Quantitative neostriatal neuroanatomy as a basis of frontostriatal circuit dysfunction in neuropsychiatric disease

Abstract

Background and Purpose: Neuropsychiatric diseases are protean, affecting cognition, emotion and behaviour, including such diseases as reactions to traumatic stress (post-traumatic stress disorder), cerebrovascular disease and the neurodegenerative dementias. There has been much interest in understanding the neural basis of neuropsychiatric disease. A model that has been employed to investigate such disease has been the endophenotype, a restricted set of phenotypic or clinical features that may have a more specific structural and hence, genetic basis. An example of an endophenotype is frontal-executive neuropsychological function, localised to the neural substrate of dorsolateral prefrontal cortex frontostriatal circuit. Consequently, it is possible to explore the structural basis of an endophenotype by studying the components of neural circuits carrying such functions. Thus, frontostriatal circuits may be useful as a structural basis for endophenotypes related to frontal cognitive function. These circuits extensively mediate cognition, emotion and behaviour within humans. The caudate nucleus and putamen, comprising the human neostriatum, serve crucial roles within frontostriatal circuits. The caudate and putamen may thus serve as a potential, quantifiable component of the structural basis for endophenotypes. It was hypothesized that functional change may be reflected in structural changes in the neostriatum due to neuroplasticity. Thus functional activation or disconnection might impact upon the structure of the caudate or putamen. Other corticostriatal circuits in addition to frontostriatal circuits may thus be affected. These studies were designed to measure the volume of the neostriatum as a quantified neuroanatomical basis of the endophenotype of frontostriatal dysfunction within specific neuropsychiatric diseases. <...>