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Patients with the semantic variant of primary progressive aphasia, also known as semantic dementia, and Alzheimer's disease have deficits in semantic memory. However, few comparative studies have been performed to determine whether these patient groups have distinct semantic memory impairments. We asked 15 patients with semantic variant primary progressive aphasia and 57 patients with Alzheimer's disease to judge semantic category membership of coloured photos and printed words that are members of familiar natural and manufactured categories, and we related performance to grey matter atrophy. We found that both semantic variant primary progressive aphasia and Alzheimer's disease are significantly impaired on this task. Moreover, patients with semantic variant primary progressive aphasia had a significantly more prominent deficit for natural objects than their own deficit judging manufactured objects. Both semantic variant primary progressive aphasia and Alzheimer's disease had atrophy that included portions of the left temporal lobe. Regression analyses related performance in semantic variant primary progressive aphasia to ventral and medial portions of the left temporal lobe, while regression analyses in Alzheimer's disease related performance to these ventral and medial temporal areas as well as lateral temporal-parietal regions in the left hemisphere. We conclude that both semantic variant primary progressive aphasia and Alzheimer's disease are significantly impaired in a simple category membership judgement task and the selective impairment for natural kinds in semantic variant primary progressive aphasia is related in part to disease in visual association cortex in ventral-medial portions of the left temporal lobe. We discuss factors that may contribute to the semantic memory deficit in semantic variant primary progressive aphasia.

Objective: A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA. Methods: We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits. Results: We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant. Conclusions: These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics.

A disabling impairment of higher-order language function can be seen in patients with Lewy body spectrum disorders such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB). We focus on script comprehension in patients with Lewy body spectrum disorders. While scripts unfold sequentially, constituent events are thought to contain an internal organization. Executive dysfunction in patients with Lewy body spectrum disorders may interfere with comprehension of this internal structure. We examined 42 patients (30 non-demented PD and 12 mildly demented PDD/DLB patients) and 12 healthy seniors. We presented 22 scripts (e.g., “going fishing”), each consisting of six events. Pilot data from young controls provided the basis for organizing associated events into clusters and arranging them hierarchically into scripts. We measured accuracy and latency to judge the order of adjacent events in the same cluster versus adjacent events in different clusters. PDD/DLB patients were less accurate in their ordering judgments than PD patients and controls. Healthy seniors and PD patients were significantly faster to judge correctly the order of highly associated within-cluster event pairs relative to less closely associated different-cluster event pairs, while PDD/DLB patients did not consistently distinguish between these event-pair types. This relative insensitivity to the clustered-hierarchical organization of events was related to executive impairment and to frontal atrophy as measured by volumetric MRI. These findings extend prior work on script processing to patients with Lewy body spectrum disorders and highlight the potential impact of frontal/executive dysfunction on the daily lives of affected patients.

Background Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI). Methods Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-oneout cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort. Results ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLDTAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP. Conclusions These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLDTAU, and emphasise the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.

We contribute a novel and interpretable dimensionality reduction strategy, eigenanatomy, that is tuned for neuroimaging data. The method approximates the eigendecomposition of an image set with basis functions (the eigenanatomy vectors) that are sparse, unsigned and are anatomically clustered. We employ the eigenanatomy vectors as anatomical predictors to improve detection power in morphometry. Standard voxel-based morphometry (VBM) analyzes imaging data voxel-by-voxel--and follows this with cluster-based or voxel-wise multiple comparisons correction methods to determine significance. Eigenanatomy reverses the standard order of operations by first clustering the voxel data and then using standard linear regression in this reduced dimensionality space. As with traditional region-of-interest (ROI) analysis, this strategy can greatly improve detection power. Our results show that eigenanatomy provides a principled objective function that leads to localized, data-driven regions of interest. These regions improve our ability to quantify biologically plausible rates of cortical change in two distinct forms of neurodegeneration. We detail the algorithm and show experimental evidence of its efficacy.

Objective: To relate fractional anisotropy changes associated with the semantic and logopenic variants of primary progressive aphasia to measures of lexical retrieval. Methods: We collected neuropsychological testing, volumetric MRI, and diffusion-weighted imaging on semantic variant primary progressive aphasia (n=11) and logopenic variant primary progressive aphasia (n=13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n=34). Fractional anisotropy was calculated and analyzed using a white matter tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to fractional anisotropy and determine regions of reduced fractional anisotropy in patients. Results: We found widespread fractional anisotropy reductions in white matter for both variants of primary progressive aphasia. Fractional anisotropy was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in semantic variant primary progressive aphasia and left superior and inferior longitudinal fasciculi in logopenic variant primary progressive aphasia. Conclusions: Semantic variant primary progressive aphasia and logopenic variant primary progressive aphasia are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the white matter disease in each phenotype may contribute to language impairments including lexical retrieval.

Objective: Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) may have overlapping clinical presentations despite distinct underlying neuropathologies, thus making in vivo diagnosis challenging. In this study, we evaluate the utility of MRI as a noninvasive screening procedure for the differential diagnosis of AD and FTLD. Methods: We recruited 185 patients with a clinically diagnosed neurodegenerative disease consistent with AD or FTLD who had a lumbar puncture and a volumetric MRI. A subset of 32 patients had genetic or autopsy-confirmed AD or FTLD. We used singular value decomposition to decompose MRI volumes and linear regression and cross-validation to predict CSF total tau (tt) and β-amyloid (Aβ 1-42 ) ratio (tt/Aβ) in patients with AD and patients with FTLD. We then evaluated accuracy of MRI-based predicted tt/Aβ using 4 converging sources including neuroanatomic visualization and categorization of a subset of patients with genetic or autopsy-confirmed AD or FTLD. Results: Regression analyses showed that MRI-predicted tt/Aβ is highly related to actual CSF tt/Aβ. In each group, both predicted and actual CSF tt/Aβ have extensively overlapping neuroanatomic correlates: low tt/Aβ consistent with FTLD is related to ventromedial prefrontal regions while high tt/Aβ consistent with AD is related to posterior cortical regions. MRI-predicted tt/Aβ is 75% accurate at identifying underlying diagnosis in patients with known pathology and in clinically diagnosed patients with known CSF tt/Aβ levels. Conclusion: MRI may serve as a noninvasive procedure that can screen for AD and FTLD pathology as a surrogate for CSF biomarkers.

