Written language preservation in glioma patients undergoing awake surgery: The value of tailored intra-operative assessment.

Written language is increasingly important, as contemporary society strongly relies on text-based communication. Nonetheless, in neurosurgical practice, language preservation has classically focused on spoken language. The current study aimed to evaluate the potential role of intra-operative assessments in the preservation of written language skills in glioma patients undergoing awake surgery. It is the first feasibility study to use a standardized and detailed Written language battery in glioma patients undergoing awakening surgery. Reading and spelling were assessed pre- and post-operatively in eleven patients. Intra-operatively, 7 cases underwent written language assessment in addition to spoken object naming. Results show that reading and spelling deficits may arise before and after glioma surgery and that written language may be differently affected than spoken language. In our case series, task-specific preservation of function was obtained in all cases when a specific written language skill was monitored intra-operatively. However, the benefits of intra-operative testing did not always generalize, and non-monitored written language tasks may not be preserved. Hence, when a specific written language skill needs to be preserved, to facilitate return to work and maintain quality of life, results indicate that intra-operative assessment of that skill is advised. An illustrative case report demonstrates how profile analyses can be used pre-operatively to identify cognitive components at risk and intra-operatively to preserve written language abilities in clinical practice.

The Auditory Agnosias: a Short Review of Neurofunctional Evidence.

PURPOSE OF REVIEW: To investigate the neurofunctional correlates of pure auditory agnosia and its varieties (global, verbal, and nonverbal), based on 116 anatomoclinical reports published between 1893 and 2022, with emphasis on hemispheric lateralization, intrahemispheric lesion site, underlying cognitive impairments. RECENT FINDINGS: Pure auditory agnosia is rare, and observations accumulate slowly. Recent patient reports and neuroimaging studies on neurotypical subjects offer insights into the putative mechanisms underlying auditory agnosia, while challenging traditional accounts. Global auditory agnosia frequently results from bilateral temporal damage. Verbal auditory agnosia strictly correlates with language-dominant hemisphere lesions. Damage involves the auditory pathways, but the critical lesion site is unclear. Both the auditory cortex and associative areas are reasonable candidates, but cases resulting from brainstem damage are on record. The hemispheric correlates of nonverbal auditory input disorders are less clear. They correlate with unilateral damage to either hemisphere, but evidence is scarce. Based on published cases, pure auditory agnosias are neurologically and functionally heterogeneous. Phenotypes are influenced by co-occurring cognitive impairments. Future studies should start from these facts and integrate patient data and studies in neurotypical individuals.

Production of Sentential Negation in German and Italian Non-fluent Aphasia.

The ability of persons with non-fluent aphasia (PWAs) to produce sentential negation has been investigated in several languages, but only in small samples. Accounts of (morpho)syntactic impairment in PWAs have emphasized various factors, such as whether the negative marker blocks or interferes with verb movement, the position of the Negation Phrase in the syntactic hierarchy or the interpretability of negation. This study investigates the ability of German- and Italian-speaking PWAs to construct negative sentences, as well as the role of verbal working memory (WM) capacity and education in task performance and production of sentential negation. German and Italian differ in the syntactic properties of the negative markers that are relevant here (nicht and non, respectively). A sentence anagram task tapping into the construction of negative and affirmative declarative sentences was administered to 9 German- and 7 Italian-speaking PWAs, and to 14 German- and 11 Italian-speaking age- and education-matched healthy volunteers. We fitted generalized linear mixed-effects models to the datasets. There was no significant difference between negative and affirmative sentences in either group of PWAs. There was a main effect of verbal WM capacity on task performance, but no interaction between verbal WM capacity and production of negative vs. affirmative sentences. Education did not affect task performance. The results are discussed in light of different linguistically-informed accounts of (morpho)syntactic impairment in non-fluent aphasia.

Cortical disorders of speech processing: Pure word deafness and auditory agnosia.

