Discordant Wada and fMRI language lateralization: a case report

Abstract

Functional MRI (fMRI) is gaining importance in the preoperative assessment of language for presurgical planning. However, inconsistencies with the Wada test might arise. This current case report describes a very rare case of an epileptic patient who exhibited bilateral distribution (right > left) in the inferior frontal gyrus (laterality index [LI] = –0.433) and completely right dominance in the superior temporal gyrus (LI = –1). However, the Wada test revealed a dissociation: his motor speech was located in the left hemisphere, while he could understand vocal instructions with his right hemisphere. A clinical implication is that the LIs obtained by fMRI should be cautiously used to determine Broca’s area in atypical patients; for example, even when complete right dominance is found in the temporal cortex in right-handed patients. Theoretically, as the spatially separated functions of motor speech and language comprehension (by the combined results of fMRI and Wada) can be further temporally separated (by the intracarotid amobarbital procedure) in this case report, these findings might provide direct support to Broca’s initial conclusions that Broca’s area is associated with acquired motor speech impairment, but not language comprehension per se. Moreover, this current finding supports the idea that once produced, motor speech can be independent from language comprehension.

Introduction

Language plays a critical role in human communication and accurately determining hemispheric language dominance is crucial for presurgical planning in patients. ¹ Intracarotid amobarbital (Wada) testing has been used for many years to assess preoperative language lateralization and predict postoperative language outcome. ² Recently, functional magnetic resonance imaging (fMRI) has gained importance in the preoperative assessment because it is noninvasive and provides better spatial resolution, which is highly concordant with Wada.^3–5 However, there may be discordances between fMRI findings and Wada that complicate determination of dominance, but these are rarely published or discussed. ³ Certain conditions that are related to the discordances should be considered.

This current case report describes a very rare case of a patient who exhibited not only a bilateral distribution (right > left, i.e. right asymmetry) of expressive language in the inferior frontal gyrus (IFG), but he also had a completely right distribution of receptive language distribution in the superior temporal gyrus (STG) during the fMRI test with a Verb Generation Task (VGT). This task has demonstrated the highest concordance across index types along with sufficiently high index values in the IFG. ⁴ However, Wada testing revealed a dissociation: the centre of motor speech was found to be in his left hemisphere, while the majority of his language comprehension was located in his right hemisphere. These inconsistencies have theoretical implications for the understanding of the brain’s organization of language processing.

Case report

In March 2012, a male right-handed college student in his early 20 s with a history of febrile convulsions since 6 months old presented to the Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Symptoms of focal onset impaired awareness seizures emerged at the age of 17, occurring several times a month initially; and then escalating to several times a day. He was prescribed 400 mg oxcarbazepine for oral administration, twice a day during the treatment. Early-life lesions were found in his left anterior temporal cortex (Figure 1, top). All identifying details have been removed. The routine procedures for preoperative assessment of language were conducted according to the World Medical Association Declaration of Helsinki. The reporting of this study conforms to CARE guidelines. ⁶

Figure 1.

Top: magnetic resonance imaging scans showing early-life lesions in the left anterior temporal cortex of a right-handed male college student in his early 20s with a history of febrile convulsions since 6 months old. Bottom: brain activation during the verb generation task overlapped on a rendered standard brain; P < 0.05, Family-Wise Error corrected. Right asymmetries were found in both the IFG (1158 versus 458; LI = –0.433) and STG (1277 versus 0; LI = –1). IFG, inferior frontal gyrus; STG, superior temporal gyrus; PreCG, precentral/central gyri; L, left; R, right. The colour version of this figure is available at: http://imr.sagepub.com.