Non-fluent/agrammatic primary progressive aphasia (naPPA) is a progressive neurodegenerative condition most prominently associated with slowed, effortful speech. A clinical imaging marker of naPPA is disease centered in the left inferior frontal lobe. We used multimodal imaging to assess large-scale neural networks underlying effortful expression in 15 patients with sporadic naPPA due to frontotemporal lobar degeneration (FTLD) spectrum pathology. Effortful speech in these patients is related in part to impaired grammatical processing, and to phonologic speech errors. Gray matter (GM) imaging shows frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Diffusion tensor imaging reveals reduced fractional anisotropy in several white matter (WM) tracts mediating projections between left frontal and other GM regions. Regression analyses suggest disruption of three large-scale GM-WM neural networks in naPPA that support fluent, grammatical expression. These findings emphasize the role of large-scale neural networks in language, and demonstrate associated language deficits in naPPA.

Objective Previous work investigating deficits in self-appraisal in behavioural-variant frontotemporal degeneration (bvFTD) has focused on a single domain: social/behavioural processes. We examined whether a domain-specific versus multi-domain model best explains degraded self-appraisal in bvFTD. Methods 49 patients with bvFTD and 73 patients with Alzheimer9s disease (AD) were administered quantitative assessments of episodic memory, naming and grammatical comprehension. Self-appraisal of cognitive test performance was assessed by asking patients to rate their performance immediately after completing each neuropsychological test. A discrepancy score was created to reflect the difference between patient performance on neuropsychological tests and self-appraisal of their test performance. Self-appraisal for each neuropsychological measure was related to grey matter (GM) density in each group using voxel-based morphometry. Results bvFTD patients were poor at evaluating their own performance on all cognitive tests, with no significant correlations between self-appraisal and actual performance. By contrast, poor self-appraisal in AD was restricted to episodic memory performance. Poor self-appraisal on each task in bvFTD and AD was related to reduced GM density in several ventral and rostral medial prefrontal regions. Crucially, poor self-appraisal for all domains in bvFTD was related to a specific area of reduced GM density in the subgenual cingulate (BA 25). Conclusion Poor self-appraisal in bvFTD affects multiple domains, and this multi-domain impairment pattern is associated with frontal disease in the subgenual cingulate.

To evaluate the distribution of white matter (WM) disease in frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to evaluate the relative usefulness of WM and gray matter (GM) for distinguishing these conditions in vivo.Patients were classified as having FTLD (n = 50) or AD (n = 42) using autopsy-validated CSF values of total-tau:β-amyloid (t-tau:Aβ(1-42)) ratios. Patients underwent WM diffusion tensor imaging (DTI) and volumetric MRI of GM. We employed tract-specific analyses of WM fractional anisotropy (FA) and whole-brain GM density analyses. Individual patient classification was performed using receiver operator characteristic (ROC) curves with FA, GM, and a combination of the 2 modalities.Regional FA and GM were significantly reduced in FTLD and AD relative to healthy seniors. Direct comparisons revealed significantly reduced FA in the corpus callosum in FTLD relative to AD. GM analyses revealed reductions in anterior temporal cortex for FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to FTLD. ROC curves revealed that a multimodal combination of WM and GM provide optimal classification (area under the curve = 0.938), with 87% sensitivity and 83% specificity.FTLD and AD have significant WM and GM defects. A combination of DTI and volumetric MRI modalities provides a quantitative method for distinguishing FTLD and AD in vivo.

To use values of cerebrospinal fluid tau and β-amyloid obtained from 2 different analytical immunoassays to differentiate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD).Cerebrospinal fluid values of total tau (T-tau) and β-amyloid 1-42 (Aβ 1-42) obtained using the Innotest enzyme-linked immunosorbent assay were transformed using a linear regression model to equivalent values obtained using the INNO-BIA AlzBio3 (xMAP; Luminex) assay. Cutoff values obtained from the xMAP assay were developed in a series of autopsy-confirmed cases and cross validated in another series of autopsy-confirmed samples using transformed enzyme-linked immunosorbent assay values to assess sensitivity and specificity for differentiating AD from FTLD.Tertiary memory disorder clinics and neuropathologic and biomarker core centers.Seventy-five samples from patients with cerebrospinal fluid data obtained from both assays were used for transformation of enzyme-linked immunosorbent assay values. Forty autopsy-confirmed cases (30 with AD and 10 with FTLD) were used to establish diagnostic cutoff values and then cross validated in a second sample set of 21 autopsy-confirmed cases (11 with AD and 10 with FTLD) with transformed enzyme-linked immunosorbent assay values.Diagnostic accuracy using transformed biomarker values.Data obtained from both assays were highly correlated. The T-tau to Aβ 1-42 ratio had the highest correlation between measures (r = 0.928, P.001) and high reliability of transformation (intraclass correlation coefficient= 0.89). A cutoff of 0.34 for the T-tau to Aβ 1-42 ratio had 90% and 100% sensitivity and 96.7% and 91% specificity to differentiate FTLD cases in the validation and cross-validation samples, respectively.Values from 2 analytical platforms can be transformed into equivalent units, which can distinguish AD from FTLD more accurately than the clinical diagnosis.

Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson’s disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body spectrum disorder (LBSD). Thirty-three patients with LBSD were given a two-alternative, forced-choice sentence-picture matching task. Sentence type, working memory, and grammatical structure were systematically manipulated in the sentences. We found that patients with PDD and DLB were significantly impaired relative to non-demented PD patients and healthy controls. The deficit in PDD/DLB was most pronounced for sentences lengthened by the strategic placement of an additional prepositional phrase and for sentences with an additional proposition due to a center-embedded clause. However, there was no effect for subject-relative versus object-relative grammatical structure. An MRI voxel-based morphometry analysis in a subset of patients showed significant gray matter thinning in the frontal lobe bilaterally, and this extended to temporal, parietal and occipital regions. A regression analysis related sentence processing difficulty in LBSD to frontal neocortex, including inferior prefrontal, premotor, and dorsolateral prefrontal regions, as well as right superior temporal cortex. These findings are consistent with the hypothesis that patients with PDD and DLB have difficulty processing sentences with increased working memory demands and that this deficit is related in part to their frontal disease.

When making a decision, humans often have to ‘coordinate’—reach the same conclusion—as another individual without explicitly communicating. Relatively, little is known about the neural basis for coordination. Moreover, previous fMRI investigations have supported conflicting hypotheses. One account proposes that individuals coordinate using a ‘gut feeling’ and that this is supported by insula recruitment. Another account proposes that individuals recruit strategic decision-making mechanisms in prefrontal cortex in order to coordinate. We investigate the neural basis for coordination in individuals with behavioral-variant frontotemporal dementia (bvFTD) who have limitations in social decision-making associated with disease in prefrontal cortex. We demonstrate that bvFTD are impaired at establishing a focal point in a semantic task (e.g. ‘Tell me any boy's name’) that requires coordination relative to a similar, control semantic task that does not. Additionally, coordination limitations in bvFTD are related to cortical thinning in prefrontal cortex. These findings are consistent with behavioral economic models proposing that, beyond a ‘gut feeling’, strategic decision-making contributes to the coordination process, including a probabilistic mechanism that evaluates the salience of a response (e.g. is ‘John’ a frequent boy's name), a hierarchical mechanism that iteratively models an opponent's likely response and a mechanism involved in social perspective taking.

Semantic dementia (SemD) IS a primary progressive form of aphasia characterized by impaired semantic memory affecting confrontation naming and the interpretation of word and object meaning.1 Two recent cases of relatively preserved musical knowledge in SemD have been reported,2,3 although the absence of detailed analyses limits our ability to learn from these patients. We describe preserved ability to perform music in a 64-year-old semiprofessional harpsichordist with SemD. Analysis of his performance of pieces from the Baroque period that were familiar and unfamiliar to him revealed remarkably preserved musical expression abilities and creativity despite profound difficulty with word and object meaning and significant left anterior temporal atrophy. These observations are consistent with a modular approach to semantic memory that dissociates long-term representations of word and object meaning from meaningful knowledge in other domains, such as music.

Pronouns are extraordinarily common in daily language yet little is known about the neural mechanisms that support decisions about pronoun reference. We propose a large-scale neural network for resolving pronoun reference that consists of two components. First, a core language network in peri-Sylvian cortex supports syntactic and semantic resources for interpreting pronoun meaning in sentences. Second, a frontal–parietal network that supports strategic decision-making is recruited to support probabilistic and risk-related components of resolving a pronoun's referent. In an fMRI study of healthy young adults, we observed activation of left inferior frontal and superior temporal cortex, consistent with a language network. We also observed activation of brain regions not associated with traditional language areas. By manipulating the context of the pronoun, we were able to demonstrate recruitment of dorsolateral prefrontal cortex during probabilistic evaluation of a pronoun's reference, and orbital frontal activation when a pronoun must adopt a risky referent. Together, these findings are consistent with a two-component model for resolving a pronoun's reference that includes neuroanatomic regions supporting core linguistic and decision-making mechanisms.

Recent investigations have supported the suggestion that phonological speech errors may reflect the simultaneous activation of more than one phonemic representation. This presents a challenge for speech error evidence which is based on the assumption of well-formedness, because we may continue to perceive well-formed errors, even when they are not produced. To address this issue, we present two tongue-twister experiments in which the articulation of onset consonants is quantified and compared to baseline measures from cases where there is no phonemic competition. We report three measure of articulatory variability: changes in tongue-to-palate contact using electropalatography (EPG, Experiment 1), changes in midsagittal spline of the tongue using ultrasound (Experiment 2), and acoustic changes manifested as voice-onset time (VOT). These three sources provide converging evidence that articulatory variability increases when competing onsets differ by one phonological feature, but the increase is attenuated when onsets differ by two features. This finding provides clear evidence, based solely on production, that the articulation of phonemes is influenced by cascading activation from the speech plan.

Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB.

Objective: Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are hypothesized to cause clinically distinct forms of primary progressive aphasia (PPA) that predominantly affect expressive speech. AD is thought to cause logopenic progressive aphasia (LPA), and FTLD may cause progressive nonfluent aphasia (PNFA). We sought to determine the value of clinical characterization, neuropsychological analysis, and MRI atrophy in predicting pathology of LPA and PNFA. Methods: Patients with LPA (n = 19) and patients with PNFA (n = 19) were evaluated with neuropsychological assessments, structural MRI, CSF analysis, and neuropathologic examination. Results: Twelve of 19 patients with LPA (63%) and 6 of 19 patients with PNFA (32%) had neuropathologic findings or CSF biomarkers consistent with AD. Neuropsychological testing showed that naming was more impaired in patients with AD, and letter-guided fluency was more affected in patients with a non-AD disorder. Voxel-based morphometry analysis revealed that in patients with AD, patients with LPA and PNFA had significant posterior-superior temporal atrophy; in patients with non-AD, patients with LPA had peri-Sylvian atrophy and patients with PNFA had dorsolateral prefrontal and insular atrophy. Receiver operator characteristic curve analysis showed that combining neuropsychological testing with MRI atrophy pattern had 90% specificity for pathology or CSF biomarkers consistent with AD, and combining clinical features with neuropsychological analysis had 100% sensitivity for pathology or CSF biomarkers consistent with AD. Conclusions: Neither PPA phenotyping nor imaging alone is a reliable predictor of pathology. Multimodal predictors, such as combining neuropsychological testing with MRI analysis, can improve noninvasive prediction of underlying pathology in nonfluent forms of PPA.

