dorsal amygdala that is directly related to individual real-time emotional experience. Moreover, this fear-evoked amygdala revealed two opposing networks of co-activation and co-deactivation, which correspond to vigilance and rest-related circuits, respectively.

Pharmacological enhancement of calcium-activated potassium channel function reduces the effects of repeated stress on fear memory

PubMed Central

Atchley, Derek; Hankosky, Emily R.; Gasparotto, Kaylyn; Rosenkranz, J. Amiel

2012-01-01

Repeated stress impacts emotion, and can induce mood and anxiety disorders. These disorders are characterized by imbalance of emotional responses. The amygdala is fundamental in expression of emotion, and is hyperactive in many patients with mood or anxiety disorders. Stress also leads to hyperactivity of the amygdala in humans. In rodent studies, repeated stress causes hyperactivity of the amygdala, and increases fear conditioning behavior that is mediated by the basolateral amygdala (BLA). Calcium-activated potassium (KCa) channels regulate BLA neuronal activity, and evidence suggests reduced small conductance KCa (SK) channel function in male rats exposed to repeated stress. Pharmacological enhancement of SK channels reverses the BLA neuronal hyperexcitability caused by repeated stress. However, it is not known if pharmacological targeting of SK channels can repair the effects of repeated stress on amygdala-dependent behaviors. The purpose of this study was to test whether enhancement of SK channel function reverses the effects of repeated restraint on BLA-dependent auditory fear conditioning. We found that repeated restraint stress increased the expression of cued conditioned fear in male rats. However, 1-EBIO (1 or 10 mg/kg) or CyPPA (5 mg/kg) administered 30 minutes prior to testing of fear expression brought conditioned freezing to control levels, with little impact on fear expression in control handled rats. These results demonstrate that enhancement of SK channel function can reduce the abnormalities of BLA-dependent fear memory caused by repeated stress. Furthermore, this indicates that pharmacological targeting of SK channels may provide a novel target for alleviation of psychiatric symptoms associated with amygdala hyperactivity. PMID:22487247

Fear processing and social networking in the absence of a functional amygdala.

PubMed

Becker, Benjamin; Mihov, Yoan; Scheele, Dirk; Kendrick, Keith M; Feinstein, Justin S; Matusch, Andreas; Aydin, Merve; Reich, Harald; Urbach, Horst; Oros-Peusquens, Ana-Maria; Shah, Nadim J; Kunz, Wolfram S; Schlaepfer, Thomas E; Zilles, Karl; Maier, Wolfgang; Hurlemann, René

2012-07-01

The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

PubMed

Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

From normal fear to pathological anxiety.

PubMed

Rosen, J B; Schulkin, J

1998-04-01

In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization- or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders.

Instructed fear learning, extinction, and recall: additive effects of cognitive information on emotional learning of fear.

PubMed

Javanbakht, Arash; Duval, Elizabeth R; Cisneros, Maria E; Taylor, Stephan F; Kessler, Daniel; Liberzon, Israel

2017-08-01

The effects of instruction on learning of fear and safety are rarely studied. We aimed to examine the effects of cognitive information and experience on fear learning. Fourty healthy participants, randomly assigned to three groups, went through fear conditioning, extinction learning, and extinction recall with two conditioned stimuli (CS+). Information was presented about the presence or absence of conditioned stimulus-unconditioned stimulus (CS-US) contingency at different stages of the experiment. Information about the CS-US contingency prior to fear conditioning enhanced fear response and reduced extinction recall. Information about the absence of CS-US contingency promoted extinction learning and recall, while omission of this information prior to recall resulted in fear renewal. These findings indicate that contingency information can facilitate fear expression during fear learning, and can facilitate extinction learning and recall. Information seems to function as an element of the larger context in which conditioning occurs.

Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

PubMed

Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

2016-10-01

Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury.

PubMed

Yoshida, Minoru; Suzuki, Megumi; Satoh, Masahiko; Yasutake, Akira; Watanabe, Chiho

2011-01-01

We evaluated the effects of prenatal exposure to low-level mercury (Hg(0)) or methylmercury (MeHg) as well as combined exposure (Hg(0) + MeHg exposure) on the neurobehavioral function of mice. The Hg(0) exposure group was exposed to Hg(0) at a mean concentration of 0.030 mg/m(3) for 6 hr/day during gestation period. The MeHg exposure was supplied with food containing 5 ppm of MeHg from gestational day 1 to postnatal day 10. The combined exposure group was exposed to both Hg(0) vapor and MeHg according to above described procedure. After delivery, when their offspring reached the age of 8 weeks, behavioral analysis was performed. Open field (OPF) tests of the offspring showed an increase and decrease in voluntary activity in male and female mice, respectively, in the MeHg exposure group. In addition, the rate of central entries was significantly higher in this group than in the control group. The results of OPF tests in the Hg(0) + MeHg exposure group were similar to those in the MeHg exposure group in both males and females. The results in the Hg(0) exposure group did not significantly differ from those in the control group in males or females. Passive avoidance response (PA) tests revealed no significant differences in avoidance latency in the retention trial between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in males or females. Morris water maze tests showed a delay in the latency to reach the platform in the MeHg and Hg(0) + MeHg exposure groups compared with the control group in males but no significant differences between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in females. The results of OPF tests revealed only slight effects of prenatal low-level Hg(0) exposure (0.03 mg/m(3)), close to the no-observable-effect level (NOEL) stated by the WHO (0.025 mg/m(3)), on the subsequent neurobehavioral function. However, prenatal exposure to 5 ppm of MeHg affected exploratory activity in the OPF test, and, in particular, male mice were highly sensitive to MeHg. The MeHg and Hg(0) + MeHg exposure groups showed similar neurobehavioral effects. Concerning the effects of prenatal mercury exposure under the conditions of this study, the effects of MeHg exposure may be more marked than those of Hg(0) exposure.

Executive Function and Temperamental Fear Concurrently Predict Deception in School-Aged Children

PubMed Central

Babkirk, Sarah; Saunders, Lauren V.; Solomon, Beylul; Kessel, Ellen M.; Crossman, Angela; Gokhan, Nurper; Dennis, Tracy A.

2015-01-01

The decision to intentionally withhold truthful information, or deception, is a key component of moral development and may be a precursor to more serious anti-social tendencies. Two factors, executive function and temperamental fear are each thought to influence childhood deception. Few studies, however, have explored deception in relation to both of these factors simultaneously. This was the goal of the present study. Executive function, as measured by a working memory task, and temperamental fear, as measured via maternal report were assessed in relation to observed deceptive behavior among 6 – 9-year-old children (N = 43). Results showed that children displaying high working memory capacity and high temperamental fear were more likely to exhibit deceptive behavior. Implications for predictors of childhood deception and applications for moral education are discussed. PMID:26880858

Fetal Neurobehavioral Development: A Tale of Two Cities.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Caulfield, Laura; Costigan, Kathleen A.; Merialdi, Mario; Nguyen, Ruby H. N.; Zavaleta, Nelly; Gurewitsch, Edith D.

2004-01-01

Longitudinal neurobehavioral development was examined in 237 fetuses of low-risk pregnancies from 2 distinct populations-Baltimore, Maryland, and Lima, Peru-at 20, 24, 28, 32, 36, and 38 weeks gestation. Data were based on digitized Doppler-based fetal heart rate (FHR) and fetal movement (FM). In both groups, FHR declined while variability,…

Neurobehavioral Syndromes in Cocaine-Exposed Newborn Infants.

ERIC Educational Resources Information Center

Lester, Barry M.; And Others

1991-01-01

The effects of fetal cocaine exposure on newborn cry characteristics were studied in 80 cocaine-exposed and 80 control infants. Findings were consistent with the notion that two neurobehavioral syndromes, excitable and depressed, can be described in cocaine-exposed infants and that these two syndromes are a result of direct neurotoxic effects and…

Bisphenol A in Relation to Behavior and Learning of School-Age Children

ERIC Educational Resources Information Center

Hong, Soon-Beom; Hong, Yun-Chul; Kim, Jae-Won; Park, Eun-Jin; Shin, Min-Sup; Kim, Boong-Nyun; Yoo, Hee-Jeong; Cho, In-Hee; Bhang, Soo-Young; Cho, Soo-Churl

2013-01-01

Bisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. Methods: Urinary BPA concentrations and behavioral and learning…

Early Malnutrition and Child Neurobehavioral Development: Insights from the Study of Children of Diabetic Mothers.

ERIC Educational Resources Information Center

Rizzo, Thomas A.; And Others

1997-01-01

Studied whether disturbances in mothers' metabolism (N=139) during pregnancy may exert long-range effects on neurobehavioral development of singleton progeny. Examined detailed pregnancy and perinatal records of mothers who experienced diabetes in pregnancy and intelligence tests of their offspring, administered at ages 7 to 11 years. All…

Neurobehaviors of Japanese Newborns in Relation to the Characteristics of Early Mother-Infant Interaction

ERIC Educational Resources Information Center

Loo, Kek Khee; Ohgi, Shohei; Howard, Judy; Tyler, Rachelle; Hirose, Taiko

2005-01-01

The authors examined the relationship between newborn neurobehavioral profiles and the characteristics of early mother-infant interaction in Nagasaki, Japan. The authors administered the Brazelton Neonatal Behavioral Assessment Scale (NBAS; T. B. Brazelton & J. K. Nugent, 1995) in the newborn period and the Nursing Child Assessment Teaching…

Impact of Tactile Stimulation on Neurobehavioral Development of Premature Infants in Assiut City

ERIC Educational Resources Information Center

Sayed, Atyat Mohammed Hassan; Youssef, Magda Mohamed E.; Hassanein, Farouk El-Sayed; Mobarak, Amal Ahmed

2015-01-01

Objective: To assess impact of tactile stimulation on neurobehavioral development of premature infants in Assiut City. Design: Quasi-experimental research design. Setting: The study was conducted in the Neonatal Intensive Care Unit at Assiut University Children Hospital, Assiut General Hospital, Health Insurance Hospital (ElMabarah Hospital) and…

Neurophysiological symptoms and aspartame: What is the connection?

PubMed

Choudhary, Arbind Kumar; Lee, Yeong Yeh

2018-06-01

Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.

MRI Features in a Canine Model of Ischemic Stroke: Correlation between Lesion Volume and Neurobehavioral Status during the Subacute Stage

PubMed Central

Kang, Byeong-Teck; Jang, Dong-Pyo; Gu, Su-Hyun; Lee, Jong-Hwan; Jung, Dong-In; Lim, Chae-Young; Kim, Ha-Jung; Kim, Young-Bo; Kim, Hyung-Joong; Woo, Eung-Je; Cho, Zang-Hee; Park, Hee-Myung

2009-01-01

The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI) and assess the correlation between the volume of the ischemic lesion and neurobehavioral status during the subacute stage of ischemic stroke. Ischemic stroke was induced in 6 healthy laboratory beagles through permanent occlusion of the middle cerebral artery (MCAO). T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), measurement of the apparent diffusion coefficient (ADC) ratio, and neurobehavioral evaluation were performed 3 times serially by using a 1.5-T MR system: before and 3 and 10 d after MCAO. Ischemic lesions demonstrated T2 hyperintensity, FLAIR hyperintensity, and DWI hyperintensity. The ADC ratio was decreased initially but then was increased at 10 d after MCAO. Ischemic lesion volumes on T2-weighted and FLAIR imaging were not significantly different from those on DWI. The lesion volume and neurobehavioral score showed strong correlation. Our results suggest that conventional MRI may be a reliable diagnostic tool during the subacute stage of canine ischemic stroke. PMID:19887030

EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss

NASA Technical Reports Server (NTRS)

Cajochen, C.; Khalsa, S. B.; Wyatt, J. K.; Czeisler, C. A.; Dijk, D. J.

1999-01-01

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1-7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

PubMed

Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

2016-06-01

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

Differential modulatory effects of morphine on acute and chronic stress induced neurobehavioral and cellular markers in rats.

PubMed

Joshi, Jagdish C; Ray, Arunabha; Gulati, Kavita

2014-04-15

The present study evaluated the effects of morphine treatments on elevated plus maze test parameters, oxidative stress markers and Hsp70 expression in normal and stressed rats. Acute and chronic stress caused neurobehavioral suppression, altered prooxidant-antioxidant balance and increased Hsp70 expression in brain homogenates in a differential manner. Morphine (1 and 5mg/kg) attenuated RS induced anxiogenesis, changes in MDA and GSH but further enhanced Hsp70 expression. Similar anxiolytic and Hsp70 enhancing effects were seen after morphine in normal rats (no RS). Exposure to chronic RS did not elicit any appreciable neurobehavioral response in EPM but enhanced MDA, lowered GSH and exaggerated the Hsp70 expression. Pretreatment with morphine did not affect the neurobehavioral response to chronic RS, but reverted the GSH and Hsp70 expression. The results suggest that morphine differentially influences acute and chronic stress induced changes in anxiety behavior and complex interactions between oxidative stress markers and Hsp70 expression which may contribute to these effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurobehavioral development in Joubert syndrome.

PubMed

Gitten, J; Dede, D; Fennell, E; Quisling, R; Maria, B L

1998-08-01

Research on children with Joubert syndrome has focused on brain structural abnormalities and associated clinical symptoms. The degree of developmental delay has not been objectively reported. We investigated the neurobehavioral development of children with Joubert syndrome through neurobehavioral assessment in the largest sample to date. Thirty-two parents of children with Joubert syndrome completed the Child Development Inventory and magnetic resonance imaging (MRI) data was gathered on 17 of these children. Results indicate that 94% were severely impaired according to the Child Development Inventory, with age being positively correlated with degree of neurobehavioral impairment. The average developmental age of our sample was 19 months (63% below chronological age). Severity of illness as measured by the General Development scale of the Child Development Inventory and severity of illness as measured by MRI (overall severity rating) did not yield consistent data regarding severity of the midbrain and cerebellar malformations. Similarly, markers of abnormal cerebral development such as cortical atrophy and delayed myelination were independent of severity of illness ratings on the Child Development Inventory. The degree of developmental delay in Joubert syndrome and the severity of gross central nervous system malformations appear independent.

Cerebellar mutism syndrome and its relation to cerebellar cognitive and affective function: Review of the literature

PubMed Central

Yildiz, Ozlem; Kabatas, Serdar; Yilmaz, Cem; Altinors, Nur; Agaoglu, Belma

2010-01-01

Tumors of the cerebellum and brainstem account for half of all brain tumors in children. The realization that cerebellar lesions produce clinically relevant intellectual disability makes it important to determine whether neuropsychological abnormalities occur in long-term survivors of pediatric cerebellar tumors. Little is known about the neurobehavioral sequale resulting specifically from the resection of these tumors in this population. We therefore reviewed neuropsychological findings associated with postoperative cerebellar mutism syndrome and discuss the further implications for cerebellar cognitive function. PMID:20436742

Recent advances in Tourette syndrome research.

PubMed

Albin, Roger L; Mink, Jonathan W

2006-03-01

Tourette syndrome (TS) is a developmentally regulated neurobehavioral disorder characterized by involuntary, stereotyped, repetitive movements. Recent anatomical and neuroimaging studies have provided evidence for abnormal basal ganglia and dopaminergic function in TS. Basic research on striatal inhibitory mechanisms and dopaminergic function complements the recent neuroimaging and anatomical data. Parallel studies of basal ganglia participation in the normal performance and learning of stereotyped repetitive behaviors or habits has provided additional insight. These lines of research have provided new pieces to the TS puzzle, and their increasing convergence is showing how those pieces can be put together.

Cross-cultural comparison of neurobehavioral performance in Asian workers.

PubMed

Chung, Jong-Hak; Sakong, Joon; Kang, Pock-Soo; Kim, Chang-Yoon; Lee, Kyeong-Soo; Jeon, Man-Joong; Sung, Nak-Jung; Ahn, Sang-Ho; Won, Kyu-Chang

2003-08-01

Widely-used neurobehavioral tests have been developed and standardized on Western populations, but studies on subject factors for Asian populations have been very limited. For the effective application and interpretation of neurobehavioral tests in Asian populations, an evaluation of the effects of subject factors, including cultural background, is necessary. A cross-cultural study was conducted to evaluate the effects of cultural background and the interaction between cultural background and education on neurobehavioral tests in Asian populations. The Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Symbol Digit, and Finger Tapping Speed) and a pegboard test were administered to 537 workers who were not exposed to chemicals at work from Fareast (Korea and Chinese), Central (Uzbekistan and Tajikistan), and South Asia (Sri Lanka and Indonesia). The Fareast Asian group exhibited better performance in adjusted test scores than other Asian groups, achieving significance for Symbol Digit and Finger Tapping Speed in both genders. The magnitude of the effect of cultural background on Symbol Digit was comparable to the effect of about 10 years of education. Cultural background did not modify the relation between years of education and Symbol Digit in either males or females. This study may provide the first evidence that cultural background has a large impact on neurobehavioral test performance, even within Asian populations, and suggests that cultural background is a critical confounding factor that must be controlled in epidemiologic studies which include Asian populations in the sample.

The accumulation of brain injury leads to severe neuropathological and neurobehavioral changes after repetitive mild traumatic brain injury.

PubMed

Gao, Huabin; Han, Zhaoli; Bai, Ruojing; Huang, Shan; Ge, Xintong; Chen, Fanglian; Lei, Ping

2017-02-15

Traumatic brain injury (TBI) is a major public health problem with long-term neurobehavioral sequela. The evidences have revealed that TBI is a risk factor for later development of neurodegenerative disease and both the single and repetitive brain injury can lead to the neurodegeneration. But whether the effects of accumulation play an important role in the neurodegenerative disease is still unknown. We utilized the Sprague Dawley (SD) rats to develop the animal models of repetitive mild TBI and single mild TBI in order to detect the neurobehavioral changes. The results of neurobehavioral test revealed that the repetitive mild TBI led to more severe behavioral injuries than the single TBI. There were more activated microglia cells and astrocytes in the repetitive mild TBI group than the single TBI group. In consistent with this, the levels of TNF-α and IL-6 were higher and the expression of IL-10 was lower in the repetitive mild TBI group compared with the single TBI group. The expression of amyloid precursor protein (APP) increased in the repetitive TBI group detected by ELISA and western blot. But the levels of total tau (Tau-5) and P-tau (ser202) seem no different between the two groups in most time point. In conclusion, repetitive mild TBI could lead to more severe neurobehavioral impairments and the effects of accumulation may be associated with the increased inflammation in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Relations among school/daycare functioning, fear of hypoglycaemia and quality of life in parents of young children with type 1 diabetes.

PubMed

Herbert, Linda J; Clary, Lauren; Owen, Victoria; Monaghan, Maureen; Alvarez, Vanessa; Streisand, Randi

2015-05-01

To investigate the type 1 diabetes-related school/daycare experiences of parents of young children and to examine the relationship among child school/daycare functioning, parent fear of hypoglycaemia and parent type 1 diabetes-related quality of life. Parents of young children who attend school/daycare must rely on others for daily type 1 diabetes management. Worry about school/daycare type 1 diabetes management may cause parental distress and contribute to diminished parent quality of life. Parental concerns about type 1 diabetes management in young children in the school/daycare setting have not been well described in the literature. Descriptive correlational and cross-sectional parent report of questionnaires design. As part of a randomised controlled trial for parents of young children with type 1 diabetes, 134 parents completed self-report measures at baseline. Data included demographic, school/daycare, and medical information, parent reports of child school/daycare functioning, parent fear of hypoglycaemia and parent type 1 diabetes-related quality of life. Parents of younger children, children on a more intensive medical regimen and children who had experienced type 1 diabetes-related unconsciousness or seizures had more school/daycare concerns. Parents who perceived their children had higher school/daycare functioning had less fear about hypoglycaemia and reported better type 1 diabetes-related quality of life. School/daycare functioning and fear of hypoglycaemia were significantly associated with parent type 1 diabetes-related quality of life. Parents' concerns about school/daycare functioning and fear of hypoglycaemia play an important role in parents' type 1 diabetes-related quality of life. Members of the healthcare team should be aware of concerns related to children attending school/daycare and provide additional support as warranted. © 2014 John Wiley & Sons Ltd.

On-Line Analysis of Physiologic and Neurobehavioral Variables During Long-Duration Space Missions

NASA Technical Reports Server (NTRS)

Brown, Emery N.

1999-01-01

The goal of this project is to develop reliable statistical algorithms for on-line analysis of physiologic and neurobehavioral variables monitored during long-duration space missions. Maintenance of physiologic and neurobehavioral homeostasis during long-duration space missions is crucial for ensuring optimal crew performance. If countermeasures are not applied, alterations in homeostasis will occur in nearly all-physiologic systems. During such missions data from most of these systems will be either continually and/or continuously monitored. Therefore, if these data can be analyzed as they are acquired and the status of these systems can be continually assessed, then once alterations are detected, appropriate countermeasures can be applied to correct them. One of the most important physiologic systems in which to maintain homeostasis during long-duration missions is the circadian system. To detect and treat alterations in circadian physiology during long duration space missions requires development of: 1) a ground-based protocol to assess the status of the circadian system under the light-dark environment in which crews in space will typically work; and 2) appropriate statistical methods to make this assessment. The protocol in Project 1, Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral will study human volunteers under the simulated light-dark environment of long-duration space missions. Therefore, we propose to develop statistical models to characterize in near real time circadian and neurobehavioral physiology under these conditions. The specific aims of this project are to test the hypotheses that: 1) Dynamic statistical methods based on the Kronauer model of the human circadian system can be developed to estimate circadian phase, period, amplitude from core-temperature data collected under simulated light- dark conditions of long-duration space missions. 2) Analytic formulae and numerical algorithms can be developed to compute the error in the estimates of circadian phase, period and amplitude determined from the data in Specific Aim 1. 3) Statistical models can detect reliably in near real- time (daily) significant alternations in the circadian physiology of individual subjects by analyzing the circadian and neurobehavioral data collected in Project 1. 4) Criteria can be developed using the Kronauer model and the recently developed Jewett model of cognitive -performance and subjective alertness to define altered circadian and neurobehavioral physiology and to set conditions for immediate administration of countermeasures.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.

PubMed

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease

PubMed Central

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A.; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD. PMID:27598339

A single administration of cortisol acutely reduces preconscious attention for fear in anxious young men.

PubMed

Putman, Peter; Hermans, Erno J; Koppeschaar, Hans; van Schijndel, Alexandra; van Honk, Jack

2007-08-01

Chronically elevated HPA activity has often been associated with fear and anxiety, but there is evidence that single administrations of glucocorticoids may acutely reduce fear. Moreover, peri-traumatic cortisol elevation may protect against development of post-traumatic stress disorder. Hypervigilant processing of threat information plays a role in anxiety disorders and although relations with HPA functioning have been established, causality of these relations remains unclear. Presently, self-reported anxiety and response time patterns on a masked emotional Stroop task with fearful faces were measured in 20 healthy young men after double-blind, placebo-controlled oral administration of 40 mg cortisol. The masked fearful Stroop task measures vocal colornaming response latencies for pictures of neutral and fearful faces presented below the threshold for conscious perception. Results showed increased response times on trials for fearful compared to neutral faces after placebo, but this emotional Stroop effect was acutely abolished by cortisol administration. This effect was most pronounced in subjects with heightened anxiety levels. This is the first evidence showing that exogenous cortisol acutely reduces anxiety-driven selective attention to threat. These results extend earlier findings of acute fear reduction after glucocorticoid administration. This suggests interactions of HPA functioning and vigilant attention in the pathogenesis of anxiety disorders. Possible neuroendocrine mechanisms of action are discussed.

Factors informing fear of reinjury after anterior cruciate ligament reconstruction.

PubMed

Ross, Cheryl A; Clifford, Amanda; Louw, Quinette A

2017-02-01

Fear of reinjury is associated with cessation of sport after anterior cruciate ligament (ACL) reconstruction despite normal postoperative knee function. The objective of this study is to describe factors informing athletes' experience of fear of reinjury post ACL reconstruction, in athletes who cited fear as the sole reason for not returning to their pre-injury level of sport. Mixed-methods study design of qualitative and a preliminary quantitative component. A conveniently selected private hospital. Ten male and two female athletes, aged between 19 and 45 years, were eligible for the interview from 68 male and 32 female potential participants (age range 17-50) who underwent an ACL reconstruction using any graft type, excluding revision or multi-ligament surgery. To explore factors informing fear of reinjury in participants citing fear of reinjury as the sole reason for not returning to sport, albeit normal knee function. From the participant interview, four themes emerged: undergoing the surgery and recovery again, nature of the pre-injury sport imposing risk of reinjury, personality traits, and social priorities. Clinicians should be aware of factors informing fear of reinjury post ACL reconstruction. Modifiable fears including pain, mode and length of rehabilitation and psychological factors should be considered during rehabilitation to potentially improve the return to sport rate.

