Pound Pup Legacy

from Functional MRI

Introduction

The recent discovery that magnetic resonance imaging can be used to map changes in brain hemodynamics that correspond to mental operations extends traditional anatomical imaging to include maps of human brain function. The ability to observe both the structures and also which structures participate in specific functions is due to a new technique called functional magnetic resonance imaging, fMRI, and provides high resolution, noninvasive reports of neural activity detected by a blood oxygen level dependent signal (Ogawa, et al, 1990 a and b, 1992, 1993; Belliveau, et al, 1990, 1991). This new ability to directly observe brain function opens an array of new opportunities to advance our understanding of brain organization, as well as a potential new standard for assessing neurological status and neurosurgical risk.

The main advantages to fMRI as a technique to image brain activity related to a specific task or sensory process include 1) the signal does not require injections of radioactive isotopes, 2) the total scan time required can be very short, i.e., on the order of 1.5 to 2.0 min per run (depending on the paradigm), and 3) the in-plane resolution of the functional image is generally about 1.5 x 1.5 mm although resolutions less than 1 mm are possible. To put these advantages in perspective, functional images obtained by the earlier method of positron emission tomography, PET, require injections of radioactive isotopes, multiple acquisitions, and, therefore, extended imaging times. Further, the expected resolution of PET images is much larger than the usual fMRI pixel size. Additionally, PET usually requires that multiple individual brain images are combined in order to obtain a reliable signal. Consequently, information on a single patient is compromised and limited to a finite number of imaging sessions. Although these limitations may serve many neuroscience applications, they are not optimally suitable to assist in a neurosurgical or treatment plan for a specific individual.

Future Role in Neurosurgical Planning

Since neurosurgery relies on a precise delineation of the structural and functional aspects of brain, the role for fMRI in neurosurgical planning is potentially very significant. The need for individualized maps of brain function is enhanced when the presence of a tumor alters the expected location of a function, or when the location of the tumor is in an area with an uncertain function such as association cortices or language-related processes. An emerging group of investigators have reported fMRI results that are consistent with electrophysiology, PET, cortical stimulation, and magneto-encephalography and serve to document that fMRI does provide a source of precise functional and structural information for Neurosurgery (Burgess, 1995; George, et al, 1995; Simpson, et al, 1995, Puce, (1995a,b); Fried, et al, 1995; Peyron, 1995; Clifford, et al, 1995; Haglund, 1995; Detre, et al, 1995; and Ives, et al, 1993). Further, the potential role of fMRI in directing decisions about surgical and diagnostic procedures has also been demonstrated (Atlas, S.W., et al, 1996).

Future Role in Pain Management

The experience of chronic and persistent pain is a debilitating condition for which the role of cortical processing is not well understood. We have focused on the identification of cortical areas that are modified by the reduction of pain following pain therapy. This novel approach to investigate the cortical representation associated with relief of pain has originated from our pilot studies where patients with chronic sympathetically maintained pain affecting one extremity (post herpetic neuralgia) were studied by comparing brain responses to light touch applied to the "now-affected" limb and to the "painful" limb before and after treatment (Hewitt, et al, 1995). These studies indicate that the cortical representation of sympathetically maintained pain involves specific and identifiable cortical activity, as well as does the relief of that pain achieved by a peripheral nerve block procedure. Continuing investigations will extend these findings to other pain treatments to determine the extent to which this finding is generalizable to other pain relief mechanisms. These preliminary studies suggest a wide range of other approaches using fMRI to investigate cortical representations of specific pain types, and therefore, new specific therapy options.

Future Role in Understanding the Physiological Basis for Cognitive and Perceptual Events

Due to the ability to image the entire 3-dimensional volume of brain, fMRI is capable of isolating many simultaneous and coordinated brain events. This "multi-level" view of brain activity can include "executive" functions and high level cognitive tasks simultaneously with the primary and secondary input such as vision and audition as well as cerebellar contributions. We are currently applying fMRI methods to identify brain structures uniquely involved with visual perceptions, language generation, comprehension of sequential information as in a movie, the execution of visually guided responses, and complex problem solving. These aspects of brain function have not previously been scrutinized with such precision, and represent some of the remaining frontiers in Neuroscience.

Future Role in Understanding the Physiological Basis for Neurological Disorders

The following example illustrates the potential of fMRI to yield new insights into physiological bases for disfunction. A 16 year old right handed female with a congenital malformation in the right posterior frontal lobe and a seizure disorder participated in a functional imaging study to identify functional sensorimotor areas. One of the patient's typical sensory seizures occured during one of the runs. This enabled us to localize fMRI signals associated with the onset of a spontaneous seizure, its progression, and the relationship to normally activated motor cortex. There was minimal movement artifact which was further reduced by alignment of the images prior to a voxel-by-voxel statistical analysis. The fMRI signals associated with the seizure were first observed in an area adjacent to the normal motor activity. MR signal amplitudes exceeded the normal functional activity by as much as a factor of 5. A sequential time analysis (6 sec intervals) revealed both local spreading of the onset focus and the emergence of subsequent foci first in the ipsilateral prefrontal areas, and the mesial surface areas. These were followed by activity in the homologous regions of the opposite hemisphere suggesting that the generalization followed a specific pattern of functional connectivity. Thus, eloquent motor activity and seizure activity were co-localized using fMRI, and the onset, progression pattern, time course, and relative MR amplitudes of the seizure event were observed (Hirsch, et al,1996). This case illustrates that fMRI may contribute to improved precision of seizure localization and understanding of seizure progression, and suggests a future direction for investigation.

Other neurological conditions currently under investigation using fMRI at Columbia include neglect syndromes, phantom pain, cerebellar dysfunction, and neural reorganization. Preliminary studies confirm that the pathways and processes involved in these neurological disorders and conditions can be observed for investigation by fMRI.

Future Role in Understanding the Physiological Basis for Cognitive and Perceptual Events

Due to the ability to image the entire 3-dimensional volume of brain, fMRI is capable of isolating many simultaneous and coordinated brain events. This "multi-level" view of brain activity can include "executive" functions and high level cognitive tasks simultaneously with the primary and secondary input such as vision and audition as well as cerebellar contributions. We are currently applying fMRI methods to identify brain structures uniquely involved with visual perceptions, language generation, comprehension of sequential information as in a movie, the execution of visually guided responses, and complex problem solving. These aspects of brain function have not previously been scrutinized with such precision, and represent some of the remaining frontiers in Neuroscience.