Neural substrate and underlying mechanisms of working memory: insights from brain stimulation studies

The concept of working memory refers to a collection of cognitive abilities and processes involved in the short-term storage of task-relevant information to guide the ongoing and upcoming behavior and therefore describes an important aspect of executive control of behavior for achieving goals. Deficits in working memory and related cognitive abilities have been observed in patients with brain damage or neuropsychological disorders and therefore it is important to better understand neural substrate and underlying mechanisms of working memory. Working memory relies on neural mechanisms that enable encoding, maintenance, and manipulation of stored information as well as integrating them with ongoing and future goals. Recently, a surge in brain stimulation studies have led to development of various noninvasive techniques for localized stimulation of prefrontal and other cortical regions in humans. These brain stimulation techniques can potentially be tailored to influence neural activities in particular brain regions and modulate cognitive functions and behavior. Combined use of brain stimulation with neuroimaging and electrophysiological recording have provided a great opportunity to monitor neural activity in various brain regions and noninvasively intervene and modulate cognitive functions in cognitive tasks. These studies have shed more light on the neural substrate and underlying mechanisms of working memory in humans. Here, we review findings and insight from these brain stimulation studies about the contribution of brain regions, and particularly prefrontal cortex, to working memory.