Thalamic aphasia secondary to glioblastoma multiforme.

BACKGROUND: Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. CASE PRESENTATION: A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. CONCLUSIONS: This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions.

The white matter architecture underlying semantic processing: A systematic review.

From a holistic point of view, semantic processes are subserved by large-scale subcortico-cortical networks. The dynamic routing of information between grey matter structures depends on the integrity of subcortical white matter pathways. Nonetheless, controversy remains on which of these pathways support semantic processing. Therefore, a systematic review of the literature was performed with a focus on anatomo-functional correlations obtained from direct electrostimulation during awake tumor surgery, and conducted between diffusion tensor imaging metrics and behavioral semantic performance in healthy and aphasic individuals. The 43 included studies suggest that the left inferior fronto-occipital fasciculus contributes to the essential connectivity that allows semantic processing. However, it remains uncertain whether its contributive role is limited to the organization of semantic knowledge or extends to the level of semantic control. Moreover, the functionality of the left uncinate fasciculus, inferior longitudinal fasciculus and the posterior segment of the indirect arcuate fasciculus in semantic processing has to be confirmed by future research.

Pure word deafness following left temporal damage: Behavioral and neuroanatomical evidence from a new case.

Pure Word Deafness (PWD) is a rare disorder, characterized by selective loss of speech input processing. Its most common cause is temporal damage to the primary auditory cortex of both hemispheres, but it has been reported also following unilateral lesions. In unilateral cases, PWD has been attributed to the disconnection of Wernicke's area from both right and left primary auditory cortex. Here we report behavioral and neuroimaging evidence from a new case of left unilateral PWD with both cortical and white matter damage due to a relatively small stroke lesion in the left temporal gyrus. Selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading and writing. Performance on dichotic listening was characterized by a reversal of the right-ear advantage typically observed in healthy subjects. Cortical thickness and gyral volume were severely reduced in the left superior temporal gyrus (STG), although abnormalities were not uniformly distributed and residual intact cortical areas were detected, for example in the medial portion of the Heschl's gyrus. Diffusion tractography documented partial damage to the acoustic radiations (AR), callosal temporal connections and intralobar tracts dedicated to single words comprehension. Behavioral and neuroimaging results in this case are difficult to integrate in a pure cortical or disconnection framework, as damage to primary auditory cortex in the left STG was only partial and Wernicke's area was not completely isolated from left or right-hemisphere input. On the basis of our findings we suggest that in this case of PWD, concurrent partial topological (cortical) and disconnection mechanisms have contributed to a selective impairment of speech sounds. The discrepancy between speech and non-speech sounds suggests selective damage to a language-specific left lateralized network involved in phoneme processing.

Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc.

Lesion localization of speech comprehension deficits in chronic aphasia.

OBJECTIVE: Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension. METHODS: Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language. RESULTS: ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG). CONCLUSIONS: Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia.

Lesion symptom mapping of manipulable object naming in nonfluent aphasia: can a brain be both embodied and disembodied?

Embodied cognition offers an approach to word meaning firmly grounded in action and perception. A strong prediction of embodied cognition is that sensorimotor simulation is a necessary component of lexical-semantic representation. One semantic distinction where motor imagery is likely to play a key role involves the representation of manufactured artefacts. Many questions remain with respect to the scope of embodied cognition. One dominant unresolved issue is the extent to which motor enactment is necessary for representing and generating words with high motor salience. We investigated lesion correlates of manipulable relative to nonmanipulable name generation (e.g., name a school supply; name a mountain range) in patients with nonfluent aphasia (N = 14). Lesion volumes within motor (BA4, where BA = Brodmann area) and premotor (BA6) cortices were not predictive of category discrepancies. Lesion symptom mapping linked impairment for manipulable objects to polymodal convergence zones and to projections of the left, primary visual cortex specialized for motion perception (MT/V5+). Lesions to motor and premotor cortex were not predictive of manipulability impairment. This lesion correlation is incompatible with an embodied perspective premised on necessity of motor cortex for the enactment and subsequent production of motor-related words. These findings instead support a graded or "soft" approach to embodied cognition premised on an ancillary role of modality-specific cortical regions in enriching modality-neutral representations. We discuss a dynamic, hybrid approach to the neurobiology of semantic memory integrating both embodied and disembodied components.

Facilitation of naming in aphasia with auditory repetition: an investigation of neurocognitive mechanisms.

