Common predictors of spoken and written language performance in aphasia, alexia, and agraphia.

Language performance requires support from central cognitive/linguistic abilities as well as the more peripheral sensorimotor skills to plan and implement spoken and written communication. Both output modalities are vulnerable to impairment following damage to the language-dominant hemisphere, but much of the research to date has focused exclusively on spoken language. In this study we aimed to examine an integrated model of language processing that includes the common cognitive processes that support spoken and written language, as well as modality-specific skills. To do so, we evaluated spoken and written language performance from 87 individuals with acquired language impairment resulting from damage to left perisylvian cortical regions that collectively constitute the dorsal language pathway. Comprehensive behavioral assessment served to characterize the status of central and peripheral components of language processing in relation to neurotypical controls (n = 38). Performance data entered into principal components analyses (with or without control scores) consistently yielded a strong five-factor solution. In line with a primary systems framework, three central cognitive factors emerged: semantics, phonology, and orthography that were distinguished from peripheral processes supporting speech production and allographic skill for handwriting. The central phonology construct reflected performance on phonological awareness and manipulation tasks and showed the greatest deficit of all the derived factors. Importantly, this phonological construct was orthogonal to the speech production factor that reflected repetition of words/non-words. When entered into regression analyses, semantics and phonological skill were common predictors of language performance across spoken and written modalities. The speech production factor was also a strong, distinct predictor of spoken naming and oral reading, in contrast to allographic skills which only predicted written output. As expected, visual orthographic processing contributed more to written than spoken language tasks and reading/spelling performance was strongly reliant on phonological and semantic abilities. Despite the heterogeneity of this cohort regarding aphasia type and severity, the marked impairment of phonological skill was a unifying feature. These findings prompt greater attention to clinical assessment and potential treatment of underlying phonological skill in individuals with left perisylvian damage.

Positive changes to written language following phonological treatment in logopenic variant primary progressive aphasia: Case report.

Phonological impairment contributes to deficits in repetition and spoken naming in logopenic variant Primary Progressive Aphasia (lvPPA), but weakened phonology can also affect written language skills. In this experimental case report, we demonstrate phonological text agraphia in a 71-year-old woman in the early stages of lvPPA that undermined her ability to write meaningful, grammatical sentences. We investigated the therapeutic value of a rigorous treatment protocol to strengthen phonological manipulation skills coupled with transcranial direct current stimulation (tDCS). Intervention took place 5 days a week for 2 weeks with active tDCS, followed by a 2-month rest period, and then a second period of phonological treatment with sham tDCS. Over the course of treatment, our participant demonstrated improved phonological transcoding and manipulation skills as well as marked improvement in the proportion of grammatically well-formed, meaningful written narratives. Improvements in spelling and letter selection were also observed. Treatment gains were documented during phonological intervention in both active tDCS and sham treatment phases and were maintained 2 months after the conclusion of intervention. Importantly, improvements were observed in the context of a progressive disorder. These data present compelling evidence regarding the impairment-based approach that targets compromised phonological skills, presenting opportunity for improving functional written communication skills relevant to the everyday lives of individuals with lvPPA.

Engaging Faculty in Shifting Toward Holistic Review: Changing Graduate Admissions Procedures at a Land-Grant, Hispanic-Serving Institution.

Purpose The aim of this tutorial is to share lessons learned from a speech, language, and hearing sciences department at a land-grant, Hispanic-serving institution (HSI) after revising the graduate admissions review process and subsequent discussions related to equity in assessment. This tutorial describes the department as a case example and includes guiding questions that may be helpful for other organizations. Method An adaptive case study approach was used and centered on supporting students at Hispanic-serving institutions. The approach was characterized by structured collaborative reflection throughout the process and engagement of relevant stakeholders at multiple levels. The adaptive method allowed for interim synthesis of stakeholder discussions to inform subsequent phases of the reflection process. Results This tutorial shares critical motivations, barriers, facilitators, and phases that were identified in moving toward holistic evaluation for graduate admissions. Targeted areas for continued improvement related to diversity, equity, and inclusion are described. Conclusions This tutorial outlines lessons learned from changing graduate admissions practices toward holistic review. Self-reflection prompts are provided for institutions and organizations considering changes to their review process. In order to best support diverse communities, increased workforce diversity is needed in the speech, language, and hearing sciences professions, and holistic review practices are recommended as one way to support increased diversity, equity, and inclusion.

