FMRI reveals functional cortex in a case of inconclusive Wada testing

OBJECTIVES: The intracarotid amobarbital test (Wada test) currently represents the gold standard for preoperative lateralization of hemispheric dominance. Here, we report an epileptic patient with a longstanding extended lesion of the left hemisphere showing absence of motor and speech dysfunction with left carotid amobarbital injection, but tetraplegia and speech arrest with right carotid injection interpreted as a neuroplastic shift of motor and language functions to the right hemisphere. In contrast to the Wada results, motor functional magnetic resonance imaging (fMRI) showed a strong left hemispheric activation with right hand movements. METHODS: Right and left hand motor fMRI was performed. FMRI results and neurophysiological information obtained by motor and sensory evoked potential measurements were compared with the Wada test results. RESULTS: Initial interpretation of neuroplastic shifts of intrinsic left hemisphere functions to the right brain was revised after fMRI results which were confirmed by motor and sensory evoked potentials. CONCLUSION: As motor inactivation usually is thought to be the most robust feature of the Wada test, this case demonstrates that fMRI may reveal residual functional cortex in cases of inconclusive Wada results.     

Factors in Children That Predict Performance on the Intracarotid Amobarbital Procedure

The intracarotid amobarbital procedure (IAP) is frequently used to determine hemispheric language dominance and memory competence in individuals with intractable epilepsy before surgical intervention. The present study focused on outcome results concerning use of this technique in children. The IAP was an effective tool in determining their hemispheric language dominance. Seven characteristics, including age, gender, dose level of sodium amobarbital, Full-Scale I.Q., hemispheric side of injection (left or right), language dominance of hemisphere injected, and order of injection (first or second) were examined as possible factors predictive of memory performance on the IAP. Results suggest that after injection of the hemisphere suspected of containing the primary seizure origin, children aged < 13 years who had the left language-dominant hemisphere injected were significantly less likely to pass IAP memory tasks than were older children or younger children who had the nondominant hemisphere injected. These findings suggest that the IAP is a reliable indicator of hemispheric memory competence in children aged > 13 years or younger children whose suspected seizure focus is located in the nondominant language hemisphere.     

Language and arithmetic--a study using the intracarotid amobarbital procedure

The intracarotid amobarbital procedure is used as a standard procedure in presurgical evaluation to assess hemispheric lateralization of language and memory, but has not been applied to investigate numerical processing. Patients with medically intractable epilepsy (n=20) were consecutively recruited during a presurgical evaluation programme. All 14 patients with left-lateralized language showed better arithmetic performance with the left hemisphere (intracarotid amobarbital procedure right), while five out of six patients with bilateral or right-hemispheric language representation showed better performance with the right hemisphere (intracarotid amobarbital procedure left). Furthermore, in patients with left-lateralized language, an interaction between intracarotid amobarbital procedure and type of arithmetic operation was found. The study suggests a close association between language lateralization and hemispheric specialization for arithmetic processing.     

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: the limits of material specificity

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.     

Lateralized cognitive dysfunction and psychotic symptoms in schizophrenia

Our understanding of hemispheric asymmetries in schizophrenia can be attributed to extensive neuropsychological and neuroimaging research on this topic; however, it has yet to be determined whether lateralized cognitive dysfunction represents a single core trait in schizophrenia or whether the lateralized impairments are domain specific. To test whether lateralized deficits are core features in schizophrenia we examined performance across a wide range of lateralized cognitive domains including attention, fluency, recognition memory, perception, and arousal. We also examined the relationship between lateralized impairments and psychotic and affective symptoms to determine whether abnormal hemispheric asymmetries were possibly state-related. The sample consisted of 43 subjects with schizophrenia and 66 normal healthy comparison subjects without psychiatric illness. Schizophrenia subjects exhibited abnormal right hemisphere performance on a test of recognition memory and abnormal left hemisphere performance on a measure of arousal. These findings suggest that lateralized cognitive disturbances in schizophrenia do not represent a single core lateralized deficit. Regarding the symptom analyses, severity of positive symptoms was related to right hemisphere cognitive impairment (including fluency and recognition memory), whereas severity of negative symptoms was related to left hemisphere cognitive impairment (including fluency). Overall, our findings suggest that lateralized dysfunction can occur in both hemispheres in schizophrenia, and that the positive psychotic symptoms may relate more to right hemisphere impairment, whereas negative psychotic symptoms may related more to left hemisphere impairment.     

