For well over a century, scientists have recognized that all the wonders of the mind are the province of the brain. Perception, attention, emotion, planning and action, learning and memory, thinking, language and all other aspects of cognition all take place in the brain.

We know that the brain is made up of vast numbers of neurons, and that each neuron may be connected with many thousands of other neurons. Basic neuroscience has taught us a great deal about the workings of the individual neurons, about the mechanisms that allow one neuron to communicate with other neurons, about the processes by which neurons develop and adapt, and about the processes that regulate the functioning of individual neurons. But how does all this neural activity give rise to human thought? This is the fundamental scientific question that researchers at the CNBC endeavor to answer, using a multidisciplinary approach.

One set of clues comes from studies of the anatomy of the human brain. Studies of the structure of the human brain (performed at autopsy) are augmented with studies of anatomy in non-human primates and other animals, using state-of-the-art neuroanatomical tracing techniques. Magnetic resonance and other imaging modalities are also used to delineate structures, trace pathways and examine function in intact, living humans and animals.

An increasingly important set of clues comes from functional imaging of the human brain. Now, advances in imaging technology are enabling investigators to examine which areas of the brain are active when people engage in thinking tasks. By recording activity of the brain in action, CNBC researchers can examine the systems of brain regions that participate in different cognitive functions, ranging from basic sensory and motor functions to complex functions like reasoning and language understanding.

To discover how brain cells actually support cognitive processes, CNBC investigators use physiological studies of neuronal activity in animals. Such studies have uncovered neurons that encode basic sensory properties of stimuli as well as others that reflect deeper cognitive analyses, such as the relative location of one object with respect to other objects of interest, the emotional content of a facial expression, the location of the animal in extrapersonal space or the anticipated reward value of environmental cues. Ongoing studies will shed light on the way the brain represents and transforms information in the performance of a wide range of cognitive activities.

Another source of information comes from the study of the functional capabilities of the normal brain as revealed by performance in cognitive tasks, and of the patterns of deficits in task performance that arise from brain damage in human subjects. Using the results of such studies, cognitive psychologists and neuropsychologists at the CNBC are exploring theories of how cognitive functions are organized in the normal brain, as well as the effects of specific brain injuries on a wide range of different aspects of cognitive function.

Researchers in the CNBC are also at the forefront of the use of computational models to explore the neural basis of cognition. Some researchers in the center model cellular and synaptic processes and the interactions of neurons in small circuits. Others examine how cognitive functions emerge from underlying neural processes, and others focus on modeling cognitive functions themselves, using both connectionist and symbolic approaches.

Taken separately, each of these tools is of limited use in revealing the workings of the mind and brain. However, by integrating these methodologies, the center can achieve greater insight into all the aspects of the neural basis of cognition, as well as the impact of brain injury and disease on the cognitive function.

The Normal Brain: Structure, Function and Development

Each part of the normal human brain plays its own special role in our cognitive functions. The cerebral cortex, the part of the brain that most strongly differentiates humans from other primates and primates from other animals, contains many subregions. Complex cognitive functions arise from the coordinated action of many parts of the brain, in much the same way that a piece of music may reflect the coordinated action of many musicians within an ensemble. At a coarse grain of analysis, the assignment of functional roles to particular parts of the brain appears to be fairly consistent across individuals, and indeed there are commonalities across species, providing clear similarities of both structure and function. Yet structure and function are sensitive to effects of experience. By watching the brain at work, in experimental subjects as well as simulation models, researchers have discovered that the specified functional roles of neurons and their interconnections with other neurons depend critically on experience. Experience triggers interactions among neurons, giving rise to normal cognitive activity and to structural features of brain organization. CNBC scientists are advancing understanding of how experience influences the emergence of function and structure through computational and experimental investigations. There is also an interest in understanding the genetic mechanisms that regulate brain development, and how they interact with effects of experience to produce the structural and functional characteristics of the brain. These lines of research may determine why experience is so important to normal brain development, and how specified biological mechanisms ordinarily shape and support the emergence of brain structure and function, leading to insights into the use of experience in treatment and remediation of various disorders of cognition.

Understanding Disorders of Cognition The intricate relationship between the brain and its higher functions is never more apparent than when the brain becomes dysfunctional. To understand the causes and effects of brain damage, CNBC researchers compare healthy and damaged brains. They hope to determine what exactly has gone wrong, and how the underlying abnormality produces the effects that it has on cognitive functions.

Scientists at the center are especially well equipped to explore the effects of brain damage resulting from traumatic injuries or disease processes on both physical structure and cognitive function. The University of Pittsburgh Medical Center serves a large population of patients with functional and/or neurological disorders, including epilepsy, stroke, Parkinson's disease, schizophrenia, affective illness and Alzheimer's disease, and employs state-of-the-art functional imaging techniques for identifying sites of neurological damage. Carnegie Mellon's expertise in cognitive psychology imparts another layer of scientific analysis of the psychological disturbances these patients experience. CNBC researchers often combine this analysis of human behavior with detailed computational modeling. Using these experimental models, they can study the neural pathways of normal brains and uncover the effects of simulated structural damage on brain function and human performance.

In patients suffering from cognitive disorders ranging from dyslexia to schizophrenia, neurodiagnostic testing with high-powered imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can pinpoint specific areas of dysfunction in the brain. The center's neuropsychologists then examine the corresponding disturbances in cognition. By finding correlations between sites in the brain that are dysfunctional biologically and particular deficits of behavior, scientists are learning more about how these functions are organized in the brain in the first place. Using computer simulations of normal performance that are then subjected to simulated brain damage, they can assess whether the hypotheses incorporated in the models provide a full understanding of the patients' behavioral deficits. Computer simulations can then be used to determine how best to retrain the damaged network to maximize recovery of function.

Work on molecular genetics at both universities is being coordinated with the study of the neural basis of cognition, in hopes that one day we will understand exactly how genetic factors contribute to disorders ranging from dyslexia and developmental delays in language to Alzheimer's disease and schizophrenic thought disorders. Ultimately, this research may lead to medications that overcome genetic deficiencies.

To learn more about the research of individual faculty and about multi-investigator research projects within the CNBC, visit the research section of our website.