The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.
Primary progressive aphasia; DTI; Networks; White matter
Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.
semantic dementia; semantic knowledge; diffusion tensor-based tractography; functional MRI; voxel-based morphometry
Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts—the superior longitudinal fasciculus including its arcuate component—was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts—the extreme capsule fiber system or the uncinate fasciculus—was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts.
We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling.
dysgraphia; primary progressive aphasia; phonology; orthography; MRI
The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. Five of nine patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings is threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.
Primary progressive aphasia; Frontotemporal dementia; Frontotemporal lobar degeneration; Logopenic aphasia
To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties.
Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined.
All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere.
Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.
Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus.
syntax; production; primary progressive aphasia; voxel-based morphometry
To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA).
This was a case-control study where 16 subjects with bvFTD, 7 with PNFA, and 4 with SMD were identified and matched by age and gender to 19 controls. All subjects had 3-T head MRI with a DTI sequence with diffusion encoding in 21 directions. Gray matter mean diffusivity (MD) was assessed using a region-of-interest (ROI) and voxel-level approach, and voxel-based morphometry was used to assess patterns of gray matter loss. White matter tract diffusivity (fractional anisotropy and radial diffusivity) was assessed by placing ROIs on tracts of interest.
In bvFTD, increased gray matter MD and gray matter loss were identified bilaterally throughout frontal and temporal lobes, with abnormal diffusivity observed in white matter tracts that connect to these regions. In SMD, gray matter loss and increased MD were identified predominantly in the left temporal lobe, with tract abnormalities observed in the inferior longitudinal fasciculus and uncinate fasciculus. In PNFA, gray matter loss and increased MD were observed in left inferior frontal lobe, insula, and supplemental motor area, with tract abnormalities observed in the superior longitudinal fasciculus.
The diffusivity of gray matter is increased in regions that are atrophic in frontotemporal dementia, suggesting disruption of the cytoarchitecture of remaining tissue. Furthermore, damage was identified in white matter tracts that interconnect these regions, supporting the hypothesis that these diseases involve different and specific brain networks.
= automated anatomic labeling;
= anterior cingulate;
= Alzheimer's Disease Research Center;
= Alzheimer's Disease Patient Registry;
= apraxia of speech;
= behavioral variant frontotemporal dementia;
= coefficient of variation;
= axial diffusivity;
= radial diffusivity;
= diffusion tensor imaging;
= fractional anisotropy;
= false discovery rate;
= field of view;
= frontotemporal dementia;
= full-width at half-maximum;
= genu of the corpus callosum;
= high-dimensional warping;
= inferior longitudinal fasciculus;
= mean diffusivity;
= magnetization prepared rapid acquisition gradient echo;
= posterior cingulate;
= progressive nonfluent aphasia;
= partial volume correction;
= region of interest;
= superior longitudinal fasciculus;
= semantic dementia;
= uncinate fasciculus.
Primary progressive aphasia (PPA) is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca’s area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face) meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer’s disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon) increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.
Alzheimer’s disease; frontotemporal dementia; logopenic aphasia; neuroimaging; nonfluent aphasia; primary progressive aphasia; semantic dementia
Classical aphasiology, based on the study of stroke sequelae, fuses speech fluency and grammatical ability. Nonfluent (Broca's) aphasia often is accompanied by agrammatism; whereas in the fluent aphasias grammatical deficits are not typical. The assumption that a similar relationship exists in primary progressive aphasia (PPA) has led to the dichotomization of this syndrome into fluent and nonfluent subtypes.
This study compared elements of fluency and grammatical production in the narrative speech of individuals with PPA to determine if they can be dissociated from one another.
Speech samples from 37 individuals with PPA, clinically assigned to agrammatic (N=11), logopenic (N=20) and semantic (N=6) subtypes, and 13 cognitively healthy control participants telling the “Cinderella Story” were analyzed for fluency (i.e., words per minute (WPM) and mean length of utterance in words (MLU-W)) and grammaticality (i.e., the proportion of grammatically correct sentences, open-to-closed-class word ratio, noun-to-verb ratio, and correct production of verb inflection, noun morphology, and verb argument structure.) Between group differences were analyzed for each variable. Correlational analyses examined the relation between WPM and each grammatical variable, and an off-line measure of sentence production.
