Basal temporal language area.

Brain (1991), 114, 743-754

BASAL TEMPORAL LANGUAGE AREA by H. LUDERS, R. P. LESSER, J. HAHN, D. S. DINNER, H. H. MORRIS, E. WYLLIE and J. GODOY (From the Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA) SUMMARY Language interference was elicited by electrical stimulation of the dominant basal temporal region in 8 out of 22 cases and in none of 7 cases with subdural electrodes implanted over the nondominant temporal lobe. Language interference was elicited by stimulation of electrodes placed over the fusiform gyrus 3—7 cm from the tip of the temporal lobe. Electrical stimulation of the basal temporal language area produced a global receptive and expressive aphasia with speech arrest at high stimulus intensities. Other higher cortical function, for example copying complex designs or memory of nonverbal information was intact, in spite of the total inability to process verbal information. At lower stimulus intensities partial aphasias with a predominant receptive component occurred. Surgical resection of the basal temporal language area produces no lasting language deficit. INTRODUCTION

Three cortical language areas were defined by Penfield and collaborators by electrical stimulation studies (Penfield and Rasmussen, 1949, 1950; Penfield and Jasper, 1954; Penfield and Roberts, 1959; Penfield and Perot, 1963). They described anterior, posterior and superior language areas which were located approximately at Broca's, Wernicke's and the supplementary motor area, respectively. The occurrence of language deficits during electrical stimulation of Broca's and Wernicke's areas were later widely confirmed by other investigators (Fedio and Van Buren, 1974; Rasmussen and Milner, 1975; Ojemann, 1978, 1979; Ojemann and Whitaker, 1978; Van Buren et al., 1978; Ojemann and Mateer, 1979; Rapport et al., 1983; Lesser etal, 1984a, 1986). Electrical stimulation studies of the human supplementary motor cortex, however, have been performed only infrequently and there are no additional reports of language interference by stimulation in that area. In 1984, we studied a patient who showed a clearly defined language deficit when stimulating the fusiform (occipitotemporal) gyrus of the dominant temporal lobe (Luders et al., 1985, 1986a). We now report on the results of stimulating the basal temporal region of 26 patients with intractable complex partial seizures who were being evaluated for surgical treatment of epilepsy. M A T E R I A L AND METHODS Twenty-nine patients had 16 or more subdural electrodes implanted over the basal temporal region for work-up for surgery for epilepsy between December 1983 and February 1986 (Luders et al., 1989). Some of the patients with the electrodes placed over the basal temporal region of the nondominant hemisphere Correspondence to: Dr H. Luders, Department of Neurology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. © Oxford University Press 1991

Downloaded from https://academic.oup.com/brain/article-abstract/114/2/743/263658 by University of California, Santa Barbara user on 10 March 2018

744

H. LUDERS AND OTHERS

were not included because no systematic stimulation studies were performed. Cases with less than 16 subdural electrodes over the basal temporal region were also excluded. The age of the patients ranged from 14 to 36 yrs, and they all had intractable complex partial seizures. All patients had presurgical EEG/video monitoring during which the anticonvulsants were discontinued and interictal and ictal epileptiform activity was recorded from surface electrodes including closely placed scalp, periorbital, nasopharyngeal, ethmoidal, and sphenoidal electrodes (Luders et al., 1982; Lesser et al., 19846; Morris and Luders, 1985). This evaluation lasted a minimum of 5 days but in selected cases up to 14 days. The information obtained from this work-up was then used to decide the type and site of insertion of the subdural electrodes. In addition, each patient had computerized tomography (CT) of the brain, cerebral angiography, dichotic testing, testing of visual fields and detailed speech and neuropsychological testing. Speech and language function was evaluated preoperatively through administration of the Boston Diagnostic Aphasic Examination, Boston Naming Test, Revised Token Test, Word Fluency Test, and assorted informal measures. This test battery was repeated at 6 months postoperatively. Magnetic resonance imaging of the brain was also performed in selected patients. Speech and short-term memory dominance was tested with intracarotid amylobarbital injections (Wada, 1949; Wada and Rasmussen, 1960). The subdural plates consisted of stainless steel electrodes, 3 mm in diameter and 0.9 mm thick which were embedded in Silastic material with a centre-to-centre distance between the electrodes of 1 cm. These electrodes were custom made and details of their design and insertion technique have been published elsewhere (Luders et al, 1987). Twenty-one patients had only one 4 x 4 plate (16 electrodes) implanted under the basal temporal region. Three patients had 4 x 4 plates inserted under both basal temporal areas. Two patients had a 4 x 6 plate (24 electrodes) implanted under one basal temporal region. In addition, all patient had extensive coverage of other cortical areas with subdural electrodes. In most cases, this consisted of a 8 x 8 plate (64 electrodes) over the temporal lobe convexity and immediately adjacent suprasylvian 'areas. A typical example with a 4 x 4 plate over the basal temporal region and an 8 x 8 plate over the convexity is shown in fig. 1. The subdural electrodes were inserted on a Thursday or Friday and, after giving the patient a short period to recover from the operation, stimulation and evoked potential studies were started the following Monday. These functional studies were in all cases completed in 1 wk. After discontinuing or decreasing

FIG. 1. X-ray of patient with a chronically implanted 4 x 5 plate of subdural electrodes over the basal temporal region and an 8 x 8 plate over the lateral convexity of the temporofrootoparietal region.


