The Geschwind–Behan–Galaburda Model (GBGM) of Cerebral Lateralization: A Critique and Prospective

REVIEW Behavioural Neurology (1996), 9, 107-113 The Geschwind-8ehan-Galaburda model (G8GM) of cerebral lateralization: a critique and prospective C.M.J. Braun Laboratoire de Neuroscience de la Cognition, and Departement de Psychologie, Universite du Quebec Montreal, Canada a Correspondence to: C.M.J. Braun, LNC-UQAM, C.P. 8888, Succ. Centre-Vil/e, Montreal, Quebec, Canada H3C 3P8 In the wake of, and as a complement to, a recently published major meta-analytic review of empirical support of the Geschwind-Behan-Galaburda model (GBGM) of cerebrallateralization (CL) the present brief essay attempts to present a critical assessment of the theoretical approach underlying the GBGM. The GBGM is criticized for having been misguided in its representation of the cerebral basis of handedness, and of the links between testosterone and immune function. Some guidelines are presented for the development of a general theory of CL, emphasizing animal research, greater interdisciplinary communication, a hierarchical model-building approach, and the relevance of neuropharmacology and psychiatry. Keywords: Cerebral laterality - Endocrine - Handedness - Immune - Neurotransmitter - Geschwind-Behan-Galaburda model INTRODUCTION The Geschwind-Behan-Galaburda model (GBGM) of cerebrallateralization (Geschwind and Galaburda, 1985) is a far reaching theory of the effects of prenatal testosterone on the development of hemispheric specialization with thymic immunity acting as a mediator. The GBGM continues to inspire behavioural neurology. Evidence to that effect is the special issue in Brain and Cognition (Bryden et al., 1994) which was entirely devoted to critical assessment of empirical evidence in support of the GBGM. That major review article, as well as the numerous commentaries, essentially led to the conclusion that there is virtually no support at all for the theory, at least as far as its claims regarding the development of hand dominance. The scientific community is coming to this conclusion after publication of several hundreds of research projects designed to test components of the theory, and yet seems to want to continue testing the model. It is the contention of the present essay that it is time to pass on to another paradigm of cerebral laterality, with an entirely different theoretical approach to the problem. 0953-4180 © 1996 Rapid Science Publishers A first major problem with the GBGM was its heavy reliance on expeditive assessment of human handedness in a general model of cerebrallateralization (CL). As Bryden and colleagues have explained (1994), the biopsychosocial complexity of human handedness has been sorely underestimated. The problem with human handedness, as an index of CL, is that it is a bad measure when extracted summarily. The ease with which it can be documented is, however, precisely the reason why it has been so popular. However, this catch-22 situation has corrupted our understanding of the cerebral aspects of handedness. Secondly, it seems disappointing, in hindsight, that the clinically based associations forming the centroid of the GBGM were drawn piecemeal, the authors not having bothered to survey, for example, sex and age curbs of all the autoimmune, allergic and infectious diseases systematically. If such had been done, using the biomolecular data available at the time, the GBGM would never have been born. For example, the GBGM would not have attributed such importance, as it did wrongly, to thymic mediation of Behavioural Neurology. Vol 9 • 1996 107 C.M.J. BRAUN brain-immune developmental interactions (St Marseille and Braun, 1995). Thirdly, more attention to animal research in neuroendocrinology and neuroimmunology would have helped inhibit some of the sweeping generalizations of the GBGM. For example, the effects of fetal"' androgens on CL could not plausibly have been reduced to slowing development of the left hemisphere. I elaborate on this in a later section. Furthermore, there was never any basis for reducing the GBGM selection of immune disorders to thymic atrophy in boys, and even less the latter to left handedness. On the other hand, normal development of the immune system does relate to CL in sexdimorphic manner in non-human species (Tobet and Fox, 1989). This is certainly a stronger basis for model building than speculation about associational clusters of immune disorde~sand non-imrtu,rne marginalities. How might we· now re-build a general model of CL? Contrary to the GBGM, a general model or theory of CL must: (1) be based' on animal research as well as human research; (2) draw the relevant material from each scientific discipline systematically and exhaustively prior to interdisciplinary integration; (3) propose theoretical models hinging not on the weakest associational clusters first but on the stronger ones; and (4) cover all the relevant scientific disciplines including neuropsychiatry and neuropharmacology. These four points will now be argued in more detail with a few examples. ANIMAL RESEARCH There are many hundreds of specific findings of CL in animal research obviously forming a complex mosaic. One of the more developed programs of research, in this general domain, is the work of Glick and colle'agues the neurodynamics of asymmetric turning behaviour in rats. The behavioural, genetic, neuropharmacokinetic, neuroendocrinological, neuroanatomical, and developmental aspects of this paradigm are now amazingly advanced (Zimmerberg 1974; Glick and Shapiro, 1985; Shapiro et al. 1986; Glick et af., 1988). This behaviour is clearly lateralized in its bodily expression as well as in its brain substrate and there is good fit between the two. The phenomenon is also sexually dimorphic, inherited, dopamine-mediated, and striatum-based. The paradigm has even been extended to the human (Bracha et al., 1987) and, therefore, an extremely interesting candidate as a prototype for continued deepening of our bioscientific understanding of CL. . Human handedness, like animal pawedness, is not on 108 Behavioural Neurology. Vol 9 • 1996 only testosterone-dependent. In fact, testosterone explains only a very small portion (barely significant) of the variance. Genetic factors are obviously tremendously important. Human research has not, however, been able to show, and probably cannot show, the specific impact of asymmetric experience with the hands on cerebral anatomical or neurochemical asymmetry. Fortunately, the issue can be addressed in animal research. Diaz et al. (1994) trained very young rats to reach for food with only one paw. They later analyzed adult brains of rats with such precocious forced right or left pawedness, and adult brains with right and left spontaneous (untrained) right or left paw preferenct? Rats with precocious forced pawednessJiad greater development of the primary motor cortex of the hemisphere contralateral to the trained paw. The paw area of the motor strip was thicker and contained fewer neuron cell bodies, sugges (...truncated)