Neuropsychological diagnosis requires a structure-function correlation model or a "Conceptual Nervous System." The unpredictably variable, widespread, and multifocal nature of pathological changes in multiple sclerosis (MS) challenges the neuropsychological localizationist assumption. To be adapted to MS pathological and clinical heterogeneity, a Conceptual Nervous System should explain impairments associated with multifocal, subcortical, and white matter lesions that cause information processing slowing and working memory/executive function impairment. Our main goal in this theoretical study was to develop a Conceptual Nervous System for MS by integrating current neuropsychological conceptions of structural-functional correlations in MS with a model of conscious mental activity developed by Ernst Pöppel , based on periodic reentrant activity between cortical and subcortical structures. Neuropsychological profiles in MS can be explained by both threshold and multiple disconnection mechanisms. The Conceptual Nervous System encompasses a functional and structural model of the human brain-mind. The functional model classifies mental function into material and formal. Material/semantic functions are modularly organized, and their impairment causes classical focal neuropsychological symptoms. Multiple sclerosis preferentially impairs formal/syntactic function related to widespread patterns of activation and temporal organization. The structural model specifies the system anatomically functions. The neuropsychological adequacy of the proposed Conceptual Nervous System to MS is analyzed by comparing its predictions to results of extant metaanalytic studies.
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