3D mapping of language networks in clinical and pre-clinical Alzheimer's disease

We investigated the associations between Boston naming and the animal fluency tests and cortical atrophy in 19 probable AD and 5 multiple domain amnestic mild cognitive impairment patients who later converted to AD. We applied a surface-based computational anatomy technique to MRI scans of the brain and then used linear regression models to detect associations between animal fluency and Boston Naming Test (BNT) performance and cortical atrophy. The global permutation-corrected significance for the maps associating BNT performance with cortical atrophy was p=.0124 for the left and p=.0196 for the right hemisphere and for the animal fluency maps p=.055 for the left and p=.073 for the right hemisphere. The degree of language impairment correlated with cortical atrophy in the left temporal and parietal lobes (BA 20, 21, 37, 39, 40, and 7), bilateral frontal lobes (BA 8, 9, and 44) and the right temporal pole (BA 38). Using a novel 3D mapping technique, we demonstrated that in AD language abilities are strongly influenced by the integrity of the perisylvian cortical regions.     

Comparison of metabolic rates, language, and memory in subcortical aphasias

Four patients with subcortical lesions and either aphasia or amnesia were compared to four patients with cortical lesions and aphasia. Each patient had [18F] fluorodeoxyglucose positron-emission computed tomography, language, and memory evaluations. Marked metabolic depression was found in the thalamus and caudate in all patients. The subcortical patients had only mild left-cortical changes, while the cortical patients showed marked cortical metabolic changes in the left hemisphere. Language changes were mild in the subcortical patients, while moderate to severe in the cortical patients. All patients showed severe verbal memory dysfunction. The only common abnormalities in the two groups were metabolic changes in the thalamus and severity of verbal memory dysfunction. These findings suggest a relationship between verbal memory and thalamic function.     

Subcortical functions in language: A working model

The current paper explains a model of subcortical language functions that focuses on dynamic interactions between the cortex, the thalamus, and the basal ganglia in the production of spoken language. The model was derived from (a) studies of subcortical lesions and language, (b) studies of subcortical stimulation and language, (c) knowledge regarding neural pathways between various cortical and subcortical structures, and (d) indications that preverbal monitoring of language occurs. In the current model, the thalamus plays roles in cortical arousal and activation and in preverbal semantic monitoring. The basal ganglia function to regulate the degree of excitation conveyed from the thalamus to the cortex and to time the release of formulated language for motor programming. Consistency with classical syndromes of aphasia and potential applications to other areas in the neurosciences are discussed. The current theory, unlike previous formulations, is specific enough that testable hypotheses can be derived.     

Brain Organization of Language after Early Unilateral Lesion: A PET Study

Neuropsychological studies suggest that good long-term language outcome is possible following extensive early left-hemisphere damage. We explored the brain organization for language in children with early unilateral lesion, using [¹⁵O]-water PET. In 12 patients with left lesion (LL) and 9 patients with right lesion (RL), cerebral blood flow changes during listening to sentences and repetition were studied. A rightward shift of language activations in the LL group was found in perisylvian areas and multiple other, mostly temporo-parietal, regions. The hypothesis of intrahemispheric reorganization in the LL group found only limited support. The number of activated regions was overall greater in the RL group. Unexpected findings included a stronger subcortical and cerebellar language involvement in the RL group. We suggest that (a) early left lesion is associated with enhanced language participation of the right hemisphere in and beyond the classical language areas, and (b) postlesional effects are in part additive (recruitment of noncanonical areas), in part subtractive (functional depression in areas normally involved in language).     

Language function and dysfunction among Chinese- and English-speaking polyglots: Cortical stimulation, Wada Testing, and clinical studies

Language functions in a group of Chinese- and English-speaking polyglots living in a multiracial society have been investigated by several methods: the effects of cortical stimulation on object-naming and reading tasks in patients who required awake craniotomy, lateralization of cerebral dominance for speech by the Wada Test, and the pattern of language loss and recovery following stroke. The data indicate that these polyglots were all left hemisphere dominant for the languages tested: no consistent evidence for increased participation by the right hemisphere for language functions was found. The cortical stimulation experiments provided data most compatible with the "differential localization" model of cerebral localization in bilingualism. The variable which most influenced performance in all of these investigations was which language was used primarily for speaking as well as reading and writing at the time of the study.     