BASAL TEMPORAL LANGUAGE AREA

745

anticonvulsants, interictal and ictal epileptiform activity was recorded from the subdural electrodes for at least 5 days. Surgery consisted of excision of all cortical areas which had shown interictal and/or ictal epileptiform activity as long as they did not include functionally important areas as defined by the electrical stimulation and evoked potential studies. More details of this work-up strategy have been published elsewhere (Lesser et al., 1984fc; Luders et al., 1987). The electrical stimulation studies included an initial screening test. All the electrodes were stimulated starting at an intensity of 1 mA. The stimulus duration was 0.3 ms, and 5 s duration trains of 50 Hz alternating polarity stimuli were delivered. The stimulus intensity was increased at 0.5 — 1 mA steps until (1) 'positive' symptoms occurred (muscle twitch, paresthaesiae, hallucinations), (2) after-discharges were elicited or (3) a maximum stimulus intensity of 15 mA was reached. During the screening stage stimulation was always 'referential' using as 'reference' an electrode which showed no after-discharges or 'positive' symptoms at an intensity of 15 mA. All the electrodes which did not show 'positive' symptoms were also screened for language disturbances by having the patient read aloud while stimulating at 0.5 mA below the afterdischarge threshold (maximum of 15 mA if no after-discharges occurred). Stimulation intensities slightly below after-discharge threshold were also used to test for other higher cortical functions. These special tests were usually only performed at electrodes in which the 'reading aloud test' showed abnormalities. Details of the tests performed at these electrodes are given in the Results section. RESULTS

Stimulation of the basal temporal region produced interference with language (speech arrest or slowing down during the 'reading aloud test') in 8 out of 22 cases with plates under the dominant temporal lobe but in none of the cases with plates under the nondominant temporal lobe. Speech arrest was noted during stimulation in at least 1 electrode in 7 out of 8 patients. These included 3 patients who had plates inserted in both sides but language interference was not elicited by electrical stimulation on either side. When stimulating the prerolandic inferior frontal region (corresponding approximately to Broca's area), language interference was elicited in 15 out of 22 patients with plates over the dominant hemisphere but in none of the 7 patients with plates over the nondominant hemisphere. When stimulating the superior temporal gyrus behind the point where the rolandic and sylvian fissures meet (corresponding approximately to Wernicke's area), language interference was elicited in 14 out of 22 patients with plates over the dominant hemisphere but in none of the 7 patients with plates over the nondominant hemisphere. Interference with language was elicited at an average of 2.7 electrodes (range 1-15) at Broca's area, 3.6 electrodes (range 1 —7) at the basal temporal area, and a 4.0 electrodes (range 1-16) at Wernicke's area. In the 8 patients in which we were able to demonstrate the existence of a basal temporal speech area, stimulation while they were asked to read aloud produced either total speech arrest or marked slowing. One patient indicated that he 'was looking at the word but was unable to spit it out' or that he 'was able to see the word but could not read it'. Another patient described it 'as being able to see but not to read the word'. The use of different intensities of stimulation also showed that the degree of language interference was a direct function of the intensity of stimulation. For example, 1 patient at 4 mA of stimulus intensity could read with no difficulty; at 4.5 mA the reading became markedly slowed and at intensities of 5 —10 mA complete speech arrest occurred. The patients were also asked to perform rapid alternating movements of the tongue and/or fingers while stimulating the electrodes where speech arrest occurred. No interference of rapid alternating movements was observed.


