The localization of cortical sites essential for language was assessed by stimulation mapping in the left, dominant hemispheres of 117 patients. Sites were related to language when stimulation at a current below the threshold for afterdischarge evoked repeated statistically significant errors in object naming. The language center was highly localized in many patients to form several mosaics of 1 to 2 sq cm, usually one in the frontal and one or more in the temporoparietal lobe. The area of individual mosaics, and the total area related to language was usually much smaller than the traditional Broca-Wernicke areas. There was substantial individual variability in the exact location of language function, some of which correlated with the patient's sex and verbal intelligence. These features were present for patients as young as 4 years and as old as 80 years, and for those with lesions acquired in early life or adulthood. These findings indicate a need for revision of the classical model of language localization. The combination of discrete localization in individual patients but substantial individual variability between patients also has major clinical implications for cortical resections of the dominant hemisphere, for it means that language cannot be reliably localized on anatomic criteria alone. A maximal resection with minimal risk of postoperative aphasia requires individual localization of language with a technique like stimulation mapping.

A model for the organization of language in the adult humans brain is derived from electrical stimulation mapping of several language-related functions: naming, reading, short-term verbal memory, mimicry of orofacial movements, and phoneme identification during neurosurgical operations under local anesthesia. A common peri-Sylvian cortex for motor and language functions is identified in the language dominant hemisphere, including sites common to sequencing of movements and identification of phonemes that may represent an anatomic substrate for the “motor theory of speech perception.” This is surrounded by sites related to short-term verbal memory, with sites specialized for such language functions as naming or syntax at the interface between these motor and memory areas. Language functions are discretely and differentially localized in association cortex, including some differential localization of the same function, naming, in multiple languages. There is substantial individual variability in the exact location of sites related to a particular function, a variability which can be partly related to the patient's sex and overall language ability and which may depend on prior brain injury and, perhaps subtly, on prior experience. A common “specific alerting response” mechanism for motor and language functions is identified in the lateral thalamus of the language–dominant hemisphere, a mechanism that may select the cortical areas appropriate for a particular language function.

Although non-invasive methods such as functional magnetic resonance imaging, electroencephalograms and magnetoencephalograms provide most of the current data about the human brain, their resolution is insufficient to show physiological processes at the cellular level. Clinical approaches sometimes allow invasive recordings to be taken from the human brain, mainly in patients with epilepsy or with movement disorders, and such recordings can sample neural activity at spatial scales ranging from single cells to distributed cell assemblies. In addition to their clinical relevance, these recordings can provide unique insights into brain functions such as movement control, perception, memory, language and even consciousness.

In a series of 40 patients undergoing an awake craniotomy for the removal of a glioma of the dominant hemisphere temporal lobe, cortical stimulation mapping was used to localize essential language sites. These sites were localized to distinct temporal lobe sectors and compared with 83 patients without tumors who had undergone language mapping for the treatment of intractable epilepsy. In patients with and without temporal lobe gliomas, the superior temporal gyrus contained significantly more language sites than the middle temporal gyrus. Both patient populations also had language sites anterior to the central sulcus in the superior temporal gyrus (12-16%). The patients without tumors had significantly more language sites in the superior temporal gyrus, compared with the superior temporal gyrus of patients with temporal lobe tumors. Multiple variables were studied for their effect on preoperative and postoperative language deficits and included age, sex, number of language sites, histology, size of the tumor, and the distance of tumor resection margins from the nearest language site. The distance of the resection margin from the nearest language site was the most important variable in determining the improvement in preoperative language deficits, the duration of postoperative language deficits, and whether the postoperative language deficits were permanent. If the distance of the resection margin from the nearest language site was > 1 cm, significantly fewer permanent language deficits occurred. Cortical stimulation mapping for the identification of essential language sites in patients with gliomas of the dominant hemisphere temporal lobe will maximize the extent of tumor resection and minimize permanent language deficits.

In patients with gliomas that are located within or adjacent to the rolandic cortex and, thus, the descending motor tracts, stimulation mapping of subcortical pathways enables the surgeon to identify these descending motor pathways during tumor removal and to achieve an acceptable rate of permanent morbidity in these high-risk functional areas.

Recent data obtained by various methods of clinical investigations suggest an organization of language in the human brain involving compartmentalization into separate systems subserving different language functions. Each system includes multiple essential areas localized in the frontal and temporoparietal cortex of the dominant hemisphere, as well as widely dispersed neurons. All components of a system are activated in parallel, possibly by ascending thalamocortical circuits. The features peculiar to cerebral language organization include not only the lateralization of essential areas to one hemisphere, but also a substantial variance in the individual patterns of localization within that hemisphere, a variance that in part relates to individual differences in verbal skills.

Optical imaging of animal somatosensory, olfactory and visual cortices has revealed maps of functional activity. In non-human primates, high-resolution maps of the visual cortex have been obtained using only an intrinsic reflection signal. Although the time course of the signal is slower than membrane potential changes, the maximum optical changes correspond to the maximal neuronal activity. The intrinsic optical signal may represent the flow of ionic currents, oxygen delivery, changes in blood volume, potassium accumulation or glial swelling. Here we use similar techniques to obtain maps from human cortex during stimulation-evoked epileptiform afterdischarges and cognitively evoked functional activity. Optical changes increased in magnitude as the intensity and duration of the afterdischarges increased. In areas surrounding the afterdischarge activity, optical changes were in the opposite direction and possibly represent an inhibitory surround. Large optical changes were found in the sensory cortex during tongue movement and in Broca's and Wernicke's language areas during naming exercises. The adaptation of high-resolution optical imaging for use on human cortex provides a new technique for investigation of the organization of the sensory and motor cortices, language, and other cognitive processes.

Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.