Translational neuroscience of basolateral amygdala lesions: Studies of urbach-wiethe disease

• Published in: Journal of neuroscience research Vol. 94; no. 6; pp. 504 - 512
• Main Authors: Koen, N., Fourie, J., Terburg, D., Stoop, R., Morgan, B., Stein, D.J., van Honk, J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2016; Wiley Subscription Services, Inc
• Subjects: Animals; Basolateral amygdala; Basolateral Nuclear Complex - injuries; Brain Injuries - complications; Brain Injuries - pathology; Central-medial amygdala; Disease Models, Animal; Fear responses; Humans; Lipoid Proteinosis of Urbach and Wiethe - etiology; Lipoid Proteinosis of Urbach and Wiethe - pathology; Translational Medical Research; Urbach-Wiethe Disease; Basolateral amygdala; Central-medial amygdala; Fear responses; Urbach-Wiethe Disease
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.23731

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. © 2016 Wiley Periodicals, Inc.