Prior phonological processing can enhance subsequent picture naming performance in individuals with aphasia, yet the neurocognitive mechanisms underlying this effect and its longevity are unknown. This study used functional magnetic resonance imaging to examine the short-term (within minutes) and long-term (within days) facilitation effects from a phonological task in both participants with aphasia and age-matched controls. Results for control participants suggested that long-term facilitation of subsequent picture naming may be driven by a strengthening of semantic-phonological connections, while semantic and object recognition mechanisms underlie more short-term effects. All participants with aphasia significantly improved in naming accuracy following both short- and long-term facilitation. A descriptive comparison of the neuroimaging results identified different patterns of activation for each individual with aphasia. The exclusive engagement of a left hemisphere phonological network underlying facilitation was not revealed. The findings suggest that improved naming in aphasia with phonological tasks may be supported by changes in right hemisphere activity in some individuals and reveal the potential contribution of the cerebellum to improved naming following phonological facilitation. Conclusions must be interpreted with caution, however, due to the comparison of corrected group control results to that of individual participants with aphasia, which were not corrected for multiple comparisons.

Clinical properties of regional thalamic hemorrhages.

BACKGROUND: Thalamic hemorrhage constitutes 6% to 25% of intracerebral hemorrhages. Vascular lesions affecting the thalamus may cause a variety of clinical symptoms. This retrospective study aims to evaluate localization of hemorrhage and clinical symptoms in patients with thalamic hemorrhage. METHODS: One hundred and one patients with thalamic hemorrhage were examined retrospectively in our department. Hemorrhages were classified into 5 groups according to computed tomography: medial (thalamoperforate), anterolateral (tuberothalamic), posterolateral (thalamogeniculate), dorsal (posterior choroidal), and global. The relation between volume, localization, and penetration to adjacent structures/ventricles of hemorrhage and risk factors, clinical features, and prognosis were evaluated. RESULTS: The study group included 101 patients. Eighty-two percent of the patients had hypertension, 19.8% had diabetes mellitus, 14.9% had cardiac disease, and 5.9% had chronic renal failure. Mean blood pressure was 173/101 mm Hg. Decreased Glasgow coma scale was significantly higher in the global hemorrhage group than in all regional groups (Chi-square, 10.54; P = .002). Medial group hemorrhages had a significantly higher rate than anterolateral, posterolateral, and dorsal intraventricular expansion. Out of speech disorders, 49% of patients had a right thalamic lesion (especially dysarthria) and 51% of patients had a left thalamic lesion (mostly aphasia). CONCLUSIONS: In the study, we detected that the most important risk factor in thalamic hemorrhage is hypertension. The prognosis is worse in global and medial group hemorrhages, especially those which rupture to the ventricle, than the other groups. Thalamic lesions cause a variety of symptoms, including forms of aphasia, such as crossed dextral aphasia.

Differential involvement of the left frontal and temporal regions in verb naming: a tDCS treatment study.

PURPOSE: In aphasic patients, some studies have already emphasized the efficacy of transcranial direct current stimulation (tDCS) during the treatment of noun retrieval deficits. To date, in the same population, there are have been no studies addressing tDCS effects in the recovery of verb retrieval deficits. In this study, we wanted to test the potential of tDCS to improve verb production in a group of aphasic patients. METHODS: Seven chronic subjects participated in an intensive language training for their difficulties in action naming. Each subject was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different conditions: anodic tDCS over Wernicke's area, anodic tDCS and sham stimulation over Broca's area. Each experimental condition was performed in five consecutive daily sessions over three weeks with 6 days of intersession interval. RESULTS: In all patients, results showed a significantly better response accuracy during the anodic tDCS over Broca's area with respect to the other two conditions which still persisted at one month after the end of the treatment suggesting a long-term effect on the recovery of their verb retrieval deficits. CONCLUSION: These findings further confirm that tDCS represents a useful new therapeutic interventions for the rehabilitation of lexical deficits in aphasic patients.

The dorsal stream contribution to phonological retrieval in object naming.

