C HAPTER 3 4 GROUP STUDIES IN EXPERIMENTAL NEUROPSYCHOLOGY Lesley K. Fellows WHY NEUROPSYCHOLOGY? individual differences in skull shape (explicitly thought to be a proxy for underlying brain structure) A fundamental assumption of neuropsychology, and in relation to individual differences in behavior. of cognitive neuroscience more generally, is that Complex traits like benevolence and wit were thus behavior has a biological basis—that it results from related to particular parts of the brain. Although the processes that are executed in the nervous system. methods are clearly flawed to the eye of the modern Following from this assumption, emotions, reader, the underlying concept of localization, that thoughts, percepts, and actions can be understood brain structure and function are related, had a major in neurobiological terms. This premise was impact on the development of clinical neurology and advanced by the philosophers of ancient Greece, of experimental neuropsychology. supported, in part, by observations of patients with The work of Broca, Wernicke, and other 19th- brain injury (Gross, 1995). The fact that damage to and early 20th-century neurologists illustrated how the brain could lead to paralysis, disorders of sensa- observation in clinical populations can (a) provide tion, or even disruptions of consciousness suggested insights into how a complex behavior (like lan- that this organ was the seat of such abilities, guage) can be segmented into simpler components although the broad claim that brain function under- (e.g., production and comprehension) and (b) how lies behavior was not without controversy over the such components can be related to specific regions centuries that followed (Crivellato & Ribatti, 2007). of the brain. Both defining the components of The 19th century saw, on the one hand, major behavior and relating these components to the developments in understanding the anatomy and brain can be done on the basis of a single, carefully physiology of the brain and, on the other, more sys- studied case (see Chapter 33 of this volume). How- tematic descriptions of behavioral changes resulting ever, the limitations of clinical observations in from neurological diseases. These advances laid the humans were also apparent in these early days. Cli- groundwork for current thinking about the brain. nicians were (and are) acutely aware of wide vari- Here again, clinical observations provided an impor- ability in the clinical presentation of a particular tant impetus, as did analyses of individual differ- pathological condition, determined both by differ- ences in normal behavior: Neurologists such as Paul ences in premorbid individual characteristics Broca and Carl Wernicke reported that focal brain (e.g., age, education, or health status) and differ- injury to specific areas within the left hemisphere ences in the specific details of the pathological pro- disrupted particular aspects of language (Feinberg & cess. Case series and group studies provide an Farah, 2006). Their thinking was influenced, in part, important means of determining the generalizability by Franz-Joseph Gall and others who developed the of inferences that can be drawn from individual concept of phrenology in about the same period. observations. Phrenology was based on observations of specific DOI: 10.1037/13620-034 APA Handbook of Research Methods in Psychology: Vol. 2. Research Designs, H. Cooper (Editor-in-Chief) 647 Copyright © 2012 by the American Psychological Association. All rights reserved. Lesley K. Fellows Gordon Holmes, a British neurologist whose cognitive process (Fellows et al., 2005; Rorden & work on the effects of penetrating brain injury in Karnath, 2004). In principle, this is a powerful form World War I soldiers helped to establish the retino- of evidence because it addresses causality. Although topic organization of primary visual cortex, poeti- cognitive neuroscience now has many other meth- cally captured the limitations of clinical observation ods available to investigate brain–behavior relations, in a lecture delivered in 1944: most provide correlational data. Standard functional neuroimaging methods, for example, reveal brain My own work on the visual cortex has regions in which blood-oxygen-level dependent been limited to observation in man. (commonly referred to as BOLD) signal (itself a cor- This has required the collection of a relate of neural activity) is correlated with a behav- large number of observations, for while ioral process of interest. These findings can be the physiologist can rely on experiments informative, but alone they are insufficient to estab- when he can select and control, . the lish that the brain regions so identified are in fact clinician must depend on the analysis of necessary for the behavior in question (Fellows et observations which are rarely so simple al., 2005; Rorden & Karnath, 2004). or clear cut.. The physiologist may be These inferential considerations are particularly compared with the builder in . hewn relevant in the study of complex behaviors, and in stones which can easily be fitted together, new areas of enquiry. Consider risky decision mak- the physician resembles the mason who ing as an example. Imagine yourself at the blackjack has to use irregular rubble and there- table, deciding how much to stake on the next card. fore requires more time and labour to Several correlated processes are likely under way in attain his end. But in some branches of your brain. You may be calculating the odds of win- neurology, the “rubble” collected and ning, integrating your recent history of wins and put together by the clinician is essential. losses, and weighing these factors to reach a deci- (Holmes, 1944/1979, pp. 440–441) sion. You may be imagining how you would spend Holmes underlined two key points: (a) that the your winnings, or how you would explain a loss to limitations inherent to studying the effects of brain your spouse. It is likely that you are experiencing injury in humans can be minimized by gathering substantial changes in arousal and autonomic tone: data from many subjects and by interpreting these A pounding heart and sweaty palms often accom- data in the context of converging evidence from pany a risky choice. Whether all of these putative other methods and (b) that the limitations are offset processes are distinct, important to the decision, or by the fact that these observations provide crucial simply correlated epiphenomena are empirical ques- insights that may not be acquired in any other way. tions. Interpreting functional magnetic resonance As this chapter will describe, there have been many imaging (fMRI) activations in this situation is not logistical, technical, and analytic advances in human easy—for example, is a given area more active lesion studies over the past century. However, because it is critically involved in risky decision Holmes’s comments on the core advantages and making or is it important in central autonomic con- limitations remain as pertinent as ever. trol, mediating the changes in sympathetic nervous system outflow that result in the pounding heart? Although careful design can help to minimize these INFERENTIAL STRENGTHS OF LESION uncertainties of interpretation, the nature of correla- STUDIES tional evidence means that they can never be elimi- Research on effects of brain injury on behavior nated entirely. Converging evidence from addresses two main issues: First, it can establish that loss-of-function methods, such as lesion studies, can a particular region of the brain is necessary for the help test necessity claims. If we take a hypothetical expression of a particular behavior, in turn, support- “risky decision” brain area as an example, a study of ing the inference that it is critical for a particular patients with damage to that area could directly test 648 Group Studies in Experimental Neuropsychology whether it was critical for the decision, for the auto- exclude potential lesion-related confounds that nomic changes that accompany that decision, or for might explain the observations in a single case; for both. Such an experiment would shed light both on example, they can establish that it is the site of dam- the critical components of decision making (do age, rather than its etiology, that underlies the autonomic changes influence choice?) and on the behavior change. brain substrates of the critical processes (e.g., Another common and related problem that can Critchley et al., 2003). be addressed by group studies is that lesions are More profoundly, the study of patients can pro- often more extensive, or less precisely located, vide biological constraints to psychological theory. than is ideal for testing a given structure–function The usual form this has taken is that of dissociation hypothesis. If the function is disrupted but the of cognitive processes. Two putative psychological lesion is large, the conclusions cannot be specific. If constructs may be considered distinct if brain injury a group of patients with lesions varying in extent disrupts one and not the other—establishing what is but overlapping in some smaller area are found to termed a function dissociation. As will be described, have a common impairment in function, one can experiments of this kind have been influential, but infer that the function likely relies on the region of how these are best designed and interpreted is not overlap that is common across patients. Recent without controversy. methods have built on this logic to allow statistical tests of structure–function