Selective disorders of auditory speech processing due to brain lesions are reviewed. Over 120 years after the first anatomic report (Dejerine and Sérieux, 1898), fewer than 80 cumulative cases of generalized auditory agnosia and pure word deafness with documented brain lesions are on record. Most patients (approximately 70%) had vascular lesions. Damage is very frequently bilateral in generalized auditory agnosia, and more frequently unilateral in pure word deafness. In unilateral cases, anatomical disconnection is not a prerequisite, and disorders may be due to functional disconnection. Regardless of whether lesions are unilateral or bilateral, speech processing difficulties emerge in the presence of damage to the superior temporal regions of the language-dominant hemisphere, suggesting that speech input is processed asymmetrically at early stages already. Extant evidence does not allow establishing whether processing asymmetry originates in the primary auditory cortex or in higher associative cortices, nor whether auditory processing in the brainstem is entirely symmetric. Results are consistent with the view that the difficulty in processing auditory input characterized by quick spectral and/or temporal changes is one of the critical dimensions of the disorder. Forthcoming studies should focus on detailed audiologic, neurolinguistic, and neuroanatomic descriptions of each case.

Language Assessment in Multilingualism and Awake Neurosurgery.

Multilingualism has become a worldwide phenomenon that poses critical issues about the language assessment in patients undergoing awake neurosurgery in eloquent brain areas. The accuracy and sensitivity of multilingual perioperative language assessment procedures is crucial for a number of reasons: they should be appropriate to detect deficits in each of the languages spoken by the patient; they should be suitable to identify language-specific cortical regions; they should ensure that each of the languages of a multilingual patient is tested at an adequate and comparable level of difficulty. In clinical practice, a patient-tailored approach is generally preferred. This is a necessary compromise since it is impossible to predict all the possible language combinations spoken by individuals and thus the availability of standardized testing batteries is a potentially unattainable goal. On the other hand, this leads to high inconsistency in how different neurosurgical teams manage the linguistic features that determine similarity or distance between the languages spoken by the patient and that may constrain the neuroanatomical substrate of each language. The manuscript reviews the perioperative language assessment methodologies adopted in awake surgery studies on multilingual patients with brain tumor published from 1991 to 2021 and addresses the following issues: (1) The language selected for the general neuropsychological assessment of the patient. (2) The procedures adopted to assess the dimensions that may constrain language organization in multilingual speakers: age and type of acquisition, exposure, proficiency, and use of the different languages. (3) The type of preoperative language assessment used for all the languages spoken by the patient. (4) The linguistic tasks selected in the intraoperative setting. The reviewed data show a great heterogeneity in the perioperative clinical workup with multilingual patients. The only exception is the task used during language mapping, as the picture naming task is highly preferred. The review highlights that an objective and accurate description of both the linguistic profile of multilingual patients and the specific properties of the languages under scrutiny can profitably support clinical management and decision making in multilingual awake neurosurgery settings.

Thematic Reanalysis in the Left Posterior Parietal Sulcus: A TMS Study.

Understanding who does what to whom is at the core of sentence comprehension. The actors that contribute to the verb meaning are labeled thematic roles. We used transcranial magnetic stimulation (TMS) to verify the possible impact of verb semantics on the thematic role encoding process that has been shown to involve the posterior portion of the left posterior parietal sulcus (PPS; Finocchiaro et al., 2015). Sixteen participants underwent TMS and sham stimulation sessions while performing an agent-decision task, in which they had to decide by key press which of the two arguments was the agent of visually presented sentences or pseudo-sentences. The (pseudo)sentences were all reversible and were presented in the active or passive diathesis. Double pulse TMS was delivered to the posterior part of the intraparietal sulcus in an event-related fashion, at two different time windows: 200-400 ms (T1) or 600-800 ms (T2) time-locked to the presentation of the (pseudo)sentence. Results showed that TMS increased accuracy on passive sentences and pseudo-sentences as compared to active sentences and to the baseline, sham condition. Indeed, the presence of a verb with a full semantic representation was not a necessary precondition for the TMS-induced facilitation of passive (pseudo)sentences. Stimulation timing had no effect on accuracy for sentences vs. pseudo-sentences. These observations support the idea that the posterior parietal site is recruited when the correct interpretation of a sentence requires reanalysis of temporarily encoded thematic roles (as in reversible passive sentences) even when the verb is not an entry in the lexicon and hence does not have a semantic representation. Results are consistent with previous evidence and deserve further investigation in larger experimental samples. Increasing the number and variety of stimulus sentences, and administering TMS to additional control sites will be key to further articulate the conclusions allowed by these initial findings.

