Mapping articulatory and grammatical subcomponents of fluency deficits in post-stroke aphasia.

Fluent speech production is a critical aspect of language processing and is central to aphasia diagnosis and treatment. Multiple cognitive processes and neural subsystems must be coordinated to produce fluent narrative speech. To refine the understanding of these systems, measures that minimize the influence of other cognitive processes were defined for articulatory deficits and grammatical deficits. Articulatory deficits were measured by the proportion of phonetic errors (articulatory and prosodic) in a word repetition task in 115 participants with aphasia following left hemisphere stroke. Grammatical deficits were assessed in 46 participants based on two measures-proportion of closed class words and proportion of words in sentences-generated during semistructured narrative speech production (telling the Cinderella story). These measures were used to identify brain regions critical for articulatory and grammatical aspects of speech production using a multivariate lesion-symptom mapping approach based on support vector regression. Phonetic error proportion was associated with damage to the postcentral gyrus and the inferior parietal lobule (particularly the supramarginal gyrus). Proportion of closed class words in narrative speech did not have consistent lesion correlates. Proportion of words in sentences was strongly associated with frontal lobe damage, particularly the inferior and middle frontal gyri. Grammatical sentence structuring relies on frontal regions, particularly the inferior and middle frontal gyri, whereas phonetic-articulatory planning and execution relies on parietal regions, particularly the postcentral and supramarginal gyri. These results clarify and extend current understanding of the functional components of the frontoparietal speech production system.

Enhanced estimations of post-stroke aphasia severity using stacked multimodal predictions.

The severity of post-stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain-behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates "stacked multimodal predictions" (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post-stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79-0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel-based lesion-to-symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp 38:5603-5615, 2017. © 2017 Wiley Periodicals, Inc.

Automated segmentation of chronic stroke lesions using LINDA: Lesion identification with neighborhood data analysis.

The gold standard for identifying stroke lesions is manual tracing, a method that is known to be observer dependent and time consuming, thus impractical for big data studies. We propose LINDA (Lesion Identification with Neighborhood Data Analysis), an automated segmentation algorithm capable of learning the relationship between existing manual segmentations and a single T1-weighted MRI. A dataset of 60 left hemispheric chronic stroke patients is used to build the method and test it with k-fold and leave-one-out procedures. With respect to manual tracings, predicted lesion maps showed a mean dice overlap of 0.696 ± 0.16, Hausdorff distance of 17.9 ± 9.8 mm, and average displacement of 2.54 ± 1.38 mm. The manual and predicted lesion volumes correlated at r = 0.961. An additional dataset of 45 patients was utilized to test LINDA with independent data, achieving high accuracy rates and confirming its cross-institutional applicability. To investigate the cost of moving from manual tracings to automated segmentation, we performed comparative lesion-to-symptom mapping (LSM) on five behavioral scores. Predicted and manual lesions produced similar neuro-cognitive maps, albeit with some discussed discrepancies. Of note, region-wise LSM was more robust to the prediction error than voxel-wise LSM. Our results show that, while several limitations exist, our current results compete with or exceed the state-of-the-art, producing consistent predictions, very low failure rates, and transferable knowledge between labs. This work also establishes a new viewpoint on evaluating automated methods not only with segmentation accuracy but also with brain-behavior relationships. LINDA is made available online with trained models from over 100 patients.

The Marin Lab at the Dawn of Cognitive Neuropsychology.

This essay discusses the intellectual developments in psychology, linguistics, and behavioral neurology that shaped Oscar Marin's approach to disorders of high cortical function. As Chief of Neurology at Baltimore City Hospitals in the 1970s, Dr Marin teamed with biopsychologist Eleanor Saffran and the author in seminal studies of acquired language disorders (aphasia) centering on core processes of syntax and semantics, and rejecting premature reductionism. The philosophical and methodological principles that motivated these studies are traced through the author's personal recollections and the published writings of the Marin lab. These principles came to be associated with the cognitive neuropsychology school of research and have important linkages to contemporary work in the neuroscience of aphasia and related cognitive disorders.

Multivariate lesion-symptom mapping using support vector regression.