Examining speech motor planning difficulties in apraxia of speech and aphasia via the sequential production of phonetically similar words.

This study investigated the underlying nature of apraxia of speech (AOS) by testing two competing hypotheses. The Reduced Buffer Capacity Hypothesis argues that people with AOS can plan speech only one syllable at a time Rogers and Storkel [1999. Planning speech one syllable at a time: The reduced buffer capacity hypothesis in apraxia of speech. Aphasiology, 13(9-11), 793-805. https://doi.org/10.1080/026870399401885]. The Program Retrieval Deficit Hypothesis states that selecting a motor programme is difficult in face of competition from other simultaneously activated programmes Mailend and Maas [2013. Speech motor programming in apraxia of speech: Evidence from a delayed picture-word interference task. American Journal of Speech-Language Pathology, 22(2), S380-S396. https://doi.org/10.1044/1058-0360(2013/12-0101)]. Speakers with AOS and aphasia, aphasia without AOS, and unimpaired controls were asked to prepare and hold a two-word utterance until a go-signal prompted a spoken response. Phonetic similarity between target words was manipulated. Speakers with AOS had longer reaction times in conditions with two similar words compared to two identical words. The Control and the Aphasia group did not show this effect. These results suggest that speakers with AOS need additional processing time to retrieve target words when multiple motor programmes are simultaneously activated.

A Retrospective Study of Long-Term Improvement on the Boston Naming Test.

Purpose Lexical retrieval impairment is a universal characteristic of aphasia and a common treatment focus. Although naming improvement is well documented, there is limited information to shape expectations regarding long-term recovery. This was the motivation for a retrospective study of longitudinal data on the Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 1983, 2000). Method BNT scores were analyzed from a heterogeneous cohort of 42 individuals with anomia associated with a range of aphasia types. The data were collected over the course of 20 years from individuals who had participated in treatment and received at least 2 BNT administrations. A linear mixed model was implemented to evaluate effects of initial BNT score, time postonset, and demographic variables. For those over 55 years of age, BNT change was evaluated relative to data from the Mayo Clinic's Older Americans Normative Studies. Results There was a significant average improvement of +7.67 points on the BNT in individuals followed for an average of 2 years. Overall, the average rate of improvement was +5.84 points per year, in contrast to a decline of 0.23 points per year in a healthy adult cohort from the Mayo Clinic's Older Americans Normative Studies. Naming recovery was approximately linear, with significant main effects of initial BNT score (i.e., initial severity) and time postonset; the greatest changes were noted in those whose initial severity was moderate. Conclusions These findings indicate a positive prognosis for naming improvement over time regardless of demographic factors and provide estimates for clinical predictions for those who seek rehabilitation during the chronic phase.

Treatment for Word Retrieval in Semantic and Logopenic Variants of Primary Progressive Aphasia: Immediate and Long-Term Outcomes.

