The role of the DLPFC in working memory

The DLPFC is a functionally complex brain region in the prefrontal cortex that encompasses several Brodmann areas including 9, 8a, 8b, and the dorsal part of 46 (Sallet et al., 2013). The DLPFC is more extensive in humans compared with other primates, indicating its important role in complex cognitive processes (Nee et al., 2016). Our understanding of the functions of the DLPFC has mainly improved through the use two different types of neuroimaging methods. First, studies of resting state connectivity, performed in the absence of an overt task, have revealed the architecture of essential brain networks. A second type of study employs paradigms in which task performance, type, or perception are correlated with precise

locations, intensities, and time-courses of DLPFC activation (Biswal et al., 1995; Damoiseaux et al., 2006; Raichle et al., 2001; Smith et al., 2009). These neuroimaging studies could enhance our knowledge about the effect of the DLPFC in the processing of information for WM (Seminowicz et al., 2017).

One study investigated the essential role of the DLPFC in WM, by presenting WM tasks (e.g. the Wechsler Memory Scale and the n-back tasks) to three subject groups including patients with DLPFC lesions, patients with non-DLPFC lesions, and a healthy group with no brain lesions. The results showed that DLPFC damage was associated with deficits in the verbal and spatial manipulation of information, supporting the role of the DLPFC in WM processes (Barbey et al., 2013). Additionally, a review article focused on WM processes in monkeys supported the critical role of the DLPFC in WM performance. The findings in studies with monkeys showed that lesions in the dorsolateral areas of the prefrontal cortices impaired WM processes, compared to lesions in dorsomedial areas. This review article emphasized the role of the DLPFC in WM processes and proposed a functional dissociation between the dorsomedial and dorsolateral prefrontal cortices concerning WM function (Levy et al., 2000). Neuroimaging studies in humans have also revealed that the left DLPFC appears to support the manipulation of information in WM, whereas the right DLPFC is necessary for the manipulation of information in a range of reasoning contexts (Wager et al., 2003).

Studies in older persons have also revealed the effects of DLPFC in WM processes. For example, one study recruited sixteen healthy young and twenty older adults to perform blocks of encoding, retrieval, and control tasks. Participants had to memorize face/name stimuli pairs

presented on a screen during the encoding block. Three letters related to the first letter of the encoded stimuli name were presented during the retrieval block. In this block, participants had to identify a target letter within the three letters. During a control block, participants simply indicated when a particular visual target (a circle) was presented. The results indicated that decreased performance during information retrieval was associated with several brain areas including the left DLPFC, which showed significantly lower gray matter volume in older persons compared with younger adults. In particular, the findings revealed that high levels of activation in the DLPFC were negatively correlated with both grey matter volume and accuracy during the retrieval block in healthy older adults compared with younger adults (Kalpouzos et al., 2012). Generally, neuroimaging studies on aging, which aimed at examining the association between brain structure/function with cognitive performance, have found age-related under- and over-recruitment of brain regions (Kalpouzos et al., 2012; Maillet et al., 2013). Under-recruitment has been related to less efficient neural networks, while over-Under-recruitment might be linked to compensatory mechanisms. According to the “Scaffolding theory,” increased activity is an indicator of such compensatory mechanisms (Park et al., 2009). This increased brain activity is elaborated in response to the structural and molecular decline of the brain and in order to optimize cognitive performance (Park et al., 2009). Scaffolding theory proposed interactions between structural integrity and brain function (Park et al., 2009). The results of the Kalpouzos study -in line with this theory- showed that older adults undergo non-uniform gray matter volume loss. Therefore, local atrophy might partially affect functional brain activity in older adults. These findings indicated an interaction between related structural differences to age-related functional under and over-recruitment (Kalpouzos et al., 2012; Maillet et al., 2013; Park et al., 2009).

Another study examined the neural correlates of WM in twenty-eight healthy middle-aged adults, compared to thirty-four young adults. Facial stimuli depicting individuals of different ages were presented during the experiment, and the task was to memorize either the spatial location or the temporal order of six facial stimuli (low-load task) or twelve facial stimuli (high-load task). An fMRI scan was obtained from all participants during the encoding and retrieval phases of both the low- and high-load memory tasks. The findings showed that greater activation of the left DLPFC was positively associated with accurate performance during low-load tasks in healthy middle-aged adults. However, in young adults this association between greater activation and increased performance was only observed during the high-load task, suggesting that alterations in prefrontal cortex activation, including the DLPFC, can contribute to WM decline at midlife (Kwon et al., 2016). In summary, empirical evidence from animal studies, and human studies on both young and older persons supports a role of the DLPFC in WM processes, particularly in the central executive system that is responsible for the manipulation of information in WM. As mentioned in (section 3.4) WM processes include the encoding, storing, manipulation, and retrieval of information (Postle, 2006; Woodman et al., 2005). In line with this, Baddeley’s WM model proposes three main WM components: the central executive system, which is responsible for manipulation of information and is also known as the supervisory attentional system; the phonological loop, which is responsible for storing and encoding verbal information; and the visuospatial sketchpad, which is responsible for storing and encoding visual information (Baddeley, 2012; Baddeley et al., 1974; Miyake et al., 1999).

Regarding the processing of information in WM and Baddeley’s WM model, studies have shown several brain areas to be activate during WM tasks. The superior frontal cortex is associated with information monitoring, updating, and manipulation during performance of WM

tasks. The ventral frontal cortex supports the rehearsal of information during information storage in WM. The anterior prefrontal, DLPFC, and ventral lateral prefrontal cortices mainly support the central executive system, which is responsible for the manipulation of information in WM (Wager et al., 2003; Wager et al., 2014).