Functional Imaging of Neurocognition

Mark D'Esposito, M.D., Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, California.

Semin Neurol. 2000;20(4) 

In This Article

Types of Hypotheses that can be Tested with Functional Neuroimaging

The concept of functional specialization is based on the premise that functional modules exist within the brain, that is, areas of the cerebral cortex that are specialized for a specific cognitive process. For example, prosopagnosia refers to the selective inability to recognize faces. Prosopagnosic patients, however, are able to recognize familiar faces such as relatives via other means such as their voice, clothes, or body shape. They are also normal in other types of visual recognition such as identifying common objects. Prosopagnosia arises following lesions of the inferomedial temporo-occipital lobe usually due to a posterior cerebral artery infarction. Most early, large clinical surveys of prosopagnosia have concluded that bilateral lesions are necessary,[62] but more recent reviews have demonstrated that prosopagnosia can occur with damage confined to the right hemisphere.[63] None of these lesion studies, however, have been able to characterize precisely the exact anatomical location that is necessary for the perception of faces. Functional imaging studies have provided such anatomical specificity.

Kanwisher et al,[64] using fMRI, found an area in the fusiform gyrus in 12 of the 15 normal, healthy subjects tested that was significantly more active when the subjects viewed faces than when they viewed assorted common objects. In further testing, the specificity of this region for processing faces was demonstrated by the findings that this "face area" also responded significantly more strongly to passive viewing of faces as compared with scrambled two-tone faces, front-view photographs of houses, and photographs of human hands. Elegantly, these experiments allowed the investigators to reject alternative accounts of the function of the face area, such as visual attention, subordinate-level classification, or general processing of any animate or human forms, demonstrating that this region is selectively involved in the perception of faces.

A major emphasis in functional MRI studies to date has been test theories regarding functional specialization. An exciting new direction for functional neuroimaging is illustrated by studies that use imaging data to test theories regarding underlying mechanisms of cognition. For example, one fMRI study attempted to answer the question, "To what extent does perception depend on attention?"[65] One position is that unattended stimuli receive very little processing,[66] whereas another position is that the processing load in a relevant task determines the extent to which irrelevant distractors are processed.[67] These alternative hypotheses were tested by asking participants in a study to perform linguistic tasks of low or high load while ignoring irrelevant visual motion in the periphery of a display. Visual motion was used as the distracting stimulus because it is known to activate a distinct region of the brain (cortical area MT or V5, another functional module in the visual system). It was reasoned that activation of MT would be a good indicator of whether processing of irrelevant visual motion had occurred. Although task and distractor were unrelated, functional imaging of motion-related activity in MT showed reduced motion processing during high load in the linguistic task. These findings supported the hypothesis that perception of irrelevant distractors depends on the relevant processing load, and, thus, perception does depend on attention.

Functional neuroimaging studies can also test hypotheses about interactions between brain regions by focusing on covariances of activation levels between regions.[68,69] These covariances have been referred to as "functional connectivity," a concept that was originally developed in reference to temporal interactions among individual cells.[70] Newer approaches, often using a statistical test called structural equation modeling, attempt to tease apart whether covariances among brain regions are due to direct or indirect interactions, a concept that has been called "effective connectivity." An example of this method by McIntosh and colleagues69 found shifting prefrontal and limbic interactions in a working memory task for faces as the retention delay increased (Fig. 5). The different interactions among brain regions at short and long delays were interpreted as a functional change. For example, strong corticolimbic interactions were found at short delays, whereas at longer delays, where the face was more difficult to maintain, strong frontocingulate-occipital interactions were found. The former finding was postulated to be due to the maintenance of an iconic representation of a face, whereas the latter finding was proposed to be due to an expanded encoding strategy resulting in more resilient memory. The network analysis provided in this study added to the original conclusions revealed by an analysis of regional means by characterizing changes in regional activity and the inter-actions between regions over time.

Network analysis of fMRI data during performance of a working memory task across three different delay periods.[69] Solid lines represent brain regions that exhibited correlated increases in activation, whereas dotted lines represent areas of correlated decreases in activation. Note the different pattern of interactions among brain regions at short and long delays.