Publications by authors named "Barak Morgan"

27 Publications

  • Page 1 of 1

First 1,000 days: enough for mothers but not for children? Long-term outcomes of an early intervention on maternal depressed mood and child cognitive development: follow-up of a randomised controlled trial.

J Child Psychol Psychiatry 2021 Jul 5. Epub 2021 Jul 5.

Developmental Neuroscience Unit, University College London, London, UK.

Background: Child cognitive development is often compromised in contexts of poverty and adversity, and these deficits tend to endure and affect the child across the life course. In the conditions of poverty and violence that characterise many low- and middle-income countries (LMIC), the capacity of parents to provide the kind of care that promotes good child development may be severely compromised, especially where caregivers suffer from depression. One avenue of early intervention focuses on the quality of the early mother-infant relationship. The aim of this study was to examine the long-term impact of an early intervention to improve the mother-infant relationship quality on child cognitive outcomes at 13 years of age. We also estimated the current costs to replicate the intervention.

Method: We re-recruited 333 children from an early childhood maternal-infant attachment intervention, 'Thula Sana', when the children were 13 years old, to assess whether there were impacts of the intervention on child cognitive outcomes, and maternal mood. We used the Kaufman Assessment Battery to assess the child cognitive development and the Patient Health Questionnaire (PHQ-9) and the Self-Reporting Questionnaire (SRQ-20) to assess maternal mental health.

Results: Effect estimates indicated a pattern of null findings for the impact of the intervention on child cognitive development. However, the intervention had an effect on caregiver psychological distress (PHQ-9, ES = -0.17 [CI: -1.95, 0.05] and SRQ-20, ES = -0.30 [CI: -2.41, -0.19]), but not anxiety. The annual cost per mother-child pair to replicate the Thula Sana intervention in 2019 was estimated at ZAR13,365 ($780).

Conclusion: In a socio-economically deprived peri-urban settlement in South Africa, a home visiting intervention, delivered by community workers to mothers in pregnancy and the first six postpartum months, had no overall effect on child cognitive development at 13 years of age. However, those caregivers who were part of the original intervention showed lasting improvements in depressed mood. Despite the fact that there was no intervention effect on long-term child outcomes, the improvements in maternal mood are important.
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http://dx.doi.org/10.1111/jcpp.13482DOI Listing
July 2021

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

N Engl J Med 2021 05;384(21):2028-2038

The affiliations of the members of the writing committee are as follows: the Department of Maternal, Newborn, Child, and Adolescent Health, and Ageing, World Health Organization, Geneva (S.P.N.R., S.Y., N.M., H.V.J., H.T., R.B.); Vardhman Mahavir Medical College and Safdarjung Hospital (S.A., P.M., N.C., J.S., P.A., K.N., I.S., K.C.A., H.C.) and the All India Institute of Medical Sciences (M.J.S.), New Delhi, and Translational Health Science and Technology Institute, Faridabad (N.W.) - all in India; Muhimbili University of Health and Allied Sciences (H.N., E.A., A.M.) and Muhimbili National Hospital (M.N., R.M.) - both in Dar es Salaam, Tanzania; the University of Malawi, College of Medicine, Blantyre, Malawi (K.K., L.G., A.T.M., V.S., Q.D.); Obafemi Awolowo University, Ile-Ife, Nigeria (C.H.A., O.K., B.P.K., E.A.A.); Kwame Nkrumah University of Science and Technology (S.N., R.L.-R., D.A., G.P.-R.) and Komfo Anokye Teaching Hospital (A.B.-Y., N.W.-B., I.N.), Kumasi, and the School of Public Health, University of Ghana, Accra (A.A.M.) - all in Ghana; Karolinska University Hospital (A.L.) and Karolinska Institute (N.B., A.L., B.W.), Stockholm; the Institute for Safety Governance and Criminology, University of Cape Town, Cape Town, South Africa (B.M.); and Stavanger University Hospital, Stavanger, Norway (S.R.).

Background: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain.

Methods: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life.

Results: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care.

Conclusions: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).
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http://dx.doi.org/10.1056/NEJMoa2026486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108485PMC
May 2021

PTSD symptoms and cortisol stress reactivity in adolescence: Findings from a high adversity cohort in South Africa.

Psychoneuroendocrinology 2020 11 22;121:104846. Epub 2020 Aug 22.

Department of Psychology, Stellenbosch University, South Africa.

Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the pathophysiology of post-traumatic stress disorder (PTSD). However, there has been little study of HPA stress reactivity in association with PTSD symptoms (PTSS) in children; and there is limited research on PTSD in low and middle-income countries, where trauma exposure is more common and co-occurring stressors more likely.