Structural connectivity between the hippocampus and cortical/subcortical area relates to cognitive impairment in schizophrenia but not in mood disorders

Cognitive impairment in schizophrenia and other psychiatric disorders is a challenge to be overcome in order to maintain patients' quality of life and social function. The neurological pathogenesis of cognitive impairment requires further elucidation. In general, the hippocampus interacts between the cortical and subcortical areas for information processing and consolidation and has an important role in memory. We examined the relationship between structural connectivity of the hippocampus and cortical/subcortical areas and cognitive impairment in schizophrenia, major depressive disorder and bipolar disorder. Subjects comprised 21 healthy controls, 19 patients with schizophrenia, 20 patients with bipolar disorder and 18 patients with major depressive disorder. Diffusion-weighted tensor images data were processed using ProbtrackX2 to calculate the structural connectivity between the hippocampus and cortical/subcortical areas. Cognitive function was assessed using the Brief Assessment of Cognition in schizophrenia composite score. Hippocampal structural connectivity index was significantly correlated with composite score in the schizophrenia group but not in the healthy control, major depressive disorder or bipolar disorder groups. There were no statistically significant differences in hippocampal structural connectivity index between the four groups. Structural connectivity between the hippocampus and cortical/subcortical areas is suggested to be a pathophysiological mechanism of comprehensive cognitive impairment in schizophrenia.     

Performance in picture naming and word comprehension: evidence for common neuronal substrates from intraoperative language mapping

Correlations of naming ability and performance in the Token Test are known from aphasia; however, the mechanisms underlying these correlations are unclear. Naming tasks are commonly used in intraoperative mapping for identification of cortical areas involved in language processing. In the present study, we measured performance in an elementary Token Test task, i.e., single word comprehension, during electrical stimulation of cortical sites at which this stimulation previously had disturbed the naming process. It was found that at about half of the sites at which naming could be disturbed electrical stimulation also led to disturbances in Token Test performance, indicating that there are common neural structures critical for performance in both tasks. These findings are discussed in terms of a multilayered semantic network in which the level of the simultaneous binding of features into concepts and the level of units that are organized with respect to semantic relations may be disturbed separately.     

Bilingual Performance on the Boston Naming Test: Preliminary Norms in Spanish and English

A total of 100 young educated bilingual adults were administered the Boston Naming Test (BNT) (Kaplan, Goodglass, & Weintraub, 1983) in both Spanish and English. Three group performance scores were obtained: English only, Spanish only, and a composite score indicating the total number of items correctly named independent of language. The scores for the entire group were significantly greater in English than in Spanish. An additional set of analyses explored individual differences in picture naming performance across the two languages as measured by the BNT. For a subset of the larger group (n= 25) there were significant differences in composite over single language scoring, but no significant differences between Spanish and English. Item analyses of correct responses were conducted in both languages to explore the construct validity of the standardized administration of the BNT with this population. There was much greater variability in responses over the Spanish items for this bilingual group. The results of a correlation analysis of information obtained from the initial questionnaire with the BNT scores in each language is also reported. The practical implications of this preliminary bilingual BNT normative data are discussed.     

Prediction of Boston Naming Test performance from vocabulary scores: preliminary guidelines for interpretation.

Patients with limited education or underdeveloped vocabulary skills may perform below the normal range on the Boston Naming Test when compared to the original published norms, even in the absence of brain damage. To reduce the frequency of false positive dysnomic classifications of patients with limited vocabulary skills, we developed a score adjustment to account for the significant shared variance between scores on this test and the WAIS-R Vocabulary subtest. Vocabulary significantly predicted performance on the Boston Naming Test (r = .65, p < .0001) in a sample of 62 outpatients who had no objective evidence of brain damage. Linear regression was used to derive expected performance on the Boston Naming Test from Vocabulary scaled scores. Relative to the original published norms, scores based on the Vocabulary subtest cut-offs produced fewer false positives and more accurately classified group membership for patients with and without objectively verified brain damage. These performance predictions are offered as tentative guidelines to assist clinicians in evaluating the presence of naming deficits by controlling for the variance associated with knowledge of vocabulary.     

The Boston Naming Test: Norm data and cue utilization in a sample of normal 6- and 7-year-old children

The object-naming abilities of 83 normal children were examined using the Boston Naming Test developed by E. Kaplan, H. Goodglass, and S. Weintraub (1976, The Boston Naming Test (experimental edition), unpublished test, Veterans Hospital, Boston, Massachusetts). There is currently a lack of available norms for this instrument, especially for populations of younger children. Cue utilization in this sample is explored and attention is focused upon possible gender differences in naming performance and cue strategies. Seven summary scores derived from the test are presented in this report. Results indicate that the Boston Naming Test can discriminate within a normal population sample of young children and provides a relatively normal distribution for six of seven derived scores. Boys were found to have a significantly greater number of items correctly named but no gender differences in cue utilization were evident. A major proportion of the children in this sample of 6- and 7-year-olds used phonological cues almost exclusively, rather than semantic cues also provided. Cue use was not related to age or spontaneously given responses, and none of the children were found to be highly proficient at using both types of cues.     