Purpose Recent studies confirm the utility of speech-language intervention in primary progressive aphasia (PPA); however, long-term outcomes, ideal dosage parameters, and relative benefits of intervention across clinical variants warrant additional investigation. The purpose of this study was to determine whether naming treatment affords significant, lasting, and generalized improvement for individuals with semantic and logopenic PPA and whether dosage manipulations significantly affect treatment outcomes. Method Eighteen individuals with PPA (9 semantic and 9 logopenic variant) underwent lexical retrieval treatment designed to leverage spared cognitive-linguistic domains and develop self-cueing strategies to promote naming. One group (n = 10) underwent once-weekly treatment sessions, and the other group (n = 8) received the same treatment with 2 sessions per week and an additional "booster" treatment phase at 3 months post-treatment. Performance on trained and untrained targets/tasks was measured immediately after treatment and at 3, 6, and 12 months post-treatment. Results Outcomes from the full cohort of individuals with PPA showed significantly improved naming of trained items immediately post-treatment and at all follow-up assessments through 1 year. Generalized improvement on untrained items was significant up to 6 months post-treatment. The positive response to treatment was comparable regardless of session frequency or inclusion of a booster phase. Outcomes were comparable across PPA subtypes, as was maintenance of gains over the post-treatment period. Conclusion This study documents positive naming treatment outcomes for a group of individuals with PPA, demonstrating strong direct treatment effects, maintenance of gains up to 1 year post-treatment, and generalization to untrained items. Lexical retrieval treatment, in conjunction with daily home practice, had a strong positive effect that did not require more than 1 clinician-directed treatment session per week. Findings confirm that strategic training designed to capitalize on spared cognitive-linguistic abilities results in significant and lasting improvement, despite ongoing disease progression, in PPA.

Auditory-Perceptual Rating of Connected Speech in Aphasia.

Purpose Auditory-perceptual assessment, in which trained listeners rate a large number of perceptual features of speech samples, is the gold standard for the differential diagnosis of motor speech disorders. The goal of this study was to investigate the feasibility of applying a similar, formalized auditory-perceptual approach to the assessment of language deficits in connected speech samples from individuals with aphasia. Method Twenty-seven common features of connected speech in aphasia were defined, each of which was rated on a 5-point scale. Three experienced researchers evaluated 24 connected speech samples from the AphasiaBank database, and 12 student clinicians evaluated subsets of 8 speech samples each. We calculated interrater reliability for each group of raters and investigated the validity of the auditory-perceptual approach by comparing feature ratings to related quantitative measures derived from transcripts and clinical measures, and by examining patterns of feature co-occurrence. Results Most features were rated with good-to-excellent interrater reliability by researchers and student clinicians. Most features demonstrated strong concurrent validity with respect to quantitative connected speech measures computed from AphasiaBank transcripts and/or clinical aphasia battery subscores. Factor analysis showed that 4 underlying factors, which we labeled Paraphasia, Logopenia, Agrammatism, and Motor Speech, accounted for 79% of the variance in connected speech profiles. Examination of individual patients' factor scores revealed striking diversity among individuals classified with a given aphasia type. Conclusion Auditory-perceptual rating of connected speech in aphasia shows potential to be a comprehensive, efficient, reliable, and valid approach for characterizing connected speech in aphasia.

Patterns of Recovery From Aphasia in the First 2 Weeks After Stroke.

Purpose Recovery from aphasia after stroke has a decelerating trajectory, with the greatest gains taking place early and the slope of change decreasing over time. Despite its importance, little is known regarding evolution of language function in the early postonset period. The goal of this study was to characterize the dynamics and nature of recovery of language function in the acute and early subacute phases of stroke. Method Twenty-one patients with aphasia were evaluated every 2-3 days for the first 15 days after onset of acute ischemic or hemorrhagic stroke. Language function was assessed at each time point with the Quick Aphasia Battery (Wilson, Eriksson, Schneck, & Lucanie, 2018), which yields an overall summary score and a multidimensional profile of 7 different language domains. Results On a 10-point scale, overall language function improved by a mean of 1.07 points per week, confidence interval [0.46, 1.71], with 19 of 21 patients showing positive changes. The trajectory of recovery was approximately linear over this time period. There was significant variability across patients, and patients with more impaired language function at Day 2 poststroke experienced greater improvements over the subsequent 2 weeks. Patterns of recovery differed across language domains, with consistent improvements in word finding, grammatical construction, repetition, and reading, but less consistent improvements in word comprehension and sentence comprehension. Conclusion Overall language function typically improves substantially and steadily during the first 2 weeks after stroke, driven mostly by recovery of expressive language. Information on the trajectory of early recovery will increase the accuracy of prognoses and establish baseline expectations against which to evaluate the efficacy of interventions. Supplemental Material https://doi.org/10.23641/asha.7811876.