Add a picture for suspense: neural correlates of the interaction between language and visual information in the perception of fear

PubMed Central

Clevis, Krien; Hagoort, Peter

2011-01-01

We investigated how visual and linguistic information interact in the perception of emotion. We borrowed a phenomenon from film theory which states that presentation of an as such neutral visual scene intensifies the percept of fear or suspense induced by a different channel of information, such as language. Our main aim was to investigate how neutral visual scenes can enhance responses to fearful language content in parts of the brain involved in the perception of emotion. Healthy participants’ brain activity was measured (using functional magnetic resonance imaging) while they read fearful and less fearful sentences presented with or without a neutral visual scene. The main idea is that the visual scenes intensify the fearful content of the language by subtly implying and concretizing what is described in the sentence. Activation levels in the right anterior temporal pole were selectively increased when a neutral visual scene was paired with a fearful sentence, compared to reading the sentence alone, as well as to reading of non-fearful sentences presented with the same neutral scene. We conclude that the right anterior temporal pole serves a binding function of emotional information across domains such as visual and linguistic information. PMID:20530540

Fearfulness moderates the link between childhood social withdrawal and adolescent reward response.

PubMed

Morgan, Judith K; Shaw, Daniel S; Forbes, Erika E

2015-06-01

Withdrawal from peers during childhood may reflect disruptions in reward functioning that heighten vulnerability to affective disorders during adolescence. The association between socially withdrawn behavior and reward functioning may depend on traits that influence this withdrawal, such as fearfulness or unsociability. In a study of 129 boys, we evaluated how boys' fearfulness and sociability at age 5 and social withdrawal at school at ages 6 to 10 and during a summer camp at age 9/10 were associated with their neural response to reward at age 20. Greater social withdrawal during childhood was associated with heightened striatal and mPFC activation when anticipating rewards at age 20. Fearfulness moderated this effect to indicate that social withdrawal was associated with heightened reward-related response in the striatum for boys high on fearfulness. Altered striatal response associated with social withdrawal and fearfulness predicted greater likelihood to have a lifetime history of depression and social phobia at age 20. These findings add greater specificity to previous findings that children high in traits related to fear of novelty show altered reward responses, by identifying fearfulness (but not low levels of sociability) as a potential underlying mechanism that contributes to reward alterations in withdrawn children. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neurobehavioral effects among inhabitants around mobile phone base stations.

PubMed

Abdel-Rassoul, G; El-Fateh, O Abou; Salem, M Abou; Michael, A; Farahat, F; El-Batanouny, M; Salem, E

2007-03-01

There is a general concern on the possible hazardous health effects of exposure to radiofrequency electromagnetic radiations (RFR) emitted from mobile phone base station antennas on the human nervous system. To identify the possible neurobehavioral deficits among inhabitants living nearby mobile phone base stations. A cross-sectional study was conducted on (85) inhabitants living nearby the first mobile phone station antenna in Menoufiya governorate, Egypt, 37 are living in a building under the station antenna while 48 opposite the station. A control group (80) participants were matched with the exposed for age, sex, occupation and educational level. All participants completed a structured questionnaire containing: personal, educational and medical histories; general and neurological examinations; neurobehavioral test battery (NBTB) [involving tests for visuomotor speed, problem solving, attention and memory]; in addition to Eysenck personality questionnaire (EPQ). The prevalence of neuropsychiatric complaints as headache (23.5%), memory changes (28.2%), dizziness (18.8%), tremors (9.4%), depressive symptoms (21.7%), and sleep disturbance (23.5%) were significantly higher among exposed inhabitants than controls: (10%), (5%), (5%), (0%), (8.8%) and (10%), respectively (P<0.05). The NBTB indicated that the exposed inhabitants exhibited a significantly lower performance than controls in one of the tests of attention and short-term auditory memory [Paced Auditory Serial Addition Test (PASAT)]. Also, the inhabitants opposite the station exhibited a lower performance in the problem solving test (block design) than those under the station. All inhabitants exhibited a better performance in the two tests of visuomotor speed (Digit symbol and Trailmaking B) and one test of attention (Trailmaking A) than controls. The last available measures of RFR emitted from the first mobile phone base station antennas in Menoufiya governorate were less than the allowable standard level. Inhabitants living nearby mobile phone base stations are at risk for developing neuropsychiatric problems and some changes in the performance of neurobehavioral functions either by facilitation or inhibition. So, revision of standard guidelines for public exposure to RER from mobile phone base station antennas and using of NBTB for regular assessment and early detection of biological effects among inhabitants around the stations are recommended.

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

PubMed

McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

2016-01-01

No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test.

Zebrafish model systems for developmental neurobehavioral toxicology.

PubMed

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D

2013-03-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. Copyright © 2013 Wiley Periodicals, Inc.

Khat Use and Neurobehavioral Functions: Suggestions for Future Studies

PubMed Central

Hoffman, Richard; al’Absi, Mustafa

2010-01-01

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures. PMID:20553832

Zebrafish Model Systems for Developmental Neurobehavioral Toxicology

PubMed Central

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D.

2014-01-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. PMID:23723169

The geriatric depression scale and the timed up and go test predict fear of falling in community-dwelling elderly women with type 2 diabetes mellitus: a cross-sectional study.

PubMed

Moreira, Bruno de Souza; Dos Anjos, Daniela Maria da Cruz; Pereira, Daniele Sirineu; Sampaio, Rosana Ferreira; Pereira, Leani Souza Máximo; Dias, Rosângela Corrêa; Kirkwood, Renata Noce

2016-03-03

Fear of falling is a common and potentially disabling problem among older adults. However, little is known about this condition in older adults with diabetes mellitus. The aims of this study were to investigate the impact of the fear of falling on clinical, functional and gait variables in older women with type 2 diabetes and to identify which variables could predict the fear of falling in this population. Ninety-nine community-dwelling older women with type 2 diabetes (aged 65 to 89 years) were stratified in two groups based on their Falls Efficacy Scale-International score. Participants with a score < 23 were assigned to the group without the fear of falling (n = 50) and those with a score ≥ 23 were assigned to the group with the fear of falling (n = 49). Clinical data included demographics, anthropometrics, number of diseases and medications, physical activity level, fall history, frailty level, cognition, depressive symptoms, fasting glucose level and disease duration. Functional measures included the Timed Up and Go test (TUG), the five times sit-to-stand test (5-STS) and handgrip strength. Gait parameters were obtained using the GAITRite® system. Participants with a fear of falling were frailer and presented more depressive symptoms and worse performance on the TUG and 5-STS tests compared with those without a fear of falling. The group with the fear of falling also walked with a lower velocity, cadence and step length and increased step time and swing time variability. The multivariate regression analysis showed that the likelihood of having a fear of falling increased 1.34 times (OR 1.34, 95 % CI 1.11-1.61) for a one-point increase in the Geriatric Depression Scale (GDS-15) score and 1.36 times (OR 1.36, 95 % CI 1.07-1.73) for each second of increase in the TUG performance. The fear of falling in community-dwelling older women with type 2 diabetes mellitus is associated with frailty, depressive symptoms and dynamic balance, functional mobility and gait deficits. Furthermore, both the GDS-15 and the TUG test predict a fear of falling in this population. Therefore, these instruments should be considered during the assessment of diabetic older women with fear of falling.

Changes in Structural Connectivity Following a Cognitive Intervention in Children With Traumatic Brain Injury.

PubMed

Yuan, Weihong; Treble-Barna, Amery; Sohlberg, McKay M; Harn, Beth; Wade, Shari L

2017-02-01

Structural connectivity analysis based on graph theory and diffusion tensor imaging tractography is a novel method that quantifies the topological characteristics in the brain network. This study aimed to examine structural connectivity changes following the Attention Intervention and Management (AIM) program designed to improve attention and executive function (EF) in children with traumatic brain injury (TBI). Seventeen children with complicated mild to severe TBI (13.66 ± 2.68 years; >12 months postinjury) completed magnetic resonance imaging (MRI) and neurobehavioral measures at time 1, 10 of whom completed AIM and assessment at time 2. Eleven matched healthy comparison (HC) children (13.37 ± 2.08 years) completed MRI and neurobehavioral assessment at both time points, but did not complete AIM. Network characteristics were analyzed to quantify the structural connectivity before and after the intervention. Mixed model analyses showed that small-worldness was significantly higher in the TBI group than the HC group at time 1, and both small-worldness and normalized clustering coefficient decreased significantly at time 2 in the TBI group whereas the HC group remained relatively unchanged. Reductions in mean local efficiency were significantly correlated with improvements in verbal inhibition and both parent- and child-reported EF. Increased normalized characteristic path length was significantly correlated with improved sustained attention. The results provide preliminary evidence suggesting that graph theoretical analysis may be a sensitive tool in pediatric TBI for detecting ( a) abnormalities of structural connectivity in brain network and ( b) structural neuroplasticity associated with neurobehavioral improvement following a short-term intervention for attention and EF.

Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish.

PubMed

Knecht, Andrea L; Truong, Lisa; Marvel, Skylar W; Reif, David M; Garcia, Abraham; Lu, Catherine; Simonich, Michael T; Teeguarden, Justin G; Tanguay, Robert L

2017-08-15

Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10μM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Neurobehavioral performance and work experience in Florida farmworkers.

PubMed

Kamel, Freya; Rowland, Andrew S; Park, Lawrence P; Anger, W Kent; Baird, Donna D; Gladen, Beth C; Moreno, Tirso; Stallone, Lillian; Sandler, Dale P

2003-11-01

Farmworkers experience many work-related hazards, including exposure to neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in central Florida who had done farm work for at least 1 month with 51 controls who had not. Most of the farmworkers had worked in one or more of three types of agriculture: ornamental ferns, nurseries, or citrus fruit. We collected information on farm work history in a structured interview and evaluated neurobehavioral performance using a battery of eight tests. Analyses were adjusted for established confounders including age, sex, education, and acculturation. Ever having done farm work was associated with poor performance on four tests--digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI), 1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74; 95% CI, -2.20 to 11.7)--but had little effect on four others: symbol digit latency, vibrotactile threshold, visual contrast sensitivity, and grip strength. Associations with farm work were similar in magnitude to associations with personal characteristics such as age and sex. Longer duration of farm work was associated with worse performance. Associations with fern work were more consistent than associations with nursery or citrus work. Deficits related to the duration of work experience were seen in former as well as current farmworkers, and decreased performance was related to chronic exposure even in the absence of a history of pesticide poisoning. We conclude that long-term experience of farm work is associated with measurable deficits in cognitive and psychomotor function.

Division III Collision Sports Are Not Associated with Neurobehavioral Quality of Life.

PubMed

Meehan, William P; Taylor, Alex M; Berkner, Paul; Sandstrom, Noah J; Peluso, Mark W; Kurtz, Matthew M; Pascual-Leone, Alvaro; Mannix, Rebekah

2016-01-15

We sought to determine whether the exposure to the sub-concussive blows that occur during division III collegiate collision sports affect later life neurobehavioral quality-of-life measures. We conducted a cross-sectional study of alumni from four division III colleges, targeting those between the ages of 40-70 years, using several well-validated quality-of-life measures for executive function, general concerns, anxiety, depression, emotional and behavior dyscontrol, fatigue, positive affect, sleep disturbance, and negative consequences of alcohol use. We used multivariable linear regression to assess for associations between collision sport participation and quality-of-life measures while adjusting for covariates including age, gender, race, annual income, highest educational degree, college grades, exercise frequency, and common medical conditions. We obtained data from 3702 alumni, more than half of whom (2132) had participated in collegiate sports, 23% in collision sports, 23% in non-contact sports. Respondents with a history of concussion had worse self-reported health on several measures. When subjects with a history of concussion were removed from the analyses in order to assess for any potential effect of sub-concussive blows alone, negative consequences of alcohol use remained higher among collision sport athletes (β-coefficient 1.957, 95% CI 0.827-3.086). There were, however, no other significant associations between exposure to collision sports during college and any other quality-of-life measures. Our results suggest that, in the absence of a history of concussions, participation in collision sports at the Division III collegiate level is not a risk factor for worse long-term neurobehavioral outcomes, despite exposure to repeated sub-concussive blows.

Microbiome Disturbances and Autism Spectrum Disorders.

PubMed

Rosenfeld, Cheryl S

2015-10-01

Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

PubMed

McHill, Andrew W; Hull, Joseph T; Wang, Wei; Czeisler, Charles A; Klerman, Elizabeth B

2018-06-05

Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.

Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans

PubMed Central

Indovina, Iole; Robbins, Trevor W.; Núñez-Elizalde, Anwar O.; Dunn, Barnaby D.; Bishop, Sonia J.

2011-01-01

Summary Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms underlying cued and contextual fear. A critical question is how personality dimensions such as trait anxiety act through these mechanisms to confer vulnerability to anxiety disorders, and whether humans' ability to overcome acquired fears depends on regulatory skills not characterized in animal models. In a neuroimaging study of fear conditioning in humans, we found evidence for two independent dimensions of neurocognitive function associated with trait vulnerability to anxiety. The first entailed increased amygdala responsivity to phasic fear cues. The second involved impoverished ventral prefrontal cortical (vPFC) recruitment to downregulate both cued and contextual fear prior to omission (extinction) of the aversive unconditioned stimulus. These two dimensions may contribute to symptomatology differences across anxiety disorders; the amygdala mechanism affecting the development of phobic fear and the frontal mechanism influencing the maintenance of both specific fears and generalized anxiety. PMID:21315265

Prevalence of falls in elderly women

PubMed Central

Vitor, Priscila Regina Rorato; de Oliveira, Ana Carolina Kovaleski; Kohler, Renan; Winter, Gabriele Regiane; Rodacki, Cintia; Krause, Maressa Priscila

2015-01-01

OBJECTIVE: To verify prevalence of falls and fear of falling, and to compare functional fitness among elderly women fallers and non-fallers. METHODS: Seventy-eight elderly women participated in this study. Cases of falls and the fear of falling were self-reported by the elderly women, while the functional fitness was measured by a set of functional tests. Mean and standard deviation were used to describe the sample. Independent t-test was used to compare functional fitness between groups. RESULTS: The prevalence of falls in this sample was 32.4%. Among women fallers, 40% self-reported a high fear of falling. CONCLUSION: It is recommended that functional and resistance exercises are included in the preventive strategies for reducing risk factors for falls and its determinants in elderly women. Level of Evidence II, Prognostic-Prospective Study. PMID:26207095

Fear of progression.

PubMed

Herschbach, Peter; Dinkel, Andreas

2014-01-01

Fear of progression (or fear of recurrence) is an appropriate, rational response to the real threat of cancer and cancer treatments. However, elevated levels of fear of progression can become dysfunctional, affecting well-being, quality of life, and social functioning. Research has shown that fear of progression is one of the most frequent distress symptoms of patients with cancer and with other chronic diseases. As a clear consensus concerning clinically relevant states of fear of progression is currently lacking, it is difficult to provide a valid estimate of the rate of cancer patients who clearly suffer from fear of progression. However, recent systematic reviews suggest that probably 50 % of cancer patients experience moderate to severe fear of progression. Furthermore, many patients express unmet needs in dealing with the fear of cancer spreading. These results underline the necessity to provide effective psychological treatments for clinical levels of fear of progression. A few psychosocial interventions for treating fear of progression have been developed so far. Our own, targeted intervention study showed that dysfunctional fear of progression can be effectively treated with a brief group therapy.

Optimism Moderates the Influence of Pain Catastrophizing on Shoulder Pain Outcome: A Longitudinal Analysis.

PubMed

Coronado, Rogelio A; Simon, Corey B; Lentz, Trevor A; Gay, Charles W; Mackie, Lauren N; George, Steven Z

2017-01-01

Study Design Secondary analysis of prospectively collected data. Background An abundance of evidence has highlighted the influence of pain catastrophizing and fear avoidance on clinical outcomes. Less is known about the interaction of positive psychological resources with these pain-associated distress factors. Objective To assess whether optimism moderates the influence of pain catastrophizing and fear avoidance on 3-month clinical outcomes in patients with shoulder pain. Methods Data from 63 individuals with shoulder pain (mean ± SD age, 38.8 ± 14.9 years; 30 female) were examined. Demographic, psychological, and clinical characteristics were obtained at baseline. Validated measures were used to assess optimism (Life Orientation Test-Revised), pain catastrophizing (Pain Catastrophizing Scale), fear avoidance (Fear-Avoidance Beliefs Questionnaire physical activity subscale), shoulder pain intensity (Brief Pain Inventory), and shoulder function (Pennsylvania Shoulder Score function subscale). Shoulder pain and function were reassessed at 3 months. Regression models assessed the influence of (1) pain catastrophizing and optimism and (2) fear avoidance and optimism. The final multivariable models controlled for factors of age, sex, education, and baseline scores, and included 3-month pain intensity and function as separate dependent variables. Results Shoulder pain (mean difference, -1.6; 95% confidence interval [CI]: -2.1, -1.2) and function (mean difference, 2.4; 95% CI: 0.3, 4.4) improved over 3 months. In multivariable analyses, there was an interaction between pain catastrophizing and optimism (β = 0.19; 95% CI: 0.02, 0.35) for predicting 3-month shoulder function (F = 16.8, R 2 = 0.69, P<.001), but not pain (P = .213). Further examination of the interaction with the Johnson-Neyman technique showed that higher levels of optimism lessened the influence of pain catastrophizing on function. There was no evidence of significant moderation of fear-avoidance beliefs for 3-month shoulder pain (P = .090) or function (P = .092). Conclusion Optimism decreased the negative influence of pain catastrophizing on shoulder function, but not pain intensity. Optimism did not alter the influence of fear-avoidance beliefs on these outcomes. Level of Evidence Prognosis, level 2b. J Orthop Sports Phys Ther 2017;47(1):21-30. Epub 5 Nov 2016. doi:10.2519/jospt.2017.7068.

Neurobehavioral and Psychosocial Issues in Klinefelter Syndrome

ERIC Educational Resources Information Center

Geschwind, Daniel H.; Dykens, Elisabeth

2004-01-01

Klinefelter Syndrome (KS) is a relatively common (1/500 to 1/1,000) genetic syndrome caused by an extra X chromosome in males, leading to an XXY karyotype. In most cases, the physical and neurobehavioral characteristics of KS are relatively mild, and KS is not usually associated with moderate or severe mental retardation. However, KS is often…

Neurobehavioral Consequences of Prenatal Exposure to Smoking at 6 to 8 Months of Age

ERIC Educational Resources Information Center

Willoughby, Michael; Greenberg, Mark; Blair, Clancy; Stifter, Cynthia

2007-01-01

Between 400,000 and 800,000 infants are born in the United States each year to women who smoked cigarettes during their pregnancy. Whereas the physical health consequences to infants of prenatal exposure to smoking are well established, the early neurobehavioral consequences are less well understood. This study investigated the neurobehavioral…

Epigenetic Regulation of Placental "NR3C1": Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

ERIC Educational Resources Information Center

Stroud, Laura R.; Papandonatos, George D.; Salisbury, Amy L.; Phipps, Maureen G.; Huestis, Marilyn A.; Niaura, Raymond; Padbury, James F.; Marsit, Carmen J.; Lester, Barry M.

2016-01-01

Epigenetic regulation of the placental glucocorticoid receptor gene ("NR3C1") was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral…

Falls and Fear of Falling After Stroke: A Case-Control Study.

PubMed

Goh, Hui-Ting; Nadarajah, Mohanasuntharaam; Hamzah, Norhamizan Binti; Varadan, Parimalaganthi; Tan, Maw Pin

2016-12-01

Falls are common after stroke, with potentially serious consequences. Few investigations have included age-matched control participants to directly compare fall characteristics between older adults with and without stroke. Further, fear of falling, a significant psychological consequence of falls, has only been examined to a limited degree as a risk factor for future falls in a stroke population. To compare the fall history between older adults with and without a previous stroke and to identify the determinants of falls and fear of falling in older stroke survivors. Case-control observational study. Primary teaching hospital. Seventy-five patients with stroke (mean age ± standard deviation, 66 ± 7 years) and 50 age-matched control participants with no previous stroke were tested. Fall history, fear of falling, and physical, cognitive, and psychological function were assessed. A χ 2 test was performed to compare characteristics between groups, and logistic regression was performed to determine the risk factors for falls and fear of falling. Fall events in the past 12 months, Fall Efficacy Scale-International, Berg Balance Scale, Functional Ambulation Category, Fatigue Severity Scale, Montreal Cognitive Assessment, and Patient Healthy Questionnaire-9 were measured for all participants. Fugl-Meyer Motor Assessment was used to quantify severity of stroke motor impairments. Twenty-three patients and 13 control participants reported at least one fall in the past 12 months (P = .58). Nine participants with stroke had recurrent falls (≥2 falls) compared with none of the control participants (P < .01). Participants with stroke reported greater concern for falling than did nonstroke control participants (P < .01). Female gender was associated with falls in the nonstroke group, whereas falls in the stroke group were not significantly associated with any measured outcomes. Fear of falling in the stroke group was associated with functional ambulation level and balance. Functional ambulation level alone explained 22% of variance in fear of falling in the stroke group. Compared with persons without a stroke, patients with stroke were significantly more likely to experience recurrent falls and fear of falling. Falls in patients with stroke were not explained by any of the outcome measures used, whereas fear of falling was predicted by functional ambulation level. This study has identified potentially modifiable risk factors with which to devise future prevention strategies for falls in patients with stroke. III. Copyright © 2016. Published by Elsevier Inc.

The central amygdala circuits in fear regulation

NASA Astrophysics Data System (ADS)

Li, Bo

The amygdala is essential for fear learning and expression. The central amygdala (CeA), once viewed as a passive relay between the amygdala complex and downstream fear effectors, has emerged as an active participant in fear conditioning. However, how the CeA contributes to the learning and expression of fear remains unclear. Our recent studies in mice indicate that fear conditioning induces robust plasticity of excitatory synapses onto inhibitory neurons in the lateral subdivision of CeA (CeL). In particular, this plasticity is cell-type specific and is required for the formation of fear memory. In addition, sensory cues that predict threat can cause activation of the somatostatin-positive CeL neurons, which is sufficient to drive freezing behavior. Here I will report our recent findings regarding the circuit and cellular mechanisms underlying CeL function in fear processing.

Neuropeptide Regulation of Fear and Anxiety: Implications of Cholecystokinin, Endogenous Opioids, and Neuropeptide Y

PubMed Central

Bowers, Mallory E.; Choi, Dennis C.; Ressler, Kerry J.

2012-01-01

The neural circuitry of fear likely underlies anxiety and fear-related disorders such as specific and social phobia, panic disorder, and posttraumatic stress disorder. The primary pharmacological treatments currently utilized for these disorders include benzodiazepines, which act on the GABAergic receptor system, and antidepressants, which modulate the monamine systems. However, recent work on the regulation of fear neural circuitry suggests that specific neuropeptide modulation of this system is of critical importance. Recent reviews have examined the roles of the hypothalamic-pituitary-adrenal axis neuropeptides as well as the roles of neurotrophic factors in regulating fear. The present review, instead, will focus on three neuropeptide systems which have received less attention in recent years but which are clearly involved in regulating fear and its extinction. The endogenous opioid system, particularly activating the μ opioid receptors, has been demonstrated to regulate fear expression and extinction, possibly through functioning as an error signal within the amygdala to mark unreinforced conditioned stimuli. The cholecystokinin (CCK) system initially led to much excitement through its potential role in panic disorder. More recent work in the CCK neuropeptide pathway suggests that it may act in concordance with the endogenous cannabinoid system in the modulation of fear inhibition and extinction. Finally, older as well as very recent data suggests that neuropeptide Y (NPY) may play a very interesting role in counteracting stress effects, enhancing extinction, and enhancing resilience in fear and stress preclinical models. Future work in understanding the mechanisms of neuropeptide functioning, particularly within well-known behavioral circuits, are likely to provide fascinating new clues into the understanding of fear behavior as well as suggesting novel therapeutics for treating disorders of anxiety and fear dysregulation. PMID:22429904

Falls, a fear of falling and related factors in older adults with complex chronic disease.