The role of the l-IPS in the comprehension of reversible and irreversible sentences: an rTMS study.

Thematic roles can be seen as semantic labels assigned to who/what is taking part in the event denoted by a verb. Encoding thematic relations is crucial for sentence interpretation since it relies on both syntactic and semantic aspects. In previous studies, repetitive transcranial magnetic stimulation (rTMS) over the left inferior intraparietal sulcus (l-IPS) selectively influenced performance accuracy on reversible passive (but not active) sentences. The effect was attributed to the fact that in these sentences the assignment of the agent and theme roles requires re-analysis of the first-pass sentence parsing. To evaluate the role of reversibility and non-canonical word order (passive voice) on the effect, rTMS was applied over l-IPS during a sentence comprehension task that included reversible and irreversible, active and passive sentences. Participants were asked to identify who/what was performing the action or who/what the action was being performed on. Stimulation of the l-IPS increased response time on reversible passive sentences but not on reversible active sentences. Importantly, no effect was found on irreversible sentences, irrespective of sentence diathesis.Results suggest that neither reversibility nor sentence diathesis alone are responsible for the effect and that the effect is likely to be triggered/constrained by a combination of semantic reversibility and non-canonical word order. Combined with the results of previous studies, and irrespective of the specific role of each feature, these findings support the view that the l-IPS is critically involved in the assignment of thematic roles in reversible sentences.

Neural correlates of object and action naming practice.

Word retrieval deficits are a common problem in patients with stroke-induced brain damage. While complete recovery of language in chronic aphasia is rare, patients' naming ability can be significantly improved by speech therapy. A growing number of neuroimaging studies have tried to pinpoint the neural changes associated with successful outcome of naming treatment. However, the mechanisms supporting naming practice in the healthy brain have received little attention. Yet, understanding these mechanisms is crucial for teasing them apart from functional reorganization following brain damage. To address this issue, we trained a group of healthy monolingual Italian speakers on naming pictured objects and actions for ten consecutive days and scanned them before and after training. Although activity during object versus action naming dissociated in several regions (lateral occipitotemporal, parietal and left inferior frontal cortices), training effects for the two word classes were similar and included activation decreases in classical language regions of the left hemisphere (posterior inferior frontal gyrus, anterior insula), potentially due to decreased lexical selection demands. Additionally, MVPA revealed training-related activation changes in the left parietal and temporal cortices associated with the retrieval of knowledge from episodic memory (precuneus, angular gyrus) and facilitated access to phonological word forms (posterior superior temporal sulcus).

The role of semantics and repair processes in article-noun gender disagreement in Italian: An ERP study.

In this sentence reading study, we used event-related potentials (ERPs) to investigate the processing mechanism of article-noun gender disagreement in two kinds of nouns in Italian. The first are nouns with syntactic gender (il trenoM 'train'; la sediaF 'chair') for which the processing and repair of gender disagreement entails only one repair option, namely for the article (morphosyntactic repair). The second kind are nouns with semantic gender (il bambinoM 'boy', la bambinaF 'girl'). Here, there are two options for processing and repairing gender mismatch: repairing the article (morphosyntactic repair) or repairing the noun (both morphosyntactic and semantic repair). Both classes of nouns elicited the LAN, indicating that gender disagreement is always registered at the morphosyntactic level. In addition, the P600 was elicited in both conditions, but was larger for semantic gender, reflecting a more complex repair for this class of nouns.