Method: We assessed the relationship between PTSS and cortisol stress reactivity in children aged 13 years (N = 291) from an impoverished South African community. HPA axis stress reactivity was indexed by salivary cortisol during the Trier Social Stress Test (TSST).

Results: In regression analyses both trauma exposure and PTSS showed small inverse associations with total cortisol output (area under the curve with respect to ground) during the TSST, but PTSS effects did not withstand correction for covariates. In addition, hierarchical linear modelling (HLM) found that PTSS were associated with alterations in the shape of the profile of cortisol reactivity that were moderated by sex. In girls, PTSS were associated with reduced linear slope but larger quadratic slopes, whereas the opposite pattern was found in boys. Thus, elevated PTSS were associated with overall blunted profiles of cortisol stress reactivity in girls, but a larger quadratic slope in boys reflects a steeper cortisol increase and decline in boys. There was no relationship between trauma exposure (with or without PTSS) and cortisol reactivity profiles in HLM analyses.

Conclusion: In children from a high adversity, low and middle income country context, sex specific associations were found between PTSS and cortisol responses to psychosocial stress. Further research should probe HPA axis functioning more comprehensively in such populations to understand the biological associations of PTSS.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104846DOI Listing
November 2020

Immediate parent-infant skin-to-skin study (IPISTOSS): study protocol of a randomised controlled trial on very preterm infants cared for in skin-to-skin contact immediately after birth and potential physiological, epigenetic, psychological and neurodevelopmental consequences.

BMJ Open 2020 07 6;10(7):e038938. Epub 2020 Jul 6.

Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.

Introduction: In Scandinavia, 6% of infants are born preterm, before 37 gestational weeks. Instead of continuing in the in-utero environment, maturation needs to occur in a neonatal unit with support of vital functions, separated from the mother's warmth, nutrition and other benefits. Preterm infants face health and neurodevelopment challenges that may also affect the family and society at large. There is evidence of benefit from immediate and continued skin-to-skin contact (SSC) for term and moderately preterm infants and their parents but there is a knowledge gap on its effect on unstable very preterm infants when initiated immediately after birth.

Methods And Analysis: In this ongoing randomised controlled trial from Stavanger, Norway and Stockholm, Sweden, we are studying 150 infants born at 28+0 to 32+6 gestational weeks, randomised to receive care immediately after birth in SSC with a parent or conventionally in an incubator. The primary outcome is cardiorespiratory stability according to the stability of the cardiorespiratory system in the preterm score. Secondary outcomes are autonomic stability, thermal control, infection control, SSC time, breastfeeding and growth, epigenetic profile, microbiome profile, infant behaviour, stress resilience, sleep integrity, cortical maturation, neurodevelopment, mother-infant attachment and attunement, and parent experience and mental health.

Ethics And Dissemination: The study has ethical approval from the Swedish Ethical Review Authority (2017/1135-31/3, 2019-03361) and the Norwegian Regional Ethical Committee (2015/889). The study is conducted according to good clinical practice and the Helsinki declaration. The results of the study will increase the knowledge about the mechanisms behind the effects of SSC for very preterm infants by dissemination to the scientific community through articles and at conferences, and to the society through parenting classes and magazines.

Study Status: Recruiting since April 2018. Expected trial termination June 2021.

Trial Registration Number: NCT03521310 (ClinicalTrials.gov).
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http://dx.doi.org/10.1136/bmjopen-2020-038938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342825PMC
July 2020

The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study.

Cell 2018 10;175(3):723-735.e16

Department of Psychology, Utrecht University, Utrecht, the Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (T). In response to T, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, T conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient T responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans.
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http://dx.doi.org/10.1016/j.cell.2018.09.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198024PMC
October 2018

Atypical maternal cradling laterality in an impoverished South African population.

Laterality 2019 May 10;24(3):320-341. Epub 2018 Aug 10.

e Department of Psychology , Stellenbosch University , Stellenbosch , South Africa.

Human studies consistently report a 60%-80% maternal left cradling preference. The dominant explanation points to an engagement of the emotionally more-attuned right brain. In contrast, we found equal incidences of left (31.3%), right (34.3%) and no-preference (34.3%) cradling in an impoverished South African population living under adverse conditions characterized by extreme dangers. We found striking differences on the Parenting Stress Index (PSI) between mothers with no cradling laterality preference and mothers with either a left or right preference. In several mammals a homologous left preference becomes stronger when acute threats prevail, rendering the rightwards shift we observed under dangerous conditions seemingly paradoxical. We propose this paradox can be resolved in terms of life-history strategy theory which predicts reduced parental investment in chronically dangerous environments. We interpret our high PSI score findings in no-preference cradlers as indicative of poorer, or at least ambivalent, maternal coping which many studies show is typically associated with reduced emotional sensitivity and responsiveness. We suggest that the latter may be a psychological mechanism mediating a partial withdrawal of parental investment in response to an enduringly adverse environment. To the best of our knowledge, this is the first study investigating cradling laterality preferences in an adverse socioeconomic environment.
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http://dx.doi.org/10.1080/1357650X.2018.1509077DOI Listing
May 2019

Thinking about the environment and theorising change: how could Life History Strategy Theory inform mHealth interventions in low- and middle-income countries?