To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA).Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to impairments in syntactic processing, motor-speech planning, and executive functioning that also occur in these patients. Patients with PNFA have left inferior frontal atrophy.A large semi-structured speech sample and neuropsychological measures of language and executive functioning were examined in 16 patients with PNFA, 12 patients with behavioral-variant frontotemporal dementia (bvFTD), and 13 age-matched controls. Speech fluency was quantified as words per minute (WPM) in the semi-structured speech sample. Stepwise linear regression analyses were used to relate WPM to grammatic, motor-speech planning, and executive aspects of patient functioning. These measures were then related to cortical thickness in 8 patients with PNFA and 7 patients with bvFTD using structural MRI.WPM was significantly reduced in patients with PNFA relative to controls and patients with bvFTD. Regression analyses revealed that only grammatic measures predicted WPM in PNFA, whereas executive measures were the only significant predictor of WPM in bvFTD. Cortical thinning was significant in PNFA relative to controls in left inferior frontal and anterior-superior temporal regions, and a regression analysis related this area to reduced WPM in PNFA. Significant cortical thinning associated with limited grammatic processing also was seen in the left inferior frontal-superior temporal region in PNFA, and this overlapped with the area of frontal-temporal thinning related to reduced WPM.Nonfluent speech in PNFA may be due in part to difficulty with grammatic processing associated with left inferior frontal and anterior-superior temporal disease.

To investigate the cognitive and neural correlates of discourse impairment in corticobasal syndrome (CBS).Difficulty communicating is a frequent clinical manifestation in patients with CBS. However, the mechanisms underlying this disabling problem are not well understood.Twenty patients with CBS and 8 healthy seniors narrated a picture story. Narratives were analyzed for maintenance of the narrative theme, identification of the overall point of the story (global connectedness), and connectedness between consecutive events (local connectedness). Discourse measures were correlated with performance on cognitive tasks and with cortical atrophy as determined by magnetic resonance imaging voxel-based morphometry.Patients with CBS referred to the narrative theme significantly less frequently than controls. Global connectedness was intact in only 6 of 20 CBS patients (30%), but preserved in all controls. Local connectedness was significantly diminished in patients relative to controls. Discourse performance in CBS was related to tasks requiring higher-order integration of visual material, but not to basic visuospatial/visuoperceptual, language, or memory function. Discourse impairment was directly related to atrophy in the right parietal lobe and bilateral dorsolateral prefrontal cortex.Our findings suggest that impaired information integration in CBS, related to parieto-frontal disease, interferes with patients' ability to narrate a coherent story.

The nature and frequency of speech production errors in neurodegenerative disease have not previously been precisely quantified. In the present study, 16 patients with a progressive form of non-fluent aphasia (PNFA) were asked to tell a story from a wordless children's picture book. Errors in production were classified as either phonemic, involving language-based deformations that nevertheless result in possible sequences of English speech segments; or phonetic, involving a motor planning deficit and resulting in non-English speech segments. The distribution of cortical atrophy as revealed by structural MRI scans was examined quantitatively in a subset of PNFA patients (N=7). The few errors made by healthy seniors were only phonemic in type. PNFA patients made more than four times as many errors as controls. This included both phonemic and phonetic errors, with a preponderance of errors (82%) classified as phonemic. The majority of phonemic errors were substitutions that shared most distinctive features with the target phoneme. The systematic nature of these substitutions is not consistent with a motor planning deficit. Cortical atrophy was found in prefrontal regions bilaterally and peri-Sylvian regions of the left hemisphere. We conclude that the speech errors produced by PNFA patients are mainly errors at the phonemic level of language processing and are not caused by a motor planning impairment.

We present a new algorithm for reliable, unbiased, multivariate longitudinal analysis of cortical and white matter atrophy rates with penalized statistical methods. The pipeline uses a step-wise approach to transform and personalize template information first to a single-subject template (SST) and then to the individual's time series data. The first stream of information flows from group template to the SST; the second flows from the SST to the individual time-points and provides unbiased, prior-based segmentation and measurement of cortical thickness. MRI-bias correction, consistent longitudinal segmentation, cortical parcellation and cortical thickness estimation are all based on strong use of the subject-specific priors built from initial diffeomorphic mapping between the SST and optimal group template. We evaluate our approach with both test-retest data and with application to a driving biological problem. We use test-retest data to show that this approach produces (a) zero change when the retest data contains the same image content as the test data and (b) produces normally distributed, low variance estimates of thickness change centered at zero when test-retest data is collected near in time to test data. We also show that our approach--when combined with sparse canonical correlation analysis--reveals plausible, significant, annualized decline in cortical thickness and white matter volume when contrasting frontotemporal dementia and normal aging.

Measures from event-related functional MRI, diffusion tensor imaging tractography and cognitive performance in a language-based task were used to test the hypothesis that both functional and structural connectivity provide independent and complementary information that aids in the identification of network components most related to the neurobiological basis for language and cognitive processing. Structural connectivity was measured by averaging fractional anisotropy (FA) over a geometric fiber bundle model that projects local white matter properties onto a centerline. In the uncinate fasciculus FA was found to predict performance on a measure of decision-making regarding homonym meaning. Functional synchronization of BOLD fMRI signals between frontal and temporal regions connected by the uncinate fasciculus was also found to predict the performance measure. Multiple regression analysis demonstrated that combining equidimensional measures of functional and structural connectivity identified the network components that most significantly predict performance.

