Connectivity constraints on cortical reorganization of neural circuits involved in object naming

Abstract

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions–reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.

Introduction

Neuropsychological and functional neuroimaging research indicates neural specificity for a small number of semantic categories in the human brain. Reports of patients with disproportionate naming impairment for one category of objects relative to other semantic categories (Caramazza and Shelton, 1998, Hillis and Caramazza, 1991, Sartori and Job, 1988, Tranel et al., 1997, Warrington and Shallice, 1984; see review in Capitani et al., 2003, Gainotti, 2000), as well as functional brain imaging studies (Damasio et al., 1996, Kriegeskorte et al., 2008, Martin et al., 1996, Rogers et al., 2005) and single cell recordings in humans (Kreiman et al., 2000, Quiroga et al., 2005) have helped chart some of the cortical networks involved in processing different categories of objects, but this issue is not without controversy (see Lambon Ralph et al. (2007) for arguments against the existence of category-specific deficits). The distinction between animate and inanimate objects has emerged as one of the principal dimensions of the organization of object knowledge. Neuroimaging studies have suggested that the major areas involved for naming animals include the left inferior temporal gyrus (lITG) and bilateral fusiform gyri; the regions involved in naming tools and other artifacts include the left posterior middle temporal gyrus (pMTG), bilateral inferior temporal gyri, left middle temporal gyrus, and left premotor region (Damasio et al., 1996, Martin et al., 1996). The relative contribution of the various areas may vary depending on the type of task used (Tyler and Moss, 2001). [For recent reviews of the neuroimaging and neuropsychological evidence on category-specificity see Martin, 2007, Mahon and Caramazza, 2009, respectively].

The view that object knowledge is distributed over a number of cortical areas gives rise to the fundamental question of how these areas are bound together into effective domain-specific cortical (-subcortical) networks. A plausible answer is that this function is carried out by long-distance subcortical connections (e.g., Mahon et al., 2009, Riesenhuber, 2007, Thomas et al., 2009). However, there is a total absence of human neurophysiological data on this subject. In the present study, we used intraoperative direct cortical and subcortical stimulation to investigate the animate and inanimate domain-specific cortical networks and their associated subcortical connecting fibers in patients undergoing the removal of gliomas. This technique allows for localization of extremely small (< 1 cm²) brain areas (Ojemann et al., 1989). During brain surgery for tumor resection it is common clinical practice to awaken patients in order to assess the functional role of restricted brain regions, so that the surgeon can maximize the extent of the exeresis without provoking cognitive impairment, particularly of language. Patients may be asked to perform a picture naming task while the surgeon temporarily inactivates restricted regions around the tumor by means of electrical stimulation. If the patient is unable to produce a response or produces an incorrect one, such as a semantic or phonemic paraphasia, the surgeon refrains from removing the stimulated region. By cumulating performance over the areas stimulated and across subjects, a map can be constructed of the functional role of different brain regions. This neurophysiological procedure allows us to assess the contribution of both cortical and subcortical structures in naming animate and inanimate objects.

Yet, because the brains of these surgical patients are likely to have reorganized as a consequence of their slowly growing tumors, the functional maps constructed in this way may differ from those obtained in healthy individuals using other methods (e.g., fMRI). By comparing the normal and reorganized cortical networks it may be possible to infer the constraints that operate on the process of reorganization itself. Although the brain's plasticity in response to sensory deprivation and other perturbations is well-established (Kujala et al., 2000, Neville and Bavelier, 2008, Thiel et al., 2001, Wong et al., 2009), and while the functional properties of the reorganized areas are under vigorous investigation (Kech et al., 2008), the factors that determine cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions.

Using intraoperative DES (Ojemann et al., 1989), we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization following perturbation of normal function.