Glob Health Action 2017 ;10(1):1320118

d Department of Psychology , Stellenbosch University , Stellenbosch , South Africa.

Background: There is a growing body of literature outlining the promise of mobile information and communication technologies to improve healthcare in resource-constrained contexts.

Methods: We reviewed the literature related to mobile information and communication technologies which aim to improve healthcare in resource-constrained contexts, in order to glean general observations regarding the state of mHealth in high-income countries (HIC) and low- and middle-income countries (LMIC).

Results: mHealth interventions in LMIC often differ substantively from those in HIC, with the former being simpler, delivered through a single digital component (an SMS as opposed to a mobile phone application, or 'app'), and, as a result, targeting only one of the many factors which impact on the activation (or deactivation) of the target behaviour. Almost as a rule, LMIC mHealth interventions lack an explicit theory of change.

Conclusion: We highlight the necessity, when designing mHealth interventions, of having a theory of change that encompasses multiple salient perspectives pertaining to human behaviour. To address this need, we explore whether the concept of Life History Strategy could provide the mHealth field with a useful theory of change. Life History Strategy Theory may be particularly useful in understanding some of the problems, paradoxes, and limitations of mHealth interventions found in LMIC. Specifically, this theory illuminates questions regarding 'light-weight' programmes which solely provide information, reminders, and other virtual 'nudges' that may have limited impact on behaviours governed by extrinsic structural factors.
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http://dx.doi.org/10.1080/16549716.2017.1320118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496081PMC
September 2018

Poverty, early care, and stress reactivity in adolescence: Findings from a prospective, longitudinal study in South Africa.

Dev Psychopathol 2017 05;29(2):449-464

University of the Witwatersrand.

A considerable body of evidence suggests that early caregiving may affect the short-term functioning and longer term development of the hypothalamic-pituitary-adrenocortical axis. Despite this, most research to date has been cross-sectional in nature or restricted to relatively short-term longitudinal follow-ups. More important, there is a paucity of research on the role of caregiving in low- and middle-income countries, where the protective effects of high-quality care in buffering the child's developing stress regulation systems may be crucial. In this paper, we report findings from a longitudinal study (N = 232) conducted in an impoverished periurban settlement in Cape Town, South Africa. We measured caregiving sensitivity and security of attachment in infancy and followed children up at age 13 years, when we conducted assessments of hypothalamus-pituitary-adrenocortical axis reactivity, as indexed by salivary cortisol during the Trier Social Stress Test. The findings indicated that insecure attachment was predictive of reduced cortisol responses to social stress, particularly in boys, and that attachment status moderated the impact of contextual adversity on stress responses: secure children in highly adverse circumstances did not show the blunted cortisol response shown by their insecure counterparts. Some evidence was found that sensitivity of care in infancy was also associated with cortisol reactivity, but in this case, insensitivity was associated with heightened cortisol reactivity, and only for girls. The discussion focuses on the potentially important role of caregiving in the long-term calibration of the stress system and the need to better understand the social and biological mechanisms shaping the stress response across development in low- and middle-income countries.
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http://dx.doi.org/10.1017/S0954579417000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659183PMC
May 2017

The Basolateral Amygdalae and Frontotemporal Network Functions for Threat Perception.

eNeuro 2017 Jan-Feb;4(1). Epub 2017 Mar 27.

Brain and Emotion Laboratory, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Oxfordlaan 55, 6229 EV Maastricht, The Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town, South Africa; Department of Computer Science, University College London, Gower Street, London WC1E 6BT, United Kingdom.