Szymanik and Zajenkowski (this issue) present investigations regarding computational modeling techniques as they apply to the comprehension of quantifiers, or noun phrases that assert a property from a set of items (e.g.. “at least 3”, “some”, or “most”). The authors present behavioral results from two experiments and distinguish several quantifier classes using reaction time data to support theoretical predictions. These findings demonstrate that reaction time increases significantly as a function of quantifier complexity and complement previous studies of quantifier comprehension (McMillan et al., 2005; McMillan et al., 2006; Troiani et al., 2009). We broadly agree with these authors’ observations — namely, that the complexities in quantifier processing may be predicted in part using neural systems modeled with minimally corresponding automata. However, these findings are best understood in the larger context of our findings that emphasize the importance of a decision-based mechanism where complexity is a function of numerical magnitude and corresponding numerical distance effects. Furthermore, parity as a property of quantifiers (odd, even) appears to be a unique semantic attribute of numerals which can interact both with task and strategy in studies of quantifier comprehension, and may not be easily described using automata-based models. In the first experiment reported by Szymanik and Zajenkowski, mean reaction times were ordered as follows: logical quantifiers, parity quantifiers, numerical quantifiers, and proportional quantifiers. These results are used to support the conclusion that parity quantifiers can be recognized using a two-state finite automaton with alternating transitions between these two states. However, such a model cannot completely account for the full complexity of parity knowledge observed. While parity can certainly be evaluated using the non-numerical strategies outlined in Szymanik (2007), parity is also a semantic property of symbolic numerical representation. Judgments of supposedly categorical concepts such as “evenness” indicate that numbers are not subjectively treated as equally odd or even (Armstrong et al., 1983). Also, the numerical property of parity has been exploited to demonstrate the presence of a spatial mental number line in magnitude processing (Dehaene et al., 1993). This effect is present in children as early as age 10 (Berch et a., 1999) and is additionally accompanied by a linguistic effect based on associations between the unmarked adjectives “even” and “right” and the marked adjectives “odd” and “left” (Nuerk et al, 2004). Thus, parity is inextricably linked with magnitude and language, and simple reaction time differences are not enough to fully capture the complexity of processes by which the brain represents, recognizes, or judges parity. The authors propose that a two-state cyclic automaton can account for the difference between first-order and parity quantifiers, and that this difference should correspond to recruitment of an executive resource relying on dorsolateral prefrontal cortical support. In our previous study (Troiani et al., 2009), numerical and parity quantifiers were lumped together, resulting in a recruitment pattern including right parietal, dorsolateral prefrontal, and inferior frontal cortex. As described in this previous article, there were no differences in neural activation between numerical and parity quantifiers. However, we did find reaction time differences, which were slightly different from those reported by Szymanik and Zajenkowski. Significant mean reaction time increases were observed between the following categories of quantifiers: logical quantifiers, cardinal quantifiers, and parity quantifiers. The disparity between our observed reaction time increases and those of Szymanik and Zajenkowski are likely due to the differences in magnitudes used. Our studies used small magnitudes (less than 3, more than 2), as compared to the larger magnitudes (less than 8, more than 7) examined in Szymanik (2007). Because the mental number line is represented logarithmically, assessing whether 7 and 8 are different will take longer than the same assessment of 2 and 3 (Dehaene, 2003). The observation that parity judgments take longer than numerical judgments in our study, whereas they took significantly less time in the Szymanik and Zajenkowski study, reflects the increase in response latency necessary to compare numbers of higher magnitude. This is not to say that parity judgments cannot be performed by a neural system approximating a two-state finite automaton. In fact, it is likely that in the absence of access to magnitude processing regions — such as in cases of lesion or atrophy—a two-state system would provide a sufficient strategy to assist in parity judgment. This strategy can be illustrated by two patients with corticobasal degeneration (CBD), re-examined from our previous study of serial quantifier processing (Troiani et al., 2009). In this study, patients assessed quantifier statements including numerical quantifiers (e.g. “at least 3”) and parity quantifiers. While overall patient performance did not differ on the quantifier types, two patients performed well above chance on parity judgments (93.8% and 86.1%). However, the judgments made by these same patients involving numerical quantifiers were much closer to chance (64.2% and 51.5%). These data suggest that some patients are able to use a strategy to assess parity, despite impairment assessing quantity, and that this strategy may utilize a two-state finite automaton. Szymanik and Zajenkowski suggest that a similarity-based categorization deficit, rather than difficulty with magnitude processing, may underlie the poorer performance of CBD patients in Troiani et al. (2009). Although the specific nature of the materials used always has potential to influence experimental variability, we do not believe that a similarity-based categorization deficit can explain the quantifier comprehension deficit in these patients. First, we used familiar, perceptually simple stimuli (balls, stars, etc). Each trial consisted only of one type of object, and the only required feature discrimination in each trial was that of color. Second, if patients’ impairment was due to a similarity-based categorization deficit, this would have been evident across all categories of stimuli. Third, the experiments previously identifying semantic categorization deficits in these patients used either novel (Koenig et al., 2007) or ambiguous (Antani et al., 2004) stimuli, and both identified a relative deficit in these patients in similarity-based vs. rule-based processing, with manipulations based on subtle instruction differences. Finally, because deciding the truth-value of a quantifier proposition is in part a rule-based categorization process, we would not expect poor performance due to the types of processing deficits that we observed in studies examining instruction-based differences. Overall, the current evidence is consistent with a role for the involvement of a finite automaton-type neural system in the evaluation of logical quantifiers. This process is likely to be supported by a network involving rostral medial frontal-posterior cingulate regions of cortex. Any quantifier requiring access to magnitude knowledge will recruit parietal regions. Furthermore, a dorsolateral frontal-parietal network is necessary for evaluations involving size differences, as both frontal and parietal regions are activated when making numerical or non-symbolic size judgments (Piazza et al., 2006). It would follow that any quantifier requiring access to symbolic or non-symbolic magnitude would recruit both dorsolateral frontal and parietal cortex, consistent with our previous findings (Troiani et al., 2009). In typical instances, parity and magnitude are intricately related (Dehaene et al., 1993; Nuerk et al., 2004), and likely rely on parietal lobe magnitude processing regions. However, other strategies of parity assessment may exist, compatible with a neural, two-state, automata-based model. Szymanik and Zajenkowski’s approach thus is not inconsistent with our model, where we emphasize the importance of magnitude processing regions in support of quantifier comprehension. It is clear that both experimental and theoretical approaches can provide complementary evidence regarding the role of quantifier representation in the brain, particularly when computational models are able to furnish concrete predictions about human data.