Reduplicative paramnesia for places: A comprehensive review of the literature and a new case report.

Reduplicative paramnesia for places (i.e., the delusional belief that a place has been duplicated or exists in two different locations) is a rare disorder observed in neurological patients. We review the existing literature on the topic, highlighting commonalities and differences among the 51 cases published since the first report in 1903. Our results highlight the combination of multiple factors in the pathogenesis of this monothematic spatial delusion. From a neurological perspective, a crucial role is played by damage to the right frontal and temporal lobe. Deficits of non-verbal memory and executive functions, along with topographical disorientation, appear to be the most common (but, not systematic) cognitive impairments. The clinical picture of the disorder is further complicated by often overlooked psychological and motivational factors. Consequently, the precise neuro-cognitive substrate of this disorder is yet to be described in detail. We stress the need for a more detailed and systematic approach exploiting neurological, neuroimaging, neuropsychological and psychopathological methods. To guide future investigations, we provide clinical- and research-oriented recommendations. Finally, we illustrate the interplay of all above-mentioned factors with a new case report.

Modelling picture naming in aphasia: The relationship between consistency and predictability of responses.

OBJECTIVE: Two aspects of aphasic picture naming were examined: response consistency, that is, the extent to which the accuracy of the response to the same stimulus is replicated in a successive examination, and response predictability, that is, the extent to which accuracy depends on the characteristics of each stimulus. METHODS: Thirty-eight aphasic participants were examined twice. The response pattern was the same across the 2 presentations (response stability) for 36 participants, who were classified into 3 groups according to the prevailing error-type (lexical-semantic, phonological, or a balance between the two error-types): Their item-consistency was quantified with Cohen's kappa. In each case the roles played by lexical frequency, precocity of acquisition and length of the target word, and visual complexity and image agreement of the stimulus picture were examined; the ability to predict response accuracy of a model simultaneously including these 5 variables was quantified by means of the McFadden index. Finally, the relationship between predictability (McFadden index) and consistency (Cohen's kappa) was analyzed. RESULTS: For 34 of 36 participants, consistency was higher than chance. Consistency was directly correlated to the prevalence of lexical-semantic errors. On regression analysis, the relationship between consistency and predictability was significant. CONCLUSIONS: Response consistency reflects the existence of a clear difficulty gradient within the items of a battery. The significant relationship between consistency and error type suggests that, in principle, lexical-semantic errors might be more predictable than phonological errors based on the characteristics of each stimulus. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Language processing from the perspective of electrical stimulation mapping.

Electrical Stimulation (ES) is a neurostimulation technique that is used to localize language functions in the brain of people with intractable epilepsy and/or brain tumors. We reviewed 25 ES articles published between 1984 and 2018 and interpreted them from a cognitive neuropsychological perspective. Our aim was to highlight ES as a tool to further our understanding of cognitive models of language. We focused on associations and dissociations between cognitive functions within the framework of two non-neuroanatomically specified models of language. Also, we discussed parallels between the ES and the stroke literatures and showed how ES data can help us to generate hypotheses regarding how language is processed. A good understanding of cognitive models of language is essential to motivate task selection and to tailor surgical procedures, for example, by avoiding testing the same cognitive functions and understanding which functions may be more or less relevant to be tested during surgery.

Evaluating Spelling in Glioma Patients Undergoing Awake Surgery: a Systematic Review.