Lesion analysis is a classic approach to study brain functions. Because brain function is a result of coherent activations of a collection of functionally related voxels, lesion-symptom relations are generally contributed by multiple voxels simultaneously. Although voxel-based lesion-symptom mapping (VLSM) has made substantial contributions to the understanding of brain-behavior relationships, a better understanding of the brain-behavior relationship contributed by multiple brain regions needs a multivariate lesion-symptom mapping (MLSM). The purpose of this artilce was to develop an MLSM using a machine learning-based multivariate regression algorithm: support vector regression (SVR). In the proposed SVR-LSM, the symptom relation to the entire lesion map as opposed to each isolated voxel is modeled using a nonlinear function, so the intervoxel correlations are intrinsically considered, resulting in a potentially more sensitive way to examine lesion-symptom relationships. To explore the relative merits of VLSM and SVR-LSM we used both approaches in the analysis of a synthetic dataset. SVR-LSM showed much higher sensitivity and specificity for detecting the synthetic lesion-behavior relations than VLSM. When applied to lesion data and language measures from patients with brain damages, SVR-LSM reproduced the essential pattern of previous findings identified by VLSM and showed higher sensitivity than VLSM for identifying the lesion-behavior relations. Our data also showed the possibility of using lesion data to predict continuous behavior scores.

Neuroanatomical dissociation for taxonomic and thematic knowledge in the human brain.

It is thought that semantic memory represents taxonomic information differently from thematic information. This study investigated the neural basis for the taxonomic-thematic distinction in a unique way. We gathered picture-naming errors from 86 individuals with poststroke language impairment (aphasia). Error rates were determined separately for taxonomic errors ("pear" in response to apple) and thematic errors ("worm" in response to apple), and their shared variance was regressed out of each measure. With the segmented lesions normalized to a common template, we carried out voxel-based lesion-symptom mapping on each error type separately. We found that taxonomic errors localized to the left anterior temporal lobe and thematic errors localized to the left temporoparietal junction. This is an indication that the contribution of these regions to semantic memory cleaves along taxonomic-thematic lines. Our findings show that a distinction long recognized in the psychological sciences is grounded in the structure and function of the human brain.

The dorsal stream contribution to phonological retrieval in object naming.

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

The neural basis of reversible sentence comprehension: evidence from voxel-based lesion symptom mapping in aphasia.

We explored the neural basis of reversible sentence comprehension in a large group of aphasic patients (n = 79). Voxel-based lesion symptom mapping revealed a significant association between damage in temporo-parietal cortex and impaired sentence comprehension. This association remained after we controlled for phonological working memory. We hypothesize that this region plays an important role in the thematic or what-where processing of sentences. In contrast, we detected weak or no association between reversible sentence comprehension and the ventrolateral pFC, which includes Broca's area, even for syntactically complex sentences. This casts doubt on theories that presuppose a critical role for this region in syntactic computations.

Localizing interference during naming: convergent neuroimaging and neuropsychological evidence for the function of Broca's area.

To produce a word, the intended word must be selected from a competing set of other words. In other domains where competition affects the selection process, the left inferior frontal gyrus (LIFG) responds to competition among incompatible representations. The aim of this study was to test whether the LIFG is necessary for resolution of competition in word production. Using a methodological approach applying the same rigorous analytic methods to neuropsychological data as is done with neuroimaging data, we compared brain activation patterns in normal speakers (using fMRI) with the results of lesion-deficit correlations in aphasic speakers who performed the same word production task designed to elicit competition during lexical selection. The degree of activation of the LIFG in normal speakers and damage to the LIFG in aphasic speakers was associated with performance on the production task. These convergent findings provide strong support for the hypothesis that the region of cortex commonly known as Broca's area (i.e., the posterior LIFG) serves to bias competitive interactions during language production.

Errorless learning in cognitive rehabilitation: a critical review.

Cognitive rehabilitation research is increasingly exploring errorless learning interventions, which prioritise the avoidance of errors during treatment. The errorless learning approach was originally developed for patients with severe anterograde amnesia, who were deemed to be at particular risk for error learning. Errorless learning has since been investigated in other memory-impaired populations (e.g., Alzheimer's disease) and acquired aphasia. In typical errorless training, target information is presented to the participant for study or immediate reproduction, a method that prevents participants from attempting to retrieve target information from long-term memory (i.e., retrieval practice). However, assuring error elimination by preventing difficult (and error-permitting) retrieval practice is a potential major drawback of the errorless approach. This review begins with discussion of research in the psychology of learning and memory that demonstrates the importance of difficult (and potentially errorful) retrieval practice for robust learning and prolonged performance gains. We then review treatment research comparing errorless and errorful methods in amnesia and aphasia, where only the latter provides (difficult) retrieval practice opportunities. In each clinical domain we find the advantage of the errorless approach is limited and may be offset by the therapeutic potential of retrieval practice. Gaps in current knowledge are identified that preclude strong conclusions regarding a preference for errorless treatments over methods that prioritise difficult retrieval practice. We offer recommendations for future research aimed at a strong test of errorless learning treatments, which involves direct comparison with methods where retrieval practice effects are maximised for long-term gains.