746


In 3 patients, more detailed aphasia testing was carried out. All 3 were unable to read simple words during electrical stimulation. Two of them were unable to repeat the word after stimulation. The third patient, however, was able to identify the word by gesticulations and could repeat it after stimulation. Two patients were asked to follow simple written commands during stimulation. Both were unable to follow the command and were also unable to repeat the command after stimulation. Two patients were given simple oral commands which they could not follow during stimulation. One of the 2 patients, however, was able to remember the command and follow it after the stimulation was over. The Token Test was also used to test for verbal comprehension. One patient was unable to follow simple one-step commands and could not remember the command after the stimulation. The other 2 patients were able to follow simple one-step commands even if it would take them more time. They also made more errors than without stimulation indicating 'I did not understand the description'. Both patients had progressively more difficulties with complex two-step commands. Confrontation naming was one of the tests most affected during stimulation. All 3 patients were totally unable to name objects during stimulation. Interestingly, however, they were clearly aware of the object presented to them during stimulation and spontaneously, or after prompting, were able to identify during the stimulation the object by gesticulations (for example, by imitating the action of cutting with his fingers when confronted with scissors). One patient even was able whistle when confronted with a whistle. They all remembered the objects after stimulation and were able to name them correctly without any difficulty. With higher intensities of stimulation, the patients were totally unable to speak during stimulation. At lower intensities they still had major difficulties in naming the objects but not infrequently were able to define its function (for example, saying "That is a ... clean teeth' for toothbrush). The patients had similar difficulties when asked to name objects in the room. One of them indicated that 'Words just did not enter my mind'. In 1 case at high stimulation intensities of 6—10 mA, the patient was totally unable to name objects in the room. At 5 mA, however, he was able to name some objects but at a considerably slower speed than without stimulation. Repetition of simple words or sentences was tested only in 2 patients. Both patients were unable to repeat words or sentences during stimulation or to remember them after stimulation when relatively high intensities were used. At relatively lower intensities of stimulation, 1 of the patients had literal paraphasias (for example, said 'episcural' when asked to repeat 'episcopal'). Simple sequential tasks were tested only in 1 patient. Simple tasks like counting forward from 1 were performed without difficulty. However, with more difficult tasks, he had progressively more problems. For example, he was unable to count forward by 3s, list correctly the days of the week or the months of the year. On a few occasions, the patient also would switch over to a more simple sequential task that he had been asked to perform before. For example, he would start counting forwards after having started to list the days of the week. He was unaware of these errors after the stimulation was over. All 3 patients had a severe agraphia during stimulation. Two of them were totally unable to write simple letters even when the order was given before the stimulation. One patient, however, was able to write letters and two digit numbers but had a striking agraphia for more complex tasks. One of the patients commented that he could 'not



747

remember what to write down' during stimulation. Two patients wrote down something they had already written before stimulation even if a different order had been given this time. At lower intensity 1 of the patients was able to follow the command correctly but made spelling errors (wrote down 'limbs are quite sour' when asked to write 'limes are quite sour'). One patient, at relatively low stimulus intensities, was asked to spell a word and then to read it. He misspelled the word and then was unable to read it. Two patients were tested for copying simple words from a card. Both had no difficulty writing the word during stimulation but they were unable to read it during stimulation. After stimulation, however, they could say the word from memory. One patient was tested for written mathematics and was unable to solve a simple problem (summation of two digits) during stimulation. He was able to remember the problem after stimulation and solve it without any difficulty. The other 2 patients were asked to solve mathematical problems given orally and were totally unable to do so even for simple addition of two digits. They could also not remember the problem after stimulation or signal during stimulation with their fingers what digits they were asked to sum. Two patients were tested with moderately complex Koh's blocks tasks and had no impairment during stimulation. All 3 patients also were able to copy complex geometrical designs (shown during stimulation for 1 - 2 s and then asked to copy from memory also during stimulation). Finally, 1 patient was asked to imitate facial expressions after confrontation with different photographs. He had no difficulty with this task during stimulation or in remembering the facial expression after the stimulation was over. In 4 of the 8 cases all the basal temporal electrodes which elicited language interference by stimulation also showed interictal or ictal epileptiform discharges. In 2 other cases, epileptiform discharges occurred only at some but not all basal temporal electrodes which caused language disturbances when stimulated. In 2 other cases, none of the basal temporal electrodes that produced language disturbances showed epileptiform discharges. The approximate anatomical location of the electrodes at which language disturbances were elicited by electrical stimulation was defined by the analysis of skull x-rays with the electrodes in place and corresponded to the fusiform (temporo-occipital gyrus) in all cases. In 3 cases the location of the electrodes was defined with more precision during surgery, confirming that they were overlying the fusiform gyrus. In all cases, the 'language electrodes' appeared to be located at least 3 cm posterior to the tip of the temporal lobe. In 5 cases, the exact anteroposterior extent of the language area was measured during surgery. The anterior border was consistently 3—3.5 cm from the anterior pole of the temporal lobe. The posterior border of the language area varied between 4 and 7 cm from the anterior temporal pole. All 8 cases with a basal temporal speech area had an extensive resection of the medial temporal structures including the amygdala and more than 4 cm of the hippocampus. In 5 cases, the resection of the temporal lobe was tailored in such a way that no basal temporal language area was included. In 2 cases, the basal temporal language area was resected completely, and in 1 case, a limited postsurgical infarct occurred which destroyed completely the basal temporal language area. This case was operated on for a second time, and the diagnosis of an infarct of the basal temporal region was confirmed by gross inspection during surgery and pathological examination. The language test battery


