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

Abstract

There is a growing literature examining working memory deficits using functional imaging and there has been great convergence in the findings, to date, but interpretations have varied. Investigators consistently observed recruitment of neural resources in clinical samples, with some examiners attributing these findings to neural inefficiency and others attributing differences to neural compensation and0or brain reorganization. It is the goal of this paper to address the current interpretation of altered brain activation in clinical imaging studies of working memory dysfunction with specific emphasis on findings in prefrontal cortex (PFC). Throughout this review, the methods used to examine brain reorganization associated with working memory dysfunction are critiqued with the goal of understanding how study design has influenced data interpretation. It is proposed that much of what has been considered "aberrant" neural activity is not indicative of neural compensation, as it has been typically defined, and does not represent brain reorganization. Instead, recruitment of neural resources in PFC can be explained by a natural, and largely overlooked, role of cognitive control in accommodating neural dysfunction secondary to brain injury and disease. This paper provides predictions based on this proposition and a critique of the current methods available for testing these predictions. (JINS, 2008, 14, 526-534.) Keywords: Plasticity, Traumatic brain injury, MS, Working memory, Reorganization, Cognitive control, Prefrontal, Functional magnetic resonance imaging An Alternative to Brain Reorganization HypothesesFunctional imaging techniques afford the unique opportunity to examine the relationships between basic brain changes and the behavioral deficits associated with brain injury and disease. There is a growing functional imaging literature examining the effects of neurological insult on working memory (WM), or the ability to maintain and0or manipulate small amounts of information for brief periods of time. In the functional imaging literature examining WM dysfunction, there has been increasing reference to "neural compensation" and "brain reorganization" to describe the altered (and almost universally increased) neural activation observed when comparing clinical samples to healthy adults. Specifically, the term "compensation" has been used to describe either transient or permanent alterations in neural activity, which operates to facilitate performance. Therefore, in this paper, the term "compensation" will be used to indicate a positive relationship between task performance and brain activation. The term "brain reorganization" has typically been used to indicate that the neural networks associated with WM have been permanently altered because of neurological insult, so that insult induces a "rewiring" of WM networks. Therefore, the primary distinction between "compensation" and "brain reorganization" is that the former may be transient whereas the latter represents permanent changes in the neural networks ...

Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

“…Despite a slight trend towards minor performance in the articulatory rehearsal task, the bipolar patients did not show any significant hypoactivation during task performance. Instead, activation was significantly enhanced in right-hemispherical cerebral and cerebellar cortex, in particular in the precentral gyrus, the intraparietal cortex, and the frontal eye field, which may be interpreted in terms of a reduced cortical efficiency resulting in stronger, possibly compensatory activation [for critical discussions see Callicott et al 2000;Henseler et al, 2008;Hillary, 2008;Tan et al 2006]. Most interestingly, however, only the patients exhibited a (pathological) activation of the right amygdala during working memory task performance (Fig.…”

The Nature of Processing Speed Deficits in Traumatic Brain Injury: is Less Brain More?

“…Previously, we have argued that, in studies measuring task accuracy alone, the resultant between group differences are at least partially attributable to unrecognized processing speed decrements (Hillary et al 2006;Hillary 2008). If the regions of neural recruitment commonly observed in TBI are coupled with task performance (as will be directly measured here), it will be important to reframe brain reorganization hypotheses as they are currently posed.…”

“…First, it was not a goal in the current study to isolate specific cognitive mechanisms (e.g., separate visual processing from decision making); the goal here was to examine rapid information processing deficit (broadly defined) associated with a rapid visual scanning task and with focus on PFC. Second, there are a number of methodological pitfalls associated with using complex subtraction scenarios in clinical samples (Price and Friston 1999;Price and Friston 2002), including differential subtraction between subjects due to performance decrements (Hillary 2008). Reaction time (RT) was recorded for all subjects, but due to a software programming error, task accuracy was not collected in 6/12 subjects with TBI.…”

“…Increased neural involvement paired with similar task accuracy between clinical and control groups has been interpreted as "neural compensation" or, alternatively, as "brain reorganization". While these two terms certainly have distinct implications for altered brain activation, (most notably its permanence), both are almost universally used to describe PFC involvement operating to bolster performance (for review see Hillary 2008). What remains a central dilemma in determining the nature of PFC recruitment in TBI (and in neurological insult more generally) is whether the recruitment of these neural resources: 1. occurs only in cases of injury and/or disruption or represents a latent support mechanism evoked during periods of cerebral challenge more generally; 2. serves to facilitate task performance or is associated with diminished performance.…”

Recruitment and Stabilization of Brain Activation Within a Working Memory Task; an fMRI Study

“…al. , 2006, and Alzheimer's disease (Gould et al 2006), and that also has been demonstrated in healthy people when they engage in demanding tasks (Hillary 2008). Future studies might determine if pharmacologic interventions can improve brain efficiency in normal and disease states.…”