Although the amygdalae play a central role in threat perception and reactions, the direct contributions of the amygdalae to specific aspects of threat perception, from ambiguity resolution to reflexive or deliberate action, remain ill understood in humans. Animal studies show that a detailed understanding requires a focus on the different subnuclei, which is not yet achieved in human research. Given the limits of human imaging methods, the crucial contribution needs to come from individuals with exclusive and selective amygdalae lesions. The current study investigated the role of the basolateral amygdalae and their connection with associated frontal and temporal networks in the automatic perception of threat. Functional activation and connectivity of five individuals with Urbach-Wiethe disease with focal basolateral amygdalae damage and 12 matched controls were measured with functional MRI while they attended to the facial expression of a threatening face-body compound stimuli. Basolateral amygdalae damage was associated with decreased activation in the temporal pole but increased activity in the ventral and dorsal medial prefrontal and medial orbitofrontal cortex. This dissociation between the prefrontal and temporal networks was also present in the connectivity maps. Our results contribute to a dynamic, multirole, subnuclei-based perspective on the involvement of the amygdalae in fear perception. Damage to the basolateral amygdalae decreases activity in the temporal network while increasing activity in the frontal network, thereby potentially triggering a switch from resolving ambiguity to dysfunctional threat signaling and regulation, resulting in hypersensitivity to threat.
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http://dx.doi.org/10.1523/ENEURO.0314-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368167PMC
October 2017

Serotonin transporter gene (SLC6A4) polymorphism and susceptibility to a home-visiting maternal-infant attachment intervention delivered by community health workers in South Africa: Reanalysis of a randomized controlled trial.

PLoS Med 2017 Feb 28;14(2):e1002237. Epub 2017 Feb 28.

NRF Centre of Excellence in Human Development, DVC Research Office, University of Witwatersrand, Johannesburg, South Africa.

Background: Clear recognition of the damaging effects of poverty on early childhood development has fueled an interest in interventions aimed at mitigating these harmful consequences. Psychosocial interventions aimed at alleviating the negative impacts of poverty on children are frequently shown to be of benefit, but effect sizes are typically small to moderate. However, averaging outcomes over an entire sample, as is typically done, could underestimate efficacy because weaker effects on less susceptible individuals would dilute estimation of effects on those more disposed to respond. This study investigates whether a genetic polymorphism of the serotonin transporter gene moderates susceptibility to a psychosocial intervention.

Methods And Findings: We reanalyzed data from a randomized controlled trial of a home-visiting program delivered by community health workers in a black, isiXhosa-speaking population in Khayelitsha, South Africa. The intervention, designed to enhance maternal-infant attachment, began in the third trimester and continued until 6 mo postpartum. Implemented between April 1999 and February 2003, the intervention comprised 16 home visits delivered to 220 mother-infant dyads by specially trained community health workers. A control group of 229 mother-infant dyads did not receive the intervention. Security of maternal-infant attachment was the main outcome measured at infant age 18 mo. Compared to controls, infants in the intervention group were significantly more likely to be securely attached to their primary caregiver (odds ratio [OR] = 1.7, p = 0.029, 95% CI [1.06, 2.76], d = 0.29). After the trial, 162 intervention and 172 control group children were reenrolled in a follow-up study at 13 y of age (December 2012-June 2014). At this time, DNA collected from 279 children (134 intervention and 145 control) was genotyped for a common serotonin transporter polymorphism. There were both genetic data and attachment security data for 220 children (110 intervention and 110 control), of whom 40% (44 intervention and 45 control) carried at least one short allele of the serotonin transporter gene. For these 220 individuals, carrying at least one short allele of the serotonin transporter gene was associated with a 26% higher rate of attachment security relative to controls (OR = 3.86, p = 0.008, 95% CI [1.42, 10.51], d = 0.75), whereas there was a negligible (1%) difference in security between intervention and control group individuals carrying only the long allele (OR = 0.95, p = 0.89, 95% CI [0.45, 2.01], d = 0.03). Expressed in terms of absolute risk, for those with the short allele, the probability of secure attachment being observed in the intervention group was 84% (95% CI [73%, 95%]), compared to 58% (95% CI [43%, 72%]) in the control group. For those with two copies of the long allele, 70% (95% CI [59%, 81%]) were secure in the intervention group, compared to 71% (95% CI [60%, 82%]) of infants in the control group. Controlling for sex, maternal genotype, and indices of socioeconomic adversity (housing, employment, education, electricity, water) did not change these results. A limitation of this study is that we were only able to reenroll 49% of the original sample randomized to the intervention and control conditions. Attribution of the primary outcome to causal effects of intervention in the present subsample should therefore be treated with caution.

Conclusions: When infant genotype for serotonin transporter polymorphism was taken into account, the effect size of a maternal-infant attachment intervention targeting impoverished pregnant women increased more than 2.5-fold when only short allele carriers were considered (from d = 0.29 for all individuals irrespective of genotype to d = 0.75) and decreased 10-fold when only those carrying two copies of the long allele were considered (from d = 0.29 for all individuals to d = 0.03). Genetic differential susceptibility means that averaging across all participants is a misleading index of efficacy. The study raises questions about how policy-makers deal with the challenge of balancing equity (equal treatment for all) and efficacy (treating only those whose genes render them likely to benefit) when implementing psychosocial interventions.