748


administered 6 months postoperatively showed no significant change in 3 cases including 2 patients in whom the basal temporal speech area was resected. One of these patients had suffered an extensive infarct of the basal temporal region including the basal temporal speech area. This patient had a mild receptive aphasia in the immediate postoperative period (only tested informally at the bedside) which had disappeared completely 6 months later during formal testing. Two of the other 4 patients who had a limited temporal resection with sparing of the basal temporal speech area showed a mild improvement in language function 6 months postoperatively; 1 had slight improvement of auditory comprehension, whereas the other showed slight improvement of auditory comprehension, verbal fluency and written expression. The other 3 patients showed mild losses. One of the patients had mild deterioration of an already preoperatively present moderate mixed aphasia. The second patient showed a slight decrease of his ready comprehension and the third patient (who had also a resection of the basal temporal language area) revealed a significant increase of literal paraphasics postoperatively. DISCUSSION

This study confirms our previous observation based on a case report (Liiders et al., 1986a) that the basal temporal region of the dominant hemisphere participates in the processing of language. The possibility that the deficit produced by electrical stimulation was unrelated to any language interference (e.g., a nonspecific disturbance of consciousness or an apraxia of speech-related muscles) was excluded by careful testing. Stimulation elicited no observable muscle twitches of the tongue or perioral muscles and also no negative motor effect was observed (Liiders etal., 1983, 1990). The possibility that the language interference was just an expression of a nonspecific disturbance of consciousness is also unlikely. In all cases, the language disturbance was elicited on numerous occasions without artefact, but it is impossible to exclude the possibility of epileptiform discharges occurring only during stimulation. The fact, however, that the patients were able to perform extremely complex nonverbal functions (e.g., pasting a stamp and closing an envelope, or copying a complex design during stimulation at an identical stimulus intensity) clearly points to the specificity of the language deficit. The observation that the patient was able to identify an object by gestures but was unable to name it (e.g., to imitate the act of sawing when confronted with a picture of a handsaw) also demonstrated this. The occasional occurrence of circumlocutions points in the same direction. In this context it is important to stress the fact that language disturbances occurred not infrequently at electrodes which gave no evidence of epileptogenicity (ictal or interictal). Similar selective disturbances of language were usually observed at Wernicke's area and less frequently at Broca's area. In other locations, an apparent interference with language was invariably associated with either (1) an after-discharge and inability to perform even simple nonverbal tasks (epileptic absence), (2) a negative motor effect (Liiders et al., 1983, 1990), or (3) a positive motor effect. Negative motor effects were noticed most frequently in the premotor region (particularly in the inferior frontal region corresponding approximately to Broca's area) and positive motor effects occurred exclusively in the perirolandic area and in the supplementary motor region. We have examined only 6 cases with chronic subdural electrodes placed over the supplementary



749

motor area (Dinner et al., 1987). These cases showed dramatic bilateral positive motor effects, bilateral negative motor effects and sensory effects. No language-specific deficits as described by Penfield and collaborators (Penfield and Jasper, 1954; Penfield and Roberts, 1959) were observed in this small sample. It is not surprising that previous studies of the effect of electrical stimulation of the human cortex did not describe a basal temporal language area. Most of them were performed during surgery. Due to time limitations, the surgeon usually restricted the stimulations while testing for language interference to areas in which previous evidence suggested the existence of language-related functions (mainly Wernicke's and Broca's area). There is only very limited evidence in the literature which would implicate the basal temporal region in the processing of language (Mills and Martin, 1912; Nielson, 1946; De Renzi et al., 1987). Excision of the anterior 5—6 cm of the dominant lobe basal temporal region is apparently not associated with any language deficit. The only reported complication was a variable degree of verbal memory deficit (Hermann and Wyler, 1988). Additionally, the basal temporal region is not readily accessible during surgery and special electrodes would be required to stimulate the fusiform gyrus. Depth electrodes usually do not permit recording or stimulation of the basal temporal region. In our laboratory, the basal temporal language area was discovered by implanting chronic basal temporal electrodes and screening systematically all electrodes for language disturbances ('reading aloud' test). It was interesting to notice that the basal temporal language area was located invariably in the fusiform (occipitotemporal) gyrus at the tip of the basal temporal region. In all these cases, there was no language-related function in the inferior temporal gyrus and, therefore, the basal temporal language area has to be considered as an entity separate from Wernicke's area which is usually situated in the posterior portion of the superior temporal gyrus. The white matter underlying the basal temporal language area is, however, in direct contact with the white matter underlying Wernicke's area (fig. 2). This proximity could be one factor that favours close interaction between Wernicke's area and the basal temporal language area. Electrical stimulation of the basal temporal region produces language deficits that are almost identical quantitatively and qualitatively with the ones observed when stimulating Wernicke's area. There are, however, major differences between these areas. As mentioned above, resection of Wernicke's area is usually associated with a severe fluent aphasia, whereas there is no clear evidence for neurological deficit following resection of the anterior tip of the temporal lobe. In this context, it is interesting to note that Penfield and Roberts (1959) reported language deficits following resection of basal temporal and inferior temporal cortex. They related these deficits to the excision of the inferior temporal cortex, quoting the evidence provided by Mills and Martin (1912) and by Nielsen (1946) that the posterior-inferior temporal gyrus of the dominant hemisphere was a 'naming center' or 'language formulation area'. Heilman et al. (1972) observed a selective anomic aphasia in 4 out of 10 patients who had an anterior temporal lobectomy. It could be speculated that these deficits were related to lesions of the basal temporal speech area, but in our experience resection of the basal temporal speech area was not associated with any lasting speech deficit. In this series, we were able to define Broca's and Wernicke's area significantly more frequently than the basal temporal speech area. Initially, we assumed that this was because