Outcomes And Results
Agrammatic and logopenic groups both had lower scores on the fluency measures and produced significantly fewer grammatical sentences than did semantic and control groups. However, only the agrammatic group evinced significantly impaired production of verb inflection and verb argument structure. In addition, some semantic participants showed abnormal open-to-closed and noun-to-verb ratios in narrative speech. When the sample was divided on the basis of fluency, all the agrammatic participants fell in the nonfluent category. The logopenic participants varied in fluency but those with low fluency showed variable performance on measures of grammaticality. Correlational analyses and scatter plots comparing fluency and each grammatical variable revealed dissociations within PPA participants, with some nonfluent participants showing normal grammatical skill.
Grammatical production is a complex construct comprised of correct usage of several language components, each of which can be selectively affected by disease. This study demonstrates that individuals with PPA show dissociations between fluency and grammatical production in narrative speech. Grammatical ability, and its relationship to fluency, varies from individual to individual, and from one variant of PPA to another, and can even be found in individuals with semantic PPA in whom a fluent aphasia is usually thought to accompany preserved ability to produce grammatical utterances.
We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit-Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit-Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion symptom mapping (VLSM) analysis of data from seventy-two patients with left hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit-Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed.
Cognitive processing speed; diffusion tensor imaging; individual differences; magnetic resonance imaging; neural pathways; neuropsychology
Aicardi syndrome is a congenital neurodevelopmental disorder associated with significant cognitive and motor impairment. Diffusion Tensor Imaging was performed on two subjects with Aicardi syndrome, as well as on two matched subjects with callosal agenesis and cortical malformations, but not a clinical diagnosis of Aicardi syndrome. Whole brain three-dimensional fiber tractography was performed, and major white matter tracts were isolated using standard tracking protocols. One Aicardi subject demonstrated an almost complete lack of normal cortico-cortical connectivity, with only the left inferior fronto-occipital fasciculus recovered by diffusion tensor tractography. A second Aicardi subject showed evidence of bilateral cingulum bundles and right uncinate fasciculus, but other cortico-cortical tracts were not recovered. Major subcortical white matter tracts, including corticospinal, pontocerebellar, and anterior thalamic radiation tracts, were recovered in both Aicardi subjects. In contrast, diffusion tensor tractography analysis on the two matched control subjects with callosal agenesis and cortical malformations recovered all major intrahemispheric cortical and subcortical white matter tracts. These results reveal a widespread disruption in the corticocortical white matter organization of individuals with Aicardi syndrome. Furthermore, such disruption in white matter organization appears to be a feature specific to Aicardi syndrome, and not shared by other neurodevelopmental disorders with similar anatomic manifestations.
In comparison to late-onset Alzheimer’s disease (LO-AD, onset
> 65), early age-of-onset Alzheimer’s disease (EO-AD, onset<65
years) more often presents with language, visuospatial and/or executive
impairment, often occurring earlier than a progressive memory deficit. The
logopenic variant of primary progressive aphasia (lv-PPA) and the posterior
cortical atrophy (PCA) have recently been described as possible atypical
variants of EO-AD. Lv-PPA is characterized by isolated language deficit,
while PCA is characterized by predominant visuospatial deficits. Severe
hemispheric grey matter (GM) atrophy associated with EO-AD, lv-PPA and PCA
has been described, but regional patterns of white matter (WM) damage are
still poorly understood.
Using structural MRI and voxel-based morphometry, we investigated WM
damage in 16 EO-AD, 13 PCA, 10 lv-PPA, and 14 LO-AD patients at
presentation, and 72 age-matched controls.