A main goal of awake surgery is to preserve language in order to facilitate return to work and maintain quality of life. Although spelling has become crucial in daily life, it has received little attention in awake surgery practice. We review assessments of spelling carried out in awake surgery studies, to inspect how current neurofunctional theories of spelling may guide pre-, intra- and post-operative neurosurgical practice. A systematic database search in Embase, Medline, PubMed and Web of Science identified studies reporting on spelling assessment in glioma patients undergoing awake surgery. Twenty-three studies were included, of which only 9 report details on spelling assessments. We evaluate the incidence of dysgraphia in glioma patients, the types of spelling errors as a function of tumor location, and the specificity of spelling sites with respect to other language functions. Post-operative dysgraphia arose in 26.9% of the patients with preserved pre-operative handwriting, and persisted in 45.0% of them at follow-up. Intra-operative stimulation interfered only with handwriting in 37.7% of the patients. A network of frontal, parietal and temporal regions was found to underlie central and peripheral spelling processes. Evidence on spelling performance in patients undergoing awake surgery for gliomas is surprisingly scarce. With the limitations inherent in the small number of observations, results converge with the neurofunctional knowledge accruing from studies of stroke cases. Such knowledge should be exploited in more thorough investigations of spelling skills in glioma patients. Implications for clinical and neuroscientific practice are discussed, as well as possible strategies to overcome current limitations.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Time reference in nonfluent and fluent aphasia: a cross-linguistic test of the PAst DIscourse LInking Hypothesis.

Recent studies by Bastiaanse and colleagues found that time reference is selectively impaired in people with nonfluent agrammatic aphasia, with reference to the past being more difficult to process than reference to the present or to the future. To account for this dissociation, they formulated the PAst DIscourse LInking Hypothesis (PADILIH), which posits that past reference is more demanding than present/future reference because it involves discourse linking. There is some evidence that this hypothesis can be applied to people with fluent aphasia as well. However, the existing evidence for the PADILIH is contradictory, and most of it has been provided by employing a test that predominantly taps retrieval processes, leaving largely unexplored the underlying ability to encode time reference-related prephonological features. Within a cross-linguistic approach, this study tests the PADILIH by means of a sentence completion task that 'equally' taps encoding and retrieval abilities. This study also investigates if the PADILIH's scope can be extended to fluent aphasia. Greek- and Italian-speaking individuals with aphasia participated in the study. The Greek group consisted of both individuals with nonfluent agrammatic aphasia and individuals with fluent aphasia, who also presented signs of agrammatism. The Italian group consisted of individuals with agrammatic nonfluent aphasia only. The two Greek subgroups performed similarly. Neither language group of participants with aphasia exhibited a pattern of performance consistent with the predictions of the PADILIH. However, a double dissociation observed within the Greek group suggests a hypothesis that may reconcile the present results with the PADILIH.

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis comparable to formal testing?

BACKGROUND: The relationship between spontaneous speech and formal language testing in people with brain tumors (gliomas) has been rarely studied. In clinical practice, formal testing is typically used, while spontaneous speech is less often evaluated quantitatively. However, spontaneous speech is quicker to sample and may be less prone to test/retest effects, making it a potential candidate for assessing language impairments when there is restricted time or when the patient is unable to undertake prolonged testing. AIM: To assess whether quantitative spontaneous speech analysis and formal testing detect comparable language impairments in people with gliomas. Specifically, we addressed (a) whether both measures detected comparable language impairments in our patient sample; and (b) which language levels, assessment times, and spontaneous speech variables were more often impaired in this subject group. METHOD: Five people with left perisylvian gliomas performed a spontaneous speech task and a formal language assessment. Tests were administered before surgery, within a week after surgery, and seven months after surgery. Performance on spontaneous speech was compared with that of 15 healthy speakers. RESULTS: Language impairments were detected more often with both measures than with either measure independently. Lexical-semantic impairments were more common than phonological and grammatical impairments, and performance was equally impaired across assessment time points. Incomplete sentences and phonological paraphasias were the most common error types. CONCLUSIONS: In our sample both spontaneous speech analysis and formal testing detected comparable language impairments. Currently, we suggest that formal testing remains overall the better option, except for cases in which there are restrictions on testing time or the patient is too tired to undergo formal testing. In these cases, spontaneous speech may provide a viable alternative, particularly if automated analysis of spontaneous speech becomes more readily available in the future. These results await replication in a bigger sample and/or other populations.

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.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years. METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments. RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed. CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.