750

Insula Sylvian Superior temporal gyrus (Wernicke)

-Inferior horn of lateral ventricle

Middle temporal gyrus

-Hippocampus

Inferior temporal gyrus Fusiform Parahippocampal gyrus gyrus FIG. 2. Section through the temporal lobe, including the basal temporal language area in the fusiform gyrus and Wernicke's area in the superior temporal gyrus.

the basal temporal speech area is usually located more posteriorly than the location in which we implanted the subdural electrodes. However, in the cases in which we were able to locate the basal temporal region it was always located relatively more anteriorly with a clearly defined posterior margin at approximately 7 cm from the tip of the temporal lobe, an area usually covered by the 4 x 4 basal temporal plate. Another possibility was that the basal temporal speech area was of a relatively smaller size and, therefore, could be 'missed' more frequently. A comparison of the number of electrodes which cover the basal temporal speech area with the number of electrodes which cover Broca's area does not support this hypothesis either. Both areas tend to be covered by approximately the same number of electrodes. We also considered the possibility that the basal temporal speech area could represent a pathological Wernicke's area 'displaced' to the basal temporal region because of pathology affecting Wernicke's area. In the majority of these patients, however, the main epileptogenic focus was in the basal temporal region (not in the temporal convexity) and in 6 of the 8 patients with a basal temporal speech area, an independent well-defined Wernicke's area was also identified by electrical stimulation on the lateral convexity of the temporal lobe in the vicinity of the sylvian fissure, and clearly differentiated from the basal temporal language area. Finally, we could assume that in some cases the basal temporal speech area is dispensable because of compensatory mechanisms. This would be similar to the anatomical substrate sustaining memory which most probably has a bilateral distribution and, therefore, memory deficits only become


BASAL T E M P O R A L L A N G U A G E AREA

751

clinically evident when damaging both medial temporal regions (Milner, 1967). The 8 cases in which we elicited major language disturbances with stimulation of the basal temporal region would be cases in which access to compensatory mechanisms would be significantly delayed. The fact that some of these cases had no language disturbances after removal of the basal temporal language area seems to indicate that with time, even these cases have access to effective compensatory mechanisms. In the first few cases in which electrical stimulation demonstrated a basal temporal language area, we carefully tailored the final temporal resection to avoid a lesion of the basal temporal language area. In 1 case, however, an infarct of the basal temporal region occurred as a complication of the surgical procedure. This case had a temporary slight aphasia in the immediate postoperative period but recovered completely when tested formally 6 months postoperatively. After that experience, we decided to resect all the epileptogenic tissue in the basal temporal region even if the results of electrical stimulation had demonstrated a basal temporal speech area. So far, we have resected the basal temporal language area in 2 cases with no language deficit exceeding the deficits observed in the earlier cases in which the resection did not include the basal temporal language area. The material, however, is still too small to analyse quantitatively the effect of resection of the basal temporal area or language functions. In 1 case a significant drop in verbal memory was seen. In all these cases, however, a significant resection of the hippocampus was also performed, and therefore it is quite likely that the drop of memory function is due to the lesion of the hippocampus. Similar drops of verbal memory function were also detected after excision of the dominant hippocampus with careful sparing of the basal temporal language area and in cases in which electrical stimulation of the basal temporal electrodes had not demonstrated language deficits. The language deficit produced by stimulation of the basal temporal region was striking, and essentially can be categorized as a global aphasia. At high intensities of stimulation there was total inability to comprehend written or spoken language, with a striking alexia, agraphia, acalculia and complete anomia and inability to repeat even simple words. This striking deficit was in clear contrast with the nonverbal performance during electrical stimulation which was essentially intact. The patients had no problems with Kohs' Blocks, were able to copy complex geometrical designs and to imitate faces without difficulties. They were even able to copy single letters or simple words (in spite of a striking agraphia) which they apparently handled like complex designs as opposed to symbols of a defined verbal meaning. The clearest dissociation between verbal and nonverbal tasks was apparent when these patients were asked to name objects by confrontation. They were able to identify objects by gesticulation but were totally unable to name them. From the highly selective language deficits described above, it is tempting to speculate that during stimulation these patients suffered a total inability to transform sounds or images with verbal meaning (letters, words, sentences or numbers) in understandable concepts. Additionally, the opposite function of generating verbal symbols (e.g., words) in response to nonverbal stimuli was also grossly affected. This suggests that the patients had no access to the verbal engrams which establish the link between symbolic verbal material and the corresponding nonverbal expressions. In other words, these considerations lead us to consider that the basal temporal language area could correspond to what Wernicke called the 'Wortschatz' which he assumed was most probably located in the dominant temporal lobe close to the posterior language area. Our findings suggest that