In this study, we investigated patients with focal neurodegenerative diseases to examine a formal linguistic distinction between classes of generalized quantifiers, like "some X" and "less than half of X." Our model of quantifier comprehension proposes that number knowledge is required to understand both first-order and higher-order quantifiers. The present results demonstrate that corticobasal degeneration (CBD) patients, who have number knowledge impairments but little evidence for a deficit understanding other aspects of language, are impaired in their comprehension of quantifiers relative to healthy seniors, Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients [F(3,77)=4.98; p.005]. Moreover, our model attempts to honor a distinction in complexity between classes of quantifiers such that working memory is required to comprehend higher-order quantifiers. Our results support this distinction by demonstrating that FTD and AD patients, who have working memory limitations, have greater difficulty understanding higher-order quantifiers relative to first-order quantifiers [F(1,77)=124.29; p.001]. An important implication of these findings is that the meaning of generalized quantifiers appears to involve two dissociable components, number knowledge and working memory, which are supported by distinct brain regions.

Much work has investigated the neural representation of specific categories of knowledge, but relatively scant attention has been paid in the cognitive neuroscience literature to the semantic processes that contribute to semantic memory. In this study, we monitored regional cortical activity with fMRI while healthy young adults evaluated visually displayed NATURAL KIND, ARTIFACT, and ABSTRACT nouns with two standard tasks: Typicality judgments and Pleasantness judgments. We observed a significant interaction effect between the category of knowledge and the type of judgment used to evaluate members of these semantic categories. Typicality judgments recruited greater temporal–occipital activation relative to Pleasantness judgments of the same category, and this was seen for comparisons of all three semantic categories. However, when contrasted with Typicality judgments, Pleasantness judgments activated a different anatomic distribution for each semantic category. These findings are consistent with a dynamic approach to semantic memory that includes at least two components: semantic knowledge and semantic processes that interpret this knowledge in several ways depending on the particular semantic challenge.

Sentence comprehension is a complex task that involves both language-specific processing components and general cognitive resources. Comprehension can be made more difficult by increasing the syntactic complexity or the presentation rate of a sentence, but it is unclear whether the same neural mechanism underlies both of these effects. In the current study, we used event-related functional magnetic resonance imaging (fMRI) to monitor neural activity while participants heard sentences containing a subject-relative or object-relative center-embedded clause presented at three different speech rates. Syntactically complex object-relative sentences activated left inferior frontal cortex across presentation rates, whereas sentences presented at a rapid rate recruited frontal brain regions such as anterior cingulate and premotor cortex, regardless of syntactic complexity. These results suggest that dissociable components of a large-scale neural network support the processing of syntactic complexity and speech presented at a rapid rate during auditory sentence processing.

We examined oral calculation in patients with corticobasal degeneration (CBD; N=17), frontotemporal dementia (FTD; N=17), and Alzheimer’s disease (AD; N=20), as well as 17 healthy seniors matched for age and education. Our calculation model involves at least three components: numerosity, combinatorial processes, and executive resources such as working memory. We assessed addition, subtraction, multiplication, and division involving small numbers (small, single-digit answers) and large numbers (larger, single- and double-digit answers). We also assessed dot counting for small numbers (2–5) and large numbers (6–9), as well as a measure of working memory. All patient groups differed from healthy seniors in oral calculation. CBD (36% correct) and FTD (65% correct) demonstrated a significant overall impairment in oral calculation relative to AD (76% correct). CBD (66% correct) had more difficulty counting dots overall relative to AD (94% correct) and FTD (86% correct), consistent with our hypothesis that the calculation deficit in CBD is due in large part to a numerosity deficit. FTD had more difficulty relative to AD in their performance of reverse digit span, consistent with our hypothesis that FTD patients’ executive resource limitation contributes to their pattern of calculation impairment. D 2002 Elsevier Science B.V. All rights reserved.

In order to identify healthcare resource use patterns associated with chronic obstructive pulmonary disease (COPD), resource utilization (RU) data collection was integrated into a randomized, double-blind placebo-controlled study of Viozan™ (sibenadet HCI). This study enrolled patients with symptomatic, smoking-related COPD, randomized to receive sibenadet or placebo for a 52-week treatment period. A questionnaire establishing typical pre-trial, COPD, randomized to RU was completed by each patient. Subsequent data were collected by means of an Interactive Voice Response System (IVRS) at 30-day intervals (14 time points) during the study and in the follow-up period. The IVRS system facilitated data collection and minimized inconvient to the patients. Subsequent data were collected by means of an Interactive Voice Response System health services during the year-long study was high.No overall trend for lower RU was associated with sibenadet therapy, which correlates with the lack of sustained clinical effect seen in studies conducted concurrently. These data do, however, provide valuable information on RU associated with COPD and insights into adjustments associated with changes in disease course. Physicians were seen to be the most common source of care for patients with COPD and more of the patients with severe COPD (stage III) than mild (stage I) were seen to utilize the most expensive resources (e.g. inpatient hospital care). For those patients who experienced an exacerbation during the trial (irrespective of treatment group), resource use was increased during the periods when an exacerbation was reported when compared with the periods before or after an exacerbation. The proportion of cases attending the physician doubled and with a trip to the Emergency Room (ER) increased approximately ninefold during the reporting period in which the exacerbation occurred compared with the previous month.This study has shown that use of an IVRS, even in elderly patients, is an effective means of gathering RU data over long periods. The study findings suggest that the advent of effective therapeutic interventions, particularly any with the ability to minimize exacerbations and limit disease progression, could impact on the health care services used and potentially reduce associated costs.