Speech motor planning in the context of phonetically similar words: Evidence from apraxia of speech and aphasia.

The purpose of this study was to test two competing hypotheses about the nature of the impairment in apraxia of speech (AOS). The Reduced Buffer Capacity Hypothesis argues that people with AOS can hold only one syllable at a time in the speech motor planning buffer. The Program Retrieval Deficit Hypothesis, states that people with AOS have difficulty accessing the intended motor program in the context where several motor programs are activated simultaneously. The participants included eight speakers with AOS, most of whom also had aphasia, nine speakers with aphasia without AOS, and 25 age-matched control speakers. The experimental paradigm prompted single word production following three types of primes. In most trials, prime and target were the same (e.g., bill-bill). On some trials, the initial consonant differed in one phonetic feature (e.g., bill-dill; Similar) or in all phonetic features (fill-bill; Different). The dependent measures were accuracy and reaction time. The results revealed a switch cost - longer reaction times in trials where the prime and target differed compared to trials where they were the same words - in all groups; however, the switch cost was significantly larger in the AOS group compared to the other two groups. These findings are in line with the prediction of the Program Retrieval Deficit Hypothesis and suggest that speakers with AOS have difficulty with selecting one program over another when several programs compete for selection.

Maximising recovery from aphasia with central and peripheral agraphia: The benefit of sequential treatments.

Maximal recovery from acquired language impairment may require progression from one behavioural treatment protocol to the next in order to build upon residual and relearned cognitive-linguistic and sensory-motor processes. We present a five-stage treatment sequence that was initiated at one year post stroke in a woman with acquired impairments of spoken and written language. As is typical of individuals with left perisylvian damage, she demonstrated marked impairment of phonological retrieval and sublexical phonology, but she also faced additional challenges due to impaired letter shape knowledge and visual attention. The treatment sequence included (1) written spelling of targeted words, (2) retraining sublexical sound-to-letter correspondences and phonological manipulation skills, (3) training strategic approaches to maximise interactive use of lexical, phonological, and orthographic knowledge, (4) lexical retrieval of spoken words, and finally (5) sentence-level stimulation to improve grammatical form of written narratives. This Phase II clinical study documented positive direct treatment outcomes along with evidence of a significant reduction in the underlying deficits and generalisation to untrained items and language tasks. Improvements on a comprehensive assessment battery were realised as functional gains in everyday written and spoken communication, including improved lexical retrieval and grammatical complexity of written narratives. This case provides a valuable example of the cumulative therapeutic benefit of sequential application of theoretically motivated treatment protocols.

The neural substrates of improved phonological processing following successful treatment in a case of phonological alexia and agraphia.

Phonological deficits are common in aphasia after left-hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals improve through treatment, the neural substrates supporting improvements are poorly understood. We measured brain activation during pseudoword reading in an individual through two treatment phases. Improvements were associated with greater activation in residual left dorsal language regions and bilateral regions supporting attention and effort. Gains were maintained, while activation returned to pre-treatment levels. This case demonstrates the neural support for improved phonology after damage to critical regions and that improvements may be maintained without markedly increased effort.

The nature and treatment of phonological text agraphia.

Phonological alexia and agraphia are written language disorders characterised by disproportionate difficulty reading and spelling nonwords in comparison to real words. In phonological alexia, it has been shown that, despite relatively accurate reading of words in isolation, text-level reading deficits are often marked and persistent. Specifically, some individuals demonstrate difficulty reading functors and affixes in sentences, a profile referred to as phonological text alexia. In this paper, we demonstrate an analogous manifestation of the phonological impairment on text-level writing and suggest the term "phonological text agraphia". We examined four individuals with phonological alexia/agraphia who also showed disproportionate difficulty writing well-formed sentences in comparison to their grammatical competence in spoken utterances. Implementation of a phonological treatment protocol resulted in significantly improved sublexical phonology skills as well as improvements in grammatical accuracy of written narratives. These findings support the notion of a common phonological impairment underlying nonword reading/spelling deficits and sentence-level difficulties.

