George A. Ojemann

CORTICAL LANGUAGE LOCALIZATION IN LEFT, DOMINANT HEMISPHERE. AN ELECTRICAL STIMULATION MAPPING INVESTIGATION IN 117 PATIENTS

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 patients 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.

Brain organization for language from the perspective of electrical 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 patients 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.

Cortical localization of temporal lobe language sites in patients with gliomas.

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.

Brain Mapping Techniques to Maximize Resection, Safety, and Seizure Control in Children with Brain Tumors

Intraoperative brain mapping techniques were used to localize language cortex, sensorimotor pathways, and seizure foci in children with supratentorial brain tumors. The methods of direct cortical and subcortical stimulation, in addition to electrocorticography, enabled us to maximize tumor resection, minimize morbidity, and eradicate epileptogenic zones which were always adjacent to, but not involving, the tumor nidus. Language localization was found to be quite variable in the children tested and anatomically unpredictable based on the preoperative neurological or radiological examination. Physiological mapping techniques, therefore, appear to be safe, reliable, and very useful for operations on tumors located within or adjacent to eloquent brain regions in the pediatric population.

Neuronal activity in the human lateral temporal lobe. I. Responses to speech.

SummarySingle and multiple unit neuronal activity was recorded from the cortex of the lateral temporal lobe in conscious humans during open brain surgery for the treatment of epilepsy. Recordings were obtained from the right and left superior, middle and inferior temporal gyrus of 34 patients (41 recording sites). Recordings were restricted to regions to be resected during subsequent surgery. This excluded recordings from language areas proper. Neuronal responses to words and sentences presented over a loudspeaker and during free conversation were recorded. No significant differences between the right and left hemisphere were obvious. All neurons in the superior temporal gyrus responded to various aspects of spoken language with temporally well defined activation/inhibition patterns, but not or only little to non-linguistic noises or tones. Excitatory responses were typically short or prolonged (up to several hundred ms) bursts of discharges at rates above 20/sec, reaching peak rates of 50–100/s. Such responses could be specifically related to certain combinations of consonants suggesting a function in categorization, they could depend on word length, could differentiate between polysyllabic and compound words of the same length or could be unspecifically related to language as such. No formant specific responses were found, but the prolonged excitations across syllables suggest that consonant/vowel combinations may play a role for some activation patterns. Responses of some neurons (or neuronal populations) depended on the attention paid to the words and sentences, or the task connected with them (repeat words, speech addressed to the patient demanding something). Neurons in the middle and inferior temporal gyrus were only little affected by listening to single words or sentences, but some were unspecifically activated by words or while listening to sentences. Excitatory responses varied within a limited range of discharge rates usually below 5–10/s. Phonetic distortion of spoken language could reduce responses in superior temporal gyrus neurons, but also the slight changes in discharge rate of middle temporal neurons could be absent during distorted and uncomprehensible speech sounds. We conclude that superior temporal gyrus neuron responses reflect some general phonetic but not semantic aspects of spoken language. Middle and inferior temporal gyrus neurons do not signal phonetic aspects of language, but may be involved in understanding language under certain conditions.

Language localization and variability

Abstract Language localization data from 11 neurosurgical patients undergoing cortical resection for medically intractable focal epilepsy were obtained by mapping with bipolar electrical stimulation at current levels below sensory and after-discharge thresholds, during an object-naming task. The topographical extent of language cortex in an individual subject can be wider than that proposed in the classic maps. Within this zone, language is discretely localized, with different sites variably committed to language as measured by the naming function. The naming data from the left cortex of eight patients, all left-brain-dominant, were pooled to determine the variability within the primary language zone. Only a narrow band of posterior, inferior frontal lobe, immediately anterior to motor strip, showed involvement in all of the patients in whom it was sampled. This is a motor speech area; it constitutes only a small portion of the frontal language area. Other infero-frontal, parietal, and postero-temporal sites showed considerable variability, with naming involvement in only 50–80% of the patients sampled. There is a suggestion that some of these patterns of language localization may correlate with poorer verbal abilities. Data were also obtained on language localization in the left insula in a patient who was left-hemisphere-dominant for language. Mapping of the right hemisphere in a left-brain-dominant patient demonstrated no naming function. Mapping of the right hemisphere in one and the left hemisphere in another patient, both of whom were right-hemisphere-dominant for language, suggests more diffuse language representation with right hemisphere dominance.

Functional Cortex and Subcortical White Matter Located within Gliomas

Some neurosurgeons state that intra-axial tumors may be resected with a low risk of neurological deficit if the tumor removal stays within the confines of the grossly abnormal tissue. This is thought to be so even when the lesion is presumably located in a functional area, providing that the adjacent normal-appearing cortex and subcortical white matter are not disturbed. This retrospective analysis presents evidence that this view is not always correct, because functioning motor, sensory, or language tissue can be located within a grossly obvious tumor or the surrounding infiltrated brain. Intraoperative stimulation mapping techniques identified 28 patients, ranging in age between 22 and 73 years, who showed evidence of functional tissue within the boundaries of infiltrative gliomas, as identified by correlation with computed tomography and magnetic resonance imaging scans, intraoperative ultrasound, gross visualization, and histological confirmation. Direct stimulation mapping of cortical and subcortical portions of the tumor during resections identified motor, sensory, naming, reading, or speech arrest function. Nineteen patients had new or worsened neurological deficits immediately after the operation, but after 3 months, only 6 continued to show new deficits whereas 18 showed no deficits and 2 improved. These results demonstrate that regardless of the degree of tumor infiltration, swelling, apparent necrosis, and gross distortion by the mass, functional cortex and subcortical white matter may be located within the tumor or the adjacent infiltrated brain. Therefore, to safely maximize glioma resection in these functional areas, intraoperative stimulation mapping may be used to identify functional cortical or subcortical tissue within, as well as adjacent to, the tumor, thus avoiding permanent injury.

Invasive recordings from the human brain: clinical insights and beyond

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.

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy

Objective: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. Methods: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). Results: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon’s horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. Conclusions: 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.

Language and the thalamus: Object naming and recall during and after thalamic stimulation

Performance on a standard test of object naming, mental arithmetic and recall from short term memory was determined during stimulation of ventrolateral thalamus (VL) at the time of stereotaxic thalamotomy, and two days after that operation. Object naming was altered during stimulation of left, but not right thalamus. Within left thalamus, repetition of the same wrong word was evoked from anteriolateral VL, while perseveration and anomia were evoked from more medial central portions of VL. Evoked changes in recall were also restricted to left VL. Fewer recall errors were seen after stimulation during input to memory, than on control trials without stimulation. More errors occurred with stimulation of the same sites at the same currents but at the time of recall. Two days after left thalamotomy, a significant anomia was identified. But naming of objects with stimulation at operation was significantly more accurate than naming of objects without stimulation at operation. These data were interpreted as suggesting that left thalamic stimulation evokes a “specific alerting response” that directs attention to information in the external environment while simultaneously blocking retrieval from memory. Both parts of this specific alerting response seem to affect both short and long term memory and are highly correlated with the degree of postoperative anomia. This specific alerting response may be the left thalamic role in language processes. Based on evoked changes in number reading right thalamus was postulated to play a role in the processing of letters and numerals.