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.

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.

The Pivotal Role of the Right Parietal Lobe in Temporal Attention.

The visual system is extremely efficient at detecting events across time even at very fast presentation rates; however, discriminating the identity of those events is much slower and requires attention over time, a mechanism with a much coarser resolution [Cavanagh, P., Battelli, L., & Holcombe, A. O. Dynamic attention. In A. C. Nobre & S. Kastner (Eds.), The Oxford handbook of attention (pp. 652-675). Oxford: Oxford University Press, 2013]. Patients affected by right parietal lesion, including the TPJ, are severely impaired in discriminating events across time in both visual fields [Battelli, L., Cavanagh, P., & Thornton, I. M. Perception of biological motion in parietal patients. Neuropsychologia, 41, 1808-1816, 2003]. One way to test this ability is to use a simultaneity judgment task, whereby participants are asked to indicate whether two events occurred simultaneously or not. We psychophysically varied the frequency rate of four flickering disks, and on most of the trials, one disk (either in the left or right visual field) was flickering out-of-phase relative to the others. We asked participants to report whether two left-or-right-presented disks were simultaneous or not. We tested a total of 23 right and left parietal lesion patients in Experiment 1, and only right parietal patients showed impairment in both visual fields while their low-level visual functions were normal. Importantly, to causally link the right TPJ to the relative timing processing, we ran a TMS experiment on healthy participants. Participants underwent three stimulation sessions and performed the same simultaneity judgment task before and after 20 min of low-frequency inhibitory TMS over right TPJ, left TPJ, or early visual area as a control. rTMS over the right TPJ caused a bilateral impairment in the simultaneity judgment task, whereas rTMS over left TPJ or over early visual area did not affect performance. Altogether, our results directly link the right TPJ to the processing of relative time.

Neural bases of orthographic long-term memory and working memory in dysgraphia.

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills.

Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study.

Neurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.

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.

Brains of verbal memory specialists show anatomical differences in language, memory and visual systems.

We studied a group of verbal memory specialists to determine whether intensive oral text memory is associated with structural features of hippocampal and lateral-temporal regions implicated in language processing. Professional Vedic Sanskrit Pandits in India train from childhood for around 10years in an ancient, formalized tradition of oral Sanskrit text memorization and recitation, mastering the exact pronunciation and invariant content of multiple 40,000-100,000 word oral texts. We conducted structural analysis of gray matter density, cortical thickness, local gyrification, and white matter structure, relative to matched controls. We found massive gray matter density and cortical thickness increases in Pandit brains in language, memory and visual systems, including i) bilateral lateral temporal cortices and ii) the anterior cingulate cortex and the hippocampus, regions associated with long and short-term memory. Differences in hippocampal morphometry matched those previously documented for expert spatial navigators and individuals with good verbal working memory. The findings provide unique insight into the brain organization implementing formalized oral knowledge systems.

A minimal standardization setting for language mapping tests: an Italian example.

During awake surgery, picture-naming tests are administered to identify brain structures related to language function (language mapping), and to avoid iatrogenic damage. Before and after surgery, naming tests and other neuropsychological procedures aim at charting naming abilities, and at detecting which items the subject can respond to correctly. To achieve this goal, sufficiently large samples of normed and standardized stimuli must be available for preoperative and postoperative testing, and to prepare intraoperative tasks, the latter only including items named flawlessly preoperatively. To discuss design, norming and presentation of stimuli, and to describe the minimal standardization setting used to develop two sets of Italian stimuli, one for object naming and one for verb naming, respectively. The setting includes a naming study (to obtain picture-name agreement ratings), two on-line questionnaires (to acquire age-of-acquisition and imageability ratings for all test items), and the norming of other relevant language variables. The two sets of stimuli have >80 % picture-name agreement, high levels of internal consistency and reliability for imageability and age of acquisition ratings. They are normed for psycholinguistic variables known to affect lexical access and retrieval, and are validated in a clinical population. This framework can be used to increase the probability of reliably detecting language impairments before and after surgery, to prepare intraoperative tests based on sufficient knowledge of pre-surgical language abilities in each patient, and to decrease the probability of false positives during surgery. Examples of data usage are provided. Normative data can be found in the supplementary materials.