Learning from errors: Exploration of the monitoring learning effect.

The present study examined spontaneous detection and repair of naming errors in people with aphasia to advance a theoretical understanding of how monitoring impacts learning in lexical access. Prior work in aphasia has found that spontaneous repair, but not mere detection without repair, of semantic naming errors leads to improved naming on those same items in the future when other factors are accounted for. The present study sought to replicate this finding in a new, larger sample of participants and to examine the critical role of self-generated repair in this monitoring learning effect. Twenty-four participants with chronic aphasia with naming impairment provided naming responses to a 660-item corpus of common, everyday objects at two timepoints. At the first timepoint, a randomly selected subset of trials ended in experimenter-provided corrective feedback. Each naming trial was coded for accuracy, error type, and for any monitoring behavior that occurred, specifically detection with repair (i.e., correction), detection without repair, and no detection. Focusing on semantic errors, the original monitoring learning effect was replicated, with enhanced accuracy at a future timepoint when the first trial with that item involved detection with repair, compared to error trials that were not detected. This enhanced accuracy resulted from learning that arose from the first trial rather than the presence of repair simply signifying easier items. A second analysis compared learning from trials of self-corrected errors to that of trials ending in feedback that were detected but not self-corrected and found enhanced learning after self-generated repair. Implications for theories of lexical access and monitoring are discussed.

Is comprehension necessary for error detection? A conflict-based account of monitoring in speech production.

Despite the existence of speech errors, verbal communication is successful because speakers can detect (and correct) their errors. The standard theory of speech-error detection, the perceptual-loop account, posits that the comprehension system monitors production output for errors. Such a comprehension-based monitor, however, cannot explain the double dissociation between comprehension and error-detection ability observed in the aphasic patients. We propose a new theory of speech-error detection which is instead based on the production process itself. The theory borrows from studies of forced-choice-response tasks the notion that error detection is accomplished by monitoring response conflict via a frontal brain structure, such as the anterior cingulate cortex. We adapt this idea to the two-step model of word production, and test the model-derived predictions on a sample of aphasic patients. Our results show a strong correlation between patients' error-detection ability and the model's characterization of their production skills, and no significant correlation between error detection and comprehension measures, thus supporting a production-based monitor, generally, and the implemented conflict-based monitor in particular. The successful application of the conflict-based theory to error-detection in linguistic, as well as non-linguistic domains points to a domain-general monitoring system.

Case series investigations in cognitive neuropsychology.

Case series methodology involves the systematic assessment of a sample of related patients, with the goal of understanding how and why they differ from one another. This method has become increasingly important in cognitive neuropsychology, which has long been identified with single-subject research. We review case series studies dealing with impaired semantic memory, reading, and language production and draw attention to the affinity of this methodology for testing theories that are expressed as computational models and for addressing questions about neuroanatomy. It is concluded that case series methods usefully complement single-subject techniques.

Density pervades: an analysis of phonological neighbourhood density effects in aphasic speakers with different types of naming impairment.

We investigated the influence of phonological neighbourhood density (PND) on the performance of aphasic speakers whose naming impairments differentially implicate phonological or semantic stages of lexical access. A word comes from a dense phonological neighbourhood if many words sound like it. Limited evidence suggests that higher density facilitates naming in aphasic speakers, as it does in healthy speakers. Using well-controlled stimuli, Experiment 1 confirmed the influence of PND on accuracy and phonological error rates in two aphasic speakers with phonological processing deficits. In Experiments 2 and 3, we extended the investigation to an aphasic speaker who is prone to semantic errors, indicating a semantic deficit and/or a deficit in the mapping from semantics to words. This individual had higher accuracy, and fewer semantic errors, in naming targets from high- than from low-density neighbourhoods. It is argued that the Results provide strong support for interactive approaches to lexical access, where reverberatory feedback between word- and phoneme-level lexical representations not only facilitates phonological level processes but also privileges the selection of a target word over its semantic competitors.