In EO-AD, PCA and lv-PPA patients, WM atrophy was centered on lateral
temporal and parietal regions, including cingulum and posterior corpus
callosum. Compared to controls, lv-PPA patients showed a more severe left
parietal damage, and PCA showed a more severe occipital atrophy. Moreover,
EO-AD had greater cingulum atrophy compared with LO-AD. LO-AD showed WM
damage in medial temporal regions and less extensive hemispheric
Patterns of WM damage in EO-AD, lv-PPA and PCA are consistent with
the clinical syndromes and GM atrophy patterns. WM injury in AD atypical
variants may contribute to symptoms and disease pathogenesis.
Alzheimer’s disease; white matter damage; cerebral network; age of onset; VBM
Whole-brain diffusion tensor tractography (DTT) at high signal-to-noise ratio and angular and spatial resolutions were utilized to study the effects of age, sex differences, and lateral asymmetries of 6 white matter pathways (arcuate fasciculus [AF], inferior longitudinal fasciculus, inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], corticospinal tract [CST], and somatosensory pathway [SS]) in 31 right-handed children (6–17 years). Fractional anisotropy (FA), a measure of the orientational variance in water molecular diffusivity, and the magnitude of water diffusivity (parallel, perpendicular, and mean diffusivity) along the pathways were quantified. Three major patterns of maturation were observed: 1) significant increase in FA with age, accompanied by significant decreases in all 3 diffusivities (e.g., left IFOF); 2) significant decreases in all three diffusivities with age without significant changes in FA (e.g., left CST); and 3) no significant age-related changes in FA or diffusivity (e.g., SS). Sex differences were minimal. Many pathways showed lateral asymmetries. In the right hemisphere, the frontotemporal (FT) segment of AF was not visualized in a substantial (29%) number of participants. FA was higher in the left hemisphere in the FT segment of AF, UF, and CST, whereas it was lower in the frontoparietal segment of AF. This study provides normative data essential for the interpretation of pediatric brain DTT measurements in both health and disease.
association and projection pathways; child and adolescent brain development; diffusion tensor tractography; hemispheric asymmetries
Objective: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval.
Methods: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) 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 FA and determine regions of reduced FA in patients.
Results: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA.
Conclusion: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.
frontotemporal dementia; primary progressive aphasia; diffusion-weighted MRI; magnetic resonance imaging; neuropsychology
Frontotemporal lobar degeneration (FTLD) can manifest as a spectrum of clinical syndromes, ranging from behavioural impairment to language or motor dysfunction. Recently, revised diagnostic criteria have been proposed for the behavioural and progressive aphasia syndromes associated with frontotemporal degeneration. The present review will summarize these diagnostic guidelines and highlight some lingering controversies in the classification of FTLD clinical syndromes. We will discuss common tools and methods used to identify the insidious changes of behavioural variant frontotemporal dementia (bvFTD), the value of new, patient-based tasks of orbitofrontal function, and the issue of a benign or ‘phenocopy’ variant of bvFTD. With regard to primary progressive aphasia (PPA), we will discuss the scope of the semantic disorder in semantic-variant PPA, the nature of the speech disorder in non-fluent, agrammatic PPA, and the preliminary utility of a logopenic PPA classification.
Recent studies have suggested that some variants of bipolar disorder (BD) may be due to hyperconnectivity between orbitofrontal (OFC) and temporal pole (TP) structures in the dominant hemisphere. Some initial MRI studies noticed that there were corpus callosum abnormalities within specific regional areas and it was hypothesized that developmentally this could result in functional or effective connectivity changes within the orbitofrontal-basal ganglia-thalamocortical circuits. Recent diffusion tensor imaging (DTI) white matter fiber tractography studies may well be superior to region of interest (ROI) DTI in understanding BD. A “ventral semantic stream” has been discovered connecting the TP and OFC through the uncinate and inferior longitudinal fasciculi and the elusive TP is known to be involved in theory of mind and complex narrative understanding tasks. The OFC is involved in abstract valuation in goal and sub-goal structures and the TP may be critical in binding semantic memory with person–emotion linkages associated with narrative. BD patients have relative attenuation of performance on visuoconstructional praxis consistent with an atypical localization of cognitive functions. Multiple lines of evidence suggest that some BD alleles are being selected for which could explain the enhanced creativity in higher-ability probands. Associations between ROI’s that are not normally connected could explain the higher incidence of artistic aptitude, writing ability, and scientific achievements among some mood disorder subjects.