This article reports a review of focal retrograde amnesia (FRA), or the phenomenon of organically based severe memory loss restricted to retrograde, or pretraumatic, memory. Cases of FRA are classified according to the type of memory loss: episodic, semantic, or both. A few different clusters of the disorder were identified. Lesions to either the anterior temporal lobes or the posterior/visual cortex can result in an FRA that devastates retrograde episodic memory, while having smaller effects on semantic memory. A number of left-hemisphere patients have FRA confined to semantic memory. There are several additional examples of FRA following minor cerebral trauma that disrupts either episodic memory alone or both episodic and semantic memory that are not accompanied by evidence of structural brain lesions. We discuss these different profiles of FRA and their implications for the understanding of memory retrieval.

We asked young adults to categorize written object descriptions into one of two categories, based on a rule or on overall similarity, while we monitored regional brain activity with functional magnetic resonance imaging (fMRI). We found significantly greater recruitment of left dorsolateral prefrontal cortex for rule-based categorization in direct comparison with similarity-based categorization. Recruitment of right ventral frontal cortex and thalamus was uniquely associated with rule-based categorization as well. These observations lend support to the claim that executive functions such as working memory, inhibitory control, and selective attention contribute to rule-based categorization. Right inferior parietal activation was uniquely associated with similarity-based categorization. This region may play an important role in overall feature configuration that is important for this form of categorization. We found other brain regions recruited for both rule-based and similarity-based categorization: Anterior cingulate cortex may support the implementation of executive functions during situations with competing response alternatives; and left inferior parietal cortex may be related to the integration of feature knowledge about objects represented in modality-specific association cortices. We also administered a degraded-similarity condition where the task of categorizing a written object description was made more difficult by perceptually degrading the stimulus materials. The degraded condition and the rule-based condition, but not the similarity-based condition, were associated with caudate activation. The caudate may support resource demands that are not specific for a particular categorization process. These findings associate partially distinct large-scale neural networks with different forms of categorization in semantic memory.

Objective: To determine the regions of white matter (WM) atrophy in corticobasal syndrome (CBS) using different methods of diffusion tensor imaging (DTI) analysis. Background CBS is a clinical syndrome mostly associated with frontotemporal lobar degeneration (FTLD), where gray matter atrophy predominantly encompasses frontal and parietal lobes. Although little is known about the pattern of WM disease in CBS, it is known that tau, the histopathological basis of corticobasal degeneration (CBD), has substantial WM burden. For neurodegenerative diseases, there is no gold standard for MRI-based WM analysis. Here, we compared two user-independent approaches in analyzing WM: tract-specific analysis (TSA) and whole-brain analysis. Both used fractional anisotropy (FA), which is sensitive to the integrity of white matter fiber tracts. Design/Methods: In 11 CBS patients and 35 demographically-matched healthy seniors, we analyzed 30-direction diffusion-weighted images. We extracted FA for each individual subject, and registered the image to a common stereotactic space. For TSA, 11 tracts were segmented from a DTI template, converted to 3D binary structures, and modeled as medial meshes to reflect maximum FA locally. For the whole-brain analysis, images were analyzed in local space, localized to a publicly available probabilistic template (ICDM-DTI-81), and then compared statistically with seniors in SPM8. Results: TSA revealed reduced FA in CBS relative to seniors in right uncinate, arcuate fasciculus, and inferior frontal-occipital fasiculus; and bilateral corpus callosum, corticospinal tract and superior longitudinal fasiculus. Whole-brain analysis also revealed reduced FA relative to seniors in the corpus callosum, corticospinal tract, fornix, inferior longitudinal fasiculus, superior longitudinal fasciculus, inferior frontal-occipital fasiculus, and external capsule. Conclusions: In addition to grey matter atrophy, CBS patients have considerable WM disease. TSA and whole-brain analyses display largely overlapping findings, validating user-independent approaches to DTI analyses of WM disease. Supported by: HD060406, NS44266, NS53488, AG15116, AG17586, AG32953, the Wyncote Foundation, NS065347, DA022807, EB006266, NS045839, EB009321, K25 AG027785. Disclosure: Dr. Chandrasekaren has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Brun has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Yushkevich has nothing to disclose. Dr. Gee has received research support from Pfizer Inc. Dr. Grossman has nothing to disclose.

Objective: To understand the visuospatial and executive factors contributing to complex figure reproduction in corticobasal syndrome (CBS). Background Patients with CBS are impaired at complex figure copy, but factors contributing to this deficit are unclear. Design/Methods: In Experiment 1, 40 CBS patients completed the modified Rey complex figure (REY) copy, backward digit span (DSB), and modified Judgment of Line Orientation (JOLO) tests, all from the Philadelphia Brief Assessment of Cognition (PBAC). In Experiment 2, 30 CBS patients completed the CERAD praxis figure copy subtest, along with the WAIS-R DSB, unusual views (UV), and dot location (DOTS) tests. Results: In Experiment 1, REY copy was correlated with DSB (r= 0.416, p Conclusions: Converging evidence from both experiments suggests that a combination of executive skills, likely revolving around mental planning ability, and visuospatial ability, related to locating objects in space, is associated with complex figure copy ability in CBS. Supported by: In part by the National Institutes of Health (NS044266 and HD060406). Disclosure: Dr. Haley has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Goldmann Gross has nothing to disclose. Dr. Boller has nothing to disclose. Dr. Kitain has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Libon has nothing to disclose. Dr. Grossman has nothing to disclose.