The patient underwent routine fMRI as part of presurgical evaluation. The VGT was applied for the fMRI test. An event-related design was implemented. There were 30 auditory nouns, including furniture, fruits, animals and vehicles. The stimulus onset asynchrony was set at 30 s. He was instructed to generate a semantically appropriate verb in Chinese for each noun (e.g. apple – eat, eat an apple) and whisper the phrase. Standard data analysis was performed using SPM12. ⁷ Brain activation during the VGT is presented in Figure 1 (bottom). The laterality index (LI, defined by [volume(left) – volume(right)]/[volume(left) + volume(right)]) was calculated.^5,8 A bilateral distribution of the expressive language (right > left) was found in the IFG (LI = −0.433); moreover, complete right dominance was observed in the STG (LI = –1) (Table 1).

Table 1.

Brain regions that were activated during the verb generation task in a right-handed male college student in his early 20s with a history of febrile convulsions since 6 months old.

Brain regions	Hemisphere	MNI coordinates			Number of voxels	Peak intensity
		X	Y	Z
Inferior frontal gyrus	R	48	12	2	1158	8.84
	L	–41	10	4	458	7.45
Precentral gyrus	R	60	–6	34	1720	13.86
	L	–54	–8	28	1310	13.00
Temporal cortex	R	66	–18	4	1277	7.68
Putamen	R	20	8	6	27	5.22
	L	–16	8	0	51	5.59
Anterior cingulate cortex	C	6	4	62	1100	8.73

P < 0.05 (versus baseline), Family-Wise Error corrected.

MNI, Montreal Neurologic Institute; R, right; L, left; C, central.

Then this patient was submitted to the Wada test 4 days after the MRI procedure. The Wada test was conducted via a transfemoral catheter and sodium amobarbital (100 mg) was administered via a bolus in about 4 seconds. All intracarotid amobarbital procedures (IAPs) were videotaped for review. The left IAP was carried out shortly after routine cerebral routine angiography (to rule out any vascular anomalies). Unilateral anaesthesia was verified by the onset of hemiplegia in his left hand after each injection and no significant crossflow through the anterior cerebral artery was observed. Specifically, the patient was instructed to count from 10 to 1 continually before receiving an amobarbital injection and then to continue counting until instructed to stop. After the injection of amobarbital, onset of hemiplegia was detected as he lost control of his left arm/hand. Critically, he stopped counting abruptly (i.e. experienced speech arrest) at that moment despite verbal encouragement to continue counting. Then he was asked to name some everyday objects visually presented to him in the following order: a mobile, a pen, beads, and a needle. However, he could not name any of the objects orally. Moreover, he was able to perform simple movements as instructed, i.e. moving his hand, watching the needle, nodding his head, opening his mouth; and he also responded when called by his name. These findings indicated he understood the instructions, therefore, his language comprehension centre was located in his right hemisphere; while he was unable to speak. The left IAP lasted for approximately 3 min and no complex instructions were given.

The right IAP was performed 30 min after the left IAP, which also lasted approximately 3 min. Similar to the left IAP, the patient was instructed to count from 10 to 1 continually before receiving an amobarbital injection and then to continue counting until instructed to stop. After administering amobarbital, onset of hemiplegia was detected as he lost control of his right hand/arm. Critically, he could not stop counting during the entire right IAP despite being told to do so multiple times. Moreover, he failed to respond to simple instructions, including: (i) rotating his hand, or putting it down, even after it was demonstrated by a doctor in front of him; (ii) naming beads or a mobile that was visually shown before him. These findings indicate that the patient’s motor speech (counting) was intact during the right IAP.

Discussion

The fMRI data revealed that this current patient displayed not only a bilateral distribution (right > left) of expressive language in the IFG, but also a completely right asymmetry of receptive language in the STG during the VGT. However, the Wada test revealed a dissociation, that the patient’s motor speech was located in the left hemisphere, as he could keep counting backward during the right IAP; while his language comprehension centre was located in the right hemisphere, as he could follow instructions during the left IAP. Therefore, there was a discordance between the Wada test and fMRI language lateralization.

