Prefrontal modulation of working memory performance in brain injury and disease

Abstract

The inter-related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge.

Exploring Neural Efficiency in Multiple Sclerosis Patients during the Symbol Digit Modalities Test: A Functional Magnetic Resonance Imaging Study

“…This pattern of results agreed with previous studies and suggests that frontal lobe activation increases in line with task difficulty, and that this brain area is recruited in order to set greater cognitive control [14,22]. Our findings also agree with those of previous studies, which have described that in early disease stages, MS patients exhibit greater activation or recruit supplementary brain areas.…”

Neuroimaging of working memory dysfunction and the dilemma with brain reorganization hypotheses

“…In the clinical imaging studies investigating WM, an interpretation that has been proposed elsewhere (Hillary et al, 2006) and is extended here, is that the increased PFC involvement on tasks of WM represents neither "compensation" operating to bolster task performance nor "brain reorganization." Instead, it is proposed that the increased neural activity in PFC commonly observed in clinical studies of WM is associated with poorer performance and largely represents transient fluctuations in the recruitment and reassignment of attentional resources, or cognitive control (Hillary et al, 2006).…”

“…Is it possible that recruitment of neural resources in mild forms of neurological impairment represents compensation and0or reorganization operating to facilitate performance, yet in cases of more severe cognitive deficit, recruitment of nearly identical neural networks is associated with neural inefficiency and correlated with diminished performance? An explanation with greater parsimony for the convergent findings to date is that the regions consistently recruited across clinical samples represent a native support mechanism(s) (Hillary et al, 2006). This explanation remains at odds, however, with studies proposing that neural activity in PFC is facilitating performance and what must ultimately be 528 F.G. Hillary determined in order to clarify this issue is the basic relationship between activation and performance in PFC.…”

“…Instead, it is proposed that the increased neural activity in PFC commonly observed in clinical studies of WM is associated with poorer performance and largely represents transient fluctuations in the recruitment and reassignment of attentional resources, or cognitive control (Hillary et al, 2006).…”

Augmented neural activity during executive control processing following diffuse axonal injury

“…28,29 TBI patients often report subjective changes associated with cognitively demanding tasks in spite of normal task performance, a dissociation that presents significant challenges with respect to diagnostics and treatment planning in the absence of measurable signs of cognitive dysfunction in patients with TBI, as well as in patients with other neuropathologies causing diffuse or multifocal damage (e.g., dementia, multiple sclerosis). Reduced cognitive efficiency, as indexed by altered functional recruitment during neuropsychologically normal task performance, may serve as a novel metric, reflecting the costs of normal behavioral performance at the neural level.…”