bipolar disorder; diffusion tensor imaging; white matter tractography; inferior longitudinal fasciculus; inferior fronto-occipital fasciculus; uncinate fasciculus; mood dysphoria; creativity; ventral semantic stream; writing ability; artistic aptitude
The logopenic variant of primary progressive aphasia is an atypical clinical variant of Alzheimer’s disease which is typically characterized by left temporoparietal atrophy on magnetic resonance imaging and hypometabolism on F-18 fluorodeoxyglucose positron emission tomography. We aimed to characterize and compare patterns of atrophy and hypometabolism in logopenic primary progressive aphasia, and determine which brain regions and imaging modality best differentiates logopenic primary progressive aphasia from typical dementia of the Alzheimer’s type.
A total of 27 logopenic primary progressive aphasia subjects underwent fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance imaging. These subjects were matched to 27 controls and 27 subjects with dementia of the Alzheimer’s type. Patterns of atrophy and hypometabolism were assessed at the voxel and region-level using Statistical Parametric Mapping. Penalized logistic regression analysis was used to determine what combinations of regions best discriminate between groups.
Atrophy and hypometabolism was observed in lateral temporoparietal and medial parietal lobes, left greater than right, and left frontal lobe in the logopenic group. The logopenic group showed greater left inferior, middle and superior lateral temporal atrophy (inferior p = 0.02; middle p = 0.007, superior p = 0.002) and hypometabolism (inferior p = 0.006, middle p = 0.002, superior p = 0.001), and less right medial temporal atrophy (p = 0.02) and hypometabolism (p<0.001), and right posterior cingulate hypometabolism (p<0.001) than dementia of the Alzheimer’s type. An age-adjusted penalized logistic model incorporating atrophy and hypometabolism achieved excellent discrimination (area under the receiver operator characteristic curve = 0.89) between logopenic and dementia of the Alzheimer’s type subjects, with optimal discrimination achieved using right medial temporal and posterior cingulate hypometabolism, left inferior, middle and superior temporal hypometabolism, and left superior temporal volume.
Patterns of atrophy and hypometabolism both differ between logopenic primary progressive aphasia and dementia of the Alzheimer’s type and both modalities provide excellent discrimination between groups.
We describe the case of girl who was born prematurely and diagnosed periventricular leukomalacia, a condition characterized by severe injury to the white matter tracts primarily surrounding the ventricles. At 12 years of age, we obtained diffusion tensor imaging (DTI) data on this child as part of a research protocol. Multiple analyses of DTI data, including tractography, showed that the left and right arcuate and superior longitudinal fasciculi were missing in the child though all other major white matter tracts were present. Standardized psychometric tests at age 12 years revealed that despite early language delays, she had average scores on expressive language, sentence repetition, and reading, functions that have been hypothesized to depend on signals carried by the arcuate fasciculus. We identified intact ventral connections between the temporal and frontal lobes through the extreme capsule fiber system and uncinate fasciculus. Preserved language and reading function after serious injury to the arcuate fasciculus highlights the plasticity of the developing brain after severe white matter injury early in life.
Arcuate fasciculus; superior longitudinal fasciculus; diffusion tensor imaging; language; reading; plasticity; premature birth
BACKGROUND AND PURPOSE
Knowledge of the anatomic basis of aphasia after stroke has both theoretic and clinical implications by informing models of cortical connectivity and providing data for diagnosis and prognosis. In this study we use diffusion tensor imaging to address the relationship between damage to specific white matter tracts and linguistic deficits after left hemisphere stroke.
MATERIALS AND METHODS
Twenty patients aged 38–77 years with a history of stroke in the left hemisphere underwent diffusion tensor imaging, structural MR imaging, and language testing. All of the patients were premorbidly right handed and underwent imaging and language testing at least 1 month after stroke.
