In the past few years our laboratory has explored two main avenues of research:
Studies of cortical evolution and development:
A distinguishing feature of the mammalian neocortex is the remarkable ability to change over a lifetime, and this is particularly dramatic during development. Such plasticity allows an individual to match the functional organization and connectivity of the cortex with the physical parameters of a specific environment, and thus optimize their behavior for that environment. This ability was likely present in the common ancestor of all mammals and evolved to varying degrees in different lineages. Recently, I have expanded our comparative studies to include a number of different rodents that vary in diel pattern, terrain niche and social organization. In this work on prairie voles, squirrels, Nile grass rats, laboratory rats, and wild caught rats, we demonstrated the remarkable match between morphological specialization, lifestyle and cortical organization at both the systems and cellular level. This work underscores the profound effects of the environment on the ultimate cortical phenotype by uncovering differences in cortical field size and cellular density in different rodents, and even between laboratory rats and the same species of wild caught rats.
Comparative work of this type helped to formulate our hypotheses that sensory experience, lifestyle, and body morphology play an enormous role in directing cortical organization. To test this hypothesis we performed a series of studies in which we modified the amount of sensory experience via peripheral manipulations very early in development and then examined the resulting functional organization of the cortex. Using the short-tailed opossum as our model we examined the effects of very early loss of vision (bilateral enucleation) on the functional organization and connectivity of “visual cortex”. We demonstrated that with early loss of vision all of what would normally be visual cortex is taken over by the spared sensory systems, and that the anatomical substrate for this functional re-organization was alterations in cortical and subcortical connections. As with our comparative work, these developmental experiments indicate that sensory driven activity present at very early stages of neural development not only sculpts existing organization laid down by genes, but can fundamentally alter the organization of the cortex, its connectivity, and its function. Importantly, our work represents the first demonstration of an anatomical substrate for the multisensory plasticity observed in humans with congenital sensory loss.
In our new experiments we manipulate the developing nervous system at either the receptor (bilateral enucleations) or central levels (cortical lesions), and rear animals in a highly specified tactile or visual environment, respectively. Our goal is to determine the extent to which we can direct and amplify recovery in early manipulated and normal animals. These studies are important for determining if in fact the cortex can be “primed” very early in development to optimize functional organization for subsequent sensory intervention. Thus, they impact largely on effective intervention strategies for congenitally or early blind individuals, or neonates suffering from cortical visual impairments due to loss of cortical tissue. From an evolutionary perspective, these studies allow us to determine the magnitude and types of alterations that can be made to the cortical phenotype by changing the specific conditions in which it develops.
Studies of parietal cortex:
More than any other species, humans have evolved a remarkable ability to physically manipulate their environment with their hands to effectively transform our culture and indeed the planet. This ability co-evolved with an enormous expansion of the neocortex and an increase in the amount of cortex associated with hand use and hand-eye coordination. In fact most of parietal cortex, particularly posterior parietal cortex, is composed of a network of cortical areas devoted to hand use, coordination of the hands, and generating coordinate systems for accurate reaching, grasping and manipulation. In the past we have examined the functional organization and connectivity of parietal areas involved in complex hand use in humans and non-human primates, described the topographic organization of both anterior and posterior parietal fields in New and Old World monkeys, and the cortical and subcortical connections of a number of these fields. We extended these studies to humans using non-invasive imaging techniques and demonstrated that there are general patterns of cortical organization and connectivity of somatosensory cortex that all primates share, but clear differences have evolved based on phylogeny and use of specialized body morphology. Specifically, New World monkeys, which lack a precision grip, have a more primitive organization of parietal cortex, with fewer cortical fields and relatively small posterior parietal cortex compared to Old World monkeys and humans. However, with the independent evolution of an opposable thumb, one New World monkey, the cebus monkey, evolved a more complex parietal cortex organization that looks more like their distant cousins (macaque monkeys), than their closer sister groups (other New World monkeys). We proposed this independent expansion of posterior parietal cortex in cebus monkeys and macaques and humans co-evolved with skeletal morphology (opposable thumb), an expansion of visual cortex, and the emergence of dense direct projections from digit representations in motor cortex to the ventral horn of the spinal cord. This in turn lead to the emergence of complex manual behavior, such as tool use which, in part, rapidly drove human evolution.
To better appreciate the role of different posterior parietal areas in specific aspects of reaching and grasping, we recently performed a series of behavioral and lesion studies. We demonstrated one area, area 5, is involved in several aspects of an intended reach and grasp, and that the loss of this area resulted in immediate and dramatic re-organization of adjacent cortical fields, and a resulting rapid recovery of manual abilities. In our newest experiments, our laboratory (in conjunction with our colleagues in the department of Biomedical Engineering) has developed a novel microfluidic cooling device (termed the cooling chip) to reversibly deactivate one or multiple areas in a network of posterior parietal areas involved in complex hand use, while the monkey performs complex manual and bimanual tasks. In these experiments we can rapidly produce “virtual lesions” to different nodes in this network to directly determine how they work in combination to produce specific aspects of a reach, grasp and manipulation. In conjunction with our colleagues in Brazil, this new technology is being used to explore similar circuits in the cebus monkey, a primate that not only evolved an opposable thumb and a precision grip, but also an extraordinary ability to use tools in the wild. This ability is more closely associated with humans and some great apes than with macaque monkeys. Thus, we can explore areas of posterior parietal cortex involved in tool use, appreciate how higher order representations, such as tool action, have emerged in primates, and if these networks and the representations they generate are constrained.