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.

Does it talk the talk? On the role of basal ganglia in emotive speech processing.

Ackermann et al.'s phylogenetic account of speech argues that the basal ganglia imbue speech with emotive content. However, a body of work on auditory/emotive processing is inconsistent with attributing this function exclusively to these structures. The account further overlooks the possibility that the emotion-integration function may be at least in part mediated by the cortico-ponto-cerebellar system.

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.

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.

Temporal stability and representational distinctiveness: key functions of orthographic working memory.

A primary goal of working memory research has been to understand the mechanisms that permit working memory systems to effectively maintain the identity and order of the elements held in memory for sufficient time as to allow for their selection and transfer to subsequent processing stages. Based on the performance of two individuals with acquired dysgraphia affecting orthographic working memory (WM; the graphemic buffer), we present evidence of two distinct and dissociable functions of orthographic WM. One function is responsible for maintaining the temporal stability of letters held in orthographic WM, while the other is responsible for maintaining their representational distinctiveness. The failure to maintain temporal stability and representational distinctiveness gives rise, respectively, to decay and interference effects that manifest themselves in distinctive error patterns, including distinct serial position effects. The findings we report have implications beyond our understanding of orthographic WM, as the need to maintain temporal stability and representational distinctiveness in WM is common across cognitive domains.

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.

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.

Posterior cerebral artery infarcts and semantic category dissociations: a study of 28 patients.

In this study we analysed the relationship between damage in the territory of the posterior cerebral artery and semantic knowledge, with special reference to category dissociations. Twenty-eight posterior cerebral artery stroke patients (18 left, 8 right and 2 bilateral posterior cerebral artery infarctions) completed a neuropsychological battery aimed at assessing semantic knowledge. The battery included picture naming, word-picture matching, a verbal semantic questionnaire and a picture reality decision task. For each participant, the lesion was reconstructed on the basis of MRI images, and was classified according to the involvement of the areas supplied by posterior cerebral artery. Defective naming scores were observed in 12 of 18 left posterior cerebral artery cases (67%), four of eight right posterior cerebral artery cases (50%), and one of two bilateral posterior cerebral artery cases (50%). Only in the bilateral posterior cerebral artery lesion case did we observe the pattern expected in pure visual agnosia, i.e. poor picture naming, poor picture reality decision, and normal verbal semantic questionnaire. Nine left posterior cerebral artery cases and two right posterior cerebral artery cases presented with poor performance on both the picture naming task and the verbal semantic questionnaire, thus suggesting semantic impairment. For 5 of the 12 left posterior cerebral artery patients who fared poorly on the naming task, biological stimuli (overall) were significantly more impaired than artifacts. In three of these five subjects, performance on plant-life stimuli was significantly less accurate than that on animals. A further left posterior cerebral artery patient presented a disproportionate impairment on plant-life stimuli only on the word-picture matching and on the questionnaire. The patterns of performance in these subjects suggest that the observed dissociations originated at the semantic level. Among left posterior cerebral artery patients, a naming deficit only occurred when damage to the fusiform gyrus extended anterior to Talairach's y-coordinate -50, and a disproportionate impairment of biological categories only when the lesion extended anterior to y = -32.5. Results show that the semantic deficit for the category of plant life is a genuine cognitive pattern, and does not depend on loss of colour knowledge. The contrast of left posterior cerebral artery strokes and herpes simplex encephalitis cases shows that the neural substrates for the semantic representation of plant life and animals are, at least in part, distinct. Middle and posterior portions of the left fusiform are crucial for the representation of plant-life knowledge, whereas left anterior temporal areas are more crucial than left posterior and basal temporal areas for the representation of knowledge about animals.