The sodium amytal test, or Wada test, named after Juhn Wada, has remained a pillar of presurgical planning and is used to identify the laterality of the dominant language and memory areas in the brain. What is perhaps less well known is that the original intent of the test was to abort seizure activity from an affected hemisphere and also to protect that hemisphere from the effects of electroconvulsive treatment. Some 80 years after Paul Broca described the frontal operculum as an essential area of expressive language and well before the age of MRI, Wada used the test to determine language dominance. The test was later adopted to study hemispheric memory dominance but was met with less consistent success because of the vascular anatomy of the mesial temporal structures. With the advent of functional MRI, the use of the Wada test has narrowed to application in select patients. The concept of selectively inhibiting part of the brain to determine its function, however, remains crucial to understanding brain function. In this review, the authors discuss the rise and fall of the Wada test, an important historical example of the innovation of clinicians in neuroscience.
Bornali Kundu, John D. Rolston and Ramesh Grandhi
Bornali Kundu, Andrea A. Brock, Dario J. Englot, Christopher R. Butson and John D. Rolston
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Jed Voss, Timothy B. Meier, Robert Freidel, Bornali Kundu, Veena A. Nair, Ryan Holdsworth, John S. Kuo and Vivek Prabhakaran
Functional MRI (fMRI) is commonly used by neurosurgeons preoperatively to identify brain regions associated with essential behaviors, such as language and motor abilities. In this study the authors investigated the relationship between patient morbidity and mortality and the distance from the tumor border area to functional activations in secondary motor and language cortices.
Patients with primary or metastatic brain tumors who underwent preoperative fMRI motor and language mapping were selected from a large database of patients with tumors. The lesion-to-activation distance (LAD) was measured in each patient relative to the supplementary motor area (SMA) for motor tasks and the presupplementary motor area (pSMA) for language tasks. The association between LAD and the incidence of deficits was investigated using the Fisher exact tests of significance. The impact of other variables, including age, handedness, sex, and tumor grade, was also investigated. In a subset of patients, logistic regression was performed to identify the likelihood of deficits based on the LAD to primary and secondary regions. Finally, Mantel-Cox log-rank tests were performed to determine whether survival time was significantly related to the LAD to secondary motor and language areas.
A significant association was observed between the LAD to the SMA and the incidence of motor deficits, with the percentage of patients with deficits dropping for those in the LAD > 2 cm group. The relationship between the LAD to the pSMA and the incidence of language deficits was not significant. Logistic regression demonstrated that the LAD to primary sensorimotor cortex does affect the incidence of motor deficits, but that the LAD to SMA does not. Finally, the authors observed no relationship between the LAD to secondary regions and patient mortality rates.
These results demonstrate that the LAD to SMA structures does affect morbidity, although not to the extent of LAD to primary structures. In addition, motor deficits are significantly associated with LAD to secondary structures, but language deficits are not. This should be considered by neurosurgeons for patient consultation and preoperative planning.
Michael Karsy, Jian Guan, Hussam Abou-Al-Shaar, Ilyas M. Eli, Bornali Kundu, Erica F. Bisson, William T. Couldwell and Rimal H. Dossani
Bornali Kundu, Amy Penwarden, Joel M. Wood, Thomas A. Gallagher, Matthew J. Andreoli, Jed Voss, Timothy Meier, Veena A. Nair, John S. Kuo, Aaron S. Field, Chad Moritz, M. Elizabeth Meyerand and Vivek Prabhakaran
Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume.
Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas.
There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD.
Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.