title: Translational neuroscience of basolateral amygdala lesions: Studies of Urbach-Wiethe disease.
abstract: Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral amygdala damage. A large body of work on amygdala lesions in rodents exists, generally employing a subregion model focused on the basolateral amygdala (BLA) and the central-medial amygdala. However, human work usually considers the amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.|Medical Research Council Unit on Anxiety and Stress Disorders, Stellenbosch, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Koen
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Fourie
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.|Department of Psychology, Utrecht University, Utrecht, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Terburg
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University and University Hospital, Lausanne, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Stoop
authors.affiliation: Department of Public Law, University of Cape Town, Cape Town, South Africa.|DST-NRF Centre of Excellence in Human Development, DVC Research Office, University of Witwatersrand, Johannesburg, South Africa.|Global Risk Governance Programme, Faculty of Law, University of Cape Town, Cape Town, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Morgan
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.|Medical Research Council Unit on Anxiety and Stress Disorders, Stellenbosch, South Africa.
authors.forename: D J
authors.initials: DJ
authors.lastname: Stein
authors.affiliation: Department of Psychology, Utrecht University, Utrecht, The Netherlands.|Institute of Infectious Disease and Molecular Medicine and Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: van Honk
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000293:injuries*; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000209:etiology* / Q000473:pathology; D057170:Translational Research, Biomedical
keywords: Basolateral amygdala; Central-medial amygdala; Fear responses; Urbach-Wiethe Disease