PubMed

Lee, JuHee; Choi, MoonKi; Kim, Chang Oh

2017-12-01

To identify factors influencing falls and the fear of falling among older adults with chronic diseases in Korea. The fear of falling and falls in older adults are significant health problems towards which healthcare providers should direct their attention. Further investigation is needed to improve nursing practice specifically decreasing risk of falls and the fear of falling in Korea. Descriptive, cross-sectional survey. A convenience sample of 108 patients was recruited at the geriatric outpatient department of a tertiary hospital in Seoul, Korea. Demographic characteristics, comorbidities, medication use, fall history, level of physical activity, activities of daily living, mobility, muscle strength, and a fear of falling were investigated. Student's t tests, chi-square tests and multiple linear regressions were used in statistical analysis. Thirty-six participants (33.3%) among 108 subjects reported experiencing ≥1 falls in the past year. Marital status and the use of antipsychotics were associated with falls, while other factors were not significantly related to falls. Only benign prostatic hypertrophy and polypharmacy were significantly related to the fear of falling in the analysis of the relationships between chronic disease, medication use and fear of falling. In the regression model, the number of comorbidities, level of physical activity, activities of daily living and mobility were predictors of a fear of falling. Medication use was marginally significant, in the model. Increasing physical activity, functional fitness and physical independence is important to decrease the fear of falling, and to encourage active and healthy lives in older adults. The findings from this study provide evidence for the development of nursing interventions for older adults. We recommend early screening for a fear of falling and nursing interventions to decrease the fear of falling through enhancing physical activity level and function. © 2017 John Wiley & Sons Ltd.

Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala

PubMed Central

Kwapis, Janine L; Alaghband, Yasaman; López, Alberto J; White, André O; Campbell, Rianne R; Dang, Richard T; Rhee, Diane; Tran, Ashley V; Carl, Allison E; Matheos, Dina P; Wood, Marcelo A

2017-01-01

Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit. PMID:27924874

Neuromotor function in ship welders after cessation of manganese exposure.

PubMed

Wastensson, Gunilla; Sallsten, Gerd; Bast-Pettersen, Rita; Barregard, Lars

2012-08-01

The aim of the present study was to investigate whether previous long-term exposure to manganese (Mn) via inhalation of welding fumes can cause persistent impairment in neuromotor function even long after cessation of exposure. Quantitative tests of tremor, motor speed, manual dexterity, diadochokinesis, eye-hand coordination and postural stability were administered to 17 retired ship welders (mean age 69 years), with mean exposure time 28 years. The welders' exposure had ceased on average 18 years before the study. A cumulative exposure index (CEI) was calculated for each of the former welders. The welders were compared with 21 referents from the same shipyards (mean age was 66 years). Former welders performed less well than referents in the grooved pegboard test, and poorer performance was associated with CEI. The performance in most of the other neurobehavioral tests was similar between groups, but the welders tended to perform slightly better than the referents in tests demanding hand steadiness. The latter finding may be due to a training effect from their former working tasks or selection bias into or out of this occupation. In the present study of welders with previous welding fume exposure, former welders and referents performed similarly in most of the neurobehavioral tests. Previous adverse effects on the neuromotor system might have ceased, and decreased neuromotor function due to normal aging processes in both groups might have disguised any slight effect of previous Mn exposure. The poorer performance in the grooved pegboard test among welders may indicate an adverse effect on motor function of long-term exposure to Mn, but this finding has to be confirmed by other studies.

BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall.

PubMed

Lonsdorf, Tina B; Golkar, Armita; Lindström, Kara M; Haaker, Jan; Öhman, Arne; Schalling, Martin; Ingvar, Martin

2015-05-01

Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition 'and' extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS- comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Fear of Crime in the Elderly: A Longitudinal Study.

ERIC Educational Resources Information Center

Fuentes, Max E.; And Others

To investigate correlates of fear of crime and physical mobility among physically vulnerable older adults, 42 community dwelling older adults twice completed a battery of tests, with 1 year intervening. The tests included Functional Health Status, Perceived Health Status, Sense of Mastery, Leave of Residence, and Fear of Crime. Crime statistics…

Impairments in Fear Conditioning in Mice Lacking the nNOS Gene

ERIC Educational Resources Information Center

Kelley, Jonathan B.; Balda, Mara A.; Anderson, Karen L.; Itzhak, Yossef

2009-01-01

The fear conditioning paradigm is used to investigate the roles of various genes, neurotransmitters, and substrates in the formation of fear learning related to contextual and auditory cues. In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) functions as a retrograde neuronal messenger that facilitates synaptic…

Age-Dependent Deficits in Fear Learning in Heterozygous BDNF Knock-Out Mice

ERIC Educational Resources Information Center

Endres, Thomas; Lessmann, Volkmar

2012-01-01

Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic factor) is well known to crucially mediate synaptic plasticity and memory formation. Whereas recent studies suggested that acute BDNF/TrkB signaling regulates amygdala-dependent fear learning, no impairments of cued fear learning were reported in heterozygous BDNF…

Association of Physical Performance and Pain With Fear of Falling Among Community—Dwelling Japanese Women Aged 65 Years and Older

PubMed Central

Tomita, Yoshihito; Arima, Kazuhiko; Kanagae, Mitsuo; Okabe, Takuhiro; Mizukami, Satoshi; Nishimura, Takayuki; Abe, Yasuyo; Goto, Hisashi; Horiguchi, Itsuko; Aoyagi, Kiyoshi

2015-01-01

Abstract Our aim was to explore the association of physical performance and pain with fear of falling among community-dwelling Japanese women. The subjects were 278 women aged 65 years and over. We collected information on fear of falling, painful joints, comorbidities, falls in the previous year, and cataracts. Walking time (distance of 6 m), chair stand time (5 times), grip strength, the timed up and go test (TUG), and functional reach were measured. The prevalence of fear of falling was 36.3%, and it increased with age, but it was not significant (P = 0.081). Multivariate logistic regression analysis showed that poor physical performance (longer walking time, longer chair stand time, weaker grip strength, and longer TUG) and pain (low back, and upper and lower extremity pain) were significantly associated with fear of falling after adjusting for age, body mass index, comorbidities, falls in the previous year, and cataracts. Maintaining physical functioning and managing pain may be important for elderly women with fear of falling. PMID:26334906

Slk19p of Saccharomyces cerevisiae Regulates Anaphase Spindle Dynamics Through Two Independent Mechanisms

PubMed Central

Havens, Kyle A.; Gardner, Melissa K.; Kamieniecki, Rebecca J.; Dresser, Michael E.; Dawson, Dean S.

2010-01-01

Slk19p is a member of the Cdc-14 early anaphase release (FEAR) pathway, a signaling network that is responsible for activation of the cell-cycle regulator Cdc14p in Saccharomyces cerevisiae. Disruption of the FEAR pathway results in defects in anaphase, including alterations in the assembly and behavior of the anaphase spindle. Many phenotypes of slk19Δ mutants are consistent with a loss of FEAR signaling, but other phenotypes suggest that Slk19p may have FEAR-independent roles in modulating the behavior of microtubules in anaphase. Here, a series of SLK19 in-frame deletion mutations were used to test whether Slk19p has distinct roles in anaphase that can be ascribed to specific regions of the protein. Separation-of-function alleles were identified that are defective for either FEAR signaling or aspects of anaphase spindle function. The data suggest that in early anaphase one region of Slk19p is essential for FEAR signaling, while later in anaphase another region is critical for maintaining the coordination between spindle elongation and the growth of interpolar microtubules. PMID:20923975

Association of Physical Performance and Pain With Fear of Falling Among Community-Dwelling Japanese Women Aged 65 Years and Older.

PubMed

Tomita, Yoshihito; Arima, Kazuhiko; Kanagae, Mitsuo; Okabe, Takuhiro; Mizukami, Satoshi; Nishimura, Takayuki; Abe, Yasuyo; Goto, Hisashi; Horiguchi, Itsuko; Aoyagi, Kiyoshi

2015-09-01

Our aim was to explore the association of physical performance and pain with fear of falling among community-dwelling Japanese women.The subjects were 278 women aged 65 years and over. We collected information on fear of falling, painful joints, comorbidities, falls in the previous year, and cataracts. Walking time (distance of 6 m), chair stand time (5 times), grip strength, the timed up and go test (TUG), and functional reach were measured.The prevalence of fear of falling was 36.3%, and it increased with age, but it was not significant (P = 0.081). Multivariate logistic regression analysis showed that poor physical performance (longer walking time, longer chair stand time, weaker grip strength, and longer TUG) and pain (low back, and upper and lower extremity pain) were significantly associated with fear of falling after adjusting for age, body mass index, comorbidities, falls in the previous year, and cataracts.Maintaining physical functioning and managing pain may be important for elderly women with fear of falling.

The impact of cumulative pain/stress on neurobehavioral development of preterm infants in the NICU.

PubMed

Cong, Xiaomei; Wu, Jing; Vittner, Dorothy; Xu, Wanli; Hussain, Naveed; Galvin, Shari; Fitzsimons, Megan; McGrath, Jacqueline M; Henderson, Wendy A

2017-05-01

Vulnerable preterm infants experience repeated and prolonged pain/stress stimulation during a critical period in their development while in the neonatal intensive care unit (NICU). The contribution of cumulative pain/stressors to altered neurodevelopment remains unclear. The study purpose was to investigate the impact of early life painful/stressful experiences on neurobehavioral outcomes of preterm infants in the NICU. A prospective exploratory study was conducted with fifty preterm infants (28 0/7-32 6/7weeks gestational age) recruited at birth and followed for four weeks. Cumulative pain/stressors (NICU Infant Stressor Scale) were measured daily and neurodevelopmental outcomes (NICU Network Neurobehavioral Scale) were examined at 36-37weeks post-menstrual age. Data analyses were conducted on the distribution of pain/stressors experienced over time and the linkages among pain/stressors and neurobehavioral outcomes. Preterm infants experienced a high degree of pain/stressors in the NICU, both in numbers of daily acute events (22.97±2.30 procedures) and cumulative times of chronic/stressful exposure (42.59±15.02h). Both acute and chronic pain/stress experienced during early life significantly contributed to the neurobehavioral outcomes, particularly in stress/abstinence (p<0.05) and habituation responses (p<0.01), meanwhile, direct breastfeeding and skin-to-skin holding were also significantly associated with habituation (p<0.01-0.05). Understanding mechanisms by which early life experience alters neurodevelopment will assist clinicians in developing targeted neuroprotective strategies and individualized interventions to improve infant developmental outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting risk in space: Genetic markers for differential vulnerability to sleep restriction

NASA Astrophysics Data System (ADS)

Goel, Namni; Dinges, David F.

2012-08-01

Several laboratories have found large, highly reliable individual differences in the magnitude of cognitive performance, fatigue and sleepiness, and sleep homeostatic vulnerability to acute total sleep deprivation and to chronic sleep restriction in healthy adults. Such individual differences in neurobehavioral performance are also observed in space flight as a result of sleep loss. The reasons for these stable phenotypic differential vulnerabilities are unknown: such differences are not yet accounted for by demographic factors, IQ or sleep need, and moreover, psychometric scales do not predict those individuals cognitively vulnerable to sleep loss. The stable, trait-like (phenotypic) inter-individual differences observed in response to sleep loss—with intraclass correlation coefficients accounting for 58-92% of the variance in neurobehavioral measures—point to an underlying genetic component. To this end, we utilized multi-day highly controlled laboratory studies to investigate the role of various common candidate gene variants—each independently—in relation to cumulative neurobehavioral and sleep homeostatic responses to sleep restriction. These data suggest that common genetic variations (polymorphisms) involved in sleep-wake, circadian, and cognitive regulation may serve as markers for prediction of inter-individual differences in sleep homeostatic and neurobehavioral vulnerability to sleep restriction in healthy adults. Identification of genetic predictors of differential vulnerability to sleep restriction—as determined from candidate gene studies—will help identify astronauts most in need of fatigue countermeasures in space flight and inform medical standards for obtaining adequate sleep in space. This review summarizes individual differences in neurobehavioral vulnerability to sleep deprivation and ongoing genetic efforts to identify markers of such differences.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

PubMed

Chervin, Ronald D; Garetz, Susan L; Ruzicka, Deborah L; Hodges, Elise K; Giordani, Bruno J; Dillon, James E; Felt, Barbara T; Hoban, Timothy F; Guire, Kenneth E; O'Brien, Louise M; Burns, Joseph W

2014-08-15

Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. ClinicalTrials.gov, ID: NCT00233194.

Exercise Training Improves Selected Aspects of Daytime Functioning in Adults with Obstructive Sleep Apnea

PubMed Central

Kline, Christopher E.; Ewing, Gary B.; Burch, James B.; Blair, Steven N.; Durstine, J. Larry; Davis, J. Mark; Youngstedt, Shawn D.

2012-01-01

Study Objectives: To explore the utility of exercise training for improving daytime functioning in adults with obstructive sleep apnea (OSA). Methods: Forty-three sedentary and overweight/obese adults aged 18-55 years with at least moderate-severity untreated OSA (apnea-hypopnea index ≥ 15) were randomized to 12 weeks of moderate-intensity aerobic and resistance exercise training (n = 27) or low-intensity stretching control treatment (n = 16). As part of a trial investigating the efficacy of exercise training on OSA severity, daytime functioning was assessed before and following the intervention. Sleepiness, functional impairment due to sleepiness, depressive symptoms, mood, and quality of life (QOL) were evaluated with validated questionnaires, and cognitive function was assessed with a neurobehavioral performance battery. OSA severity was measured with one night of laboratory polysomnography before and following the intervention. Results: Compared with stretching control, exercise training resulted in significant improvements in depressive symptoms, fatigue and vigor, and aspects of QOL (p < 0.05). Sleepiness and functional impairment due to sleepiness also were improved following exercise versus control to a similar degree in terms of effect sizes (d > 0.5), though these changes were not statistically significant. No neurobehavioral performance improvements were found. Reduced fatigue following exercise training was mediated by a reduction in OSA severity, but changes in OSA severity did not significantly mediate improvement in any other measure of daytime functioning. Conclusions: These data provide preliminary evidence that exercise training may be helpful for improving aspects of daytime functioning of adults with OSA. Larger trials are needed to further verify the observed improvements. Trial Registration: Clinicaltrials.gov identification number NCT00956423. Citation: Kline CE; Ewing GB; Burch JB; Blair SN; Durstine JL; Davis JM; Youngstedt SD. Exercise training improves selected aspects of daytime functioning in adults with obstructive sleep apnea. J Clin Sleep Med 2012;8(4):357-365. PMID:22893765

Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders. PMID:25232313

Occupational solvent exposure and brain function: an fMRI study.

PubMed

Tang, Cheuk Ying; Carpenter, David M; Eaves, Emily L; Ng, Johnny; Ganeshalingam, Nimalya; Weisel, Clifford; Qian, Hua; Lange, Gudrun; Fiedler, Nancy L

2011-07-01

Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. Solvent-exposed workers' performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices--areas serving working memory function and attention--was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.

Occupational Solvent Exposure and Brain Function: An fMRI Study

PubMed Central

Carpenter, David M.; Eaves, Emily L.; Ng, Johnny; Ganeshalingam, Nimalya; Weisel, Clifford; Qian, Hua; Lange, Gudrun; Fiedler, Nancy L.

2011-01-01

Background: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. Objectives: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. Methods: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. Results: Solvent-exposed workers’ performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices—areas serving working memory function and attention—was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. Conclusions: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work. PMID:21296712

An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome.

PubMed

Gilbert, Mary E; Hedge, Joan M; Valentín-Blasini, Liza; Blount, Benjamin C; Kannan, Kurunthachalam; Tietge, Joseph; Zoeller, R Thomas; Crofton, Kevin M; Jarrett, Jeffrey M; Fisher, Jeffrey W

2013-03-01

Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 µg/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 μg iodine/kg chow, D1) to deficient (Diet 5: 25 µg iodine/kg chow, D5). Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21. Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21. Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine. T4 was reduced in the fetal brain but was not altered in the neonatal brain. Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults. These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption.

The Observer Effect and Its Impact on Staff Behavior in an Acquired Brain Injury Neurobehavioral Treatment Setting

ERIC Educational Resources Information Center

Guercio, John M.; Dixon, Mark R.

2011-01-01

Staff in three neurobehavioral residential settings (5 in each residence for a total of 15 staff) were trained on specific positive interaction behaviors in a multiple baseline design. Staff in each of the residences were provided with recommended behaviors for interacting with residents through an observational procedure where they observed and…

Three Scoring Approaches to the Neurobehavioral Symptom Inventory for Measuring Clinical Change in Service Members Receiving Intensive Treatment for Combat-Related mTBI.

PubMed

Dretsch, Michael; Bleiberg, Joseph; Williams, Kathy; Caban, Jesus; Kelly, James; Grammer, Geoffrey; DeGraba, Thomas

2016-01-01

To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

DTIC Science & Technology

2016-10-01

are related to mechanism of injury as well as white matter integrity using diffusion tensor imaging (DTI). We are also collecting and analyzing...APOE ε4] and brain-derived neurotrophic factor [BDNF]) to brain integrity , neuropsychological functioning, and neurobehavioral outcome. 15. SUBJECT...contribution of genetic factors (Apolipoprotein-E ε-4 [APOE ε4] and brain-derived neurotrophic factor [BDNF]) to brain integrity , neuropsychological

Alter spontaneous activity in amygdala and vmPFC during fear consolidation following 24 h sleep deprivation.

PubMed

Feng, Pan; Becker, Benjamin; Feng, Tingyong; Zheng, Yong

2018-05-15

Sleep deprivation (SD) has been associated with cognitive and emotional disruptions, however its impact on the acquisition of fear and subsequent fear memory consolidation remain unknown. To address this question, we measured human brain activity before and after fear acquisition under conditions of 24 h sleep deprivation versus normal sleep using resting-state functional magnetic resonance imaging (rs-fMRI). Additionally, we explored whether the fear acquisition-induced change of brain activity during the fear memory consolidation window can be predicted by subjective fear ratings and autonomic fear response, assessed by skin conductance responses (SCR) during acquisition. Behaviorally, the SD group demonstrated increased subjective and autonomic fear responses compared to controls at the stage of fear acquisition. During the stage of fear consolidation, the SD group displayed decreased ventromedial prefrontal cortex (vmPFC) activity and concomitantly increased amygdala activity. Moreover, in the SD group fear acquisition-induced brain activity changes in amygdala were positively correlated with both, subjective and autonomic fear indices during acquisition, whereas in controls changes vmPFC activity were positively correlated with fear indices during acquisition. Together, the present findings suggested that SD may weaken the top-down ability of the vmPFC to regulate amygdala activity during fear memory consolidation. Moreover, subjective and objective fear at fear acquisition stage can predict the change of brain activity in amygdala in fear memory consolidation following SD. Copyright © 2018 Elsevier Inc. All rights reserved.

Behavioral Assessment of NIH Swiss Mice Acutely Intoxicated with Tetramethylenedisulfotetramine

PubMed Central

Flannery, Brenna M.; Silverman, Jill L.; Bruun, Donald A.; Puhger, Kyle R.; McCoy, Mark R.; Hammock, Bruce D.; Crawley, Jacqueline N.; Lein, Pamela J.

2014-01-01

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15 mg/kg, ip) and then were rescued from lethality by administration of diazepam (5 mg/kg, ip) approximately 20 min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72 seconds. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1 week, 1 month and 2 months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2 months post-TETS intoxication. The general absence of long-term behavioral deficits in TETS-intoxicated mice on these six assays suggests that the neurobehavioral consequences of TETS exposure described in human survivors of acute TETS intoxication are likely due to sustained seizure activity, rather than a direct effect of the chemical itself. Future research efforts are directed towards developing an animal model that better recapitulates the SE and seizure duration reported in humans acutely intoxicated with TETS. PMID:25446016

Evaluating and treating neurobehavioral symptoms in professional American football players

PubMed Central

Possin, Katherine L.; Hess, Christopher P.; Huang, Eric J.; Grinberg, Lea T.; Nolan, Amber L.; Cohn-Sheehy, Brendan I.; Ghosh, Pia M.; Lanata, Serggio; Merrilees, Jennifer; Kramer, Joel H.; Berger, Mitchel S.; Miller, Bruce L.; Yaffe, Kristine; Rabinovici, Gil D.

2015-01-01

Summary In the aftermath of multiple high-profile cases of chronic traumatic encephalopathy (CTE) in professional American football players, physicians in clinical practice are likely to face an increasing number of retired football players seeking evaluation for chronic neurobehavioral symptoms. Guidelines for the evaluation and treatment of these patients are sparse. Clinical criteria for a diagnosis of CTE are under development. The contribution of CTE vs other neuropathologies to neurobehavioral symptoms in these players remains unclear. Here we describe the experience of our academic memory clinic in evaluating and treating a series of 14 self-referred symptomatic players. Our aim is to raise awareness in the neurology community regarding the different clinical phenotypes, idiosyncratic but potentially treatable symptoms, and the spectrum of underlying neuropathologies in these players. PMID:26336629

Reconsideration of the WHO NCTB Strategy and Test Selection

PubMed Central

Anger, W. Kent

2014-01-01

The World Health Organization-recommended Neurobehavioral Core Test Battery (NCTB) became the international standard for identifying adverse human behavioral effects due to neurotoxic chemical exposure when it was first proposed in 1983. Since then the WHO NCTB has been repeatedly cited as the basis for test selection in human neurotoxicology research. A Discussion Group was held before the International Symposium on Neurobehavioral Methods and effects in Occupational and Environmental Health to review the NCTB and reconsider it’s tests. The workshop made three consensus recommendations to the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP): a ‘screening’ battery of broadly sensitive tests is needed as guidance to the field of human neurotoxicologythe SCNP should convene a panel to reconsider the functions measured and the tests in the WHO NCTBThree disciplines should be represented in the panel recommending a revised NCTB: Neuropsychology; Experimental Psychology; Neurology This recommendation will be pursued at the next meeting of the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP). PMID:25172409

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

PubMed

Ray, A; Gulati, K; Rai, N

2017-01-01

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness. © 2017 Elsevier Inc. All rights reserved.

Managing neurobehavioral capability when social expediency trumps biological imperatives

PubMed Central

Spaeth, Andrea M.; Goel, Namni; Dinges, David F.

2013-01-01

Sleep, which is evolutionarily conserved across species, is a biological imperative that cannot be ignored or replaced. However, the percentage of habitually sleep-restricted adults has increased in recent decades. Extended work hours and commutes, shift work schedules, and television viewing are particularly potent social factors that influence sleep duration. Chronic partial sleep restriction, a product of these social expediencies, leads to the accumulation of sleep debt over time and consequently increases sleep propensity, decreases alertness, and impairs critical aspects of cognitive functioning. Significant interindividual variability in the neurobehavioral responses to sleep restriction exists—this variability is stable and phenotypic—suggesting a genetic basis. Identifying vulnerability to sleep loss is essential as many adults cannot accurately judge their level of impairment in response to sleep restriction. Indeed, the consequences of impaired performance and the lack of insight due to sleep loss can be catastrophic. In order to cope with the effects of social expediencies on biological imperatives, identification of biological (including genetic) and behavioral markers of sleep loss vulnerability as well as development of technological approaches for fatigue management are critical. PMID:22877676

Behavioral effects of subchronic inhalation of toluene in adult rats.

PubMed

Beasley, Tracey E; Evansky, Paul A; Gilbert, Mary E; Bushnell, Philip J

2010-01-01

Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent. Published by Elsevier Inc.

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

PubMed

Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Fear-conditioning mechanisms associated with trait vulnerability to anxiety in humans.

PubMed

Indovina, Iole; Robbins, Trevor W; Núñez-Elizalde, Anwar O; Dunn, Barnaby D; Bishop, Sonia J

2011-02-10

Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms underlying cued and contextual fear. A critical question is how personality dimensions such as trait anxiety act through these mechanisms to confer vulnerability to anxiety disorders, and whether humans' ability to overcome acquired fears depends on regulatory skills not characterized in animal models. In a neuroimaging study of fear conditioning in humans, we found evidence for two independent dimensions of neurocognitive function associated with trait vulnerability to anxiety. The first entailed increased amygdala responsivity to phasic fear cues. The second involved impoverished ventral prefrontal cortical (vPFC) recruitment to downregulate both cued and contextual fear prior to omission (extinction) of the aversive unconditioned stimulus. These two dimensions may contribute to symptomatology differences across anxiety disorders; the amygdala mechanism affecting the development of phobic fear and the frontal mechanism influencing the maintenance of both specific fears and generalized anxiety. Copyright © 2011 Elsevier Inc. All rights reserved.