752


the 'Wortschatz' area is not located around the posterior language area but actually coincides with the basal temporal language area. It was also interesting to note in these patients that a change in the intensity of stimulation significantly modified the type of aphasia. With relatively low levels of stimulation, the patients were able to perform some verbal functions, and this gave us an opportunity to evaluate which of the different verbal deficits were affected most severely. For example, at low stimulation intensities, the patients were able to read, even if relatively slowly, and could repeat simple words but with literal paraphasias. They could also perform sequential tasks, but with more complex sequences there was a tendency to perseverate (they returned to the simpler sequence during the stimulation period). They were even able to spell some simple words but with frequent misspellings. In clear contrast with the improvement in the functions enumerated above, lower stimulus intensities were consistently associated with a more or less complete anomia even for very simple words. This last observation would be consistent with the hypothesis that these patients have essentially no access to verbal engrams as was explained above. These studies also point out very clearly the striking differences between the results obtained from lesions (e.g., strokes or tumours) and from studies of electrical stimulation. Well-documented lesions during surgery in 3 of the cases reported here were not associated with any language deficit postoperatively. These observations suggest that most probably in patients with permanent lesions of the basal temporal language area compensatory mechanisms become effective. It is possible that verbal engrams are stored, not only in the basal temporal language area, but also at other sites. During an abrupt interference of the basal temporal language area, as produced by electrical stimulation, the patient would not have sufficient time to gain access to engrams stored elsewhere. With time, however, the patient could access effectively intact engrams stored elsewhere. This same phenomenon could also explain why with prolonged stimulation the patients have a tendency to recover some functions at the end of the stimulation. Another interesting difference with lesion studies is the fact that inactivation of a very small cortical area by electrical stimulation is frequently sufficient to produce a striking global aphasia. This is in clear contrast with lesions which usually only produce aphasias with relatively extensive dominant lobe cortical lesions. This difference could also be related to the acuteness of the electrical stimulation which does not allow for compensatory mechanisms. Finally, it is interesting to note that electrical stimulation produces relatively similar deficits in the 3 language areas we were able to investigate systematically: Broca's, Wernicke's and the basal temporal language areas. In all these areas, electrical stimulation elicited speech arrest and clear comprehension deficits (Lesser et al., 1986; Liiders et al., 1986a, b). The only important difference was the observation that in Broca's area electrical stimulation frequently also produced a negative motor effect which affected preferentially voluntary muscles involved in fine movements including those participating in speech (Liiders et al., 1983, 1991). From these observations the question arises as to whether the difference between the predominantly expressive aphasias with lesions in Broca's area are due to the simultaneous involvement of language and negative motor areas, whereas lesions of Wernicke's area, where no negative motor area exists, are always limited to a selective involvement of language areas. In other words, the hypothesis which evolves from these stimulation studies is that lesions of selective language circuitry involving any of these 3 language centres would be relatively uniform. Interference