Neural substrates of sublexical processing for spelling.

We used fMRI to examine the neural substrates of sublexical phoneme-grapheme conversion during spelling in a group of healthy young adults. Participants performed a writing-to-dictation task involving irregular words (e.g., choir), plausible nonwords (e.g., kroid), and a control task of drawing familiar geometric shapes (e.g., squares). Written production of both irregular words and nonwords engaged a left-hemisphere perisylvian network associated with reading/spelling and phonological processing skills. Effects of lexicality, manifested by increased activation during nonword relative to irregular word spelling, were noted in anterior perisylvian regions (posterior inferior frontal gyrus/operculum/precentral gyrus/insula), and in left ventral occipito-temporal cortex. In addition to enhanced neural responses within domain-specific components of the language network, the increased cognitive demands associated with spelling nonwords engaged domain-general frontoparietal cortical networks involved in selective attention and executive control. These results elucidate the neural substrates of sublexical processing during written language production and complement lesion-deficit correlation studies of phonological agraphia.

Phonological Processing in Primary Progressive Aphasia.

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.

Treatment for Alexia With Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling.

PURPOSE: Damage to left ventral occipito-temporal cortex can give rise to written language impairment characterized by pure alexia/letter-by-letter (LBL) reading, as well as surface alexia and agraphia. The purpose of this study was to examine the therapeutic effects of a combined treatment approach to address concurrent LBL reading with surface alexia/agraphia. METHOD: Simultaneous treatment to address slow reading and errorful spelling was administered to 3 individuals with reading and spelling impairments after left ventral occipito-temporal damage due to posterior cerebral artery stroke. Single-word reading/spelling accuracy, reading latencies, and text reading were monitored as outcome measures for the combined effects of multiple oral re-reading treatment and interactive spelling treatment. RESULTS: After treatment, participants demonstrated faster and more accurate single-word reading and improved text-reading rates. Spelling accuracy also improved, particularly for untrained irregular words, demonstrating generalization of the trained interactive spelling strategy. CONCLUSION: This case series characterizes concomitant LBL with surface alexia/agraphia and demonstrates a successful treatment approach to address both the reading and spelling impairment.

Processing deficits for familiar and novel faces in patients with left posterior fusiform lesions.

Pure alexia (PA) arises from damage to the left posterior fusiform gyrus (pFG) and the striking reading disorder that defines this condition has meant that such patients are often cited as evidence for the specialisation of this region to processing of written words. There is, however, an alternative view that suggests this region is devoted to processing of high acuity foveal input, which is particularly salient for complex visual stimuli like letter strings. Previous reports have highlighted disrupted processing of non-linguistic visual stimuli after damage to the left pFG, both for familiar and unfamiliar objects and also for novel faces. This study explored the nature of face processing deficits in patients with left pFG damage. Identification of famous faces was found to be compromised in both expressive and receptive tasks. Discrimination of novel faces was also impaired, particularly for those that varied in terms of second-order spacing information, and this deficit was most apparent for the patients with the more severe reading deficits. Interestingly, discrimination of faces that varied in terms of feature identity was considerably better in these patients and it was performance in this condition that was related to the size of the length effects shown in reading. This finding complements functional imaging studies showing left pFG activation for faces varying only in spacing and frontal activation for faces varying only on features. These results suggest that the sequential part-based processing strategy that promotes the length effect in the reading of these patients also allows them to discriminate between faces on the basis of feature identity, but processing of second-order configural information is most compromised due to their left pFG lesion. This study supports a view in which the left pFG is specialised for processing of high acuity foveal visual information that supports processing of both words and faces.

Bidirectional iterative parcellation of diffusion weighted imaging data: separating cortical regions connected by the arcuate fasciculus and extreme capsule.