Executive Function and Temperamental Fear Concurrently Predict Deception in School-Aged Children

ERIC Educational Resources Information Center

Babkirk, Sarah; Saunders, Lauren V.; Solomon, Beylul; Kessel, Ellen M.; Crossman, Angela; Gokhan, Nurper; Dennis, Tracy A.

2015-01-01

The decision to intentionally withhold truthful information, or deception, is a key component of moral development and may be a precursor to more serious anti-social tendencies. Two factors, executive function (EF) and temperamental fear are each thought to influence childhood deception. Few studies, however, have explored deception in relation to…

Anger, Fear, Uncertainty, and Attitudes: A Test of the Cognitive-Functional Model.

ERIC Educational Resources Information Center

Nabi, Robin L.

2002-01-01

Explains that the cognitive-functional model of discrete negative emotions and attitude change attempts to bridge the theoretical gap between "emotional" and "rational" approaches to persuasion by focusing on how emotions motivate attention to and processing of persuasive messages. Explores the effects two emotions, anger and fear, and two levels…

Genetic Correlation between Alcohol Preference and Conditioned Fear: Exploring a Functional Relationship

PubMed Central

Chester, Julia A.; Weera, Marcus M.

2016-01-01

Post-traumatic stress disorder (PTSD) and alcohol-use disorders have a high rate of co-occurrence, possibly because they are regulated by common genes. In support of this idea, mice selectively bred for high (HAP) alcohol preference show greater fear potentiated startle (FPS), a model for fear-related disorders such as PTSD, compared to mice selectively bred for low (LAP) alcohol preference. This positive genetic correlation between alcohol preference and FPS behavior suggests that the two traits may be functionally related. This study examined the effects of fear conditioning on alcohol consumption and the effects of alcohol consumption on the expression of FPS in male and female HAP2 and LAP2 mice. In experiment 1, alcohol consumption (g/kg) under continuous-access conditions was monitored daily for 4 weeks following a single fear-conditioning or control treatment (foot shock and no shock). FPS was assessed three times (once at the end of the 4-week alcohol access period, once at 24 h after removal of alcohol, and once at 6–8 days after removal of alcohol), followed by two more weeks of alcohol access. Results showed no change in alcohol consumption, but alcohol-consuming, fear-conditioned, HAP2 males showed increased FPS at 24 h during the alcohol abstinence period compared to control groups. In experiment 2, alcohol consumption under limited-access conditions was monitored daily for 4 weeks. Fear-conditioning or control treatments occurred four times during the first 12 days and FPS testing occurred four times during the second 12 days of the 4-week alcohol consumption period. Results showed that fear conditioning increased alcohol intake in both HAP2 and LAP2 mice immediately following the first conditioning session. Fear-conditioned HAP2 but not LAP2 mice showed greater alcohol intake compared to control groups on drinking days that occurred between fear conditioning and FPS test sessions. FPS did not change as a function of alcohol consumption in either line. These results in mice help shed light on how a genetic propensity toward high alcohol consumption may be related to the risk for developing PTSD and co-morbid alcohol-use disorders in humans. PMID:27908524

A multi-component cognitive behavioural intervention for the treatment of fear of falling after hip fracture (FIT-HIP): protocol of a randomised controlled trial.

PubMed

Scheffers-Barnhoorn, Maaike N; van Haastregt, Jolanda C M; Schols, Jos M G A; Kempen, Gertrudis I J M; van Balen, Romke; Visschedijk, Jan H M; van den Hout, Wilbert B; Dumas, Eve M; Achterberg, Wilco P; van Eijk, Monica

2017-03-20

Hip fracture is a common injury in the geriatric population. Despite surgical repair and subsequent rehabilitation programmes, functional recovery is often limited, particularly in individuals with multi-morbidity. This leads to high care dependency and subsequent use of healthcare services. Fear of falling has a negative influence on recovery after hip fracture, due to avoidance of activity and subsequent restriction in mobility. Although fear of falling is highly prevalent after hip fracture, no structured treatment programme is currently available. This trial will evaluate whether targeted treatment of fear of falling in geriatric rehabilitation after hip fracture using a multi-component cognitive behavioural intervention (FIT-HIP), is feasible and (cost) effective in reducing fear of falling and associated activity restriction and thereby improves physical functioning. This multicentre cluster randomised controlled trial will be conducted among older patients with hip fracture and fear of falling who are admitted to a multidisciplinary inpatient geriatric rehabilitation programme in eleven post-acute geriatric rehabilitation units. Fifteen participants will be recruited from each site. Recruitment sites will be allocated by computer randomisation to either the control group, receiving usual care, or to the intervention group receiving the FIT-HIP intervention in addition to usual care. The FIT-HIP intervention is conducted by physiotherapists and will be embedded in usual care. It consists of various elements of cognitive behavioural therapy, including guided exposure to feared activities (that are avoided by the participants). Participants and outcome assessors are blinded to group allocation. Follow-up measurements will be performed at 3 and 6 months after discharge from geriatric rehabilitation. (Cost)-effectiveness and feasibility of the intervention will be evaluated. Primary outcome measures are fear of falling and mobility. Targeted treatment of fear of falling may improve recovery and physical and social functioning after hip fracture, thereby offering benefits for patients and reducing healthcare costs. Results of this study will provide insight into whether fear of falling is modifiable in the (geriatric) rehabilitation after hip fracture and whether the intervention is feasible. Netherlands Trial Register: NTR 5695 .

Psychophysiological Investigation of Combat Veterans with Subthreshold Post-traumatic Stress Disorder Symptoms.

PubMed

Costanzo, Michelle; Jovanovic, Tanja; Norrholm, Seth D; Ndiongue, Rochelle; Reinhardt, Brian; Roy, Michael J

2016-08-01

Military service members (SMs) with subthreshold combat-related post-traumatic stress disorder (PTSD) symptoms often have clinically significant functional impairment, even though they do not meet full PTSD criteria. We therefore assessed the psychophysical responses of SMs, upon their return from Afghanistan or Iraq, to a fear conditioning paradigm to better understand the biological underpinnings of symptom severity. Heart rate (HR), skin conductance, electromyography startle, and respiratory rate (RR) were monitored throughout three distinct phases of the paradigm-fear acquisition, fear inhibition, and fear extinction-while plasma catecholamines (epinephrine, norepinephrine, and dopamine) were measured at the end of fear inhibition. Those with higher PTSD symptom severity demonstrated elevations in HR and startle response to danger cues; elevated self-reported depression and anxiety; impaired functional status; poor skin conductance discrimination between danger and safety; and increases in HR and RR during fear extinction. Moreover, an inverse relationship was seen between plasma dopamine and HR during fear inhibition for those with high symptoms. Overall, the physiological responses we observed in our subthreshold PTSD population parallel what has been previously observed in full PTSD, making a case for addressing subthreshold PTSD symptoms in combat veterans. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Sex Differences in Fear of Falling among Older Adults with Low Grip Strength.

PubMed

Lim, Eunju

2016-05-01

Fear of falling is not only a risk factor for falls, but it is also an important clinical predictor of functional decline in older adults. This study identified sex differences in fear of falling and related factors in older adults with low grip strength. The data of 902 older adults from the 2012 Korean National Survey, conducted as a research project by the Korea Employment Information Service, were analyzed. Grip strength, activities of daily living, cognitive function, depressive symptoms, and fear of falling were assessed. Multiple regression analysis was performed by a simultaneous data entry method. Fear of falling was greater in older women with low grip strength than in their male equivalents (P<0.001). Regression analysis showed that age, fall experience within the previous 2 yr, activities of daily living, and depressive symptoms collectively accounted for 15.3% (P<0.001) of the variance among men. Meanwhile, age, fall experience within the previous 2 yr, grip strength, activities of daily living, and depressive symptoms collectively accounted for 13.4% (P<0.001) of the variance among women. Thus, the predictors of fear of falling differ between older men and women with low grip strength. Therefore, sex differences must be considered when developing intervention strategies for reducing fear of falling in this demographic.

Social Fears and Social Phobia in the United States: Results from the National Comorbidity Survey Replication

PubMed Central

Ruscio, Ayelet Meron; Brown, Timothy A.; Chiu, Wai Tat; Sareen, Jitender; Stein, Murray B.; Kessler, Ronald C.

2008-01-01

Background Despite heightened awareness of the clinical significance of social phobia, information is still lacking about putative subtypes, functional impairment, and treatment-seeking. New epidemiologic data on these topics are presented from the National Comorbidity Survey Replication (NCS-R). Methods The NCS-R is a nationally representative household survey fielded in 2001–2003. The WHO Composite International Diagnostic Interview (CIDI 3.0) was used to assess 14 performance and interactional fears and DSM-IV social phobia. Results The estimated lifetime and 12-month prevalence of social phobia are 12.1% and 7.1%. Performance and interactional fears load onto a single latent factor, and there is little evidence for distinct subtypes based either on the content or number of fears. Social phobia is associated with significant psychiatric comorbidity, role impairment, and treatment-seeking, all of which have a dose-response relationship with number of social fears. However, social phobia is the focus of clinical attention in only about half of cases where treatment is obtained. Among non-comorbid cases, those with the most fears were least likely to receive social phobia treatment. Conclusions Social phobia is a common, under-treated disorder that leads to significant functional impairment. Increasing numbers of social fears are associated with increasingly severe manifestations of the disorder. PMID:17976249

Acute and chronic effects of selective serotonin reuptake inhibitor treatment on fear conditioning: implications for underlying fear circuits.

PubMed

Burghardt, N S; Bauer, E P

2013-09-05

Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of a spectrum of anxiety disorders, yet paradoxically they may increase symptoms of anxiety when treatment is first initiated. Despite extensive research over the past 30 years focused on SSRI treatment, the precise mechanisms by which SSRIs exert these opposing acute and chronic effects on anxiety remain unknown. By testing the behavioral effects of SSRI treatment on Pavlovian fear conditioning, a well characterized model of emotional learning, we have the opportunity to identify how SSRIs affect the functioning of specific brain regions, including the amygdala, bed nucleus of the stria terminalis (BNST) and hippocampus. In this review, we first define different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. We examine the results of numerous rodent studies investigating how acute SSRI treatment modulates fear learning and relate these effects to the known functions of serotonin in specific brain regions. With these findings, we propose a model by which acute SSRI administration, by altering neural activity in the extended amygdala and hippocampus, enhances both acquisition and expression of cued fear conditioning, but impairs the expression of contextual fear conditioning. Finally, we review the literature examining the effects of chronic SSRI treatment on fear conditioning in rodents and describe how downregulation of N-methyl-d-aspartate (NMDA) receptors in the amygdala and hippocampus may mediate the impairments in fear learning and memory that are reported. While long-term SSRI treatment effectively reduces symptoms of anxiety, their disruptive effects on fear learning should be kept in mind when combining chronic SSRI treatment and learning-based therapies, such as cognitive behavioral therapy. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The roles of Eph receptors in contextual fear conditioning memory formation.

PubMed

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

2015-10-01

Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Posterior insular cortex is necessary for conditioned inhibition of fear

PubMed Central

Foilb, Allison R.; Flyer-Adams, Johanna G.; Maier, Steven F.; Christianson, John P.

2016-01-01

Veridical detection of safety versus danger is critical to survival. Learned signals for safety inhibit fear, and so when presented, reduce fear responses produced by danger signals. This phenomenon is termed conditioned inhibition of fear. Here, we report that CS+/CS− fear discrimination conditioning over 5 days in rats leads the CS− to become a conditioned inhibitor of fear, as measured by the classic tests of conditioned inhibition: summation and retardation of subsequent fear acquisition. We then show that NMDA-receptor antagonist AP5 injected to posterior insular cortex (IC) before training completely prevented the acquisition of a conditioned fear inhibitor, while intra-AP5 to anterior and medial IC had no effect. To determine if the IC contributes to the recall of learned fear inhibition, injections of the GABAA agonist muscimol were made to posterior IC before a summation test. This resulted in fear inhibition per se, which obscured inference to the effect of IC inactivation with recall of the safety cue. Control experiments sought to determine if the role of the IC in conditioned inhibition learning could be reduced to simpler fear discrimination function, but fear discrimination and recall were unaffected by AP5 or muscmiol, respectively, in the posterior IC. These data implicate a role of posterior IC in the learning of conditioned fear inhibitors. PMID:27523750

A role for the interoceptive insular cortex in the consolidation of learned fear.

PubMed

Casanova, José Patricio; Madrid, Carlos; Contreras, Marco; Rodríguez, María; Vasquez, Mónica; Torrealba, Fernando

2016-01-01

A growing body of evidence suggests that learned fear may be related to the function of the interoceptive insular cortex. Using an auditory fear conditioning paradigm in rats, we show that the inactivation of the posterior insular cortex (pIC), the target of the interoceptive thalamus, prior to training produced a marked reduction in fear expression tested 24h later. Accordingly, post-training anisomycin infused immediately, but not 6h after, also reduced fear expression tested the following day, supporting a role for the pIC in consolidation of fear memory. The long-term (ca. a week) and reversible inactivation of the pIC with the sodium channel blocker neosaxitoxin, immediately after fear memory reactivation induced a progressive decrease in the behavioral expression of conditioned fear. In turn, we observed that fear memory reactivation is accompanied by an enhanced expression of Fos and Zif268, early genes involved in neural activity and plasticity. Taken together these data indicate that the pIC is involved in the regulation of fear memories. Copyright © 2015 Elsevier B.V. All rights reserved.

Tourette Syndrome: Overview and Classroom Interventions. A Complex Neurobehavioral Disorder Which May Involve Learning Problems, Attention Deficit Hyperactivity Disorder, Obsessive Compulsive Symptoms, and Stereotypical Behaviors.

ERIC Educational Resources Information Center

Fisher, Ramona A.; Collins, Edward C.

Tourette Syndrome is conceptualized as a neurobehavioral disorder, with behavioral aspects that are sometimes difficult for teachers to understand and deal with. The disorder has five layers of complexity: (1) observable multiple motor, vocal, and cognitive tics and sensory involvement; (2) Attention Deficit Hyperactivity Disorder; (3)…

Association between traumatic stress load, psychopathology, and cognition in the Philadelphia Neurodevelopmental Cohort.

PubMed

Barzilay, Ran; Calkins, Monica E; Moore, Tyler M; Wolf, Daniel H; Satterthwaite, Theodore D; Cobb Scott, J; Jones, Jason D; Benton, Tami D; Gur, Ruben C; Gur, Raquel E

2018-04-15

Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8-21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009-2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered. Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition. Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.

Neurobehavioral Differences Between Mice Receiving Distinct Neuregulin Variants as Neonates; Impact on Sensitivity to MK-801

PubMed Central

Kato, T.; Abe, Y.; Hirokawa, S.; Iwakura, Y.; Mizuno, M.; Namba, H.; Nawa, H.

2015-01-01

Neuregulin-1 (NRG1) is a well-recognized risk gene for schizophrenia and is often implicated in the neurodevelopmental hypothesis of this illness. Alternative splicing and proteolytic processing of the NRG1 gene produce more than 30 structural variants; however, the neuropathological roles of individual variants remain to be characterized. On the basis of the neurodevelopmental hypothesis of schizophrenia, we administered eNRG1 (0.1~1.0 µg/g), a core epidermal growth factor-like (EGF) domain common for all splicing NRG1 variants, to neonatal mice and compared their behavioral performance with mice challenged with a full mature form of type 1 NRG1 variant. During the neonatal stage, recombinant eNRG1 protein administrated from the periphery passed the blood-brain barrier and activated its receptor (ErbB4) in the brain. In adults, the mice receiving the highest dose exhibited lower locomotor activity and deficits in prepulse inhibition and tonedependent fear learning, although the hearing reduction of the eNRG1-treated mice may explain these behavioral deficits. Neonatal eNRG1 treatment also significantly potentiated MK-801-driven locomotor activity in an eNRG1 dose-dependent manner. In parallel eNRG1 treatment enhanced MK-801-driven c-Fos induction and decreased immunoreactivity for NMDA receptor subunits in adult brain. In contrast, mice that had been treated with the same molar dose of a full mature form of type 1 NRG1 as neonates did not exhibit hypersensitivity to MK-801. However, both animal models exhibited similar hypersensitivity to methamphetamine. Collectively, our findings suggest that aberrant peripheral NRG1 signals during neurodevelopment alter later behavioral traits and auditory functions in the NRG1 subtype-dependent manner. PMID:25817857

A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats.

PubMed

Sampath, Dayalan; Sabitha, K R; Hegde, Preethi; Jayakrishnan, H R; Kutty, Bindu M; Chattarji, Sumantra; Rangarajan, Govindan; Laxmi, T R

2014-10-15

As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus-amygdala-cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions. Copyright © 2014 Elsevier B.V. All rights reserved.

Dual Functions of Perirhinal Cortex in Fear Conditioning

PubMed Central

Kent, Brianne A.; Brown, Thomas H.

2012-01-01

The present review examines the role of perirhinal cortex (PRC) in Pavlovian fear conditioning. The focus is on rats, partly because so much is known, behaviorally and neurobiologically, about fear conditioning in these animals. In addition, the neuroanatomy and neurophysiology of rat PRC have been described in considerable detail at the cellular and systems levels. The evidence suggests that PRC can serve at least two types of mnemonic functions in Pavlovian fear conditioning. The first function, termed "stimulus unitization," refers to the ability to treat two or more separate items or stimulus elements as a single entity. Supporting evidence for this perceptual function comes from studies of context conditioning as well as delay conditioning to discontinuous auditory cues. In a delay paradigm, the conditional stimulus (CS) and unconditional stimulus (US) overlap temporally and co-terminate. The second PRC function entails a type of "transient memory." Supporting evidence comes from studies of trace cue conditioning, where there is a temporal gap or trace interval between the CS offset and the US onset. For learning to occur, there must be a transient CS representation during the trace interval. We advance a novel neurophysiological mechanism for this transient representation. These two hypothesized functions of PRC are consistent with inferences based on non-aversive forms of learning. PMID:22903623

Accessible Neurobehavioral Anger-Related Markers for Vulnerability to Post-Traumatic Stress Symptoms in a Population of Male Soldiers

PubMed Central

Lin, Tamar; Gilam, Gadi; Raz, Gal; Or-Borichev, Ayelet; Bar-Haim, Yair; Fruchter, Eyal; Hendler, Talma

2017-01-01

Identifying vulnerable individuals prone to develop post-traumatic stress symptoms (PTSS) is of paramount importance, especially in populations at high risk for stress exposure such as combat soldiers. While several neural and psychological risk factors are known, no post-traumatic stress disorder (PTSD) biomarker has yet progressed to clinical use. Here we present novel and clinically applicable anger-related neurobehavioral risk markers for military-related PTSS in a large cohort of Israeli soldiers. The psychological, electrophysiological and neural (Simultaneous recording of scalp electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]) reaction to an anger-inducing film were measured prior to advanced military training and PTSS were recorded at 1-year follow-up. Limbic modulation was measured using a novel approach that monitors amygdala modulation using fMRI-inspired EEG, hereafter termed amygdala electrical fingerprint (amyg-EFP). Inter-subject correlation (ISC) analysis on fMRI data indicated that during movie viewing participants’ brain activity was synchronized in limbic regions including the amygdala. Self-reported state-anger and amyg-EFP modulation successfully predicted PTSS levels. State-anger significantly accounted for 20% of the variance in PTSS, and amyg-EFP signal modulation significantly accounted for additional 15% of the variance. Our study was limited by the moderate PTSS levels and lack of systematic baseline symptoms assessment. These results suggest that pre-stress neurobehavioral measures of anger may predict risk for later PTSS, pointing to anger-related vulnerability factors that can be measured efficiently and at a low cost before stress exposure. Possible mechanisms underlying the association between the anger response and risk for PTSS are discussed. PMID:28326027

Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients.

PubMed

García-Cazorla, Angels; Oyarzabal, Alfonso; Fort, Joana; Robles, Concepción; Castejón, Esperanza; Ruiz-Sala, Pedro; Bodoy, Susanna; Merinero, Begoña; Lopez-Sala, Anna; Dopazo, Joaquín; Nunes, Virginia; Ugarte, Magdalena; Artuch, Rafael; Palacín, Manuel; Rodríguez-Pombo, Pilar; Alcaide, Patricia; Navarrete, Rosa; Sanz, Paloma; Font-Llitjós, Mariona; Vilaseca, Ma Antonia; Ormaizabal, Aida; Pristoupilova, Anna; Agulló, Sergi Beltran

2014-04-01

Inactivating mutations in the BCKDK gene, which codes for the kinase responsible for the negative regulation of the branched-chain α-keto acid dehydrogenase complex (BCKD), have recently been associated with a form of autism in three families. In this work, two novel exonic BCKDK mutations, c.520C>G/p.R174G and c.1166T>C/p.L389P, were identified at the homozygous state in two unrelated children with persistently reduced body fluid levels of branched-chain amino acids (BCAAs), developmental delay, microcephaly, and neurobehavioral abnormalities. Functional analysis of the mutations confirmed the missense character of the c.1166T>C change and showed a splicing defect r.[520c>g;521_543del]/p.R174Gfs1*, for c.520C>G due to the presence of a new donor splice site. Mutation p.L389P showed total loss of kinase activity. Moreover, patient-derived fibroblasts showed undetectable (p.R174Gfs1*) or barely detectable (p.L389P) levels of BCKDK protein and its phosphorylated substrate (phospho-E1α), resulting in increased BCKD activity and the very rapid BCAA catabolism manifested by the patients' clinical phenotype. Based on these results, a protein-rich diet plus oral BCAA supplementation was implemented in the patient homozygous for p.R174Gfs1*. This treatment normalized plasma BCAA levels and improved growth, developmental and behavioral variables. Our results demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans and support the rationale for dietary intervention. © 2014 WILEY PERIODICALS, INC.

Albeit nocturnal, rats subjected to traumatic brain injury do not differ in neurobehavioral performance whether tested during the day or night.

PubMed

Niesman, Peter J; Wei, Jiahui; LaPorte, Megan J; Carlson, Lauren J; Nassau, Kileigh L; Bao, Gina C; Cheng, Jeffrey P; de la Tremblaye, Patricia; Lajud, Naima; Bondi, Corina O; Kline, Anthony E

2018-02-05

Behavioral assessments in rats are overwhelmingly conducted during the day, albeit that is when they are least active. This incongruity may preclude optimal performance. Hence, the goal of this study was to determine if differences in neurobehavior exist in traumatic brain injured (TBI) rats when assessed during the day vs. night. The hypothesis was that the night group would perform better than the day group on all behavioral tasks. Anesthetized adult male rats received either a cortical impact or sham injury and then were randomly assigned to either Day (1:00-3:00p.m.) or Night (7:30-9:30p.m.) testing. Motor function (beam-balance/walk) was conducted on post-operative days 1-5 and cognitive performance (spatial learning) was assessed on days 14-18. Corticosterone (CORT) levels were quantified at 24h and 21days after TBI. No significant differences were revealed between the TBI rats tested during the Day vs. Night for motor or cognition (p's<0.05). CORT levels were higher in the Night-tested TBI and sham groups at 24h (p<0.05), but returned to baseline and were no longer different by day 21 (p>0.05), suggesting an initial, but transient, stress response that did not affect neurobehavioral outcome. These data suggest that the time rats are tested has no noticeable impact on their performance, which does not support the hypothesis. The finding validates the interpretations from numerous studies conducted when rats were tested during the day vs. their natural active period. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurobehavioral effects of postnatal exposure to low-level mercury vapor and/or methylmercury in mice.