753

at any point within this probably closely interconnected system produces almost identical deficits. The differences noted in clinical lesions studies would not be the results of selective damage to language centres but the result of an associated deficit secondary to lesions of independent systems anatomically closely associated with language areas. A typical example would be a lesion of Broca's area which, according to this hypothesis, would be usually associated with a marked expressive aphasia because of the anatomical proximity of the negative motor area. From the discussion presented above emerges the hypothesis that Wernicke's language area functions in close association with the basal temporal language area. Identification of the symbolic meaning of auditory or verbal words, which classically is considered a function of Wernicke's area, is only achieved by activation of verbal engrams which we assume are stored in the basal language area. Like other memory functions, the engrams would be stored bilaterally but access to the dominant basal temporal language area is relatively faster because that pathway is used on a routine basis. The assumption of a close interaction of the basal temporal and Wernicke's language area would require extensive direct anatomical connections between these two language areas. Indeed, studies by Rosene and Van Hoesen (1977) demonstrated that in monkeys the parahippocampus acts as a relay station of the extensive connections that exist between the hippocampus and the neocortex. These anatomical connections are certainly consistent with the hypothesis that Wernicke's and the basal temporal language areas interact extensively in the processing of verbal material. A diagrammatic representation of the way this interaction can be conceived has been presented elsewhere (Liiders et al., 1987). REFERENCES DE RBNZI E, ZAMBOUN A, CRISI G (1987) The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain, 110, 1099 — 1116. DINNER DS, LODERS H, MORRIS HH, WYLLIE E, KRAMER RE (1987) Human supplementary motor area

(SMA) electrical stimulation study. Epilepsia, 28, 619. FEDIO P, VAN BUREN JM (1974) Memory deficits during electrical stimulation of the speech cortex in conscious man. Brain and Language, 1, 29—42. HEILMAN KM, WILDER BJ, MALZONE WF (1972) Anomic aphasia following anterior temporal lobectomy. Transactions of the American Neurological Association, 97, 291—293. HERMANN BP, WYLER AR (1988) Effects of anterior temporal lobectomy on language function: a controlled study. Annals of Neurology, 23, 585-588. LESSER RP, LUEDERS H, DINNER DS, HAHN J, COHEN L (1984a) The location of speech and writing functions

in the frontal language area: results of extraoperative cortical stimulation. Brain, 107, 275—291. LESSER RP, DINNER DS, LODERS H, MORRIS HH (1984ft) Differential diagnosis and treatment of intractable

seizures. Cleveland Clinic Quarterly, 51, 227-240. LESSER RP, LODERS H, MORRIS HH, DINNER DS, KLEM G, HAHN J et al. (1986) Electrical stimulation

of Wernicke's area interferes with comprehension. Neurology, Cleveland, 36, 658—663. LODERS H, HAHN J, LESSER RP, DINNER DS, ROTHNER D, ERENBERG G (1982) Localization of epileptogenic

spike foci: comparative study of closely spaced scalp electrodes, nasopharyngeal, sphenoidal, subdural, and depth electrodes. In: Advances in Epileptology: The Xlllth Epilepsy International Symposium. Edited by H. Akimoto, H. Kazamatsuri, M. Seino and A. A. Ward. New York: Raven Press, pp. 185 -189. LODERS H, LESSER RP, DINNER DS, MORRIS HH, HAHN J (1983) Inhibition of motor activity elicited

by electrical stimulation of the human cortex. Epilepsia, 24, 519. LODERS H, LESSER RP, HAHN JF, DINNER DS, MORRIS HH, HARRISON M (1985) Language disturbances

produced by electrical stimulation of the basal temporal region. Annals of Neurology, 18, 151. LODERS H, LESSER RP, HAHN J, DINNER DS, MORRIS H, RESOR S et al. (1986a) Basal temporal language

area demonstrated by electrical stimulation. Neurology, Cleveland, 36, 505-510.


754


LODERS H, LESSER RP, DINNER DS, MORRIS HH, WYLLIE E, KLEM G (19866) Comprehension deficits

elicited by electrical stimulation of Broca's area. Epilepsia, 27, 598—599. LODERS H, LESSER RP, DINNER DS, MORRIS HH, HAHN JF, FRIEDMAN L et al. (1987) Commentary:

chronic intracranial recording and stimulation with subdural electrodes. In: Surgical Treatment of the Epilepsies. Edited by J. Engel. New York: Raven Press, pp. 297-321. LODERS H, HAHN J, LESSER RP, DINNER DS, MORRIS HH, WYLLIE Eel al. (1989) Basal temporal subdural

electrodes in the evaluation of patients with intractable epilepsy. Epilepsia, 30, 131-142. LODERS H, DINNER DS, MORRIS HH, LESSER RP, WYLLIE E, GODOY J (1991) A negative motor response