Objective: Demonstrate that patients with Lewy body spectrum disorder (LBSD), including Parkinson9s disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), have impaired decision-making related to frontal/executive dysfunction. Background Individuals often coordinate with each other when making decisions. For example, we provide a less typical boy9s name in a random list ( John =9%) than when instructed to coordinate responses with another participant ( John =50%; Mehta, 1994). We propose that coordination is supported by a probabilistic mechanism that evaluates the likelihood of a response (e.g., John is more frequent than Alfred ) and a hierarchical control mechanism that models a partner9s response (e.g., I think my partner will respond John ). Areas of dorsolateral and rostral prefrontal cortex (PFC) have been implicated in probabilistic and hierarchical control mechanisms, respectively. Design/Methods: LBSD patients (PD=9; PDD/DLB=12) and healthy elderly controls (N=22) answered 10 questions probing various semantic categories (e.g., a boy9s name). In the Survey condition, participants could provide any response. In the Coordination condition, participants were instructed to respond with the same answer they think an anonymous partner would give. Responses were quantified using a measure of semantic representativeness, the focal index (FI; e.g., Alfred has a lower FI than John ). Patients underwent neuropsychological testing. Volumetric MRI analysis related cortical thinning to coordination performance. Results: An FI-difference score (Coordination-Survey) confirmed that while PD patients coordinate similarly to seniors, PDD/DLB patients are significantly impaired when asked to coordinate their responses [t(32)=2.54, p Conclusions: PDD/DLB patients have impaired coordination related to frontal/executive dysfunction. We suggest a degraded decision-making network in these patients involving areas of PFC related to probability estimation and hierarchical control mechanisms. Supported by: NIH grants NS44266, NS53488, AG15116, AG17586, AG32953, and HD060406, as well as the Wyncote Foundation. Disclosure: Dr. Goldmann Gross has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Kitain has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Grossman has nothing to disclose.

Objective: Demonstrate the ability of volumetric MRI to distinguish patients with corticobasal syndrome (CBS) who have underlying Alzheimer9s disease (AD) from those with non-AD pathology. Background CBS is associated with various pathologies including AD and frontotemporal lobar degeneration (e.g., corticobasal degeneration and progressive supranuclear palsy). A ratio of cerebrospinal fluid (CSF) tau to amyloid beta 1-42 ≥ 0.34 has been associated with underlying AD in autopsy-validated studies. We compared gray matter (GM) and white matter (WM) imaging in CBS patients with CSF suggestive of AD versus non-AD pathology. Design/Methods: High-resolution T1 and diffusion-weighted images were available for 18 CBS patients (CBS-AD=8, CBS-nonAD=10) and 35 matched controls. For T1 images, we performed a probabilistic segmentation to compute GM density. We extracted fractional anisotropy (FA) along WM tracts from 30-direction diffusion tensor images. GM density and FA for the CBS-AD and CBS-nonAD groups were compared to controls using two-sample t-tests. We identified GM and WM regions that differed between patients and controls (p Results: All CBS patients showed GM atrophy in bilateral parietal and temporal cortex relative to controls. GM atrophy was also present in bilateral inferior and dorsolateral prefrontal cortex in CBS-nonAD patients. FA was reduced in posterior corpus callosum and superior longitudinal fasciculus in both groups. CBS-nonAD patients also showed reduced FA in anterior corpus callosum and uncinate. In the ROC curve analysis, three GM regions (right intraparietal sulcus, right inferior frontal cortex, anterior cingulate) and one WM region (anterior corpus callosum) distinguished between CBS-AD and CBS-nonAD patients (p Conclusions: Volumetric MRI can distinguish CBS patients likely to have underlying AD from those with non-AD pathology. The ability to predict underlying pathology in CBS non-invasively is essential as disease-specific therapies become available. Supported by: NIH grants NS44266, NS53488, AG15116, AG17586, AG32953, HD060406, NS065347, and NS045839, as well as the Wyncote Foundation. Disclosure: Dr. Goldmann Gross has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Grossman has nothing to disclose.

Objective: To evaluate behavioral variant frontotemporal dementia (bvFTD) patients9 abilities to coordinate language with a communicative partner. Background bvFTD is characterized by executive limitations and a disorder of behavioral/social comportment but with relatively spared language. Effective communication requires a speaker and a conversational partner to “coordinate” in order to optimize communicative clarity. Coordination involves adjusting speech and comprehension to accommodate a partner9s perspective. Previous work has demonstrated coordination limitations in bvFTD, but it is unknown whether coordination limitations impact communication. Design/Methods: 7 bvFTD patients and 12 healthy seniors (HS) were presented with a two-scene story in which a target animal moved from one position to another in each scene. “Competitors” were included in each scene and were the same animal type (e.g., pig) but differed by one of three types of visual features (color, size, pattern). Therefore, participants were required to use appropriate adjectives to describe the target animal. Participants were instructed to describe the scene with sufficient clarity so a communicative partner could understand which animal was moving. Each story contained either zero (“pig”), one (“red pig”) or three (“large, red, spotted pig”) competitors. Participants9 responses were transcribed and we coded for accuracy producing the correct adjective(s). We used voxel-based morphometry (VBM) to relate coordination limitations to gray matter (GM) atrophy in bvFTD. Results: We observed a Group by Competitors interaction for accuracy [F=12.4; p Conclusions: bvFTD have limitations coordinating with a conversational partner and this may be due in part to executive limitations associated with caudate atrophy. Supported by: HD060406,NS44266,NS53488,AG15116,AG17586,AG32953,The Wyncote Foundation. Disclosure: Dr. McMillan has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Khella has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Grossman has nothing to disclose.

Psychologists normally attribute the surfacing of phonological speech errors to one of two factors: editing of the speech plan [Levelt (1989)] or feedback between word and phoneme levels [Dell (1986)]. This paper assesses the relative contributions of each factor, focusing on the perception and articulation of elicited speech errors. Experiments one and two measure the likelihood of phonological exchange errors as a function of phonetic similarity [Frisch (1996)], using the SLIP paradigm and a tongue‐twister task. Both experiments show that error likelihood increases with phonetic similarity between intended and actual utterance, an effect easy to account for in terms of feedback but not in terms of editing. Experiment three uses EPG to analyze the tongue‐twister utterances: many errors occur at the articulatory level but are not easily perceived in the speech signal. Preliminary analysis suggests three patterns of error: (1) substitution of segments, which may be the result of editing; (2) simultaneous double articulation, hypothesized to be the result of residual activation due to feedback; and (3) overlapping double articulation, representing partial execution of one articulation before substitution with another. Taking these findings together, we hope to evaluate the relative contributions of editing and feedback to phonological speech errors.

Background: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories.Methods: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients.Results: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy.Conclusion: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.