Revisiting Lenneberg's Hypotheses About Early Developmental Plasticity: Language Organization After Left-Hemisphere Perinatal Stroke.

Abstract

A prominent theme in the literature on brain injury and recovery has been the notion of early developmental plasticity (Kennard 1940, Kolb et al. 2000). This has been a particular focus in work on language. In healthy adults, language is virtually always lateralized to the left hemisphere (LH; Broca 1861, Gazzaniga & Sperry 1967). However, Basser (1962) and Lenneberg (1967) compiled published case studies, their own patient histories, and available medical records of children and adults with left and right hemisphere lesions or hemispherectomy to determine whether there were systematic effects of hemisphere and age of insult on the development or recovery of language. From these data, Lenneberg (1967) concluded that, when even massive injuries to one hemisphere occurred before age 2, most children developed language normally or with only some delay; and these outcomes were the same regardless of which hemisphere was affected. This led him to argue that initially, before cerebral dominance was fully established, the two hemispheres were equipotential for language. This was less true for older children and was definitively no longer true for adults, who showed strong LH specificity for language interference and some recovery from mild aphasias, but did not recover completely from severe aphasias or left hemispherectomies. Using the Wada test (briefly anesthetizing one hemisphere and then the other; see Loring et al. 1992) to determine which hemisphere controls speech, Rasmussen & Milner (1977) showed that in children, depending on the age at injury, speech that is ordinarily in the left hemisphere could be controlled successfully by the right hemisphere or by an alternate region of the damaged left hemisphere. Similar reorganization was not observed in adults, even decades after injury. These generalizations have long formed the classic picture of recovery of language function. However, recent research on organization after early injury in children has not always found such consistent outcomes. Some studies have found good language abilities after focal brain injury in children, but others have not (Banich et al. 1990, Ballantyne et al. 2007, Levine et al. 2005, Moesch, Max, & Tranel 2005, Montour-Proulx et al. 2004, Stiles et al. 2012, Westmacott et al. 2010). Relatively few studies of neural reorganization have been done with children, also with somewhat inconsistent outcomes (see, e.g., Mbwana et al. 2009, Rosenberger et al. 2009, and You et al. 2011 for language reorganization with epilepsy, and Booth et al. 2000, Dick et al. 2013, Fair et al. 2006, 2010, Jacola et al. 2006, Liegeois et al. 2004, Raja et al. 2010, Staudt et al. 2002, 2007, and Tillema et al. 2008 on perinatal stroke). This variation of outcomes may be due to true variation among children, or to the inclusion of children with a variety of types and causes of focal brain injuries (e.g., periventricular leukomalacia, moya moya, vasculitis, tumors, and hemorrhagic or arterial ischemic strokes) or the effects of other medical problems that are often comorbid with stroke in children (e.g., seizures and seizure medications, heart disease and reduced cortical perfusion, or sickle cell anemia). It might also be due to variation in the ages at which participants were evaluated (see Bates et al. 2001, showing that children with focal brain injuries may show developmental delays but later reach normal levels of performance). There has also been little consistency in investigators’ views of the principles governing developmental plasticity for language. Only a few researchers have proposed hypotheses about what areas or networks in the brain are capable of subserving language in the face of early brain injury, and these proposals are in sharp conflict. Vargha-Khadem et al. (1985) suggested that the left hemisphere is uniquely suited for language and that successful reorganization of language is limited to LH brain areas. (See also Raja et al. 2010, who have argued that the remaining left hemisphere voxel activity correlates best with language proficiency after left hemisphere perinatal stroke). Staudt (2002) and Gaillard and colleagues (Gaillard et al. 2007, Berl et al. 2014, Mbwana et al. 2009) have argued that left hemisphere areas or their precise right hemisphere homologues can subserve language when there are early left hemisphere abnormalities. In contrast, Bates et al. (1997) have suggested that the young brain is highly plastic; they argue that “the human capacity for language is not localized at birth,” implying that reasonably normal language skills might be able to develop in numerous other brain regions. Bedny et al. (2011) have argued that congenitally blind individuals utilize even occipital cortex (including V1) during spoken language processing. Can this wide range of brain areas indeed support language? In our ongoing work we seek to understand the forces that lead language to develop in only certain brain areas in the healthy child and also to understand what areas can support language after early brain injury. An important literature is the work of the Gaillard lab (Gaillard et al. 2007, Berl et al. 2014, Mbwana et al. 2009) using functional magnetic resonance imaging (fMRI) to examine the organization of language over development and how it is affected by early and continuing epilepsy (and the brain abnormalities that cause them). In response to chronic epilepsy, cortical processing of language is frequently restructured, with some or all language function shifted to the right hemisphere. Their work has shown a limited number of ways in which language is organized across a very large number of children: in the usual left hemisphere areas, in the precisely homotopic right hemisphere areas, or in the usual left hemisphere temporal areas combined with the homotopic right hemisphere frontal areas. No other patterns of language organization appear in their subjects. However, while chronic seizures can be clinically devastating for children, they apparently exert relatively mild effects on cortical organization: 75 % of children with early chronic seizures retain the typical left hemisphere pattern of language organization. To examine language after very early damage to the brain, we are focusing on perinatal arterial ischemic stroke, a relatively rare neurological event but one whose characteristics may provide an excellent model for examining the neural organization of language after early brain injury and for gaining insight into important principles of neural plasticity for language. In perinatal stroke, the injuries are typically much larger than in pediatric epilepsy but are relatively stereotyped in anatomy; approximate time of onset is clear; and in most patients there are not continuing seizures or long periods of time on antiepileptic medications. This makes our perinatal population an important contrast to Gaillard et al.’s work on epilepsy.