PubMed

Yoshida, Minoru; Lee, Jin-Yong; Satoh, Masahiko; Watanabe, Chiho

2018-01-01

This study examined the effects on neurobehavioral function of exposure to low-level mercury vapor (Hg 0 ), methylmercury (MeHg) in female mice and the combination of Hg 0 and MeHg during postnatal development. Postnatal mice were exposed to Hg 0 at a mean concentration of 0.188 mg/m 3 Hg 0 and supplied with food containing 3.85 μg/g of MeHg from day 2 to day 28 after delivery. The combined exposure group was exposed to both Hg 0 and MeHg, using the same procedure. When their offspring reached the age of 11 weeks, behavioral analyses were performed. The behavioral effects in mice were evaluated based on locomotive activity and rate of center entries in the open field (OPF), learning activity in the passive avoidance response (PA) and spatial learning ability in the radial maze (RM). Total locomotive activity in the OPF significantly decreased in the Hg 0 , MeHg and combined exposure groups compared with the control group. The proportion of entries to central area in the OPF was significantly higher in the combined exposure group than in the control group, while those in the Hg 0 or MeHg exposure group did not differ from the control group. Other behavioral tests did not reveal significant differences among the groups. Behavioral anomalies were more distinctive after combined exposure compared to Hg 0 or MeHg exposure alone. The brain Hg concentration of offspring, immediately after exposure, was highest in the combined exposure group, exceeding 2 μg/g, followed by the MeHg and Hg 0 exposure groups. Thus, the enhancement of neurobehavioral effects in the combined exposure group was associated with higher brain mercury concentration.

Division III Collision Sports Are Not Associated with Neurobehavioral Quality of Life

PubMed Central

Taylor, Alex M.; Berkner, Paul; Sandstrom, Noah J.; Peluso, Mark W.; Kurtz, Matthew M.; Pascual-Leone, Alvaro; Mannix, Rebekah

2016-01-01

Abstract We sought to determine whether the exposure to the sub-concussive blows that occur during division III collegiate collision sports affect later life neurobehavioral quality-of-life measures. We conducted a cross-sectional study of alumni from four division III colleges, targeting those between the ages of 40–70 years, using several well-validated quality-of-life measures for executive function, general concerns, anxiety, depression, emotional and behavior dyscontrol, fatigue, positive affect, sleep disturbance, and negative consequences of alcohol use. We used multivariable linear regression to assess for associations between collision sport participation and quality-of-life measures while adjusting for covariates including age, gender, race, annual income, highest educational degree, college grades, exercise frequency, and common medical conditions. We obtained data from 3702 alumni, more than half of whom (2132) had participated in collegiate sports, 23% in collision sports, 23% in non-contact sports. Respondents with a history of concussion had worse self-reported health on several measures. When subjects with a history of concussion were removed from the analyses in order to assess for any potential effect of sub-concussive blows alone, negative consequences of alcohol use remained higher among collision sport athletes (β-coefficient 1.957, 95% CI 0.827-3.086). There were, however, no other significant associations between exposure to collision sports during college and any other quality-of-life measures. Our results suggest that, in the absence of a history of concussions, participation in collision sports at the Division III collegiate level is not a risk factor for worse long-term neurobehavioral outcomes, despite exposure to repeated sub-concussive blows. PMID:26193380

Combined Socio-Behavioral Evaluation Improves the Differential Diagnosis Between the Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: In Search of Neuropsychological Markers.

PubMed

Dodich, Alessandra; Cerami, Chiara; Cappa, Stefano F; Marcone, Alessandra; Golzi, Valeria; Zamboni, Michele; Giusti, Maria Cristina; Iannaccone, Sandro

2018-01-01

Current diagnostic criteria for behavioral variant of frontotemporal dementia (bvFTD) and typical Alzheimer's disease (AD) include a differential pattern of neuropsychological impairments (episodic memory deficit in typical AD and dysexecutive syndrome in bvFTD). There is, however, large evidence of a frequent overlap in neuropsychological features, making the differential diagnosis extremely difficult. In this retrospective study, we evaluated the diagnostic value of different cognitive and neurobehavioral markers in bvFTD and AD patient groups. We included 95 dementia patients with a clinical and biomarker evidence of bvFTD (n = 48) or typical AD (n = 47) pathology. A clinical 2-year follow-up confirmed clinical classification. Performances at basic cognitive tasks (memory, executive functions, visuo-spatial, language) as well as social cognition skills and neurobehavioral profiles have been recorded. A stepwise logistic regression model compared the neuropsychological profiles between groups and assessed the accuracy of cognitive and neurobehavioral markers in discriminating bvFTD from AD. Statistical comparison between patient groups proved social cognition and episodic memory impairments as main cognitive signatures of bvFTD and AD neuropsychological profiles, respectively. Only half of bvFTD patients showed attentive/executive deficits, questioning their role as cognitive marker of bvFTD. Notably, the large majority of bvFTD sample (i.e., 70%) poorly performed at delayed recall tasks. Logistic regression analysis identified social cognition performances, Frontal Behavioral Inventory and Mini-Mental State Examination scores as the best combination in distinguishing bvFTD from AD. Social cognition tasks and socio-behavioral questionnaires are recommended in clinical settings to improve the accuracy of early diagnosis of bvFTD.

Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)

PubMed Central

Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

2016-01-01

The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

Towards a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

PubMed Central

Mattson, Sarah N.; Roesch, Scott C.; Fagerlund, Åse; Autti-Rämö, Ilona; Jones, Kenneth Lyons; May, Philip A.; Adnams, Colleen M.; Konovalova, Valentina; Riley, Edward P.

2010-01-01

Background A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study we define a preliminary profile using neuropsychological data from a multisite study. Methods Data were collected using a broad neurobehavioral protocol from two sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol-exposed group included children with and with out fetal alcohol syndrome (FAS). From 547 neuropsychological, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA). Results The results indicated that a 2-class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and non-exposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol-exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone. Conclusions We used data from two sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure. PMID:20569243

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

PubMed

Singh, K P; Tripathi, Nidhi

2015-05-01

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamic Circadian Modulation in a Biomathematical Model for the Effects of Sleep and Sleep Loss on Waking Neurobehavioral Performance

PubMed Central

McCauley, Peter; Kalachev, Leonid V.; Mollicone, Daniel J.; Banks, Siobhan; Dinges, David F.; Van Dongen, Hans P. A.

2013-01-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation—and thereby sensitivity to neurobehavioral impairment from sleep loss—is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation—and thus sensitivity to sleep loss—depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work. Citation: McCauley P; Kalachev LV; Mollicone DJ; Banks S; Dinges DF; Van Dongen HPA. Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance. SLEEP 2013;36(12):1987-1997. PMID:24293775

Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics upon oral exposure.

PubMed

Rafiee, Mohammad; Dargahi, Leila; Eslami, Akbar; Beirami, Elmira; Jahangiri-Rad, Mahsa; Sabour, Siamak; Amereh, Fatemeh

2018-02-01

The increasing use of plastics has raised concerns about pollution of freshwater by these polymeric materials. Knowledge about their potential effects on environmental and public health is limited. Recent publications have suggested that the degradation of plastics will result in the release of nano-sized plastic particles to the environment. Therefore, it is of utmost importance to gain knowledge about whether and how nanoplastics affect living organisms. The present study aimed to analyse potential neurobehavioral effects of polystyrene nanoparticles (PS-NPs) after long-term exposure on rat. Potential effects of PS-NPs were investigated using four test dosages (1, 3, 6, and 10 mg PS-NPs/kg of body weight/day) administrated orally with adult Wistar male rats for five weeks. Neurobehavioral tests were chosen to assess a variety of behavioral domains. Particle diameters in test suspensions were determined through dynamic light scattering and showed an average hydrodynamic diameter of approximately 38.92 nm. No statistically significant behavioral effects were observed in all tests performed (p > 0.05). In the elevated plus maze, PS-NPs-exposed rats showed greater number of entries into open arms compared to controls. Also, PS-NPs had no significant influence on body weight of animals. Taking into account the subtle and transient nature of neurobehavioral consequences, however, these results underline the possibility of even pristine plastic nanoparticles to induce behavioral alteration in the rest of the food web, including for marine biota and humans. Indeed even though studied neurobehavioral effects in our study was not statistically significant, the observed subtle effects may be clinically considerable. Copyright © 2017 Elsevier Ltd. All rights reserved.

Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

PubMed

Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

2015-03-01

The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

Cognitive requirements of competing neuro-behavioral decision systems: some implications of temporal horizon for managerial behavior in organizations

PubMed Central

Foxall, Gordon R.

2014-01-01

Interpretation of managerial activity in terms of neuroscience is typically concerned with extreme behaviors such as corporate fraud or reckless investment (Peterson, 2007; Wargo et al., 2010a). This paper is concerned to map out the neurophysiological and cognitive mechanisms at work across the spectrum of managerial behaviors encountered in more day-to-day contexts. It proposes that the competing neuro-behavioral decisions systems (CNBDS) hypothesis (Bickel et al., 2012b) captures well the range of managerial behaviors that can be characterized as hyper- or hypo-activity in either the limbically-based impulsive system or the frontal-cortically based executive system with the corresponding level of activity encountered in the alternative brain region. This pattern of neurophysiological responding also features in the Somatic Marker Hypothesis (Damasio, 1994) and in Reinforcement Sensitivity Theory (RST; Gray and McNaughton, 2000; McNaughton and Corr, 2004), which usefully extend the thesis, for example in the direction of personality. In discussing these theories, the paper has three purposes: to clarify the role of cognitive explanation in neuro-behavioral decision theory, to propose picoeconomics (Ainslie, 1992) as the cognitive component of competing neuro-behavioral decision systems theory and to suggest solutions to the problems of imbalanced neurophysiological activity in managerial behavior. The first is accomplished through discussion of the role of picoeconomics in neuro-behavioral decision theory; the second, by consideration of adaptive-innovative cognitive styles (Kirton, 2003) in the construction of managerial teams, a theme that can now be investigated by a dedicated research program that incorporates psychometric analysis of personality types and cognitive styles involved in managerial decision-making and the underlying neurophysiological bases of such decision-making. PMID:24744719

Cognition and behavior in pre-pubertal children with Prader-Willi syndrome and associations with sleep-related breathing disorders.

PubMed

Festen, Dederieke A M; Wevers, Maaike; de Weerd, Al W; van den Bossche, Renilde A S; Duivenvoorden, Hugo J; Hokken-Koelega, Anita C S

2008-12-01

Prader-Willi syndrome (PWS) is characterized by hypotonia, hypogonadism, obesity, and short stature. Neurobehavioral abnormalities, cognitive impairment, and sleep-related breathing disorders (SRBD) are common. In the general population associations between neurobehavioral and cognitive abnormalities and SRBD have been found. We investigated cognition, behavior, and SRBD in children with PWS. Thirty-one pre-pubertal PWS children were evaluated (5 with paternal deletion, 14 with maternal disomy, 4 with imprinting-center mutation, and in 8 the defect was not specified). Cognition was assessed by Wechsler scale subtests, and behavior by parent-questionnaires. Polysomnography was performed. Cognition, behavior, and associations with SRBD were evaluated. All cognitive subtests were significantly below O SDS, with the lowest median (interquartile range) scores for the Block design subtest (-2.7 SDS (-3.0 to -0.3)). In 60%, verbal subtests were less affected than performance subtests. Parents reported problem behavior related to "emotions/behavior not adapted to the social situation" and "insensitivity to social information." All children had SRBD, with an Apnea Hypopnea Index of 4.1/hr (2.6-7.9). One performance subtest score was significantly higher in children with better sleep efficiency, and daytime sleepiness was associated with more autistic-like social impairment. In contrast to our expectations, behavior was worse in children with better sleep-related breathing. In pre-pubertal PWS children, cognition is impaired. Neurobehavioral abnormalities are common, particularly autistic-like social impairment. Sleep efficiency was associated with better performance on one of the performance subtests, and neurobehavioral abnormalities were associated with daytime sleepiness. In contrast, we could not confirm a positive association of neurobehavioral abnormalities with SRBD in PWS. Copyright (c) 2008 Wiley-Liss, Inc.

Self-Reported Fear Predicts Functional Performance and Second ACL Injury After ACL Reconstruction and Return to Sport: A Pilot Study.

PubMed

Paterno, Mark V; Flynn, Kaitlyn; Thomas, Staci; Schmitt, Laura C

Outcomes after anterior cruciate ligament reconstruction (ACLR) are highly variable. Previous studies have failed to report the relationship between fear, objective measures of function, and reinjury rates. The purpose of this study was to determine whether fear was related to functional performance measures and risk of second ACL injury after ACLR and return to sport (RTS). Fear will be associated with performance on functional testing and second ACL injury rate. Prospective cohort study. Level 2. A total of 40 patients cleared to RTS after ACLR completed the Tampa Scale of Kinesiophobia (TSK-11), hop testing, and quadriceps strength testing, bilaterally. Patients were tracked for 12 months after RTS to identify the incidence of second ACL injury. Chi-square analyses determined whether patients with high fear (TSK-11, ≥17) were more likely to have lower levels of activity, greater asymmetry on functional testing, and higher reinjury rates. Patients with greater fear on the TSK-11 (≥17) at RTS were 4 times (odds ratio [OR], 3.73; 95% CI, 0.98-14.23) more likely to report lower levels of activity, 7 times (OR, 7.1; 95% CI, 1.5-33.0) more likely to have a hop limb symmetry lower than 95%, and 6 times (OR, 6.0; 95% CI, 1.3-27.8) more likely to have quadriceps strength symmetry lower than 90%. Patients who went on to suffer an ipsilateral second ACL injury had a greater TSK-11 score at the time of RTS (mean, 19.8 ± 4.0) than those who did not suffer a second ACL injury (mean, 16.4 ± 3.6) ( P = 0.03). Patients with a TSK-11 score of 19 or greater at the time of RTS were 13 times (relative risk, 13.0; 95% CI, 2.1-81.0) more likely to suffer a second ACL tear within 24 months after RTS. Patients with greater self-reported fear were less active, presented with lower single-leg hop performance and isometric quadriceps strength, and had an increased risk of suffering a second ACL injury in the 24 months after RTS. Self-reported fear of movement/reinjury after ACLR at the time of RTS may be an important measure to incorporate into discharge criteria prior to release to return to pivoting and cutting sports after ACLR.

Characteristics of walking, activity, fear of falling, and falls in community-dwelling older adults by residence.

PubMed

Wert, David M; Talkowski, Jaime B; Brach, Jennifer; VanSwearingen, Jessie

2010-01-01

Research focusing on community-dwelling older adults includes adults living in senior living residences (SLR) and independent community residences (ICR). Walking, physical activity, fear of falling, and fall history may differ on the basis of residence. We describe characteristics of walking, physical activity, fear of falling, and fall history between community-dwelling older adults by residence. Participants of this secondary analysis included community-dwelling older adults from independent living units within a senior life care community (SLR) and older adults recruited from the Pittsburgh community (ICR). Demographic information and physical (gait speed and physical activity), psychosocial (fear of falling and confidence in walking), and fall history measures were collected. Adults living in SLR compared with those in ICR were older, were more likely to live alone, and had greater disease burden. Compared with individuals in ICR, individuals in SLR reported less fear of falling (Survey of Activity and Fear of Falling in the Elderly tool fear results 0.24 and 0.50, respectively). Fewer older adults in SLR compared with those in ICR reported falling in the past year. Older adults living in SLR compared with those in ICR had similar physical function but differed in report of fear of falling and fall history. Recognizing the possible differences in psychosocial function by place of residence is important for health care providers and researchers conducting interventions and studies for community-dwelling older adults.

A Model of Amygdala-Hippocampal-Prefrontal Interaction in Fear Conditioning and Extinction in Animals

ERIC Educational Resources Information Center

Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard J.; Myers, Catherine E.

2013-01-01

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus…

The association between fear of falling and quality of life for balance impairments based on hip and ankle strategies in the drug On- and Off-phase of patients with idiopathic Parkinson' disease.

PubMed

Mehdizadeh, Maryam; Lajevardi, Laleh; Habibi, Seyed Amir Hassan; ArabBaniasad, Mina; Baghoori, Delaram; Daneshjoo, Fatemeh; Taghizadeh, Ghorban

2016-01-01

Background: Despite the negative effect of fear of falling during functioning and social participation of patients with Parkinson' disease, so far, only few studies have investigated its effect on the quality of life in these patients. We aimed to investigate the association between fear of falling and quality of life controlling for balance impairments based on hip and ankle strategy in drug On- and Off-phase of patients with idiopathic Parkinson' disease. Methods: In this non-experimental cross-sectional study, 139 patients with idiopathic Parkinson' disease (100 male, 39 female) by mean± SD age of 60.2±12.27 years, mean±SD time since diagnosis of 6.7±5.53 years and mean±SD Hoehn and Yahr stage of 2.8±1.49 were selected by a simple non-probability method. Balance function was measured by a functional reach test with hip and ankle strategy. The Persian version of the selfcompleted Fall Efficacy Scale-International and Parkinson's disease quality of life questionnaire was used to evaluate fear of falling and quality of life, respectively. Results: The results showed that the score of all dimensions of quality of life (i.e., mobility, activities of daily living, emotional wellbeing, stigma, social support, cognition, communication and bodily discomfort) were significantly affected by the intensity of fear of falling. Multiple regression analysis indicated a significant association between fear of falling and quality of life in a way that fear of falling explained 11% to 47% and 12% to 43% of variance in drug On-phase, as well as 8% to 45% and 9% to 48% of variance in the drug Off-phase in dimensions of quality of life after controlling for balance function based on hip and ankle strategy, respectively. In the drug On-phase, the strongest association (R=0.85, p<0.001) was found between fear of falling and mobility dimension of quality of life. In the drug Off-phase, the strongest relation was observed between fear of falling and mobility (R=0.82, p<0.001) as well as activities of daily living (R=0.78-0.79, p<0.001) dimensions. Conclusion: This study found that fear of falling affects the quality of life of patients with Parkinson' disease beyond its relationship with balance impairments based on the hip and ankle strategy in both drug On- and Off-phase.

A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

ERIC Educational Resources Information Center

Wilson, Yvette M.; Murphy, Mark

2009-01-01

There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury

PubMed Central

Cohen-Yeshurun, Ayelet; Willner, Dafna; Trembovler, Victoria; Alexandrovich, Alexander; Mechoulam, Raphael; Shohami, Esther; Leker, Ronen R

2013-01-01

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions. PMID:23695434

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury.

PubMed

Cohen-Yeshurun, Ayelet; Willner, Dafna; Trembovler, Victoria; Alexandrovich, Alexander; Mechoulam, Raphael; Shohami, Esther; Leker, Ronen R

2013-08-01

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.

Living in Fear of Your Child's Pain: The Parent Fear of Pain Questionnaire

PubMed Central

Simons, Laura E.; Smith, Allison; Kaczynski, Karen; Basch, Molly

2015-01-01

Fear and avoidance have been consistently associated with poor pain-related outcomes in children. In the context of the pediatric pain experience, parent distress and behaviors can be highly influential. The current study validated the Parent Fear of Pain Questionnaire (PFOPQ) to assess a parent's fears and avoidance behaviors associated with their child's pain. Using the PFOPQ in conjunction with measures of parent and child pain-related variables, we tested the Interpersonal Fear Avoidance Model (IFAM). The sample comprised of 321 parents and their child with chronic or new-onset pain who presented to a multidisciplinary outpatient pain clinic. An exploratory factor analysis yielded a 4-factor structure for the PFOPQ consisting of Fear of Pain, Fear of Movement, Fear of School, and Avoidance. As hypothesized, Fear of Pain was most closely related to parent pain catastrophizing and child fear of pain, while Avoidance was most closely related to parent protective behaviors and child avoidance of activities. In testing the IFAM, parent behavior contributed directly and indirectly to child avoidance while parent fear and catastrophizing contributed indirectly to child avoidance through parent behavior and child fear and catastrophizing, in turn, influencing child functional disability levels. The current study provides the first measure of parent pain-related fears and avoidance behaviors and evaluates the theorized IFAM. These results underscore the important influence of parents on child pain-related outcomes and puts forth a psychometrically sound measure to assess parent fear and avoidance in the context of their child's pain. PMID:25630026

Living in fear of your child's pain: the Parent Fear of Pain Questionnaire.

PubMed

Simons, Laura E; Smith, Allison; Kaczynski, Karen; Basch, Molly

2015-04-01

Fear and avoidance have been consistently associated with poor pain-related outcomes in children. In the context of the pediatric pain experience, parent distress and behaviors can be highly influential. This study validated the Parent Fear of Pain Questionnaire (PFOPQ) to assess a parent's fears and avoidance behaviors associated with their child's pain. Using the PFOPQ in conjunction with measures of parent and child pain-related variables, we tested the interpersonal fear-avoidance model (IFAM). The sample comprised 321 parents and their child with chronic or new-onset pain who presented to a multidisciplinary outpatient pain clinic. An exploratory factor analysis yielded a 4-factor structure for the PFOPQ consisting of Fear of Pain, Fear of Movement, Fear of School, and Avoidance. As hypothesized, Fear of Pain was most closely related to parent pain catastrophizing and child fear of pain, whereas Avoidance was most closely related to parent protective behaviors and child avoidance of activities. In testing the IFAM, parent behavior contributed directly and indirectly to child avoidance, whereas parent fear and catastrophizing contributed indirectly to child avoidance through parent behavior and child fear and catastrophizing, in turn, influencing child functional disability levels. This study provides the first measure of parent pain-related fears and avoidance behaviors and evaluates the theorized IFAM. These results underscore the important influence of parents on child pain-related outcomes and put forth a psychometrically sound measure to assess parent fear and avoidance in the context of their child's pain.

Fear learning and memory across adolescent development Hormones and Behavior Special Issue: Puberty and Adolescence

PubMed Central

Pattwell, Siobhan S.; Lee, Francis S.; Casey, B.J.

2013-01-01

Throughout the past several decades, studies have uncovered a wealth of information about the neural circuitry underlying fear learning and extinction that has helped to inform treatments for fear-related disorders such as post-traumatic stress and anxiety. Yet, up to 40 percent of people do not respond to such treatments. Adolescence, in particular, is a developmental stage during which anxiety disorders peak, yet little is known about the development of fear-related neural circuitry during this period. Moreover, pharmacological and behavioral therapies that have been developed are based on mature circuitry and function. Here, we review neural circuitry implicated in fear learning and data from adolescent mouse and human fear learning studies. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective. PMID:23998679

Fear learning and memory across adolescent development: Hormones and Behavior Special Issue: Puberty and Adolescence.

PubMed

Pattwell, Siobhan S; Lee, Francis S; Casey, B J

2013-07-01

Throughout the past several decades, studies have uncovered a wealth of information about the neural circuitry underlying fear learning and extinction that has helped to inform treatments for fear-related disorders such as post-traumatic stress and anxiety. Yet, up to 40% of people do not respond to such treatments. Adolescence, in particular, is a developmental stage during which anxiety disorders peak, yet little is known about the development of fear-related neural circuitry during this period. Moreover, pharmacological and behavioral therapies that have been developed are based on mature circuitry and function. Here, we review neural circuitry implicated in fear learning and data from adolescent mouse and human fear learning studies. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective. Copyright © 2013 Elsevier Inc. All rights reserved.

Retrieving fear memories, as time goes by…

PubMed Central

Do Monte, Fabricio H.; Quirk, Gregory J.; Li, Bo; Penzo, Mario A.

2016-01-01

Fear conditioning researches have led to a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, knowledge about the retrieval of fear memories is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring clarity and raise awareness on the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points after conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus, and its BDNFergic efferents to the central nucleus of the amygdala, for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change across time, and the functional benefits of recruiting structures such as the paraventricular nucleus into the retrieval circuit. PMID:27217148

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders.

PubMed

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-10-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)-amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC-amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC-amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC-amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC-amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. © 2014 The British Pharmacological Society.

Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

PubMed

Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

2017-04-01

Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

Why do fearful facial expressions elicit behavioral approach? Evidence from a combined approach-avoidance implicit association test.

PubMed

Hammer, Jennifer L; Marsh, Abigail A

2015-04-01

Despite communicating a "negative" emotion, fearful facial expressions predominantly elicit behavioral approach from perceivers. It has been hypothesized that this seemingly paradoxical effect may occur due to fearful expressions' resemblance to vulnerable, infantile faces. However, this hypothesis has not yet been tested. We used a combined approach-avoidance/implicit association test (IAT) to test this hypothesis. Participants completed an approach-avoidance lever task during which they responded to fearful and angry facial expressions as well as neutral infant and adult faces presented in an IAT format. Results demonstrated an implicit association between fearful facial expressions and infant faces and showed that both fearful expressions and infant faces primarily elicit behavioral approach. The dominance of approach responses to both fearful expressions and infant faces decreased as a function of psychopathic personality traits. Results suggest that the prosocial responses to fearful expressions observed in most individuals may stem from their associations with infantile faces. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans

PubMed Central

Chao, Linda L.; Rothlind, Johannes C.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Weiner, Michael W.