The role of the limbic system in experiential phenomena of temporal lobe epilepsy

Experiential phenomena occurring in spontaneous seizures or evoked by brain stimulation were reported by 18 of 29 patients with medically intractable temporal lobe epilepsy who were investigated with chronic, stereotaxically implanted intracerebral electrodes. The phenomena mainly consisted of perceptual (visual or auditory) hallucinations or illusions, memory flashbacks, illusions of familiarity, forced thinking, or emotions. Experiential phenomena did not occur unless a seizure discharge or electrical stimulation involved limbic structures. For such phenomena to occur, seizure discharge or electrical stimulation did not have to implicate temporal neocortex. This was true even for perceptual experiential phenomena. Many experiential responses elicited by electrical stimulation, particularly when applied to the amygdala, were not associated with electrical afterdischarge. Limbic activation by seizure discharge or electrical stimulation may add an affective dimension to perceptual and mnemonic data processed by the temporal neocortex, which may be required for endowing them with experiential immediacy.     

Memory following intracarotid amobarbital injection contralateral to hippocampal damage

We examined the relationship between memory performance and hippocampal damage in temporal lobe epileptics undergoing the intracarotid amobarbital sodium procedure (IAP). Overall memory performance in the course of IAP was correlated with seizure lateralization. The hemisphere of seizure focus had impaired IAP memory in 63% (19/30) of the patients. The IAP memory performance following perfusion of the hemisphere contralateral to severe hippocampal lesions was impaired in five of six patients. These patients also exhibited hypometabolism of the impaired temporal lobe as determined independently by positron emission tomography. The single patient with a severely damaged hippocampus who did not demonstrate IAP memory impairment with contralateral hemisphere injection did not exhibit perfusion of the ipsilateral posterior cerebral artery with amobarbital. Memory performance following intracarotid amobarbital injection contralateral to a less severely damaged hippocampus was impaired in 14 of 24 patients and was not related to extent of hippocampal damage, temporal lobe hypometabolism of labeled glucose, perfusion of the ipsilateral posterior cerebral artery, hemispheric language dominance, or order of injection. These results indicate that impaired memory performance during IAP may reflect severe hippocampal damage and/or epileptogenic abnormality.     

Body side of motor symptom onset in Parkinson's disease is associated with memory performance.

The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction.     

Asymmetries in the Effect of Side of Seizure Onset on Recognition Memory Following Intracarotid Amobarbital Injection

Summary: Purpose : To assess inter hemispheric differences in recognition memory for objects during the intracarotid amobarbital sodium procedure (IAP).
Methods : The recognition memory for real objects of patients with either right (RTLE, n = 28) or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after left and right intracarotid amobarbital sodium injection.
Results : There were no differences between groups on baseline performance. Performance following injection ipsilateral to the side of seizure focus was relatively lower for the LTLE as compared with the RTLE group, but this difference did not reach statistical significance. However, performance following injection contralateral to the side of seizure focus was significantly lower for the RTLE as compared with the LTLE group. Within-group differences in performance after ipsilateral as compared with contralateral injection were significant for the RTLE but not the LTLE group. The difference in inter hemispheric asymmetry in IAP memory performance between RTLE and LTLE groups was reflected in decreased ability to classify LTLE patients as compared with RTLE patients about side of seizure onset, using a clinically applicable decision rule.
Conclusions : Recognition memory during the IAP for real objects, simultaneously named and presented visually during encoding, is mediated effectively by both the left and right hemisphere when there is no seizure focus present. However, memory appears to be more vulnerable to the presence of a seizure focus in the right as compared with the left hemisphere.     

Is hemispheric language dominance relevant in musical hallucinations? Two case reports

It has been suggested that musical hallucinations are often due to a focal brain lesion predominantly of right hemispheric pathologies. We report about two patients with musical hallucinations associated with a brain tumor of the right hemisphere. Although both patients were right-handed, one of them had a right hemispheric dominance for language as proven by the Wada test. The musical ability as measured by the Seashore test was not impaired. We conclude that the language dominance of the hemisphere is not primarily relevant for the development of musical hallucinations.     