Trial Registration: Current Controlled Trials ISRCTN25664149.
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http://dx.doi.org/10.1371/journal.pmed.1002237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330451PMC
February 2017

Humans and monkeys use different strategies to solve the same short-term memory tasks.

Learn Mem 2016 11 17;23(11):644-647. Epub 2016 Oct 17.

Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4415, USA

The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory.
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http://dx.doi.org/10.1101/lm.041764.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066608PMC
November 2016

The dynamic consequences of amygdala damage on threat processing in Urbach-Wiethe Disease. A commentary on Pishnamazi et al. (2016).

Cortex 2017 03 25;88:192-197. Epub 2016 Jul 25.

Brain and Emotion Laboratory, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, J-Block, Groote Schuur Hospital, Cape Town, South Africa. Electronic address:

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http://dx.doi.org/10.1016/j.cortex.2016.07.013DOI Listing
March 2017

The role of the basolateral amygdala in the perception of faces in natural contexts.

Philos Trans R Soc Lond B Biol Sci 2016 May;371(1693)

Brain and Emotion Laboratory, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Oxfordlaan 55, 6229 EV Maastricht, The Netherlands Department of Psychiatry and Mental Health, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town, South Africa

The amygdala is a complex structure that plays its role in perception and threat-related behaviour by activity of its specific nuclei and their separate networks. In the present functional magnetic resonance imaging study, we investigated the role of the basolateral amygdala in face and context processing. Five individuals with focal basolateral amygdala damage and 12 matched controls viewed fearful or neutral faces in a threatening or neutral context. We tested the hypothesis that basolateral amygdala damage modifies the relation between face and threatening context, triggering threat-related activation in the dorsal stream. The findings supported this hypothesis. First, activation was increased in the right precentral gyrus for threatening versus neutral scenes in the basolateral amygdala damage group compared with the control group. Second, activity in the bilateral middle frontal gyrus, and left anterior inferior parietal lobule was enhanced for neutral faces presented in a threatening versus neutral scene in the group with basolateral amygdala damage compared with controls. These findings provide the first evidence for the neural consequences of basolateral amygdala damage during the processing of complex emotional situations.
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http://dx.doi.org/10.1098/rstb.2015.0376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843614PMC
May 2016

Infant Mental Health Research in Africa: a call for action for research in the next 10 years.

Glob Ment Health (Camb) 2015 2;2:e7. Epub 2015 Jun 2.

Global Risk Governance Program, Department of Public Law, University of Cape Town, Cape Town, South Africa.

Background: Less than 3% of articles published in the peer reviewed literature include data from low- and middle-income countries - where 90% of the world's infants live.

Methods: In this paper, we discuss the context of infancy in Africa and the conditions of adversity obtaining in Africa.

Results: We discuss the implications of poverty on parenting, and linked to this outline the impact of maternal depression on infant development.

Conclusions: We outline three features of the field of infant mental health research in Africa, and issue a call for action about what we believe is needed in order to develop the field in the next decade.
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http://dx.doi.org/10.1017/gmh.2015.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269628PMC
June 2015

Impaired acquisition of classically conditioned fear-potentiated startle reflexes in humans with focal bilateral basolateral amygdala damage.

Soc Cogn Affect Neurosci 2015 Sep 30;10(9):1161-8. Epub 2014 Dec 30.

Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands, Department of Psychiatry and Mental Health, University of Cape Town, 7925 Cape Town, South Africa, and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.

Based on studies in rodents, the basolateral amygdala (BLA) is considered a key site for experience-dependent neural plasticity underlying the acquisition of conditioned fear responses. In humans, very few studies exist of subjects with selective amygdala lesions and those studies have only implicated the amygdala more broadly leaving the role of amygdala sub-regions underexplored. We tested a rare sample of subjects (N = 4) with unprecedented focal bilateral BLA lesions due to a genetic condition called Urbach-Wiethe disease. In a classical delay fear conditioning experiment, these subjects showed impaired acquisition of conditioned fear relative to a group of matched control subjects (N = 10) as measured by fear-potentiation of the defensive eye-blink startle reflex. After the experiment, the BLA-damaged cases showed normal declarative memory of the conditioned association. Our findings provide new evidence that the human BLA is essential to drive fast classically conditioned defensive reflexes.
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http://dx.doi.org/10.1093/scan/nsu164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560935PMC
September 2015

The role of human basolateral amygdala in ambiguous social threat perception.

Cortex 2014 Mar 31;52:28-34. Epub 2013 Dec 31.

Experimental Psychology, Utrecht University, The Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, South Africa.