Cerebral asymmetry for speech in neonates: A behavioral measure

This paper reports a finding of hemispheric brain asymmetry for speech in short-gestation infants (mean gestational AGE = 36 weeks). Using a new measure—degree of reduction in limb tremors following exposure to speech stimuli compared to two control groups, one hearing orchestral music, the other no patterned stimuli—we found that speech disproportionately affected right limb movements. It is not clear whether the effect is due to asymmetries in cortical or subcortical processing. This provides evidence against the notion that brain specialization for language functions necessarily appears over time; rather, specialization for some functions (e.g., speech reception) must be present at birth.     

Sigmund Freud and the diagram-maker school of aphasiology.

Published 100 years ago, Freud's monograph on aphasia, Zur Auffassung der Aphasien, is an incisive analysis of the so-called diagram-makers, those aphasiologists who would reduce brain and language to simple schemes of circumscribed cortical centers linked by unidirectional subcortical pathways. Chief architects of the diagram-maker school were Wernicke and Lichtheim, and their formulations of conduction aphasia and the transcortical aphasias were particular targets of Freud's trenchant criticism. Freud argued against functional differentiation within left hemisphere perisylvian language regions, and he suggested that traditional aphasic syndromes were artifacts of lesions that included cortical language regions and deeper white matter pathways not directly involved with language. He provided an innovative classification of aphasia based on types of associations presumed to be affected. Freud, however, failed to adduce new clinical or pathological observations; he was perhaps unnecessarily harsh in challenging authorities in the field of aphasia; and his theory had to compete with a straightforward and already entrenched anatomical view of language representation. Despite Freud's lucid argumentation, his carefully crafted monograph was never widely noted.     

Analysis of voice impairment in aphasia after stroke-underlying neuroanatomical substrates

Phonation is a fundamental feature of human communication. Control of phonation in the context of speech-language disturbances has traditionally been considered a characteristic of lesions to subcortical structures and pathways. Evidence suggests however, that cortical lesions may also implicate phonation. We carried out acoustic and perceptual analyses of the phonation of /a/ in 60 males with aphasia (20 Wernicke's, 20 Broca's, 20 subcortical aphasia) and 20 males matched in age with no neurological or speech-language disturbances. All groups with aphasia were significantly more impaired on the majority of acoustic and perceptual measures as compared with the control speakers. Within the subjects with aphasia, subjects with subcortical aphasia were more impaired on most measures compared to subjects with Broca's aphasia, and they, in turn, more impaired than those with Wernicke's aphasia. Lesions in regions involved in sound production-perception result in dysfunction of the entire neurocognitive system of articulation-phonological language processing.     

Subcortical Aphasia

We critically review the literature on subcortical aphasia, suggest that a number of traditional concepts regarding mechanisms of aphasia are inconsistent with now abundant data, and propose several new hypotheses. The absence of aphasia in 17 reported cases of dominant hemisphere striatocapsular infarction and the finding of nearly every conceivable pattern of language impairment in 33 different reported cases of striatocapsular infarction provide strong evidence against a major direct role of the basal ganglia in language and against disconnection or diaschisis as mechanisms of nonthalamic subcortical aphasia. However, detailed consideration of the vascular events leading to striatocapsular infarction strongly suggests that associated linguistic deficits are predominantly related to sustained cortical hypoperfusion and infarction not visible on structural imaging studies. Thalamic disconnection, as may occur with striatocapsular infarcts with extension to the temporal stem and putamenal hemorrhages, may also contribute to the language deficits in some patients. Review of the literature on thalamic infarction, in conjunction with previously unreported anatomic details of four cases, suggests that what infarcts in the tuberothalamic artery territory and the occasional infarcts in the paramedian artery territory associated with aphasia have in common is damage to the frontal lobe–inferior thalamic peduncle–nucleus reticularis–center median system that may be involved in regulating the thalamic gate in attentional processes. Disruption of attentional gating in the pulvinar and lateral posterior nuclei resulting from such lesions may impair selection of specific neuronal networks in the projection field of these nuclei that serve as the substrate for lexical–semantic function, which is in effect a disruption of a type of working memory, as defined by Goldman–Rakic. We define this as a defect of selective engagement.     

