Recent technological developments have allowed researchers to examine the brain while the person is actually completing a task. This is done through functional magnetic resonance imaging (fMRI), which affords us an opportunity to learn a great deal about how the brain works. Researchers in the Department of Physical Medicine and Rehabilitation at UMDNJ-New Jersey Medical School (NJMS) have applied fMRI to the study of patients with multiple sclerosis (MS) and traumatic brain injury (TBI) to increase our understanding of the impact of the illness or injury on brain functions. Most research to date has focused on working memory and has shown altered patterns of cerebral activation during working memory tasks in both patients with MS and TBI. While this research continues, investigations have expanded to include additional imaging tools and other areas of cognitive functioning.
Advances in brain imaging are now allowing investigators to examine brain activity during actual performance of various cognitive tasks. Initiated by John DeLuca, PhD, researchers in the Department of Physical Medicine and Rehabilitation at NJMS have been conducting groundbreaking research in using fMRI to examine cerebral activity in TBI and MS over the past six years.
Much of the early functional neuro-imaging work we conducted focused on the identification of patterns of cerebral activation in different clinical populations during the performance of working memory tasks. It is well known that working memory is an area of cognition that is quite vulnerable to disruption in many neurological illnesses. However, the functional cerebral representation of impaired working memory performance has, until recently, remained unknown. In an investigation of working memory performance in TBI, we were able to show that similar cortical regions were activated in both TBI and healthy control groups. Compared to the healthy controls, however, the TBI group displayed activation that was more dispersed throughout the brain and more lateralized to the right hemisphere (Figure 1). These findings have implications for the role of effort in brain activity in TBI, and may also provide insights into how the human brain organizes and processes information following a traumatic injury.
Figure 1: Patterns of cerebral activation during a working memory task in TBI
Figure 2: Patterns of cerebral activation during a working memory task in MS
From this initial work in TBI, we expanded our neuro-imaging research efforts to include the investigation of working memory in patients with MS. Results of this research have been quite fruitful, demonstrating that individuals with MS show altered patterns of cerebral activation when performing a working memory task as well. Specifically, individuals with MS show increased right prefrontal cortex activation and increased right temporal lobe activation compared to healthy controls. Interestingly, when dividing MS participants into those with and without cognitive impairment, activation patterns within the healthy control group and the MS group without cognitive impairment were noted in similar brain regions, consistent with published observations in healthy samples. That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS group with cognitive impairment showed greater right frontal and right parietal lobe activation, when compared with the healthy group (Figure 2). Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairment, and not solely a function of MS. We have also extended our research studies of this population to include investigations of the role of the cerebellum in the working memory impairment seen in MS. Within the cerebellum, individuals with MS demonstrated no detectable activations in four cerebellar substructures that were significantly active in controls (i.e., right vermis, right dentate nucleus, right tonsil and cerebellar peduncle). This significantly decreased cerebellar activation in the MS group suggests that the cerebellum may play a role in the working memory impairment observed in MS.
Since the launching of these initial studies of working memory in TBI and MS, this line of research has expanded to include new investigators in the department (Jean Lengenfelder, PhD, Glenn Wylie, D.Phil) who have widened the areas of cognition under investigation. In collaboration with myself and Dr. DeLuca, these researchers have focused their efforts on the study of executive control functions in general as well as the relationship of executive control functions to learning in both TBI and MS.
In addition to the fMRI work described above, we have also applied other state-of-the-art imaging technologies to the investigation of cognitive impairment in neurological illness and injury. These technologies have included magnetic resonance spectroscopy (MRS), as well as Near Infrared Spectroscopy (NIRS). Led by Dr. DeLuca, researchers in the Department of Physical Medicine and Rehabilitation have already begun to apply NIRS to the investigation of cognition in individuals with neurological impairment. Specifically, functional near-infrared spectroscopy is currently being used to examine patterns of cerebral blood oxygenation in order to differentiate between individuals with TBI and MS compared to healthy controls during attention and working memory tasks. The aim of this research is the establishment of NIRS as a well-validated imaging procedure, similar to MRI or fMRI. The unique portability, noninvasiveness, enhanced temporal resolution, insensitivity to movement artifacts and low cost of NIRS offer significant advantages for the application of the technology to the clinical examination of individuals with neurological illnesses and injury beyond that which is currently available through MRI and fMRI. Thus, NIRS holds significant promise for use in persons with TBI and MS and has several potential future applications in medical rehabilitation.
With the development of new technologies, new methods for understanding the brain are becoming available. In that light, future neuro-imaging research we will be embarking on will apply diffusion tensor imaging (DTI) to assist in mapping specific pathways in the brain.
Funding sources making this work possible have included the Henry H. Kessler Foundation, the Hyde and Watson Foundation, the F.M. Kirby Foundation, the National Institutes of Health, the National Multiple Sclerosis Society, and the Health Resources and Services Administration of the Department of Health and Human Services.
Nancy D. Chiaravalloti, PhD, is associate director of the Neuropsychology and the Neuroscience Laboratory at KMRREC and assistant professor in the Department of Physical Medicine and Rehabilitation at UMDNJ-New Jersey Medical School. Dr. Chiaravalloti is a neuropsychologist who has focused her research on the identification of the cognitive effects of neurological illness and injury as well as the cognitive rehabilitation of new learning and memory abilities. A graduate of Muhlenberg College and MCP Hahnemann University, she completed her internship at Brown University before coming to NJMS for post-doctoral studies.