2010-01-01

Background Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Methods Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002–2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. Results GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p≤0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. Conclusions These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. PMID:20580739

Posterior insular cortex is necessary for conditioned inhibition of fear.

PubMed

Foilb, Allison R; Flyer-Adams, Johanna G; Maier, Steven F; Christianson, John P

2016-10-01

Veridical detection of safety versus danger is critical to survival. Learned signals for safety inhibit fear, and so when presented, reduce fear responses produced by danger signals. This phenomenon is termed conditioned inhibition of fear. Here, we report that CS+/CS- fear discrimination conditioning over 5 days in rats leads the CS- to become a conditioned inhibitor of fear, as measured by the classic tests of conditioned inhibition: summation and retardation of subsequent fear acquisition. We then show that NMDA-receptor antagonist AP5 injected to posterior insular cortex (IC) before training completely prevented the acquisition of a conditioned fear inhibitor, while intra-AP5 to anterior and medial IC had no effect. To determine if the IC contributes to the recall of learned fear inhibition, injections of the GABAA agonist muscimol were made to posterior IC before a summation test. This resulted in fear inhibition per se, which obscured inference to the effect of IC inactivation with recall of the safety cue. Control experiments sought to determine if the role of the IC in conditioned inhibition learning could be reduced to simpler fear discrimination function, but fear discrimination and recall were unaffected by AP5 or muscimol, respectively, in the posterior IC. These data implicate a role of posterior IC in the learning of conditioned fear inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Epigenetic mechanisms in fear conditioning: Implications for treating post-traumatic stress disorder

PubMed Central

Kwapis, Janine L.; Wood, Marcelo A.

2014-01-01

Post-traumatic stress disorder (PTSD) and other anxiety disorders stemming from dysregulated fear memory are problematic and costly. Understanding the molecular mechanisms that contribute to the formation and maintenance of these persistent fear associations is critical to developing treatments for PTSD. Epigenetic mechanisms, which control gene expression to produce long-lasting changes in cellular function, may support the formation of fear memory underlying PTSD. Here, we address the role of epigenetic mechanisms in the formation, storage, updating, and extinction of fear memories and discuss methods of targeting these epigenetic mechanisms to reduce the initial formation of fear memory or to enhance its extinction. Epigenetic mechanisms may provide a novel target for pharmaceutical and other treatments to reduce aversive memory contributing to PTSD. PMID:25220045

Deficits in facial affect recognition among antisocial populations: a meta-analysis.

PubMed

Marsh, Abigail A; Blair, R J R

2008-01-01

Individuals with disorders marked by antisocial behavior frequently show deficits in recognizing displays of facial affect. Antisociality may be associated with specific deficits in identifying fearful expressions, which would implicate dysfunction in neural structures that subserve fearful expression processing. A meta-analysis of 20 studies was conducted to assess: (a) if antisocial populations show any consistent deficits in recognizing six emotional expressions; (b) beyond any generalized impairment, whether specific fear recognition deficits are apparent; and (c) if deficits in fear recognition are a function of task difficulty. Results show a robust link between antisocial behavior and specific deficits in recognizing fearful expressions. This impairment cannot be attributed solely to task difficulty. These results suggest dysfunction among antisocial individuals in specified neural substrates, namely the amygdala, involved in processing fearful facial affect.

Fear of pain in children and adolescents with neuropathic pain and CRPS

PubMed Central

Simons, Laura E.

2015-01-01

A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Due to faulty nerve signaling, individuals with neuropathic pain and CRPS may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to down-regulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear as well as evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with CRPS suggest breakthroughs in our ability to ameliorate these issues. PMID:26785161

Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.

PubMed

Simons, Laura E

2016-02-01

A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to downregulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

Prefrontal consolidation supports the attainment of fear memory accuracy

PubMed Central

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. PMID:25031365

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

PubMed

Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

2014-01-01

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

When scientific paradigms lead to tunnel vision: lessons from the study of fear

NASA Astrophysics Data System (ADS)

Paré, Denis; Quirk, Gregory J.

2017-03-01

For the past 30 years, research on the amygdala has largely focused on the genesis of defensive behaviors as its main function. This focus originated from early lesion studies and was supported by extensive anatomical, physiological, and pharmacological data. Here we argue that while much data is consistent with the fear model of amygdala function, it has never been directly tested, in part due to overreliance on the fear conditioning task. In support of the fear model, amygdala neurons appear to signal threats and/or stimuli predictive of threats. However, recent studies in a natural threat setting show that amygdala activity does not correlate with threats, but simply with the movement of the rat, independent of valence. This was true for both natural threats as well as conditioned stimuli; indeed there was no evidence of threat signaling in amygdala neurons. Similar findings are emerging for prefrontal neurons that modulate the amygdala. These recent developments lead us to propose a new conceptualization of amygdala function whereby the amygdala inhibits behavioral engagement. Moreover, we propose that the goal of understanding the amygdala will be best served by shifting away from fear conditioning toward naturalistic approach and avoidance paradigms that involve decision-making and a larger repertoire of spontaneous and learned behaviors, all the while keeping an open mind.

The development of attention to dynamic facial emotions

PubMed Central

Heck, Alison; Hock, Alyson; White, Hannah; Jubran, Rachel; Bhatt, Ramesh S.

2016-01-01

Appropriate processing of emotions is paramount for successful social functioning. Adults’ enhanced attention to negative emotions such as fear is thought to be a critical aspect of this adaptive functioning. Prior studies indicate that increased attention to fear relative to positive or neutral emotions begins at around 7 months of age, and it has been suggested that this negativity bias is related to self-locomotion. However, these studies mostly used static faces, potentially limiting information available to the infants. In the current study, 3.5-month-olds (n = 24) and 5-month-olds (n = 24) were exposed to dynamic faces expressing fear, happy, or neutral emotions and a distracting peripheral checkerboard. The 5-month-olds looked proportionally longer at the face compared with the checkerboard when the face was fearful than when it was happy or neutral. Conversely, the 3.5-month-olds did not differentiate their attention as a function of emotion. These results indicate that the onset of enhanced attention to fear occurs between 3.5 and 5 months of age. This finding raises questions about the developmental mechanisms that drive attentional bias given that the idea of the onset of self-locomotion being a catalyst for the development of negativity bias might no longer hold. PMID:27064842

Reduction of pain-related fear and increased function and participation in work-related upper extremity pain (WRUEP): effects of exposure in vivo.

PubMed

de Jong, Jeroen R; Vlaeyen, Johan W S; van Eijsden, Marjon; Loo, Christoph; Onghena, Patrick

2012-10-01

There is increasing evidence that pain-related fear influences the development and maintenance of pain disability, presumably mediated through the fear-related avoidance of valued activities. Individually tailored graded exposure in vivo (GEXP) has been demonstrated to reduce pain-related fear and increase functional abilities in patients with chronic low back pain, neck pain, and complex regional pain syndrome. The current study aimed to test whether these effects generalize towards patients with work-related upper extremity pain. A sequential replicated and randomized single-case experimental phase design with multiple measurements was used. Within each participant, GEXP was compared to a no-treatment baseline period and a no-treatment 6-month follow-up period. Eight patients who reported a high level of pain-related fear were included in the study. Daily changes in pain catastrophizing, pain-related fear, and pain intensity were assessed using a diary, and subjected to randomization tests. Before the start of the baseline period, just after GEXP, and at 6-month follow-up, clinically relevant changes of pain catastrophizing, pain-related fear, perceived harmfulness of physical activity, pain disability, and participation/autonomy were verified. When GEXP was introduced, levels of pain catastrophizing and pain-related fear decreased significantly. Clinically relevant improvements were observed for pain disability, perceived participation, and autonomy. These favourable changes were maintained until 6-month follow-up. The findings of the current study underscore the external validity of a cognitive-behavioural GEXP treatment for patients with chronic pain reporting increased pain-related fear. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Dutch version of the Fear of Pain Questionnaire for adolescents with chronic pain.

PubMed

Dekker, Carolien; Bastiaenen, Caroline H G; de Vries, Janneke E; Simons, Laura E; Goossens, Mariëlle E J B; Verbunt, Jeanine A M C F

2018-06-01

Fear of pain is important in the development and maintenance of chronic pain. The Fear of Pain Questionnaire-Child version has been developed to assess pain related fear in children and adolescents. Translating the original questionnaire into Dutch, and investigating internal consistency and construct validity to enable use in the Dutch pain rehabilitation setting for treatment and research. Cross-sectional validation study: After forward and back translation of the FOPQ-C, adolescents (11-22 years old) with chronic musculoskeletal pain completed an assessment containing the Dutch Fear of Pain Questionnaire, and questionnaires about demographics, pain catastrophizing, functional disability, and pain intensity. Internal consistency and construct validity were evaluated through exploratory factor analysis (principal axis factoring with oblique rotation) and hypotheses testing using pain catastrophizing, functional disability, and pain intensity as comparative constructs. Eighty-six adolescents completed the assessment. Exploratory factor analysis resulted in a two-factor structure, explaining 43% of the variance. Internal consistency was strong (Cronbach's α = 0.92 total scale, α = 0.88 factor 1, and α = .86 factor 2). Five out of 6 hypotheses were confirmed. The Dutch version demonstrated good internal consistency and good construct validity in a population of adolescents with chronic musculoskeletal pain. Implications for rehabilitation The Fear of Pain Questionnaire-Child version was developed to measure fear of pain and avoidance in children and adolescents with chronic pain. Identification of fear of pain and activities that are being avoided are important during screening and assessment of the adolescent for chronic pain rehabilitation treatment. The presence of fear of pain and/or avoidance behavior is important information to shape and target multidisciplinary rehabilitation treatment.

Thalamocortical interactions underlying visual fear conditioning in humans.

PubMed

Lithari, Chrysa; Moratti, Stephan; Weisz, Nathan

2015-11-01

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans. © 2015 Wiley Periodicals, Inc.

Sex differences in disinhibition and its relationship to physical abuse in a sample of stimulant-dependent patients.

PubMed

Winhusen, Theresa; Lewis, Daniel

2013-04-01

Research suggests that impulsivity is a vulnerability factor for developing stimulant dependence, that women develop dependence more quickly than men, and that physical abuse can increase impulsivity and may have greater adverse health consequences in women. This study sought to tie these findings together by evaluating: (1) sex differences in disinhibition prior to lifetime initiation of stimulant abuse and (2) the relationship between physical abuse and disinhibition in stimulant-dependent patients. The Frontal Systems Behavior Scale (FrSBe) is a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses pre-morbid functioning and has a specific cutoff for defining clinically significant abnormalities. Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 118 methamphetamine- and/or cocaine-dependent participants. Lifetime physical abuse was measured by the Addiction Severity Index (ASI). The proportion reporting clinically significant disinhibition was significantly higher in women (64.9%) than in men (45.0%, p=0.04), with no significant difference on the other FrSBe scales. Physical abuse in women, but not men, was associated with worse functioning, with physically abused, relative to non-abused, women having a significantly greater proportion with clinically significant disinhibition (p<0.01) and total neurobehavioral abnormalities (p<0.01). These findings suggest that women may have significantly greater disinhibition than men prior to lifetime initiation of stimulant abuse and that physical abuse in women is associated with greater disinhibition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

PubMed

Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

2001-11-01

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

PubMed Central

Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

2001-01-01

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed. PMID:11713003

Manifestations, acquisition and diagnostic categories of dental fear in a self-referred population.

PubMed

Moore, R; Brødsgaard, I; Birn, H

1991-01-01

This study aimed to clarify how manifestations and acquisition relate to diagnostic categories of dental fear in a population of self-referred dental fear patients, since diagnostic criteria specifically related to dental fear have not been validated. DSM III-R diagnostic criteria for phobias were used to compare with four existing dental fear diagnostic categories, referred to as the Seattle system. Subjects were 208 persons with dental fear who were telephone interviewed, of whom a subsample of 155 responded to a mailed Dental Anxiety Scale (DAS), State-Trait Anxiety Inventory and a modified FSS-II Geer Fear Scale (GFS). Personal interviews and a Dental Beliefs Scale of perceived trust and social interaction with dentists were also used to evaluate a subsample of 80 patients selected by sex and high dental fear. Results showed that the majority of the 80 patients (66%), suffered from social embarrassment about their dental fear problem and their inability to do something about it. The largest cause of their fear (84%) was reported to be traumatic dental experiences, especially in childhood (70%). A minority of patients (16%) could not isolate traumatic experiences and had a history of general fearfulness or anxiety. Analysis of GFS data for the 155 subjects showed that fear of snakes and injuries were highest among women; heights and injections among men. Fear of blood was rarely reported. Spearman correlations between GFS individual items and DAS scores indicated functional independence between dental fear and common fears such as blood, injections and enclosures in most cases. Only in specific types of dental fear did these results support Rachman and Lopatka's contention that fears are thought to summate.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of nursing staff survivor responses to hospital restructuring and downsizing.

PubMed

Burke, Ronald J

2005-01-01

This study examines correlates of 4 archetypal survivor responses to organizational restructuring and downsizing proposed by Mishra and Spreitzer: hopeful, obliging, cynical, and fearful. Data were collected from 744 long-term nursing staff survivors of hospital restructuring and downsizing using questionnaires. Three types of correlates were considered: work outcomes, indicators of psychologic well-being, and perceptions of hospital functioning. Greater endorsement of cynical and fearful restructuring responses was associated with more negative work outcomes and lower psychologic well-being. Greater endorsement of both cynical and fearful responses was also found to be associated with more negative perceptions of hospital functioning and effectiveness.

How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear

PubMed Central

Kroes, Marijn C W; Tona, Klodiana-Daphne; den Ouden, Hanneke E M; Vogel, Susanne; van Wingen, Guido A; Fernández, Guillén

2016-01-01

Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers. PMID:26462618

Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex.

PubMed

Feng, Pan; Becker, Benjamin; Zheng, Yong; Feng, Tingyong

2018-02-01

Sleep plays an important role for successful fear memory consolidation. Growing evidence suggests that sleep disturbances might contribute to the development and the maintenance of posttraumatic stress disorder (PTSD), a disorders characterized by dysregulations in fear learning mechanisms, as well as exaggerated arousal and salience processing. Against this background, the present study examined the effects of sleep deprivation (SD) on the acquisition of fear and the subsequent neural consolidation. To this end, the present study assessed fear acquisition and associated changes in fMRI-based amygdala-functional connectivity following 24 h of SD. Relative to non-sleep deprived controls, SD subjects demonstrated increased fear ratings and skin conductance responses (SCR) during fear acquisition. During fear consolidation SD inhibited increased amygdala-ventromendial prefrontal cortex (vmPFC) connectivity and concomitantly increased changes in amygdala-insula connectivity. Importantly, whereas in controls fear indices during acquisition were negatively associated with amygdala-vmPFC connectivity during consolidation, fear indices were positively associated with amygdala-insula coupling following SD. Together the findings suggest that SD may interfere with vmPFC control of the amygdala and increase bottom-up arousal signaling in the amygdala-insula pathway during fear consolidation, which might mediate the negative impact of sleep disturbances on PSTD symptomatology.

Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure☆

PubMed Central

Frick, Andreas; Gingnell, Malin; Marquand, Andre F.; Howner, Katarina; Fischer, Håkan; Kristiansson, Marianne; Williams, Steven C.R.; Fredrikson, Mats; Furmark, Tomas

2014-01-01

Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD. PMID:24239689

Altered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy.

PubMed

Roos, Annerine; Robertson, Frances; Lochner, Christine; Vythilingum, Bavanisha; Stein, Dan J

2011-09-12

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

Signs of neurobehavioral dysfunction in a sample of learning disabled children: stability and concurrent validity.

PubMed

Morrison, D C; Hinshaw, S P; Carte, E T

1985-12-01

Of 270 learning disabled children with average intelligence and significant delays in reading comprehension a sample of 37 were evaluated for signs of neurobehavioral dysfunction. All such signs--primitive reflexes, equilibrium reactions, and postrotary nystagmus--were reliably assessed. A subsample of 19 children was compared with developmentally normal and mentally retarded samples for the occurrence of tonic neck reflexes and equilibrium reactions. The learning disabled children consistently showed deviancies like those of the retarded children; both of these groups differed from the normal children on most measures. These deviant responses persisted over a 9-mo. period for the learning disabled group. Compared with norms, the total learning disabled sample displayed hyponystagmus, and this depressed nystagmus persisted for 11 mo. Results are discussed in relation to the lack of correlation among the various signs of neurobehavioral dysfunction in the learning disabled children.

Neurobehavioral phenotype in Prader-Willi syndrome.

PubMed

Whittington, Joyce; Holland, Anthony

2010-11-15

The focus of this article is on the lifetime development of people with Prader-Willi syndrome (PWS) and specifically on the neurobehavioral phenotype. We consider studies of this aspect of the phenotype (the "behavioral phenotype" of the syndrome) that have confirmed that there are specific behaviors and psychiatric disorders, the propensities to which are increased in those with PWS, and cannot be accounted for by other variables such as IQ or adaptive behavior. Beginning with a description of what is observed in people with PWS, we review the evolving PWS phenotype and consider how some aspects of the phenotype might be best explained, and how this complex phenotype may relate to the equally complex genotype. We then consider in more detail some of the neurobehavioral aspects of the phenotype listed above that raise the greatest management problems for parents and carers. © 2010 Wiley-Liss, Inc.

Public-speaking fears in a community sample. Prevalence, impact on functioning, and diagnostic classification.

PubMed

Stein, M B; Walker, J R; Forde, D R

1996-02-01

Recent epidemiologic studies have revealed that social phobia is more prevalent than has been previously believed. An unresolved issue is the extent to which public-speaking fears constitute a recognizable form of social phobia in a community sample and, moreover, to what extent these fears are associated with functional morbidity. To examine the prevalence and impact of public-speaking fears and their relationship to social phobia in a community sample, we conducted a randomized telephone survey of 499 residents of Winnipeg, Manitoba, a medium-sized midwestern metropolitan area. One third of the respondents reported that they had excessive anxiety when they spoke to a large audience. The onset of fears was early (ie, 50%, 75%, and 90% by the ages of 13, 17, and 20 years, respectively). Anxious cognitions about public speaking included the following fears: doing or saying something embarrassing (64%), one's mind going blank (74%), being unable to continue talking (63%), saying foolish things or not making sense (59%), and trembling, shaking, or showing other signs of anxiety (80%). In total, 10% (n = 49) of the respondents reported that public-speaking anxiety had resulted in a marked interference with their work (2%), social life (1%), or education (4%), or had caused them marked distress (8%). Twenty-three persons (5%) had public-speaking anxiety in isolation (ie, without evidence of additional kinds of social fears). These data support the inclusion of severe forms of public-speaking fears within the social phobia construct and, furthermore, suggest that public-speaking anxiety may have a detrimental impact on the lives of many individuals in the community.

Evaluation of Short-Term Bioassays to Predict Functional Impairment, Development of Neurobehavioral Bioassays in Laboratory Animals, Directory of Institutions/Individuals.

DTIC Science & Technology

1980-10-01

0vna /eet &ku, 1 -0 - /.)GP-urna reenaway, James Konz // Oct&l =80 A Supported by - - US Army Medical Research and Development Command Fort Detrick...Contracting Officer’s Technical Representative: Mary C. Henry, Ph.D. D -A US Army Medical Bioengineering Research and Development Laboratory Fort Detrick...Virginia__22102 ______________ 11. CONTROLLING OFFICE NAME AND AD13RESS 12. REPORT DATE U.S. Army Medical Research and Development Commani October 1980 Fort

Impact of fear of falling in long term care: an integrative review.

PubMed

Lach, Helen W; Parsons, Jill L

2013-08-01

Long term care elders with fear of falling may restrict their activity resulting in declines in function and excess disability. To further explore this problem, a review of the literature was conducted. The search yielded 26 studies on the epidemiology of fear of falling in nursing homes and assisted living as well as intervention studies in these settings. Fear of falling is common, affecting more than 50% of long term care elders and is associated with negative outcomes, including falls, functional impairments, depression, and poor quality of life. Longitudinal studies are rare. There were few intervention studies, with most testing exercise programs, including balance training, such as t'ai chi, and little research testing other approaches. Few conclusions can be drawn about interventions, as most sample sizes were small and the interventions and measurement varied widely. Additional research is needed to identify long term care residents most in need of intervention, and the best ways to reduce fear of falling and its consequences. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

PubMed

Rauch, Scott L; Shin, Lisa M; Phelps, Elizabeth A

2006-08-15

The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.

Long-term memory deficits in Pavlovian fear conditioning in Ca2+/calmodulin kinase kinase alpha-deficient mice.

PubMed

Blaeser, Frank; Sanders, Matthew J; Truong, Nga; Ko, Shanelle; Wu, Long Jun; Wozniak, David F; Fanselow, Michael S; Zhuo, Min; Chatila, Talal A

2006-12-01

Signaling by the Ca(2+)/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase alpha (CaMKKalpha) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKalpha mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKalpha mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKalpha in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.

Interference effects of transcranial direct current stimulation over the right frontal cortex and adrenergic system on conditioned fear.

PubMed

Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza

2017-11-01

The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.

Healthy body, healthy mind?: the effectiveness of physical activity to treat ADHD in children.

PubMed

Halperin, Jeffrey M; Berwid, Olga G; O'Neill, Sarah

2014-10-01

Data from animal studies provide convincing evidence that physical exercise enhances brain development and neurobehavioral functioning in areas believed to be impaired in children with attention-deficit/hyperactivity disorder (ADHD). To a lesser but still compelling extent, results from studies in typically developing children and adults indicate beneficial effects of exercise on many of the neurocognitive functions that have been shown to be impaired in children with ADHD. Together, these data provide a strong rationale for why a program of structured physical exercise might serve as an effective intervention for children with ADHD. Copyright © 2014 Elsevier Inc. All rights reserved.

Early life programming of fear conditioning and extinction in adult male rats.

PubMed

Stevenson, Carl W; Spicer, Clare H; Mason, Rob; Marsden, Charles A

2009-12-28

The early rearing environment programs corticolimbic function and neuroendocrine stress reactivity in adulthood. Although early environmental programming of innate fear has been previously examined, its impact on fear learning and memory later in life remains poorly understood. Here we examined the role of the early rearing environment in programming fear conditioning and extinction in adult male rats. Pups were subjected to maternal separation (MS; 360 min), brief handling (H; 15 min), or animal facility rearing (AFR) on post-natal days 2-14. As adults, animals were tested in a 3-day fear learning and memory paradigm which assessed the acquisition, expression and extinction of fear conditioning to an auditory cue; the recall of extinction was also assessed. In addition, contextual fear was assessed prior to cued extinction and its recall. We found that the acquisition of fear conditioning to the cue was modestly impaired by MS. However, no early rearing group differences were observed in cue-induced fear expression. In contrast, both the rate of extinction and extinction recall were attenuated by H. Finally, although contextual fear was reduced after extinction to the cue, no differences in context-induced fear were observed between the early rearing groups. These results add to a growing body of evidence supporting an important role for early environmental programming of fear conditioning and extinction. They also indicate that different early rearing conditions can program varying effects on distinct fear learning and memory processes in adulthood.

Cortisol increases the return of fear by strengthening amygdala signaling in men.

PubMed

Kinner, Valerie L; Wolf, Oliver T; Merz, Christian J

2018-05-01

Relapses represent a major limitation to the long-term remission of pathological fear and anxiety. Stress modulates the acquisition and expression of fear memories and appears to promote fear recovery in patients with anxiety disorders. However, the neural correlates underlying stress hormone effects on the return of fear in humans remain unexplored. Likewise, little is known about the interactions between sex and stress hormones on return of fear phenomena. In this functional magnetic resonance imaging study, 32 men and 32 women were exposed to a fear renewal paradigm with fear acquisition in context A and extinction in context B. On the following day, participants received either cortisol or placebo 40 min before return of fear was tested in both contexts in a renewal and reinstatement test. Cortisol increased differential conditioned skin conductance responses in the extinction context B following reinstatement in men but not in women. On the neural level, this effect was characterized by enhanced fear-related activation in the right amygdala in men, while an activation decrement in this region was observed after cortisol treatment in women. Our results revealed that cortisol promotes the return of fear in men by strengthening a key node of the fear network - the amygdala. We thereby provide novel insights into a sex-specific mechanism mediating stress-induced fear recovery which may translate into different relapse risks and treatment strategies for men and women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using novel control groups to dissect the amygdala's role in Williams syndrome.