The clinical implication is that the LIs obtained by fMRI should be used cautiously to identify Broca’s area for atypical patients,^9–11 even if bilateral distributions (right > left) in expressive language and completely right distribution in receptive language were revealed through the fMRI approach. We speculated that the most likely reason for this dissociation is related with his handedness. ¹² Previous studies have revealed that left-handedness is associated with a higher prevalence of right hemisphere dominance for language/Broca’s area, while right-handedness is associated with left dominance.^4,11 These current findings are in line with these previous studies, indicating that although considerable early life injury in this patient could have affected his language distribution, and there is likely partial migration of language skills in him, handedness may still play a critical role. One clinical implication is that right-handed patients with right asymmetries should be considered atypical and extra care should be taken for them.

The current case report may have theoretical implications regarding the roles of Broca’s area in cognitive neuroscience. Paul Broca initially suggested that Broca’s Area was involved in motor speech production only. ¹³ However, later research has implicated Broca’s area in diverse cognitive functions, such as language comprehension. ¹⁴ For instance, activation in the left-IFG was modulated by sentence comprehension; ¹⁵ and disturbing the left-IFG led to comprehension deficits.^13,16 Although these findings have significantly increased the understanding of the neural basis of language, whether motor speech and language comprehension can be dissociated remains a question. ¹⁷ Yet, this question is very difficult to address in participants with intact language functions. First, the peaks that are activated by multiple language functions (such as vocal production and language comprehension) are typically widely overlapping and hard to be distinguished in the Left-IFG among healthy volunteers. ¹⁸ Secondly, language comprehension is a prerequisite for formulating meaningful sentences, ¹⁹ indicating that brain regions associated with these functions should be co-activated temporally. Thirdly, this point is also not easily addressed in patients with typical left language dominance during the IAP, as the STG is also involved in language comprehension.^4,11 Indeed, overt word production was associated with high gamma activity changes in both the Wernicke's area and Broca's area. ²⁰ The findings from this rare case, where only the right STG and the majority of the right-IFG were activated during the VGT, suggest that his ability for language comprehension should largely or entirely reside within his right hemisphere. Therefore, the spatially separated functions of motor speech and language comprehension (by fMRI and Wada) can be further temporally separated (by IAP) in this case report. Combined, this report supports Broca’s initial conclusions associating acquired motor speech impairment with Broca’s area. ²¹ Moreover, these current findings also suggest that motor speech, once produced, can be independent from language comprehension in this patient, as he continued counting during the right IAP when his language comprehension ability was largely compromised; and Broca’s area was not responsible for language comprehension per se, since he could follow instructions in the left IAP when Broca’s area was under the influence of sodium amobarbital. The possibility that his ability to understand complex sentences was impaired during the left IAP cannot be excluded.

One limitation is that only the VGT was used in the clinical analysis of this current case. Although the patient was explicitly instructed to articulate the verb out (i.e. perform motor speech), very overt mouth movements were not allowed due to the nature of fMRI; and language comprehension is a prerequisite for this task in order to formulate a meaningful verb. This limitation helps explain the concordant results of the right asymmetries during the VGT task, as well as the lateralized language comprehension during the left IAP in this current patient. While this task demonstrated the highest concordance to determine Broca’s area, ⁴ it is possible that the VGT mapped only part of the patient's language skills and more complementary fMRI tasks could have generated a signal distribution more concordant with the Wada test.

In conclusion, this report described a rare patient who exhibited right asymmetries both in the IFG and STG during a VGT task during the fMRI approach, while showing a dissociation between motor speech and language comprehension during Wada testing. These current findings extend previous suggestions that the LIs obtained by fMRI should be used cautiously to identify Broca’s area in atypical patients. For example, in right-handed patients who exhibit right asymmetries both in the IFG and STG. Theoretically, this report supports Broca’s initial conclusions that Broca’s area is associated with acquired motor speech impairment, but not language comprehension per se; and once produced, motor speech can be independent from language comprehension.