Affective self-report during the intracarotid sodium amobarbital test: group differences.

Emotional reactions are sometimes observed during the intracarotid sodium amobarbital test. For instance, euphoric/indifference reactions can be seen during right hemisphere inactivation and catastrophic reactions may accompany left hemisphere inactivation. Less dramatic changes can also be detected in affective self-report during left and right hemisphere amobarbital tests, with more negative affect reported during left hemisphere inactivation and either neutral or mildly positive affective states reported during right hemisphere inactivation. The current study not only replicated this effect, but in addition, found significant group differences. The first group (right way) showed a pattern of affective self-report during left and right amobarbital tests entirely consistent with prior findings, while a second group (wrong way) showed results that behaved in a diametrically opposite fashion. A third group (no change) showed little, if any, difference in affective self-report during left and right amobarbital tests. The major factor distinguishing the wrong way group from the other two appeared to be an asymmetrical distribution of left and right temporal lobe lesions in the former group. In contrast, the factor differentiating the right way group from the no change group appeared to be the relative degree of left hemisphere inactivation during the left hemisphere amobarbital test. The results are discussed not only in terms of their impact on theories of cerebral lateralization for emotion, but also in terms of methodological issues in this field.     

Cerebral language lateralization: evidence from intracarotid amobarbital testing

Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable.     

Disturbances of the body schema in relation to language impairment and hemispheric locus of lesion

The relationship of disturbances of the body schema to hemispheric locus of lesion and sensory aphasic disorder was assessed by giving verbal and non-verbal tests of right-left orientation, finger recognition, and autotopagnosis to patients with unilateral cerebral disease. The study was restricted to right-handed patients who were free from general mental impairment or confusion. The tests were also given to a group of control patients whose performances defined the range of normal performance in each test. A significant proportion of patients with sensory aphasic disorder performed defectively on all the tests, non-verbal as well as verbal, the relative frequency of failure in this group ranging from 10 to 67% for the different tests. There were, however, a number of patients with sensory aphasic disorder who performed adequately on most of the tests. Defective performance on the part of non-aphasic patients with lesions of either the left or the right hemisphere was quite rare in the case of 19 of the 20 tests. The exceptional test was the task of imitating lateral movements from Head's battery, on which both non-aphasic groups performed relatively poorly. The patients with lesions of the right hemisphere were significantly inferior to those with left hemisphere disease on this test. The findings are interpreted as indicating that sensory aphasic disorder is a necessary but not sufficient condition for the occurrence of some types of bilateral `body schema' disturbance in patients with unilateral disease. It is postulated that the sufficient condition is a combination of aphasic disorder with somatosensory impairment. Bilateral impairment of the `body schema' does not appear to have a differential relationship to hemispheric locus of lesion per se.     

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low‐intensity with depth electrodes implanted in the occipito‐parieto‐temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito‐parieto‐temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Hum Brain Mapp 35:3360–3371, 2014. © 2013 Wiley Periodicals, Inc .     

Linguistic perseveration in dominant-side intracarotid amobarbital tests.

148 patients with medically intractable complex-partial seizures received bilateral intracarotid amobarbital tests. In 21 patients (14.2%), there were inappropriate responses (intrusions: N = 10; perseverations: N = 11) to a series repetition task (counting backwards) given immediately before amobarbital injection. Five cases from the perseveration subgroup are discussed in detail. In these patients, linguistic perseveration occurred with left-sided amobarbital injection, although they were all found to have left hemispheric speech dominance according to language testing during the amobarbital procedure. It is argued that these perseverations are best explained as a right hemispheric continuation of a speech motor program previously initiated by the left hemisphere.     