(NMR) elicited by electrical stimulation of the human frontal cortex. In: Frontal Lobe Seizures and Epilepsies. Editied by P. Chauvel, A. V. Delgado-Escueta, E. Halgren and J. Bancaud. New York: Raven Press. In press. MILLS CK, MARTIN E (1912) Aphasia and agraphia in some practical surgical relations. Journal of the American Medical Association, 59, 1513 — 1518. MILNER B (1967) Brain mechanisms suggested by studies of temporal lobes. In: Brain Mechanisms Underlying Speech and Language. Edited by C. H. Millikan and F. L. Darley. New York: Grune and Stratton, pp. 122-145. MORRIS HH, LODERS H (1985) Electrodes. Electroencephalography and Clinical Neurophysiology, Supplement 37, 3—26. NIELSEN JM (1946) Agnosia, Apraxia, Aphasia. Their Value in Cerebral Localization. New York: Paul B. Hoeber. OJEMANN GA (1978) Organization of short-term verbal memory in language areas of human cortex: evidence from electrical stimulation. Brain and Language, 5, 331—340. OJEMANN GA (1979) Individual variability in cortical localization of language. Journal ofNeurosurgery, 50, 164-169. OJEMANN GA, WHITAKER HA (1978) Language localization and variability. Brain and Language, 6, 239-260. OJEMANN G, MATEER C (1979) Human language cortex: localization of memory, syntax, and sequential motor-phoneme identification systems. Science, 205, 1401 — 1403. PENFIELD W, RASMUSSEN T (1949) Vocalization and arrest of speech. Archives of Neurology and Psychiatry, Chicago, 61, 2 1 - 2 7 . PENFIELD W, RASMUSSEN T (1950) The Cerebral Cortex ofMan: A Clindal Study ofLocalization of Function. New York: Macmillan. PENFIELD W, JASPER H (1954) Epilepsy and the Functional Anatomy of the Human Brain. Boston: Little, Brown, and London: J. and A. Churchill. PENFIELD W, ROBERTS L (1959) Speech and Brain-Mechanisms. Princeton: Princeton University Press, and London: Oxford University Press. PENFIELD W, PEROT P (1963) The brain's record of auditory and visual experience: a final summary and discussion. Brain, 86, 595-696. RAPPORT RL, TAN CT, WHITAKER HA (1983) Language function and dysfunction among Chinese- and English-speaking polyglots: cortical stimulation, Wada testing, and clinical studies. Brain and Language, 18, 342-366. RASMUSSEN T, MILNER B (1975) Clinical and surgical studies of the cerebral speech areas in man. In: Otfried Foerster Symposium on Cerebral Localization. Edited by K. G. Fulch, D. Creutzfeldt and G. C. Galbraith. New York: Springer, pp. 238-257. ROSENE DL, VAN HOESEN GW (1977) Hippocampal efferents reach widespread areas of cerebral cortex and amygdala in the rhesus monkey. Science, 198, 315-317. VAN BUREN JM, FEDIO P, FREDERICK GC (1978) Mechanism and localization of speech in the

parietotemporal cortex. Neurosurgery, 2, 233—239. WADA J (1949) A new method for the determination of the side of cerebral speech dominance. A preliminary report on the intracarotid injection of sodium amytal in man. Igaku to Seibutsugaku (Medicine and Biology), 14, 221-222 (in Japanese). WADA J, RASMUSSEN T (1960) Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance: experimental and clinical observations. Journal ofNeurosurgery, 17, 266—282. {Received August 23, 1988. Revised November 3, 1989. Accepted April 24, 1990)


Bidirectional neural connectivity between basal temporal and posterior language areas in humans.

Language universals engage Broca's area.

The emergence of temporal language in Nicaraguan Sign Language.

Language function following anterior temporal lobectomy.

Basal cell carcinoma of the temporal bone.

Advantages of sentence-level fMRI language tasks in presurgical language mapping for temporal lobe epilepsy.

Temporal Attention as a Scaffold for Language Development.

Predictors of language lateralization in temporal lobe epilepsy.

Age-dependent mesial temporal lobe lateralization in language fMRI.

Human Temporal Cortical Single Neuron Activity during Language: A Review.

Temporal Characteristics of Nasalization: Language Specific or Not?

Unusual ictal foreign language automatisms in temporal lobe epilepsy.

Temporal reliability and lateralization of the resting-state language network.

Sulcal and gyral anatomy of the basal occipital-temporal lobe.

Impairment of temporal organization of speech in basal ganglia diseases.

Saccade-related activity in the lateral intraparietal area. I. Temporal properties; comparison with area 7a.

Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex.

Contribution of the basal ganglia to spoken language: is speech production like the other motor skills?

Probabilistic White Matter Atlases of Human Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Visual and Visuospatial Networks.

Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey. I. Temporal lobe afferents.

Changes of spatial and temporal frequency tuning properties of neurons in the middle temporal area of aged rhesus monkeys.

Thalamic and other subcortical projections to area MT (visual area of superior temporal sulcus) in the marmoset Callithrix jacchus.

The language skeleton after dissecting meaning: A functional segregation within Broca's Area.

Language and visual perception associations: meta-analytic connectivity modeling of Brodmann area 37.