Previous studies have shown that the amygdala (AMG) plays a role in how affective signals are processed. Animal research has allowed this role to be better understood and has assigned to the basolateral amygdala (BLA) an important role in threat perception. Here we show that, when passively exposed to bodily threat signals during a facial expressions recognition task, humans with bilateral BLA damage but with a functional central-medial amygdala (CMA) have a profound deficit in ignoring task-irrelevant bodily threat signals.
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http://dx.doi.org/10.1016/j.cortex.2013.12.010DOI Listing
March 2014

Generous economic investments after basolateral amygdala damage.

Proc Natl Acad Sci U S A 2013 Feb 22;110(7):2506-10. Epub 2013 Jan 22.

Department of Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands.

Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the basolateral amygdala (BLA) subserves instrumental behaviors and regulates the central-medial amygdala, which subserves impulsive behaviors. The human amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.
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http://dx.doi.org/10.1073/pnas.1217316110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574920PMC
February 2013

Paradoxical facilitation of working memory after basolateral amygdala damage.

PLoS One 2012 8;7(6):e38116. Epub 2012 Jun 8.

MRC Medical Imaging Research Unit, Department of Human Biology, University of Cape Town, Cape Town, South Africa.

Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038116PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371039PMC
February 2015

Should neonates sleep alone?

Biol Psychiatry 2011 Nov 29;70(9):817-25. Epub 2011 Jul 29.

MRC Medical Imaging Research Unit, University of Cape Town, Western Cape, South Africa.

Background: Maternal-neonate separation (MNS) in mammals is a model for studying the effects of stress on the development and function of physiological systems. In contrast, for humans, MNS is a Western norm and standard medical practice. However, the physiological impact of this is unknown. The physiological stress-response is orchestrated by the autonomic nervous system and heart rate variability (HRV) is a means of quantifying autonomic nervous system activity. Heart rate variability is influenced by level of arousal, which can be accurately quantified during sleep. Sleep is also essential for optimal early brain development.

Methods: To investigate the impact of MNS in humans, we measured HRV in 16 2-day-old full-term neonates sleeping in skin-to-skin contact with their mothers and sleeping alone, for 1 hour in each place, before discharge from hospital. Infant behavior was observed continuously and manually recorded according to a validated scale. Cardiac interbeat intervals and continuous electrocardiogram were recorded using two independent devices. Heart rate variability (taken only from sleep states to control for level of arousal) was analyzed in the frequency domain using a wavelet method.

Results: Results show a 176% increase in autonomic activity and an 86% decrease in quiet sleep duration during MNS compared with skin-to-skin contact.

Conclusions: Maternal-neonate separation is associated with a dramatic increase in HRV power, possibly indicative of central anxious autonomic arousal. Maternal-neonate separation also had a profoundly negative impact on quiet sleep duration. Maternal separation may be a stressor the human neonate is not well-evolved to cope with and may not be benign.
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http://dx.doi.org/10.1016/j.biopsych.2011.06.018DOI Listing
November 2011

Guilt and pride are heartfelt, but not equally so.

Psychophysiology 2011 Jul 10;48(7):888-99. Epub 2010 Dec 10.

ACSENT Laboratory, Department of Psychology, University of Cape Town, Rondebosch, South Africa.

We examined the cardiovascular physiology of guilt and pride to elucidate physiological substrates underpinning the behavioral motivations of these moral emotions. Although both emotions motivate prosocial behavior, guilt typically inhibits ongoing behavior, whereas pride reinforces current behavior. To succeed in eliciting real emotions, we used a novel social interaction task. We found dissociable sympathetic activation during guilt and pride; specifically, Guilt participants experienced prolonged cardiac sympathetic arousal as measured by preejection period (PEP), whereas Pride participants experienced transient non-cardiac somatic arousal and a shift to low frequency (LF) power in the cardiac spectrogram. This dissociation supports their distinctive motivational functions. Higher self-reported Behavioral Inhibition System (BIS) sensitivity was furthermore uniquely associated with guilt, supporting its function as a punishment cue.
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http://dx.doi.org/10.1111/j.1469-8986.2010.01157.xDOI Listing
July 2011

Socially explosive minds: the triple imbalance hypothesis of reactive aggression.

J Pers 2010 Feb;78(1):67-94

Department of Psychology, Experimental Psychology, Utrecht University, Heidelberglaan2, 3584 CS Utrecht, The Netherlands.