Meaningful speech, as exemplified in object naming, calls on knowledge of the mappings between word meanings and phonological forms. Phonological errors in naming (e.g. GHOST named as 'goath') are commonly seen in persisting post-stroke aphasia and are thought to signal impairment in retrieval of phonological form information. We performed a voxel-based lesion-symptom mapping analysis of 1718 phonological naming errors collected from 106 individuals with diverse profiles of aphasia. Voxels in which lesion status correlated with phonological error rates localized to dorsal stream areas, in keeping with classical and contemporary brain-language models. Within the dorsal stream, the critical voxels were concentrated in premotor cortex, pre- and postcentral gyri and supramarginal gyrus with minimal extension into auditory-related posterior temporal and temporo-parietal cortices. This challenges the popular notion that error-free phonological retrieval requires guidance from sensory traces stored in posterior auditory regions and points instead to sensory-motor processes located further anterior in the dorsal stream. In a separate analysis, we compared the lesion maps for phonological and semantic errors and determined that there was no spatial overlap, demonstrating that the brain segregates phonological and semantic retrieval operations in word production.

The differential contributions of pFC and temporo-parietal cortex to multimodal semantic control: exploring refractory effects in semantic aphasia.

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

"Are there lexicons?" A study of lexical and semantic processing in word-meaning deafness suggests "yes".

A controversial issue in the cognitive neuroscience of language is the question whether independent lexical representations need to be included in cognitive models. Recent models claim to account for the available data without including phonological or orthographic lexicons. These models base their lexical decision ("Is it a word or not?") either on familiarity of the input string or alternatively, on semantic information. These two alternatives were evaluated in a series of experiments with an individual suffering from word-meaning deafness. This is a rare disorder of auditory word comprehension which affects mapping of a word's phonology to its meaning. The participant, BB, was unaffected by the 'word-likeness' of nonwords with comparable accuracy for plausible and abstruse nonwords. She was further able to make lexical decisions despite her severe impairment in comprehending the word's meaning. Lexical and semantic processing were assessed on an item-specific basis providing a methodological advancement over previous studies. The comprehension tasks involved word-picture matching as well as definition tasks. The results suggest that BB's lexical decisions are based neither on familiarity of the input string nor on semantic information, which was largely unavailable. The only alternative are lexical representations on which she could base her decisions.

Speech perception, rapid temporal processing, and the left hemisphere: a case study of unilateral pure word deafness.

The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. One way to investigate the cognitive and neural underpinnings of speech perception is by investigating patients with speech perception deficits but with preserved ability in other domains of language. One such case is reported here: patient NL shows highly impaired speech perception despite normal hearing ability and preserved semantic knowledge, speaking, and reading ability, and is thus classified as a case of pure word deafness (PWD). NL has a left temporoparietal lesion without right hemisphere damage and DTI imaging suggests that he has preserved cross-hemispheric connectivity, arguing against an account of PWD as a disconnection of left lateralized language areas from auditory input. Two experiments investigated whether NL's speech perception deficit could instead result from an underlying problem with rapid temporal processing. Experiment 1 showed that NL has particular difficulty discriminating sounds that differ in terms of rapid temporal changes, be they speech or non-speech sounds. Experiment 2 employed an intensive training program designed to improve rapid temporal processing in language impaired children (Fast ForWord; Scientific Learning Corporation, Oakland, CA) and found that NL was able to improve his ability to discriminate rapid temporal differences in non-speech sounds, but not in speech sounds. Overall, these data suggest that patients with unilateral PWD may, in fact, have a deficit in (left lateralized) temporal processing ability, however they also show that a rapid temporal processing deficit is, by itself, unable to account for this patient's speech perception deficit.

The role of Broca's area in regular past-tense morphology: an event-related potential study.

It has been suggested that damage to anterior regions of the left hemisphere results in a dissociation in the perception and lexical activation of past-tense forms. Specifically, in a lexical-decision task in which past-tense primes immediately precede present-tense targets, such patients demonstrate significant priming for irregular verbs (spoke-speak), but, unlike control participants, fail to do so for regular verbs (looked-look). Here, this behavioral dissociation was first confirmed in a group of eleven patients with damage to the pars opercularis (BA 44) and pars triangularis (BA 45) of the left inferior frontal gyrus (i.e., Broca's area). Two conditions containing word-onset orthographic-phonological overlap (bead-bee, barge-bar) demonstrated that the disrupted regular-verb priming was accompanied by, and covaried with, disrupted ortho-phonological priming, regardless of whether prime stimuli contained the regular inflectional rhyme pattern. Further, the dissociation between impaired regular-verb and preserved irregular-verb priming was shown to be continuous rather than categorical; priming for weak-irregular verbs (spent-spend) was intermediate in size between that of regular verbs and strong verbs. Such continuous dissociations grounded in ortho-phonological relationships between present- and past-tense forms are predicted by single-system, connectionist approaches to inflectional morphology and not predicted by current dual-system, rule-based models. Event-related potential data demonstrated that N400 priming effects were intact for both regular and irregular verbs, suggesting that the absence of significant regular-verb priming in the response time data did not result from a disruption of lexical access, and may have stemmed instead from post-lexical events such as covert articulation, segmentation strategies, and/or cognitive control.

TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia.

BACKGROUND: We sought to describe the antemortem clinical and neuroimaging features among patients with frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP). METHODS: Subjects were recruited from a consecutive series of patients with a primary neuropathologic diagnosis of FTLD-TDP and antemortem MRI. Twenty-eight patients met entry criteria: 9 with type 1, 5 with type 2, and 10 with type 3 FTLD-TDP. Four patients had too sparse FTLD-TDP pathology to be subtyped. Clinical, neuropsychological, and neuroimaging features of these cases were reviewed. Voxel-based morphometry was used to assess regional gray matter atrophy in relation to a group of 50 cognitively normal control subjects. RESULTS: Clinical diagnosis varied between the groups: semantic dementia was only associated with type 1 pathology, whereas progressive nonfluent aphasia and corticobasal syndrome were only associated with type 3. Behavioral variant frontotemporal dementia and frontotemporal dementia with motor neuron disease were seen in type 2 or type 3 pathology. The neuroimaging analysis revealed distinct patterns of atrophy between the pathologic subtypes: type 1 was associated with asymmetric anterior temporal lobe atrophy (either left- or right-predominant) with involvement also of the orbitofrontal lobes and insulae; type 2 with relatively symmetric atrophy of the medial temporal, medial prefrontal, and orbitofrontal-insular cortices; and type 3 with asymmetric atrophy (either left- or right-predominant) involving more dorsal areas including frontal, temporal, and inferior parietal cortices as well as striatum and thalamus. No significant atrophy was seen among patients with too sparse pathology to be subtyped. CONCLUSIONS: FTLD-TDP subtypes have distinct clinical and neuroimaging features, highlighting the relevance of FTLD-TDP subtyping to clinicopathologic correlation.

Crossed aphasia and visuo-spatial neglect following a right thalamic stroke: a case study and review of the literature.

Crossed aphasia in dextrals (CAD) following pure subcortical lesions is rare. This study describes a right-handed patient with an ischemic lesion in the right thalamus. In the post-acute phase of the stroke, a unique combination of 'crossed thalamic aphasia' was found with left visuo-spatial neglect and constructional apraxia. On the basis of the criteria used in Mariën et al. [67], this case-report is the first reliable representative of vascular CAD following an isolated lesion in the right thalamus. Furthermore, this paper presents a detailed analysis of linguistic and cognitive impairments of 'possible' and 'reliable' subcortical CAD-cases published since 1975. Out of 25 patients with a pure subcortical lesion, nine cases were considered as 'possibly reliable or reliable'. A review of these cases reveals that: 1) demographic data are consistent with the general findings for the entire group of vascular CAD, 2) the neurolinguistic findings do not support the data in the general CAD-population with regard to a) the high prevalence of transcortical aphasia and b) the tendency towards a copresence of an oral versus written language dissociation and a 'mirror-image' lesion-aphasia profile, 3) subcortical CAD is not a transient phenomenon, 4) the lesion-aphasia correlations are not congruent with the high incidence of anomalous cases in the general CAD-population, 5) neuropsychological impairments may accompany subcortical CAD.

[Sensory syndrome and aphasia after left insular infarct]. / L'insula, une île oubliée? Troubles sensitifs et troubles du langage après infarctus insulaire gauche.

INTRODUCTION: Sensorial impairment without hemiplegia is usually caused by a thalamic lesion. CASE REPORT: A 28-year-old woman presented with hemianesthesia associated with aphasia following a left insular lesion, subsequent to subarachnoid hemorrhage. Brain MRI Flair sequence revealed a high intensity signal in the left insular and frontal subcortical regions. Insular infarct was diagnosed, associated with hemorrhagic sequelae. DISCUSSION/CONCLUSION: Study of the normal and pathologic insular cortex suggest several implications of the region in somatosensory and language functions. However, the insular cortex has been mainly associated with central pain. Lasting objective hypoesthesia has been very rarely documented. The left insular cortex has also been implicated in speech apraxia but our patient presented with fluent aphasia mostly affecting the rhythm of speech, as it has been observed in thalamic aphasia.