The opercular-subopercular syndrome: four cases with review of the literature

We present four cases of the 'opercular syndrome' of volitional paresis of the facial, lingual, and laryngeal muscles (bilateral facio-glosso-pharyngo-masticatory paresis). Case histories and CT brain images are presented, along with a review of the literature concerning this long-recognized but little-known syndrome. The neuroanatomic basis of the syndrome classically involves bilateral lesions of the frontal operculum. We propose, on the basis of our cases and others, that the identical syndrome can arise from lesions of the corticobulbar tracts, not involving the cortical operculum. Our cases included one with bilateral subcortical lesions, one with a unilateral left opercular lesion and a possible, non-visualized right hemisphere lesion, one with unilateral cortical and unilateral subcortical pathology, and one with bilateral cortical lesions. These lesion localizations suggest that any combination of cortical or subcortical lesions of the operculum or its connections on both sides of the brain can produce a syndrome indistinguishable from the classical opercular syndrome. We propose the new term 'opercular-subopercular syndrome' to encompass cases with predominantly or partially subcortical lesions.     

Neuroanatomical profiles of bilingual children

The goal of the present study was to examine differences in cortical thickness, cortical surface area, and subcortical volume between bilingual children who are highly proficient in two languages (i.e., English and Spanish) and bilingual children who are mainly proficient in one of the languages (i.e., Spanish). All children (N = 49) learned Spanish as a native language (L1) at home and English as a second language (L2) at school. Proficiency of both languages was assessed using the standardized Woodcock Language Proficiency Battery. Five‐minute high‐resolution anatomical scans were acquired with a 3‐Tesla scanner. The degree of discrepancy between L1 and L2 proficiency was used to classify the children into two groups: children with balanced proficiency and children with unbalanced proficiency. The groups were comparable on language history, parental education, and other variables except English proficiency. Values of cortical thickness and surface area of the transverse STG, IFG‐pars opercularis, and MFG, as well as subcortical volume of the caudate and putamen, were extracted from FreeSurfer. Results showed that children with balanced bilingualism had thinner cortices of the left STG, left IFG, left MFG and a larger bilateral putamen, whereas unbalanced bilinguals showed thicker cortices of the same regions and a smaller putamen. Additionally, unbalanced bilinguals with stronger foreign accents in the L2 showed reduced surface areas of the MFG and STS bilaterally. The results suggest that balanced/unbalanced bilingualism is reflected in different neuroanatomical characteristics that arise from biological and/or environmental factors.     

Dichotic listening pattern in conduction aphasia

This paper reports a finding of hemispheric brain asymmetry for speech in short-gestation infants (mean gestational age = 36 weeks). Using a new measure—degree of reduction in limb tremors following exposure to speech stimuli compared to two control groups, one hearing orchestral music, the other no patterned stimuli—we found that speech disproportionately affected right limb movements. It is not clear whether the effect is due to asymmetries in cortical or subcortical processing. This provides evidence against the notion that brain specialization for language functions necessarily appears over time; rather, specialization for some functions (e.g., speech reception) must be present at birth.     

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer's disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.     

Performance of normal elderly on the Boston Naming Test

The Boston Naming Test has enjoyed increasing use in many research studies since its introduction. However, there is little normative data on the age group above 60 years of age. This study presents data from a sample of 58 well-defined healthy elderly males and females between the ages of 60 and 85. In comparison with published normative data, our sample has higher means, smaller standard deviations, and narrower ranges. These results suggest that aging alone does not significantly alter recognition-cued word-finding ability as defined by the Boston Naming Test. Also there is remarkably consistent performance throughout our age range.     

Language Mapping with Verbs and Sentences in Awake Surgery: A Review

Intraoperative language mapping in awake surgery is typically conducted by asking the patient to produce automatic speech and to name objects. These tasks might not map language with sufficient accuracy, as some linguistic processes can only be triggered by tasks that use verbs and sentences. Verb and sentence processing tasks are currently used during surgery, albeit sparsely. Medline, PubMed, and Web of Science records were searched to retrieve studies focused on language mapping with verbs/sentences in awake surgery. We review the tasks reported in the published literature, spell out the language processes assessed by each task, list the cortical and subcortical regions whose stimulation inhibited language processing, and consider the types of errors elicited by stimulation in each region. We argue that using verb tasks allows a more thorough evaluation of language functions. We also argue that verb tasks are preferable to object naming tasks in the case of frontal lesions, as lesion and neuroimaging data demonstrate that these regions play a critical role in verb and sentence processing. We discuss the clinical value of these tasks and the current limitations of the procedure, and provide some guidelines for their development. Future research should aim toward a differentiated approach to language mapping – one that includes the administration of standardized and customizable tests and the use of longitudinal neurocognitive follow-up studies. Further work will allow researchers and clinicians to understand brain and language correlates and to improve the current surgical practice.