The psychobiological basis of reactive aggression, a condition characterized by uncontrolled outbursts of socially violent behavior, is unclear. Nonetheless, several theoretical models have been proposed that may have complementary views about the psychobiological mechanisms involved. In this review, we attempt to unite these models and theorize further on the basis of recent data from psychological and neuroscientific research to propose a comprehensive neuro-evolutionary framework: The Triple Imbalance Hypothesis (TIH) of reactive aggression. According to this model, reactive aggression is essentially subcortically motivated by an imbalance in the levels of the steroid hormones cortisol and testosterone (Subcortical Imbalance Hypothesis). This imbalance not only sets a primal predisposition for social aggression, but also down-regulates cortical-subcortical communication (Cortical-Subcortical Imbalance Hypothesis), hence diminishing control by cortical regions that regulate socially aggressive inclinations. However, these bottom-up hormonally mediated imbalances can drive both instrumental and reactive social aggression. The TIH suggests that reactive aggression is differentiated from proactive aggression by low brain serotonergic function and that reactive aggression is associated with left-sided frontal brain asymmetry (Cortical Imbalance Hypothesis), especially observed when the individual is socially threatened or provoked. This triple biobehavioral imbalance mirrors an evolutionary relapse into violently aggressive motivational drives that are adaptive among many reptilian and mammalian species, but may have become socially maladaptive in modern humans.
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http://dx.doi.org/10.1111/j.1467-6494.2009.00609.xDOI Listing
February 2010

The testosterone-cortisol ratio: A hormonal marker for proneness to social aggression.

Int J Law Psychiatry 2009 Jul-Aug;32(4):216-23. Epub 2009 May 15.

Department of Psychology, Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands.

Social aggression is an escalating hazard for individuals and society. It is most frequently observed as impulsive-reactive aggression in antisocial personality disorder (APD), but in psychopathic aggressive personalities instrumental social aggression is more prominent. However, the psychobiological mechanisms underlying human social aggression are still poorly understood. Here we propose a psychobiological mechanism that may explain human social aggression wherein the steroid hormones cortisol and testosterone play a critical role. High levels of testosterone and low levels of cortisol have been associated with social aggression in several species but it seems that in those individuals wherein these hormonal markers combine social aggression is most violent. In this review we discuss fundamental and clinical research which underscores the potential of the testosterone-cortisol ratio as a possible marker for criminal aggressive tendencies.
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http://dx.doi.org/10.1016/j.ijlp.2009.04.008DOI Listing
November 2009

Gray's BIS/BAS dimensions in non-comorbid, non-medicated social anxiety disorder.

World J Biol Psychiatry 2009 ;10(4 Pt 3):925-8

Medical Imaging Research Unit, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa.

Gray's behavioural inhibition and behavioural activation (BIS/BAS) neural systems model has led to research on approach and withdrawal as the two most fundamental dimensions of affective behaviour, and their role in psychopathology. Although Gray proposed the BIS as the neurological basis of anxiety, there are no reports examining approach and withdrawal predispositions in social anxiety disorder. Here we report approach and withdrawal predispositions in a group of 23 non-medicated individuals with social anxiety disorder (SAD) without co-morbid depression and in 48 normal controls. Results show increased BIS and decreased BAS fun-seeking in SAD subjects thereby underscoring Gray's dimensional model.
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http://dx.doi.org/10.1080/15622970802571695DOI Listing
March 2010

Interrelations between motivational stance, cortical excitability, and the frontal electroencephalogram asymmetry of emotion: a transcranial magnetic stimulation study.

Hum Brain Mapp 2008 May;29(5):574-80

Department of Experimental Psychology, Utrecht University, The Netherlands. [email protected] fss.uu.nl

Several electrophysiological studies have provided evidence for the frontal asymmetry of emotion. In this model the motivation to approach is lateralized to the left, whereas the motivation to avoidance is lateralized to the right hemisphere. The aim of the present experiment was to seek evidence for this model by relating electrophysiological and phenomenological indices of frontal asymmetry to a direct measure of cortical excitability. Frontal asymmetrical resting states of the electroencephalogram and motivational tendencies indexed by the Carver and White questionnaire were compared with neural excitability of the left and right primary motor cortex as assessed by transcranial magnetic stimulation in 24 young healthy right-handed volunteers. In agreement with the model of frontal asymmetry, predominant left over right frontal cortical excitability was associated with enhanced emotional approach relative to emotional avoidance. Moreover, the asymmetries of brain excitability and approach-avoidance motivational predispositions were both reflected by frontal beta (13-30 Hz) electroencephalogram asymmetries. In conclusion, the currently demonstrated interconnections between cortical excitability, electrophysiological activity, and self-reported emotional tendencies for approach or avoidance support the frontal asymmetry of emotion model and provide novel insights into its biological underpinnings.
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http://dx.doi.org/10.1002/hbm.20417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870764PMC
May 2008

The effect of pH on the kinetics of spontaneous Fe(II) oxidation by O2 in aqueous solution--basic principles and a simple heuristic description.

