Natural exposure to domoic acid causes behavioral perseveration in Wild Sea lions: Neural underpinnings and diagnostic application

Domoic acid is a naturally occurring algal toxin that causes neurological symptoms and mortality in exposed marine life. California sea lions (Zalophus californianus) are the most visible victims, and suffer epilepsy and progressive hippocampal atrophy. Despite its reliable neurological effects, little is known about how exposure to domoic acid alters behavior, which is critical for understanding the impact of toxic exposure on long-term survival in sea lions and other exposed animals, including humans. Better understanding of the behavioral effects may also inform veterinary diagnosis and treatment. Anecdotally, exposed sea lions have been reported to show enhanced perseverative behavior. To assess the neurobehavioral effects of domoic acid, we compared veterinary diagnoses, measures of hippocampal volume from in vivo MRI, and behavioral measures of habituation and dishabituation in 27 wild sea lions undergoing rehabilitation. The sample was divided post-hoc between subjects with clear veterinary diagnoses of chronic domoic acid toxicosis and those with no evidence of the disease. In the behavioral task, subjects were exposed repeatedly to sounds from two source locations, and, following a short delay, exposed again. Veterinary diagnosis of domoic acid toxicosis was associated with extent of hippocampal damage, predicted delayed habituation in phase 1, and enhanced dishabituation in phase 2. Receiver operating characteristic analysis indicated that delayed habituation in phase 1 was diagnostically predictive. Enhanced dishabituation in phase 2 was correlated with reduced right ventral hippocampal volume. Together, delayed habituation and enhanced dishabituation following domoic acid exposure indicate a clinically relevant and potentially maladaptive behavioral pattern of perseveration.