Replication of an evoked potential study of lateralized hemispheric dysfunction in schizophrenics

Visual (VEP) and auditory (AEP) evoked potentials (EPs) were measured to replicate previous findings concerning lateralized hemispheric dysfunction in chronic schizophrenic patients in a new sample. Measures of EP waveform stability (Zr') showed greater hemispheric asymmetry in 26 unmedicated chronic schizophrenics than in 26 matched nonpatients, and relatively lower left and right hemisphere values in schizophrenics. Similar hemispheric differences were not found between medicated patients and matched nonpatients; medication was associated with higher left and lower right hemisphere stability. EP amplitudes were lower with medications, the lowest amplitudes found in patients receiving nonphenothiazine or nonpiperazines as opposed to phenothiazine-piperazine drugs. Medications were associated with amplitude asymmetries not observed in unmedicated patients. This study confirms greater than normal hemispheric asymmetry of VEP and AEP waveshape stability measures in chronic schizophrenics, and lower left than right hemisphere stability suggesting left hemisphere dysfunction. Alteration of EP asymmetries by antipsychotic medications suggests that medication effects may obscure evidence of lateralized dysfunction in schizophrenics.     

Neuropsychological laterality indices of schizophrenia: interactions with gender

Neurobehavioral laterality indices were examined across motor, sensory, language versus spatial, and verbal memory versus spatial memory domains for 75 patients with schizophrenia (45 men, 30 women) and 75 demographically matched healthy controls. Patients were impaired across tasks, and laterality results varied by domain. There was no evidence for diagnosis by hemisphere interactions in motor, sensory, or memory tasks. However, patients were more impaired in language than in spatial domains, which suggests relatively greater left hemisphere dysfunction. This finding was mediated by the sex of the participant. While patients as a group showed greater language than spatial impairment, male patients showed expected superiority in spatial relative to language performance, whereas female patients performed the same on both functions. These results underscore the importance of examining sex differences in laterality effects. The findings also demonstrate that, although the left hemisphere model of schizophrenia may be partially supported by data on higher cognitive functions, this support does not extend to more basic motor and sensory domains.     

Hemispheric asymmetry in categorical versus coordinate visuospatial processing revealed by temporary cortical deactivation.

Kosslyn (1987) proposed that the left hemisphere is better than the right hemisphere at categorical visuospatial processing while the right hemisphere is better than the left hemisphere at coordinate visuospatial processing. In 134 patients, one hemisphere (and then usually the other) was temporarily deactivated by intracarotid injection of sodium amobarbital. After a hemisphere was deactivated, a cognitive test battery was conducted, which included categorical and coordinate visuospatial tasks. Using this technique, the processing capabilities of the intact hemisphere could be determined, thus directly testing Kosslyn's hypothesis regarding hemispheric specialization. Specifically, if the left hemisphere does preferentially process categorical visuospatial relationships, then its deactivation should result in more errors during categorical tasks than right hemisphere deactivation and vise versa for the right hemisphere regarding coordinate tasks. The pattern of results obtained in both categorical and coordinate tasks was consistent with Kosslyn's hypothesis when task difficulty was sufficiently high. However, when task difficulty was low, a left hemispheric processing advantage was found for both types of tasks indicating that: (1) the left hemisphere may be better at "easy" tasks regardless of the type of task and (2) the proposed hemispheric processing asymmetry may only become apparent during sufficiently demanding task conditions. These results may explain why some investigators have failed to find a significant hemispheric processing asymmetry in visuospatial categorical and coordinate tasks.     

Alexithymia, gender, and hemispheric functioning

It has been hypothesized that alexithymia is related to an impairment of the right hemisphere or a deficiency in interhemispheric transfer. We used the Toronto Alexithymia Scale-20 (TAS-20) and the tactile finger localization task of Zeitlin et al. to test these relationships on nonclinical samples of college men and women, and also considered the role of short-term memory. Among 47 men, the TAS-20 facets of difficulty identifying feelings or difficulty describing feelings were correlated with poorer performance by the right compared with the left hemisphere in uncrossed trials and poorer interhemispheric transfer of information on crossed trials; short-term memory was not related. Thus, both hemispheric hypotheses were supported for men. However, among 58 women, alexithymia was completely unrelated to either index of hemispheric functioning; instead, poorer short-term memory (specifically digits backwards) strongly predicted poorer interhemispheric transfer. We conclude that deficiencies in right hemisphere function and interhemispheric transfer may contribute to alexithymia in men, but not in women.