Chemosphere 2007 Aug 21;68(11):2080-4. Epub 2007 Mar 21.

Department of Human Biology, University of Cape Town, Rondebosch 7701, South Africa.

The spontaneous chemical oxidation of Fe(II) to Fe(III) by O(2) is a complex process involving meta-stable partially oxidized intermediate species such as green rusts, which ultimately transform into a variety of stable iron oxide end-products such as hematite, magnetite, goethite and lepidocrocite. Although in many practical situations the nature of the end-products is of less interest than the oxidation kinetics, it is difficult to find in the literature a description of all the basic steps and principles governing the kinetics of these reactions. This paper uses basic aquatic-chemistry equilibrium theory as the framework upon which to present a heuristic model of the oxidation kinetics of Fe(II) species to ferric iron by O(2). The oxidation rate can be described by the equation (in units of mol Fe(II)/(l min)): -d[Fe(2+)]/dt = 6 x 10(-5)[Fe(2+)]+1.7[Fe(OH)(+)]+4.3 x 10(5)[Fe(OH)(2)(0)]. This rate equation yields a sigmoid-shaped curve as a function of pH; at pH values below approximately 4, the Fe(2+) concentration dominates and the rate is independent of pH. At pH> approximately 5, [Fe(OH)(2)(0)] determines the rate because it is far more readily oxidized than both Fe(2+) and FeOH(+). Between pH 5 and 8 the Fe(OH)(2)(0) concentration rises steeply with pH and the overall oxidation rate increases accordingly. At pH values> approximately 8 [Fe(OH)(2)(0)] no longer varies with pH and the oxidation rate is again independent of pH. The paper presents a heuristic overview of the pH dependent kinetics of aqueous ferrous oxidation by O(2(aq)) which we believe will be useful to professionals at both research and technical levels.
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http://dx.doi.org/10.1016/j.chemosphere.2007.02.015DOI Listing
August 2007

Behavioral inhibition: a neurobiological perspective.

Authors:
Barak E Morgan

Curr Psychiatry Rep 2006 Aug;8(4):270-8

MRC/UCT Medical Imaging Research Unit, Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Behavioral inhibition (BI) during early childhood has been associated with subsequent development of anxiety disorders. However, understanding of the neuroanatomical substrates of BI in humans generally has not kept pace with that of anxiety disorders. Recent interpretations and implementations of Gray's and Kagan's concepts of BI are examined from the perspective of current neurobiological models. Particular attention is given to evidence pointing to conceptual and operational limitations of self-report scales purported to measure trait BI in adults, and especially to inconsistent correlations between such behavioral inhibition system (BIS) scores and amygdala and autonomic responses to fear- or startle-inducing stimuli. Evidence showing a dissociation of both BI and trait anxiety from the amygdala is considered. Possible reasons for the poor association between BIS and trait anxiety self-report scale scores and predicted physiological outputs of the BIS are identified. Reasons to distinguish between the neural bases of BI as against trait anxiety also are discussed. The need to critically examine the role of the amygdala in BI and trait anxiety, as well as to consider other brain areas that appear to be involved in subserving these emotional traits, is emphasized.
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http://dx.doi.org/10.1007/s11920-006-0062-7DOI Listing
August 2006

Rapid, simple, and accurate method for measurement of VFA and carbonate alkalinity in anaerobic reactors.

Environ Sci Technol 2002 Jun;36(12):2736-41

Faculty of Agricultural Engineering, Technion--Israel Institute of Technology, Haifa.

This paper presents a new simple, rapid, and accurate method suitable for on-site measurement of volatile fatty acids (VFA) and carbonate alkalinity in anaerobic reactors. This titrimetric method involves eight pH observations, and typically, the full procedure takes approximately 15 min. An important feature of the method is a built-in quality control mechanism allowing the user a rapid means of assessing the reliability of the experimental procedure. To evaluate the accuracy of the method, both laboratory-made waters and industrial UASB effluent were tested. High accuracy for both VFA and carbonate alkalinity measurements (error within 2% and 1%, respectively) plus good repetition (average standard deviation of 6.7% and 1.45%, respectively) was obtained. The method takes into account the effects of the phosphate, ammonium, and sulfide weak acid subsystems. Appraisal of the effect of an input error in these subsystems revealed that VFA measurement is fairly insensitive to phosphate and ammonium concentrations. It is, however, sensitive to H2S loss during titration where the sulfide concentration is higher than approximately 10 mg/Las S. With regard to the carbonate alkalinity measurement, error in concentration of either phosphate or sulfide or H2S loss might result in a significant error. Short guidelines for correct execution of the method are given in an appendix.
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http://dx.doi.org/10.1021/es011169vDOI Listing
June 2002
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