In Search of the Neural Underpinnings and a Functional Definition of the Elusive "Working Memory"

Recent evidence of domain-specific working memory (WM) systems has identified the areas and networks which are involved in phonological, orthographic, and semantic WM, as well as in higher level domain-general WM functions. The contribution of these areas throughout the process of verbal learning and recall is still unclear. In the present study, we asked, what is the contribution of domain-specific specialized WM systems in the course of verbal learning and recall? To answer this question, we regressed the perfusion data from pseudo-continuous arterial spin labeling (pCASL) MRI with all the immediate, consecutive, and delayed recall stages of the Rey Auditory Verbal Learning Test (RAVLT) from a group of patients with Primary Progressive Aphasia (PPA), a neurodegenerative syndrome in which language is the primary deficit. We found that the early stages of verbal learning involve the areas with subserving phonological processing (left superior temporal gyrus), as well as semantic WM memory (left angular gyrus, AG_L). As learning unfolds, areas with subserving semantic WM (AG_L), as well as lexical/semantic (inferior temporal and fusiform gyri, temporal pole), and episodic memory (hippocampal complex) become more involved. Finally, a delayed recall depends entirely on semantic and episodic memory areas (hippocampal complex, temporal pole, and gyri). Our results suggest that AG_L subserving domain-specific (semantic) WM is involved only during verbal learning, but a delayed recall depends only on medial and cortical temporal areas.