This paper introduces a Bidirectional Iterative Parcellation (BIP) procedure designed to identify the location and size of connected cortical regions (parcellations) at both ends of a white matter tract in diffusion weighted images. The procedure applies the FSL option "probabilistic tracking with classification targets" in a bidirectional and iterative manner. To assess the utility of BIP, we applied the procedure to the problem of parcellating a limited set of well-established gray matter seed regions associated with the dorsal (arcuate fasciculus/superior longitudinal fasciculus) and ventral (extreme capsule fiber system) white matter tracts in the language networks of 97 participants. These left hemisphere seed regions and the two white matter tracts, along with their right hemisphere homologues, provided an excellent test case for BIP because the resulting parcellations overlap and their connectivity via the arcuate fasciculi and extreme capsule fiber systems are well studied. The procedure yielded both confirmatory and novel findings. Specifically, BIP confirmed that each tract connects within the seed regions in unique, but expected ways. Novel findings included increasingly left-lateralized parcellations associated with the arcuate fasciculus/superior longitudinal fasciculus as a function of age and education. These results demonstrate that BIP is an easily implemented technique that successfully confirmed cortical connectivity patterns predicted in the literature, and has the potential to provide new insights regarding the architecture of the brain.

Writing treatment for aphasia: a texting approach.

PURPOSE: Treatment studies have documented the therapeutic and functional value of lexical writing treatment for individuals with severe aphasia. The purpose of this study was to determine whether such retraining could be accomplished using the typing feature of a cellular telephone, with the ultimate goal of using text messaging for communication. METHOD: A 31-year-old man with persistent Broca's aphasia, severe apraxia of speech, global dysgraphia, and right hemiparesis participated in this study. Using a multiple baseline design, relearning and maintenance of single-word spellings (and oral naming) of targeted items were examined in response to traditional Copy and Recall Treatment (CART) for handwriting and a new paradigm using 1-handed typing on a cell phone keyboard (i.e., a texting version of CART referred to as T-CART). RESULTS: Marked improvements were documented in spelling and spoken naming trained in either modality, with stronger maintenance for handwriting than cell phone typing. Training resulted in functional use of texting that continued for 2 years after treatment. CONCLUSIONS: These results suggest that orthographic retraining using a cell phone keyboard has the potential to improve spelling knowledge and provide a means to improve functional communication skills. Combined training with both handwriting and cell phone typing should be considered in order to maximize the durability of treatment effects.

Dysfunctional visual word form processing in progressive alexia.

Progressive alexia is an acquired reading deficit caused by degeneration of brain regions that are essential for written word processing. Functional imaging studies have shown that early processing of the visual word form depends on a hierarchical posterior-to-anterior processing stream in occipito-temporal cortex, whereby successive areas code increasingly larger and more complex perceptual attributes of the letter string. A region located in the left lateral occipito-temporal sulcus and adjacent fusiform gyrus shows maximal selectivity for words and has been dubbed the 'visual word form area'. We studied two patients with progressive alexia in order to determine whether their reading deficits were associated with structural and/or functional abnormalities in this visual word form system. Voxel-based morphometry showed left-lateralized occipito-temporal atrophy in both patients, very mild in one, but moderate to severe in the other. The two patients, along with 10 control subjects, were scanned with functional magnetic resonance imaging as they viewed rapidly presented words, false font strings, or a fixation crosshair. This paradigm was optimized to reliably map brain regions involved in orthographic processing in individual subjects. All 10 control subjects showed a posterior-to-anterior gradient of selectivity for words, and all 10 showed a functionally defined visual word form area in the left hemisphere that was activated for words relative to false font strings. In contrast, neither of the two patients with progressive alexia showed any evidence for a selectivity gradient or for word-specific activation of the visual word form area. The patient with mild atrophy showed normal responses to both words and false font strings in the posterior part of the visual word form system, but a failure to develop selectivity for words in the more anterior part of the system. In contrast, the patient with moderate to severe atrophy showed minimal activation of any part of the visual word form system for either words or false font strings. Our results suggest that progressive alexia is associated with a dysfunctional visual word form system, with or without substantial cortical atrophy. Furthermore, these findings demonstrate that functional MRI has the potential to reveal the neural bases of cognitive deficits in neurodegenerative patients at very early stages, in some cases before the development of extensive atrophy.