PubMed

Thornton-Wells, Tricia A; Avery, Suzanne N; Blackford, Jennifer Urbano

2011-07-01

Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.

Depth of processing and recall of threat material in fearful and nonfearful individuals.

PubMed

Wenzel, Amy; Zetocha, Kimberlee; Ferraro, F Richard

2007-09-01

Although many studies have examined the nature of memory distortions in anxious individuals, few have considered biases in specific memory processes, such as encoding or retrieval. To investigate whether the presentation of threat material facilitates encoding biases, spider fearful (n=63), blood fearful (n=73), and nonfearful (n=75) participants encoded spider related, blood related, and neutral words as a function of three levels of processing (i.e., structural, semantic, and self referent). Participants subsequently completed either a free recall or a recognition task. All participants demonstrated a partial depth of processing effect, such that they recalled more words encoded in the self referent condition than in the other two conditions, but groups did not differ in their recall of stimuli as a function of word type. Relative to participants in the other groups, spider fearful participants had fewer spider related intrusions in the recall condition, and they made fewer errors in responding to structural and semantic encoding questions when spider related words were presented. These results contribute to an increasingly large body of literature suggesting that anxious individuals are not characterized by a memory bias toward threat, and they raise the possibility that individuals with spider fears process threat-relevant information differently than individuals with blood fears.

The Role Of Basal Forebrain Cholinergic Neurons In Fear and Extinction Memory

PubMed Central

Knox, Dayan

2016-01-01

Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. PMID:27264248

Single dose of l-dopa makes extinction memories context-independent and prevents the return of fear

PubMed Central

Haaker, Jan; Gaburro, Stefano; Sah, Anupam; Gartmann, Nina; Lonsdorf, Tina B.; Meier, Kolja; Singewald, Nicolas; Pape, Hans-Christian; Morellini, Fabio; Kalisch, Raffael

2013-01-01

Traumatic events can engender persistent excessive fear responses to trauma reminders that may return even after successful treatment. Extinction, the laboratory analog of behavior therapy, does not erase conditioned fear memories but generates competing, fear-inhibitory “extinction memories” that, however, are tied to the context in which extinction occurred. Accordingly, a dominance of fear over extinction memory expression—and, thus, return of fear—is often observed if extinguished fear stimuli are encountered outside the extinction (therapy) context. We show that postextinction administration of the dopamine precursor l-dopa makes extinction memories context-independent, thus strongly reducing the return of fear in both mice and humans. Reduced fear is accompanied by decreased amygdala and enhanced ventromedial prefrontal cortex activation in both species. In humans, ventromedial prefrontal cortex activity is predicted by enhanced resting-state functional coupling of the area with the dopaminergic midbrain during the postextinction consolidation phase. Our data suggest that dopamine-dependent boosting of extinction memory consolidation is a promising avenue to improving anxiety therapy. PMID:23754384

Continuing the search for the engram: examining the mechanism of fear memories.

PubMed

Josselyn, Sheena A

2010-07-01

The goal of my research is to gain insight using rodent models into the fundamental molecular, cellular and systems that make up the base of memory formation. My work focuses on fear memories. Aberrant fear and/or anxiety may be at the heart of many psychiatric disorders. In this article, I review the results of my research group; these results show that particular neurons in the lateral amygdala, a brain region important for fear, are specifically involved in particular fear memories. We started by showing that the transcription factor CREB (cAMP/Ca(2+) response element binding protein) plays a key role in the formation of fear memories. Next, we used viral vectors to overexpress CREB in a subset of lateral amygdala neurons. This not only facilitated fear memory formation but also "drove" the memory into the neurons with relatively increased CREB function. Finally, we showed that selective ablation of the neurons overexpressing CREB in the lateral amygdala selectively erased the fear memory. These findings are the first to show disruption of a specific memory by disrupting select neurons within a distributed network.

Comparison at 32-37 Weeks Postconception of Infants Born 1983-1989 and 1995-2004 on the Neurobehavioral Assessment of the Preterm Infant

ERIC Educational Resources Information Center

Brown, Josephine V.; Bakeman, Roger; Sampers, Jackie S.; Korner, Anneliese F.; Constantinou, Janet C.; Anand, K. J. S.

2008-01-01

In spite of numerous recent outcome studies of extremely low birth weight (ELBW) infants, no data exist on their development prior to term. In this study we traced and compared the neurobehavioral development of 251 ELBW (less than 1,000 g) and 240 low birth weight (LBW; 1,000 g-2,500 g) preterms born between 1995 and 2004 from 32 to 37 weeks…

A face versus non-face context influences amygdala responses to masked fearful eye whites.

PubMed

Kim, M Justin; Solomon, Kimberly M; Neta, Maital; Davis, F Caroline; Oler, Jonathan A; Mazzulla, Emily C; Whalen, Paul J

2016-12-01

The structure of the mask stimulus is crucial in backward masking studies and we recently demonstrated such an effect when masking faces. Specifically, we showed that activity of the amygdala is increased to fearful facial expressions masked with neutral faces and decreased to fearful expressions masked with a pattern mask-but critically both masked conditions discriminated fearful expressions from happy expressions. Given this finding, we sought to test whether masked fearful eye whites would produce a similar profile of amygdala response in a face vs non-face context. During functional magnetic resonance imaging scanning sessions, 30 participants viewed fearful or happy eye whites masked with either neutral faces or pattern images. Results indicated amygdala activity was increased to fearful vs happy eye whites in the face mask condition, but decreased to fearful vs happy eye whites in the pattern mask condition-effectively replicating and expanding our previous report. Our data support the idea that the amygdala is responsive to fearful eye whites, but that the nature of this activity observed in a backward masking design depends on the mask stimulus. © The Author (2016). Published by Oxford University Press.

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior.

PubMed

Egaña-Ugrinovic, Gabriela; Sanz-Cortés, Magdalena; Couve-Pérez, Constanza; Figueras, Francesc; Gratacós, Eduard

2014-09-01

The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk. © 2014 John Wiley & Sons, Ltd.

Rehabilitation following pediatric traumatic brain injury: variability in adherence to psychosocial quality-of-care indicators.

PubMed

Ennis, Stephanie K; Jaffe, Kenneth M; Mangione-Smith, Rita; Konodi, Mark A; MacKenzie, Ellen J; Rivara, Frederick P

2014-01-01

To examine variations in processes of pediatric inpatient rehabilitation care related to family-centered care, management of neurobehavioral and psychosocial needs, and community reintegration after traumatic brain injury. Nine acute rehabilitation facilities from geographically diverse areas of the United States. A total of 174 children with traumatic brain injury. Retrospective chart review. Adherence to care indicators (the number of times recommended care was delivered or attempted divided by the number of times care was indicated). Across facilities, adherence rates (adjusted for difficulty of delivery) ranged from 33.6% to 73.1% (95% confidence interval, 13.4-53.9, 58.7-87.4) for family-centered processes, 21.3% to 82.5% (95% confidence interval, 6.6-36.1, 67.6-97.4) for neurobehavioral and psychosocial processes, and 22.7% to 80.3% (95% confidence interval, 5.3-40.1, 68.1-92.5) for community integration processes. Within facilities, standard deviations for adherence rates were large (24.3-34.9, family-centered domain; 22.6-34.2, neurobehavioral and psychosocial domain; and 21.6-40.5, community reintegration domain). The current state of acute rehabilitation care for children with traumatic brain injury is variable across different quality-of-care indicators addressing neurobehavioral and psychosocial needs and facilitating community reintegration of the patient and the family. Individual rehabilitation facilities demonstrate inconsistent adherence to different indicators and inconsistent performance across different care domains.

Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance.

PubMed

McCauley, Peter; Kalachev, Leonid V; Mollicone, Daniel J; Banks, Siobhan; Dinges, David F; Van Dongen, Hans P A

2013-12-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation--and thereby sensitivity to neurobehavioral impairment from sleep loss--is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation--and thus sensitivity to sleep loss--depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work.

Emotional environments retune the valence of appetitive versus fearful functions in nucleus accumbens

PubMed Central

Reynolds, Sheila M; Berridge, Kent C

2009-01-01

The nucleus accumbens mediates both appetitive motivation for rewards and fearful motivation toward threats, which are generated in part by glutamate-related circuits organized in a keyboard fashion. At rostral sites of the medial shell, localized glutamate disruptions typically generate intense appetitive behaviors in rats, but the disruption incrementally generates fearful behaviors as microinjection sites move more caudally. We found that exposure to stressful environments caused caudal fear-generating zones to expand rostrally, filling ~90% of the shell. Conversely, a preferred home environment caused fear-generating zones to shrink and appetitive-generating zones to expand caudally, filling ~90% of the shell. Thus, the emotional environments retuned the generation of motivation in corticolimbic circuits. PMID:18344996

Prefrontal consolidation supports the attainment of fear memory accuracy.

PubMed

Vieira, Philip A; Lovelace, Jonathan W; Corches, Alex; Rashid, Asim J; Josselyn, Sheena A; Korzus, Edward

2014-08-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. © 2014 Vieira et al.; Published by Cold Spring Harbor Laboratory Press.

Adolescents and Alcohol: Acute Sensitivities, Enhanced Intake, and Later Consequences*

PubMed Central

Spear, Linda Patia

2014-01-01

Adolescence is an evolutionarily conserved developmental period characterized by notable maturational changes in brain along with various age-related behavioral characteristics, including the propensity to initiate alcohol and other drug use and consume more alcohol per occasion than adults. After a brief review of adolescent neurobehavioral function from an evolutionary perspective, the paper will turn to assessment of adolescent alcohol sensitivity and consequences, with a focus on work from our laboratory. After summarizing evidence showing that adolescents differ considerably from adults in their sensitivity to various effects of alcohol, potential contributors to these age-typical sensitivities will be discussed, and the degree to which these findings are generalizable to other drugs and to human adolescents will be considered. Recent studies are then reviewed to illustrate that repeated alcohol exposure during adolescence induces behavioral, cognitive, and neural alterations that are highly specific, replicable, persistent and dependent on the timing of the exposure. Research in this area is in its early stages, however, and more work will be necessary to characterize the extent of these neurobehavioral alterations and further determine the degree to which observed effects are specific to alcohol exposure during adolescence. PMID:24291291

Neurobehavioral and self-awareness changes after traumatic brain injury: Towards new multidimensional approaches.

PubMed

Arnould, A; Dromer, E; Rochat, L; Van der Linden, M; Azouvi, P

2016-02-01

Neurobehavioral and self-awareness changes are frequently observed following traumatic brain injury (TBI). These disturbances have been related to negative consequences on functional outcomes, caregiver distress and social reintegration, representing therefore a challenge for clinical research. Some studies have recently been conducted to specifically explore apathetic and impulsive manifestations, as well as self-awareness impairments in patients with TBI. These findings underlined the heterogeneity of clinical manifestations for each behavioral disturbance and the diversity of psychological processes involved. In this context, new multidimensional approaches taking into account the various processes at play have been proposed to better understand and apprehend the complexity and dynamic nature of these problematic behaviors. In addition, the involvement of social and environmental factors as well as premorbid personality traits have increasingly been addressed. These new multidimensional frameworks have the potential to ensure targeted and effective rehabilitation by allowing a better identification and therefore consideration of the various mechanisms involved in the onset of problematic behaviors. In this context, the main objective of this position paper was to demonstrate the interest of multidimensional approaches in the understanding and rehabilitation of problematic behaviors in patients with TBI. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The association of pain and fear of movement/reinjury with function during anterior cruciate ligament reconstruction rehabilitation.

PubMed

Chmielewski, Terese L; Jones, Debi; Day, Tim; Tillman, Susan M; Lentz, Trevor A; George, Steven Z

2008-12-01

Cross-sectional. To measure fear of movement/reinjury levels and determine the association with function at different timeframes during anterior cruciate ligament (ACL) reconstruction rehabilitation. We hypothesized that fear of movement/reinjury would decrease during rehabilitation and be inversely related with function. Fear of movement/reinjury can prevent return to sports after ACL reconstruction, but it has not been studied during rehabilitation. Demographic data and responses on the shortened version of Tampa Scale for Kinesiophobia (TSK-11), 8-Item Short-Form Health Survey (SF-8), and International Knee Documentation Committee (IKDC) subjective form were extracted from a clinical database for 97 patients in the first year after ACL reconstruction. Three groups were formed: group 1, less than or equal to 90 days; group 2, 91 to 180 days; group 3: 181 to 372 days post-ACL reconstruction. Group differences in TSK-11 score, SF-8 bodily pain rating, and IKDC scores were determined. Hierarchical linear regression models were created for each group, with IKDC score as the dependent variable and demographic factors, SF-8 bodily pain rating, and TSK-11 score as independent variables. TSK-11 score was higher in group 1 than in group 3 (P < .05). Across the groups, SF-8 bodily pain rating decreased (P < .001) and IKDC score increased (P < .001). SF-8 bodily pain rating was a significant factor in the regression model for all groups, whereas TSK-11 score only contributed to the regression model in group 3 (partial correlation, -0.529). Pain was consistently associated with function across the timeframes studied. Fear of movement/reinjury levels appear to decrease during ACL reconstruction rehabilitation and are associated with function in the timeframe when patients return to sports. Prognosis, level 4.

Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear

PubMed Central

Pape, Hans-Christian; Pare, Denis

2009-01-01

The last ten years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate to the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled to the fact that the underlying circuitry is evolutionarily well conserved makes it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances, came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses. PMID:20393190

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

PubMed

Randall, Cameron L; Wright, Casey D; Chernus, Jonathan M; McNeil, Daniel W; Feingold, Eleanor; Crout, Richard J; Neiswanger, Katherine; Weyant, Robert J; Shaffer, John R; Marazita, Mary L

2017-01-01

Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p < 5 × 10 -8 for all) near the genes TMEM65 , NEFM , NEFL , AGPAT4 , and PARK2 . Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

A model of the generation of ataque de nervios: the role of fear of negative affect and fear of arousal symptoms.

PubMed

Hinton, Devon E; Lewis-Fernández, Roberto; Pollack, Mark H

2009-01-01

This article examines a model of the generation of ataque de nervios, according to which both fear of negative affectivity and fear of arousal symptoms are associated with the emergence of ataques. We examine the relationship of fear of negative affectivity and fear of arousal to the severity of ataque de nervios during the last month and the last 6 months among Caribbean Latinos residing in the United States. The measures include a Fear of Anger Scale and the Anxiety Sensitivity Index (ASI), the ASI augmented with two items that assess fear of arousal symptoms common in ataques: chest tightness and a sense of inner heat. In keeping with the model of ataque generation, one-way analysis of variances (ANOVAs) and discriminant function analyses illustrated that items assessing "fear of negative affect" and "fear of somatic and psychological symptoms of arousal" both differentiated well among the levels of ataque severity. In addition, key ataque symptoms-mental incapacitation fears, shakiness, chest tightness, palpitations, and a sense of inner heat-were the best discriminators among levels of ataque severity. In patients with severe ataques, the scores of "fear of negative affect" and "fear of ataque-de-nervios-type somatic and psychological symptoms" were extremely elevated. This further suggests that both these types of fears are associated with this idiom of distress and that the specific content of the fears is linked to the symptom picture of the idiom. This suggests specific therapeutic targets for the treatment of ataque, namely, the reduction of anxiety sensitivity (and more generally negative-emotion and arousal sensitivity) using cognitive behavioral therapy (CBT), relaxation, and mindfulness techniques.

MicroRNA-Mediated Rescue of Fear Extinction Memory by miR-144-3p in Extinction-Impaired Mice.

PubMed

Murphy, Conor P; Li, Xiang; Maurer, Verena; Oberhauser, Michael; Gstir, Ronald; Wearick-Silva, Luis Eduardo; Viola, Thiago Wendt; Schafferer, Simon; Grassi-Oliveira, Rodrigo; Whittle, Nigel; Hüttenhofer, Alexander; Bredy, Timothy W; Singewald, Nicolas

2017-06-15

MicroRNA (miRNA)-mediated control of gene expression suggests that miRNAs are interesting targets and/or biomarkers in the treatment of anxiety- and trauma-related disorders, where often memory-associated gene expression is adversely affected. The role of miRNAs in the rescue of impaired fear extinction was assessed using the 129S1/SvlmJ (S1) mouse model of impaired fear extinction. miRNA microarray analysis, reverse transcription polymerase chain reaction, fluorescent in situ hybridization, lentiviral overexpression, and Luciferase reporter assays were used to gain insight into the mechanisms underlying miRNA-mediated normalization of deficient fear extinction. Rescuing impaired fear extinction via dietary zinc restriction was associated with differential expression of miRNAs in the amygdala. One candidate, miR-144-3p, robustly expressed in the basolateral amygdala, showed specific extinction-induced, but not fear-induced, increased expression in both extinction-rescued S1 mice and extinction-intact C57BL/6 (BL6) mice. miR-144-3p upregulation and effects on subsequent behavioral adaption was assessed in S1 and BL6 mice. miR-144-3p overexpression in the basolateral amygdala rescued impaired fear extinction in S1 mice, led to enhanced fear extinction acquisition in BL6 mice, and furthermore protected against fear renewal in BL6 mice. miR-144-3p targets a number of genes implicated in the control of plasticity-associated signaling cascades, including Pten, Spred1, and Notch1. In functional interaction studies, we revealed that the miR-144-3p target, PTEN, colocalized with miR-144-3p in the basolateral amygdala and showed functional downregulation following successful fear extinction in S1 mice. These findings identify a fundamental role of miR-144-3p in the rescue of impaired fear extinction and suggest this miRNA as a viable target in developing novel treatments for posttraumatic stress disorder and related disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Using functional theory to promote HIV testing: the impact of value-expressive messages, uncertainty, and fear.

PubMed

Hullett, Craig R

2006-01-01

This study tests the utility of the functional theory of attitudes and arousal of fear in motivating college students to get tested for HIV. It is argued from the perspective of functional theory that value-expressive appeals to get tested for the purpose of taking care of one's own health could be effective if that goal is desired by message targets who are sexually active and unaware of their sexually transmitted disease status. As part of the process, the effectiveness of these appeals is increased by the arousal of uncertainty and fear. A model detailing the mediating processes is proposed and found to be consistent with the data. Overall, messages advocating testing for the self-interested reason of one's own health were more effective than messages advocating testing for the goal of protecting one's partners.

Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits

PubMed Central

Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

2016-01-01

Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA. PMID:27918273

The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

PubMed Central

Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

2014-01-01

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

Individual Differences in the Flexibility of Peripersonal Space.

PubMed

Hunley, Samuel B; Marker, Arwen M; Lourenco, Stella F

2017-01-01

The current study investigated individual differences in the flexibility of peripersonal space (i.e., representational space near the body), specifically in relation to trait claustrophobic fear (i.e., fear of suffocating or being physically restricted). Participants completed a line bisection task with either a laser pointer (Laser condition), allowing for a baseline measure of the size of one's peripersonal space, or a stick (Stick condition), which produces expansion of one's peripersonal space. Our results revealed that individuals high in claustrophobic fear had larger peripersonal spaces than those lower in claustrophobic fear, replicating previous research. We also found that, whereas individuals low in claustrophobic fear demonstrated the expected expansion of peripersonal space in the Stick condition, individuals high in claustrophobic fear showed less expansion, suggesting decreased flexibility. We discuss these findings in relation to the defensive function of peripersonal space and reduced attentional flexibility associated with trait anxieties.

Acquired fears reflected in cortical sensory processing: A review of electrophysiological studies of human classical conditioning

PubMed Central

Miskovic, Vladimir; Keil, Andreas

2012-01-01

The capacity to associate neutral stimuli with affective value is an important survival strategy that can be accomplished by cell assemblies obeying Hebbian learning principles. In the neuroscience laboratory, classical fear conditioning has been extensively used as a model to study learning related changes in neural structure and function. Here, we review the effects of classical fear conditioning on electromagnetic brain activity in humans, focusing on how sensory systems adapt to changing fear-related contingencies. By considering spatio-temporal patterns of mass neuronal activity we illustrate a range of cortical changes related to a retuning of neuronal sensitivity to amplify signals consistent with fear-associated stimuli at the cost of other sensory information. Putative mechanisms that may underlie fear-associated plasticity at the level of the sensory cortices are briefly considered and several avenues for future work are outlined. PMID:22891639

The Biology of Fear

PubMed Central

Adolphs, Ralph

2013-01-01

Each of us has felt afraid, and we can all recognize fear in many animal species. Yet there is no consensus in the scientific study of fear. Some argue that “fear” is a psychological construct rather than discoverable through scientific investigation. Others argue that the term “fear” cannot properly be applied to animals because we cannot know whether they feel afraid. Studies in rodents show that there are highly specific brain circuits for fear, whereas findings from human neuroimaging seem to make the opposite claim. Here I review the field and urge three approaches that could reconcile the debates. For one, we need a broadly comparative approach that would identify core components of fear conserved across phylogeny. This also pushes us towards the second point of emphasis: an ecological theory of fear that is essentially functional. Finally, we should aim even to incorporate the conscious experience of being afraid, reinvigorating the study of feelings across species. PMID:23347946

Ventromedial prefrontal cortex activity and rapid eye movement sleep are associated with subsequent fear expression in human subjects.

PubMed

Spoormaker, V I; Gvozdanovic, G A; Sämann, P G; Czisch, M

2014-05-01

In humans, activity patterns in the ventromedial prefrontal cortex (vmPFC) have been found to be predictive of subsequent fear memory consolidation. Pioneering work in rodents has further shown that vmPFC-amygdala theta synchronization is correlated with fear memory consolidation. We aimed to evaluate whether vmPFC activity during fear conditioning is (1) correlated with fear expression the subsequent day and whether (2) this relationship is mediated by rapid eye movement (REM) sleep. We analyzed data from 17 young healthy subjects undergoing a fear conditioning task, followed by a fear extinction task 24 h later, both recorded with simultaneous skin conductance response (SCR) and functional magnetic resonance imaging measurements, with a polysomnographically recorded night sleep in between. Our results showed a correlation between vmPFC activity during fear conditioning and subsequent REM sleep amount, as well as between REM sleep amount and SCR to the conditioned stimulus 24 h later. Moreover, we observed a significant correlation between vmPFC activity during fear conditioning and SCR responses during extinction, which was no longer significant after controlling for REM sleep amount. vmPFC activity during fear conditioning was further correlated with sleep latency. Interestingly, hippocampus activity during fear conditioning was correlated with stage 2 and stage 4 sleep amount. Our results provide preliminary evidence that the relationship between REM sleep and fear conditioning and extinction observed in rodents can be modeled in healthy human subjects, highlighting an interrelated set of potentially relevant trait markers.

Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children

PubMed Central

Fiedler, Nancy; Rohitrattana, Juthasiri; Siriwong, Wattasit; Suttiwan, Panrapee; Strickland, Pam Ohman; Ryan, P. Barry; Rohlman, Diane S.; Panuwet, Parinya; Barr, Dana Boyd; Robson, Mark G.

2015-01-01

The use of pesticides for crop production has grown rapidly in Thailand during the last decade, resulting in significantly greater potential for exposure among children living on farms. Although some previous studies assessed exposures to pesticides in this population, no studies have been conducted to evaluate corresponding health effects. Twenty-four children from a rice farming community (exposed) and 29 from an aquaculture (shrimp) community (control) completed the study. Participants completed a neurobehavioral test battery three times at 6 month intervals: Session I: preliminary orientation; Session II: high pesticide use season; Session III: low pesticide-use season. Only sessions II and III were used in the analyses. High and low pesticide use seasons were determined by pesticide use on rice farms. Urinary metabolites of organophosphates (OPs) and pyrethroids (PYR) were analyzed from first morning void samples collected the day of neurobehavioral testing. Rice farm participants had significantly higher concentrations of dialkylphosphates (DAPs) (common metabolites of OPs) and TCPy (a specific metabolite of chlorpyrifos) than aquaculture farm children regardless of season. But, TCPy was significantly higher during the low rather than the high pesticide use season for both participant groups. Rice farm children had significantly higher DCCA, a metabolite of PYR, than aquaculture participants only during the high exposure season. Otherwise, no significant differences in PYR metabolites were noted between the participant groups or seasons. No significant adverse neurobehavioral effects were observed between participant groups during either the high or low pesticide use season. After controlling for differences in age and the Home Observation for Measurement of the Environment (HOME) scores, DAPs, TCPy, and PYR were not significant predictors of adverse neurobehavioral performance during either season. Increasing DAP and PYR metabolites predicted some relatively small improvement in latency of response. However, due to the small sample size and inability to characterize chronic exposure, any significant differences observed should be regarded with caution. PMID:25721160

Cerebral oxygenation in the beach chair position for shoulder surgery in regional anesthesia: impact on cerebral blood flow and neurobehavioral outcome.