Lower fractional anisotropy (FA) values in the superior longitudinal and arcuate fasciculi of the left hemisphere, an indication of greater damage to these tracts, were correlated with decreased ability to repeat spoken language. Comprehension deficits after stroke were associated with lower FA values in the arcuate fasciculus of the left hemisphere. The findings for repetition were independent of MR imaging ratings of the degree of damage to cortical areas of the left hemisphere involved in language function. There were no findings for homotopic tracts in the right hemisphere.
This study provides support for a specific role for damage to the superior longitudinal and arcuate fasciculi in the left hemisphere in patients with deficits in repetition of speech in aphasia after stroke.
Primary progressive aphasia is a neurodegenerative disorder that was recently classified into three types: fluent (semantic), nonfluent, and logopenic. The logopenic variant is the least common one and is closely related to Alzheimer's disease in comparison to the other two variants that are closely related to frontotemporal dementia. We report the case of a middle-aged woman who presented to our center with progressive aphasia that was undiagnosed for two years. The patient's neurological evaluation including positron emission tomography is consistent with a logopenic variant of primary progressive aphasia.
Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non-fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as ‘fluent’ or ‘non-fluent’, however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously. Secondly, we aimed to determine the neuroanatomical correlates of changes along these different dimensions. We recorded, transcribed and analysed speech samples for 50 patients with primary progressive aphasia, along with neurodegenerative and normal control groups. Patients were scanned with magnetic resonance imaging, and voxel-based morphometry was used to identify regions where atrophy correlated significantly with motor speech and linguistic features. Speech samples in patients with the non-fluent variant were characterized by slow rate, distortions, syntactic errors and reduced complexity. In contrast, patients with the semantic variant exhibited normal rate and very few speech or syntactic errors, but showed increased proportions of closed class words, pronouns and verbs, and higher frequency nouns, reflecting lexical retrieval deficits. In patients with the logopenic variant, speech rate (a common proxy for fluency) was intermediate between the other two variants, but distortions and syntactic errors were less common than in the non-fluent variant, while lexical access was less impaired than in the semantic variant. Reduced speech rate was linked with atrophy to a wide range of both anterior and posterior language regions, but specific deficits had more circumscribed anatomical correlates. Frontal regions were associated with motor speech and syntactic processes, anterior and inferior temporal regions with lexical retrieval, and posterior temporal regions with phonological errors and several other types of disruptions to fluency. These findings demonstrate that a multidimensional quantification of connected speech production is necessary to characterize the differences between the speech patterns of each primary progressive aphasic variant adequately, and to reveal associations between particular aspects of connected speech and specific components of the neural network for speech production.
primary progressive aphasia; progressive non-fluent aphasia; semantic dementia; logopenic progressive aphasia; speech production
The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject’s intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7–68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left > Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.
Diffusion tensor imaging; fiber tracking; uncinate fasciculus; child; adult; brain development; aging; lifespan
Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6–68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.
Lifespan; White matter fiber tract development; Association; Projection; Commissural pathways; Aging; Nonlinear trajectories; Diffusion tensor imaging; Tractography
Patients with primary progressive aphasia (PPA) vary considerably in terms of which brain regions are impacted, as well as in the extent to which syntactic processing is impaired. Here we review the literature on the neural basis of syntactic deficits in PPA. Structural and functional imaging studies have most consistently associated syntactic deficits with damage to left inferior frontal cortex. Posterior perisylvian regions have been implicated in some studies. Damage to the superior longitudinal fasciculus, including its arcuate component, has been linked with syntactic deficits, even after gray matter atrophy is taken into account. These findings suggest that syntactic processing depends on left frontal and posterior perisylvian regions, as well as intact connectivity between them. In contrast, anterior temporal regions, and the ventral tracts that link frontal and temporal language regions, appear to be less important for syntax, since they are damaged in many PPA patients with spared syntactic processing.
syntax; primary progressive aphasia; voxel-based morphometry; functional MRI; diffusion tensor imaging