A large, searchable, web-based database of aphasic performance on picture naming and other tests of cognitive function.

Many research questions in aphasia can only be answered through access to substantial numbers of patients and to their responses on individual test items. Since such data are often unavailable to individual researchers and institutions, we have developed and made available the Moss Aphasia Psycholinguistics Project Database: a large, searchable, web-based database of patient performance on psycholinguistic and neuropsychological tests. The database contains data from over 240 patients covering a wide range of aphasia subtypes and severity, some of whom were tested multiple times. The core of the archive consists of a detailed record of individual-trial performance on the Philadelphia (picture) Naming Test. The database also contains basic demographic information about the patients and patients' overall performance on neuropsychological assessments as well as tests of speech perception, semantics, short-term memory, and sentence comprehension. The database is available at http://www.mappd.org/ .

Anterior temporal involvement in semantic word retrieval: voxel-based lesion-symptom mapping evidence from aphasia.

Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernicke's area.

The parietal lobe and language.

Although the parietal lobe was considered by many of the earliest investigators of disordered language to be a major component of the neural systems instantiating language, most views of the anatomic substrate of language emphasize the role of temporal and frontal lobes in language processing. We review evidence from lesion studies as well as functional neuroimaging, demonstrating that the left parietal lobe is also crucial for several aspects of language. First, we argue that the parietal lobe plays a major role in semantic processing, particularly for "thematic" relationships in which information from multiple sensory and motor domains is integrated. Additionally, we review a number of accounts that emphasize the role of the left parietal lobe in phonologic processing. Although the accounts differ somewhat with respect to the nature of the linguistic computations subserved by the parietal lobe, they share the view that the parietal lobe is essential for the processes by which sound-based representations are transcoded into a format that can drive action systems. We suggest that investigations of the linguistic capacities of the parietal lobe constrained by the understanding of the parietal lobe in action and multimodal sensory integration may serve to enhance not only our understanding of language, but also the relationship between language and more basic brain functions.

The timing of spontaneous detection and repair of naming errors in aphasia.

This study examined the timing of spontaneous self-monitoring in the naming responses of people with aphasia. Twelve people with aphasia completed a 615-item naming test twice, in separate sessions. Naming attempts were scored for accuracy and error type, and verbalizations indicating detection were coded as negation (e.g., "no, not that") or repair attempts (i.e., a changed naming attempt). Focusing on phonological and semantic errors, we measured the timing of the errors and of the utterances that provided evidence of detection. The effects of error type and detection response type on error-to-detection latencies were analyzed using mixed-effects regression modeling. We first asked whether phonological errors and semantic errors differed in the timing of the detection process or repair planning. Results suggested that the two error types primarily differed with respect to repair planning. Specifically, repair attempts for phonological errors were initiated more quickly than repair attempts for semantic errors. We next asked whether this difference between the error types could be attributed to the tendency for phonological errors to have a high degree of phonological similarity with the subsequent repair attempts, thereby speeding the programming of the repairs. Results showed that greater phonological similarity between the error and the repair was associated with faster repair times for both error types, providing evidence of error-to-repair priming in spontaneous self-monitoring. When controlling for phonological overlap, significant effects of error type and repair accuracy on repair times were also found. These effects indicated that correct repairs of phonological errors were initiated particularly quickly, whereas repairs of semantic errors were initiated relatively slowly, regardless of their accuracy. We discuss the implications of these findings for theoretical accounts of self-monitoring and the role of speech error repair in learning.

Semantic weight and verb retrieval in aphasia.

Individuals with agrammatic aphasia may have difficulty with verb production in comparison to nouns. Additionally, they may have greater difficulty producing verbs that have fewer semantic components (i.e., are semantically "light") compared to verbs that have greater semantic weight. A connectionist verb-production model proposed by Gordon and Dell (2003) learns through error correction to "divide the labor" between syntax and semantics. Verbs that are semantically heavier come to depend less on syntax and more on semantics. For lighter verbs, the reverse is true. We performed this study to clarify the role of semantic weight in aphasic verb production and to test the prediction from Gordon and Dell that a brain lesion that impairs the syntactic input to verb retrieval will impair lighter verbs more than heavier ones. Consistent with this prediction, we found that the decrement for lighter verbs was present in a group with agrammatic aphasia but not in a matched group without agrammatism.