PubMed

Aguirre, José A; Märzendorfer, Olivia; Brada, Muriel; Saporito, Andrea; Borgeat, Alain; Bühler, Philipp

2016-12-01

Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. University hospital operating room. Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values (P<.05). There was no decrease in either the regional cerebral saturation (P=.136) or the maximal blood flow of the middle cerebral artery (P=.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of 3 tests). Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on cerebral blood flow and cerebral oxygenation. However, some impact on neurobehavioral outcome 24 hours after surgery was observed. Copyright © 2016 Elsevier Inc. All rights reserved.

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

PubMed Central

Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to cover the lifespan of the laboratory mouse using a battery of neurobehavioral techniques. PMID:26793076

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

PubMed

Saenen, Nelly D; Provost, Eline B; Viaene, Mineke K; Vanpoucke, Charlotte; Lefebvre, Wouter; Vrijens, Karen; Roels, Harry A; Nawrot, Tim S

2016-10-01

Children's neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10μm exposure (PM2.5, PM10) was monitored on each examination day. At the child's residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention. Copyright © 2016. Published by Elsevier Ltd.

Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

PubMed

Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

2018-04-02

Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential Genetic and Epigenetic Regulation of catechol-O-methyltransferase is Associated with Impaired Fear Inhibition in Posttraumatic Stress Disorder.

PubMed

Norrholm, Seth Davin; Jovanovic, Tanja; Smith, Alicia K; Binder, Elisabeth; Klengel, Torsten; Conneely, Karen; Mercer, Kristina B; Davis, Jennifer S; Kerley, Kimberly; Winkler, Jennifer; Gillespie, Charles F; Bradley, Bekh; Ressler, Kerry J

2013-01-01

The catechol-O-methyltransferase (COMT) enzyme is critical for the catabolic regulation of synaptic dopamine, resulting in altered cortical functioning. The COMT Val(158)Met polymorphism has been implicated in human mental illness, with Met/Met homozygotes associated with increased susceptibility to posttraumatic stress disorder (PTSD). Our primary objective was to examine the intermediate phenotype of fear inhibition in PTSD stratified by COMT genotype (Met/Met, Val/Met, and Val/Val) and differential gene regulation via methylation status at CpG sites in the COMT promoter region. More specifically, we examined the potential interaction of COMT genotype and PTSD diagnosis on fear-potentiated startle during fear conditioning and extinction and COMT DNA methylation levels (as determined using genomic DNA isolated from whole blood). Participants were recruited from medical and gynecological clinics of an urban hospital in Atlanta, GA, USA. We found that individuals with the Met/Met genotype demonstrated higher fear-potentiated startle to the CS- (safety signal) and during extinction of the CS+ (danger signal) compared to Val/Met and Val/Val genotypes. The PTSD+ Met/Met genotype group had the greatest impairment in fear inhibition to the CS- (p = 0.006), compared to Val carriers. In addition, the Met/Met genotype was associated with DNA methylation at four CpG sites, two of which were associated with impaired fear inhibition to the safety signal. These results suggest that multiple differential mechanisms for regulating COMT function - at the level of protein structure via the Val(158)Met genotype and at the level of gene regulation via differential methylation - are associated with impaired fear inhibition in PTSD.

A Derived Transfer of Simple Discrimination and Self-Reported Arousal Functions in Spider Fearful and Non-Spider-Fearful Participants

ERIC Educational Resources Information Center

Smyth, Sinead; Barnes-Holmes, Dermot; Forsyth, John P.

2006-01-01

Two experiments investigated the derived transfer of functions through equivalence relations established using a stimulus pairing observation procedure. In Experiment 1, participants were trained on a simple discrimination (A1+/A2-) and then a stimulus pairing observation procedure was used to establish 4 stimulus pairings (A1-B1, A2-B2, B1-C1,…

Prospective Study on the Impact of Fear of Falling on Functional Decline among Community Dwelling Elderly Women.

PubMed

Choi, Kyungwon; Jeon, Gyeong-Suk; Cho, Sung-Il

2017-04-27

Fear of falling (FOF) is expected to have effects on functional decline in the elderly. In this study, we examined over 2 years the effect of change in FOF on functional decline in community dwelling elderly. We conducted a secondary analysis using data from elderly women, 70 years of age and older, who participated in the Korean Longitudinal Study of Aging (KLoSA). Participants were divided into four categories according to change in FOF between the 2010 and 2012 surveys. Multiple logistic regression analysis was conducted regarding the effects of changes in FOF on functional decline after controlling for variables as known risk factors for functional decline. Rates of functional decline were highest in the "consistently having FOF" group, whereas they were lowest in the "consistently no FOF" group in both 2010 and 2012. Characteristics independently associated with functional decline were change in FOF, depressive symptoms, low frequency of meeting friends, and fear-induced activity avoidance. Longer exposure to FOF was associated with an increased risk of functional decline. FOF is an important health problem that deserves attention in its own right. Public health approaches for elderly persons should address early detection, prevention, and intervention programs for FOF.

A virtual reality system for neurobehavioral and functional MRI studies.

PubMed

Baumann, Stephen; Neff, Chris; Fetzick, Scott; Stangl, Gregg; Basler, Lee; Vereneck, Ray; Schneider, Walter

2003-06-01

We are developing a VR system of integrated software and hardware for scientific research and clinical application. The system is sufficiently flexible and broad-based in appeal that neurobehavioral researchers from a variety of disciplines might be interested in using it for basic research and clinical studies. The system runs on a standard Windows-based personal computer with a high-performance graphics card. Options allow a head-mounted display, dataglove, simultaneous physiological monitoring or use within neuroimaging machines such as magnetic resonance imaging (MRI) scanners. Currently, the software consists of a virtual world of nearly a dozen interconnected environments that the subject can freely navigate. Additional environments can be built and easily added to the application. A startup interface provides menus for selecting characters and objects that a researcher might want to put at specific locations within the simulation. Interactivity is provided for many typical objects such as doors, chairs and money. There are more than 50 characters in the world, most of them animated or interactive. All movements and actions of the subject within the world are tracked and recorded to an Excel spreadsheet for data analysis. Overlay maps are available as navigational aids. Concurrent physiological data can be acquired on up to 16 channels. The system provides synchronization of the VR simulation with physiological recordings and functional MR images. A spatial navigation memory task was performed with the integrated VR/fMRI system, and some pilot data is presented that shows robust activation in multiple cortical areas appropriate to the task.

Metacognitive Control of Categorial Neurobehavioral Decision Systems

PubMed Central

Foxall, Gordon R.

2016-01-01

The competing neuro-behavioral decision systems (CNDS) model proposes that the degree to which an individual discounts the future is a function of the relative hyperactivity of an impulsive system based on the limbic and paralimbic brain regions and the relative hypoactivity of an executive system based in prefrontal cortex (PFC). The model depicts the relationship between these categorial systems in terms of the antipodal neurophysiological, behavioral, and decision (cognitive) functions that engender normal and addictive responding. However, a case may be made for construing several components of the impulsive and executive systems depicted in the model as categories (elements) of additional systems that are concerned with the metacognitive control of behavior. Hence, this paper proposes a category-based structure for understanding the effects on behavior of CNDS, which includes not only the impulsive and executive systems of the basic model but a superordinate level of reflective or rational decision-making. Following recent developments in the modeling of cognitive control which contrasts Type 1 (rapid, autonomous, parallel) processing with Type 2 (slower, computationally demanding, sequential) processing, the proposed model incorporates an arena in which the potentially conflicting imperatives of impulsive and executive systems are examined and from which a more appropriate behavioral response than impulsive choice emerges. This configuration suggests a forum in which the interaction of picoeconomic interests, which provide a cognitive dimension for CNDS, can be conceptualized. This proposition is examined in light of the resolution of conflict by means of bundling. PMID:26925004

Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase α to schizophrenia

PubMed Central

Takahashi, Nagahide; Nielsen, Karin Sandager; Aleksic, Branko; Petersen, Steffen; Ikeda, Masashi; Kushima, Itaru; Vacaresse, Nathalie; Ujike, Hiroshi; Iwata, Nakao; Dubreuil, Véronique; Mirza, Naheed; Sakurai, Takeshi; Ozaki, Norio; Buxbaum, Joseph D.; Sap, Jan

2011-01-01

Background Solid evidence links schizophrenia (SZ) susceptibility to neurodevelopmental processes involving tyrosine phosphorylation-mediated signaling. Mouse studies implicate the Ptpra gene, encoding protein tyrosine phosphatase RPTPα, in the control of radial neuronal migration, cortical cytoarchitecture, and oligodendrocyte differentiation. The human gene encoding RPTPα, PTPRA, maps to a chromosomal region (20p13) associated with susceptibility to psychotic illness. Methods We characterized neurobehavioral parameters, as well as gene expression in the central nervous system, of mice with a null mutation in the Ptpra gene. We searched for genetic association between polymorphisms in PTPRA and schizophrenia risk (2 independent cohorts; total of 1420 cases and 1377 controls), and we monitored PTPRA expression in prefrontal dorsolateral cortex of SZ patients (35 cases, 2 control groups of 35 cases) Results We find that Ptpra−/− mice reproduce neurobehavioral endophenotypes of human SZ: sensitization to metamphetamine-induced hyperactivity, defective sensorimotor gating, and defective habituation to a startle response. Ptpra loss of function also leads to reduced expression of multiple myelination genes, mimicking the hypomyelination-associated changes in gene expression observed in post mortem patient brains. We further report that a polymorphism at the PTPRA locus is genetically associated with SZ, and that PTPRA mRNA levels are reduced in post mortem dorsolateral prefrontal cortex of subjects with SZ. Conclusion The implication of this well-studied signaling protein in SZ risk and endophenotype manifestation provides novel entry points into the etiopathology of this disease. PMID:21831360

Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury

PubMed Central

Wang, Lu; Espinoza, Herbert M.; MacDonald, James W.; Bammler, Theo K.; Williams, Chase R.; Yeh, Andrew; Louie, Ke’ale W.; Marcinek, David J.; Gallagher, Evan P.

2016-01-01

Pacific salmon exposed to sublethal concentrations of organophosphate pesticides (OP) have impaired olfactory function that can lead to loss of behaviors that are essential for survival. These exposures often involve mixtures and can occur at levels below those which inhibit acetylcholinesterase (AChE). In this study, juvenile Coho salmon were exposed for 24 h to either 0.1, 0.5, or 2.5 ppb chlorpyrifos (CPF), 2, 10, or 50 ppb malathion (MAL), or binary mixtures of 0.1 CPF:2 ppb MAL, 0.5 CPF:10 ppb MAL, or 2.5 CPF:10 ppb MAL to mimic single and binary environmental exposures. Microarray analysis of olfactory rosettes from pesticide-exposed salmon revealed differentially expressed genes involved in nervous system function and signaling, aryl hydrocarbon receptor signaling, xenobiotic metabolism, and mitochondrial dysfunction. Coho exposed to OP mixtures exhibited a more pronounced loss in detection of a predatory olfactory cue relative to those exposed to single compounds, whereas respirometry experiments demonstrated that exposure to OPs, individually and in mixtures, reduced maximum respiratory capacity of olfactory rosette mitochondria. The observed molecular, biochemical, and behavioral effects occurred largely in the absence of effects on brain AChE. In summary, our results provide new insights associated with the sublethal neurotoxic effects of OP mixtures relevant to environmental exposures involving molecular and cellular pathways of injury to the salmon olfactory system that underlie neurobehavioral injury. PMID:26494550

Nursing care of the brain injury patient on a locked neurobehavioral unit.

PubMed

Becker, Christine

2012-01-01

Behavioral problems after a brain injury can be extremely challenging for those working with brain injured people. Nursing staff must be familiar with commonly used post brain injury medications and their effects, behavioral management plans, appropriate use of restrictive devices, and verbal or physical crisis intervention techniques when necessary. Rehabilitation nurses caring for brain injured patients on a locked neurobehavioral unit must maintain continual training and specific competence in this environment to ensure patient and staff safety. © 2012 Association of Rehabilitation Nurses.

A Neurobehavioral Study of Rats Using a Model Perfluorinated Acid, NDFDA.

DTIC Science & Technology

1982-07-13

1 AD-Alla 560 DISTICT OFVCOLUMBIAUUNIV WASHIrGTON, DEPT OF BIOLOGY F662 NEUROEHA IORAL STUDY OF RATS USING A MODEL PERFLUORINATEO AC--ETCU U JUL A2 I...S. TYPE OF REPORT & PERIOD COVERED A NEUROBEHAVIORAL STUDY OF RATS USING A MODEL Final Report PERFLUORINATED ACID, NDFDA ___nu; 6. PERFORMING O IG...OPT0 Y&’ A@E(ben Des Btntete AFOSR-TR" FINAL RPORT A NEUROBUEIAVIORAL STUDY ON RATS USING A MODEL PERFLUORINATED ACID , NDFDA Prepared by: Inez R

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders

PubMed Central

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-01-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)–amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC–amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC–amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC–amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC–amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24835117

Post-Session Administration of USP Methylene Blue Facilitates the Retention of Pathological Fear Extinction and Contextual Memory in Phobic Adults

PubMed Central

Telch, Michael J.; Bruchey, Aleksandra K.; Rosenfield, David; Cobb, Adam R.; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F.

2015-01-01

Objective Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Method Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Results Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Conclusions Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session. PMID:25018057

The role of basal forebrain cholinergic neurons in fear and extinction memory.

PubMed

Knox, Dayan

2016-09-01

Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.

PubMed

Telch, Michael J; Bruchey, Aleksandra K; Rosenfield, David; Cobb, Adam R; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F

2014-10-01

Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber. Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber, with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation. Consistent with predictions, participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo. In contrast, participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining. Methylene blue's enhancement of contextual memory was unrelated to initial or posttraining claustrophobic fear. Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.

Childbirth Fear: Relation to Birth and Care Provider Preferences.

PubMed

Stoll, Kathrin; Fairbrother, Nichole; Thordarson, Dana S

2018-01-01

The purpose of this study was to assess how preferences for place of birth and mode of birth relate to different dimensions of childbirth fear and whether there is an association between Canadian women's prenatal fear of childbirth and the type and quality of prenatal care they received. A link to an online survey was posted on Canadian pregnancy and birth websites; 409 women completed the survey that included sociodemographic questions, questions about the current pregnancy and previous pregnancy experiences (if applicable), and the Childbirth Fear Questionnaire, a validated 40-item scale that measures 9 dimensions of childbirth fear. Women under physician care and those with a preference for cesarean birth were generally more fearful of pain associated with vaginal birth, fear of loss of sexual pleasure and attractiveness, and fear of harm to themselves or their infant. Conversely, women under the care of midwives and women who preferred to give birth vaginally were more fearful of interventions. Women who preferred a cesarean birth were significantly more likely to report that fear of childbirth interfered with daily functioning, compared to women who preferred a vaginal birth. Satisfaction with care was associated with lower scores on the Childbirth Fear Questionnaire full and subscales, especially among midwifery clients. At present there are no guidelines in Canada or the United States for the treatment and/or referral of pregnant women who suffer from childbirth fear. Until such guidelines are developed, findings from the current study can help maternity care providers identify and address specific fears among women in their care and understand how different fear domains relate to care provider choice, satisfaction with care, and women's preferences for place and mode of birth. © 2018 by the American College of Nurse-Midwives.

Morbid obesity is associated with fear of movement and lower quality of life in patients with knee pain-related diagnoses.

PubMed

Vincent, Heather K; Lamb, Kelley M; Day, Tim I; Tillman, Susan M; Vincent, Kevin R; George, Steven Z

2010-08-01

To compare fear of movement in patients with different body mass index (BMI) values referred for rehabilitative care of the knee and to examine whether this fear contributed to self-reported knee-related function. We hypothesized that fear of movement would be elevated with increasing BMI and that fear would correspond with lower self-report knee-related function and lower quality of life (QOL). Retrospective cross-sectional study. Outpatient therapy clinic affiliated with a tertiary care hospital. Patients with knee pain diagnoses (n = 278) were stratified into 4 BMI groups (in < or =25 kg/m(2) nonobese; 25-29.9 kg/m(2) overweight; 30-39.9 kg/m(2) obese; > or =40 kg/m(2) morbidly obese). The Tampa Scale of Kinesiophobia (TSK; fear of movement), International Knee Documentation (IKDC; knee function), and Short-Form 8 (SF-8; QOL) scores were main outcomes. Pain and straight leg raise test scores also were collected. After review of the medical records, descriptive statistics and nonparametric tests were performed, and TSK, QOL, and SF-8 scores were compared. Hierarchical regression modeling determined the contribution of TSK scores to the variance of IKDC scores. Pain scores were greatest in the nonobese group and lowest in the morbidly obese group (7.5 +/- 2.6 points vs 4.8 +/- 3.1 points; P < .05). TSK scores in morbidly obese patients were greater than in nonobese patients (27.1 +/- 7.7 points vs 22.0 +/- 6.6 points; P = .002). The SF-8 mental-physical subscores were 27% to 32% lower in the morbidly obese than nonobese patients (both P < .0001). IKDC scores were lower in the morbidly obese than nonobese patients (32.1 +/- 19.2 points vs 50.9 +/- 23.8 points; P = .0001). Pain severity and TSK scores contributed 28.6% and 7.1% to the variance of the IKDC scores (overall R(2) = 68.6). Morbid obesity is associated with elevated fear of movement. Pain was the strongest predictor of IKDC scores, and fear of movement enhanced this predictive value of the regression model. Despite lower absolute pain severity in the morbidly obese group, this fear may influence IKDC scores in this population. Morbidly obese patients might benefit from rehabilitation activities that reduce fear of movement to optimize participation in rehabilitation activity. Copyright © 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Recreational physical activity levels in healthy older women: the importance of fear of falling.

PubMed

Bruce, David G; Devine, Amanda; Prince, Richard L

2002-01-01

To examine whether fear of falling is a probable cause of reduced recreational physical activity levels in healthy older women. Cross-sectional analysis of baseline data from a longitudinal study. One thousand five hundred older, ambulatory women (aged 70-85), selected at random from the electoral roll. Self-reported recreational physical activity levels and fear of falling, demographic variables, anthropometric variables and measures of disability, and physical and cognitive function. The study subjects had low levels of physical and cognitive impairments; 24.1% of the group was obese (body mass index> 30). Twenty-six percent of the women did not participate in recreational physical activity; 39% participated in sufficient activity to gain probable health benefits. Although the women who did not participate in recreational activities were most likely to report fear of falling (45.2%), it was common in the group as a whole (33.9%), including the most active women (27.0%). Independent risk factors for nonparticipation in physical activity were fear of falling (odds ratio (OR)=0.70, 95% confidence interval (CI)=0.54-0.90, P=.006), obesity (OR=0.50, 95% CI=0.38-0.66, P=.001), and slower times on the timed up-and-go test (OR=0.88, 95% CI=0.84-0.92, P=.001). Fear of falling was also independently associated with lower recreational physical activity levels in women who were active (beta=-0.09, P=.003). Subgroup analysis suggested that fear of falls affected activity levels at a predisability stage in women with mildly impaired mobility. Fear of falling is common in healthy, high-functioning older women and is independently associated with reduced levels of participation in recreational physical activity. Fear of falling is an important psychological barrier that may need to be overcome in programs attempting to improve activity levels in older women.

Fear-Specific Amygdala Function in Children and Adolescents on the Fragile X Spectrum: A Dosage Response of the FMR1 Gene

PubMed Central

Kim, So-Yeon; Burris, Jessica; Bassal, Frederick; Koldewyn, Kami; Chattarji, Sumantra; Tassone, Flora; Hessl, David; Rivera, Susan M.

2014-01-01

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS. PMID:23146966

Sex differences in extinction recall in posttraumatic stress disorder: A pilot fMRI study

PubMed Central

Shvil, Erel; Sullivan, Gregory M.; Schafer, Scott; Markowitz, John C.; Campeas, Miriam; Wager, Tor D.; Milad, Mohammed R.; Neria, Yuval

2014-01-01

Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology. PMID:24560771

Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function

PubMed Central

Rebello, Tahilia J.; Yu, Qinghui; Goodfellow, Nathalie M.; Caffrey Cagliostro, Martha K.; Teissier, Anne; Morelli, Emanuela; Demireva, Elena Y.; Chemiakine, Alexei; Rosoklija, Gorazd B.; Dwork, Andrew J.; Lambe, Evelyn K.; Ansorge, Mark S.

2014-01-01

Early-life serotonin [5-hydroxytryptamine (5-HT)] signaling modulates brain development, which impacts adult behavior, but 5-HT-sensitive periods, neural substrates, and behavioral consequences remain poorly understood. Here we identify the period ranging from postnatal day 2 (P2) to P11 as 5-HT sensitive, with 5-HT transporter (5-HTT) blockade increasing anxiety- and depression-like behavior, and impairing fear extinction learning and memory in adult mice. Concomitantly, P2–P11 5-HTT blockade causes dendritic hypotrophy and reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote fear extinction. By contrast, the neighboring prelimbic (PL) pyramidal neurons, which normally inhibit fear extinction, become more excitable. Excitotoxic IL but not PL lesions in adult control mice reproduce the anxiety-related phenotypes. These findings suggest that increased 5-HT signaling during P2–P11 alters adult mPFC function to increase anxiety and impair fear extinction, and imply a differential role for IL and PL neurons in regulating affective behaviors. Together, our results support a developmental mechanism for the etiology and pathophysiology of affective disorders and fear-related behaviors. PMID:25209278

[Are pathological (or vital) anxiety and common fear the same experiences? A controlled study].

PubMed

Ramos Brieva, J A; Montejo Iglesias, M L; Ponce de León, C; del Valle López, P; Lafuente López, R; Cordero Villafáfila, A; Baca García, E

1996-01-01

Some authors affirm that the anxiety of panic attacks is endogenous and of different quality that the common fear. But objective clinical data don't exist that confirm that observation. The authors study by means of a discriminant analysis the description of the anxiety made by subject with panic attacks and normal subjects with common fear. It meet a discriminant function that shows the existence of qualitative differences between both experiences. It seem to have achieved enough empirical support in order to sustain that the anxiety of panic attacks and the common fear are two qualitatively different experiences; presumably due to their several origin.

Tryptophan depletion decreases the recognition of fear in female volunteers.

PubMed

Harmer, C J; Rogers, R D; Tunbridge, E; Cowen, P J; Goodwin, G M

2003-06-01

Serotonergic processes have been implicated in the modulation of fear conditioning in humans, postulated to occur at the level of the amygdala. The processing of other fear-relevant cues, such as facial expressions, has also been associated with amygdala function, but an effect of serotonin depletion on these processes has not been assessed. The present study investigated the effects of reducing serotonin function, using acute tryptophan depletion, on the recognition of basic facial expressions of emotions in healthy male and female volunteers. A double-blind between-groups design was used, with volunteers being randomly allocated to receive an amino acid drink specifically lacking tryptophan or a control mixture containing a balanced mixture of these amino acids. Participants were given a facial expression recognition task 5 h after drink administration. This task featured examples of six basic emotions (fear, anger, disgust, surprise, sadness and happiness) that had been morphed between each full emotion and neutral in 10% steps. As a control, volunteers were given a famous face classification task matched in terms of response selection and difficulty level. Tryptophan depletion significantly impaired the recognition of fearful facial expressions in female, but not male, volunteers. This was specific since recognition of other basic emotions was comparable in the two groups. There was also no effect of tryptophan depletion on the classification of famous faces or on subjective state ratings of mood or anxiety. These results confirm a role for serotonin in the processing of fear related cues, and in line with previous findings also suggest greater effects of tryptophan depletion in female volunteers. Although acute tryptophan depletion does not typically affect mood in healthy subjects, the present results suggest that subtle changes in the processing of emotional material may occur with this manipulation of serotonin function.