Accordingly, we initiated two large-scale clinical studies to examine the degree of concordance between the MSI and invasive procedures for determining hemispheric dominance and for identifying language-specific cortex within the dominant hemisphere, namely the Wada procedure and electrocortical stimulation mapping. In the first of these studies we obtained excellent concordance between MSI-based estimates of hemispheric dominance and Wada results, in a series of 50 consecutive patients (see Breier et al., 1999 for a report on the first 26 patients). Using MSI and Wada indices, three distinct groupings of language laterality scores were identified. As expected, the majority of patients belonged to a group that exhibited a strong left hemisphere-favoring asymmetry. These patients displayed 20% or more activity sources in the left over the right perisylvian region. A second group exhibited a strongly right hemisphere favoring-asymmetry, while a third exhibited relatively bilaterally symmetrical data. The two methods agreed completely regarding the members of each of these groups.

Non-invasive testing of lateralization for language function, using a methodology such as MSI, has a number of advantages over the Wada procedure. These include elimination of health risk, potential for test-retest reliability studies, and ability to use a number of different tasks of extended duration. In addition, the problems inherent in the Wada procedure, including potential over- or under-anesthetization and anomalous distribution of anesthetic due to crossflow or atypical vascularization, are eliminated. Furthermore, while the Wada procedure provides only data regarding lateralization of language function, MSI is capable of providing data regarding precise intrahemispheric localization of areas involved in language function as well, and these data has been shown to be valid by comparison with intraoperative electrocortical stimulation, to be described below. Up to the present time, a total of 50 consecutive patients, including 15 children, have been mapped through MSI and the Wada procedure. The concordance between the results of both procedures remains essentially perfect. In addition to continuing the Wada-MSI comparison with more patients, we are in the process of establishing maps specific to verbal memory. The ultimate goal is to replace the Wada procedure with MSI in the presurgical assessment of hemispheric dominance in all our epilepsy patients.

Fig 1.

MSI - MRI co-registered scan from a representative patient who was judged to be left-hemisphere dominant for language, based on the Wada procedure. Note the clear preponderance in the number of MSI-derived cerebral activity sources in perisylvian areas of the left over the right hemisphere.

In a second ongoing study, that now numbers 20 consecutive patients, we have demonstrated and we continue to demonstrate the concordance between MSI and direct cortical stimulation for mapping receptive language cortex (Papanicolaou et al., 1999; Simos et al., 1999a,b). These patients underwent surgery for resection of tumors (n = 4), cavernous angioma (n = 1) or epileptogenic tissue (n = 15). In all cases planned excision potentially involved language-specific cortex. Surgery was performed in the left temporal lobe in 18 cases and in the right perisylvian region in one left- handed patient. Areas specialized for receptive language function were identified preoperatively by MSI mapping as the region(s) that consistently displayed activation during both versions of our verbal task (i.e., one involving spoken and the other printed words) or two repetitions of the auditory version of the task. Electrical stimulation mapping was performed intraoperatively in 15 cases and extraoperatively in the remaining patients, using multicontact subdural grids placed on the lateral surface of the temporal lobe. In the former cases the site of effective electrical stimulation was noted by the surgeon and documented photographically. In several cases a frameless strereotaxy system was used for localization. Then, the images containing the MSI map and the marked site(s) of successful electrical stimulation were compared. For those patients who underwent extraoperative stimulation mapping, comparison of MSI and stimulation mapping results was performed directly by overlaying MSI-derived activity sources on high resolution MRI scans acquired after grid placement. In this way, the exact location of source clusters in relation to specific electrode contacts could be determined.

A perfect agreement has been found, thus far, between MSI-based non-invasive mapping of receptive language-specific brain areas and intra- and extraoperative language mapping using electrocortical stimulation. The results attest to the validity of MSI-based localization of language-specific cortex by demonstrating that regions that contain clusters of activity sources, accounting for late EF components, are indeed those that play a crucial role in receptive language functions. These findings highlight the utility of the MSI mapping protocol, especially in patients with atypical language representation. For example, the MSI technique was successful in determining bilateral language representation in a left-handed patient and also in identifying areas involved in receptive language function located outside of the traditional anatomical borders of Wernicke’s area. In all of these atypical cases, MSI-derived information was found to be extremely useful in surgical planning by: (a) helping to determine the optimal extent of the craniotomy, (b) helping to assess surgical risk and, (c) helping to tailor the location and extent of the cortical resection. Importantly, the localization accuracy of the procedure was apparently unaffected by the type and extent of brain pathology, or the presence of preoperative language and cognitive deficits. These cases will be discussed in some detail in the next section of this review dealing with brain plasticity issues.

The two clinical studies reviewed above do not only provide external validation of the accuracy of the MSI-derived language maps, rendering MSI the first and currently only method for routinely obtaining reliable and valid functional images, but they constitute the first systematic use of functional images of mechanisms of higher functions in neurosurgical practice.

Fig 2.

Preoperative MRI scan from a patient with a left posterior inferior temporal cyst. Clusters of MSI-derived activity sources obtained in the context of two repetitions of a word recognition task are shown as red or yellow circles. Crossed lines indicate sites of effective intraoperative electrical stimulation documented