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Neural dynamics of semantic categorization in semantic variant of primary progressive aphasia

  1. V Borghesani  Is a corresponding author
  2. CL Dale
  3. S Lukic
  4. LBN Hinkley
  5. M Lauricella
  6. W Shwe
  7. D Mizuiri
  8. S Honma
  9. Z Miller
  10. B Miller
  11. JF Houde
  12. ML Gorno-Tempini
  13. SS Nagarajan
  1. Memory and Aging Center, Department of Neurology, University of California, San Francisco, United States
  2. Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States
  3. Department of Otolaryngology, University of California, San Francisco, United States
  4. Department of Neurology, Dyslexia Center University of California, San Francisco, United States
Research Article
Cite this article as: eLife 2021;10:e63905 doi: 10.7554/eLife.63905
5 figures, 3 tables and 1 additional file

Figures

Experimental paradigm, behavioral performance, and cortical atrophy.

(A) Cartoon representation of the experimental setting. Colored drawings were presented for 2 s, with an inter-stimuli interval jittered between 1.7 and 2.1 s. Subjects responded with a button press with their dominant hand. (B) Behavioral performance during the semantic categorization tasks in controls and semantic variant primary progressive aphasia (svPPA) patients, across the two stimuli conditions (living vs. nonliving items). There were no statistically significant effects of diagnosis, category, nor their interaction neither in percentage accuracy (healthy controls [HC]: living: 97.1 ± 6.6, nonliving: 96.8 ± 6.6; svPPA: living: 91.5 ± 6.2, nonliving: 95.9 ± 8.1) nor in reaction times (HC: living: 826.3 ± 112.5, nonliving: 856.9 ± 104.4; svPPA: living: 869.8 ± 179.8, nonliving: 911.1 ± 194.45). (C) Voxel-based morphometry (VBM)-derived atrophy pattern showing significantly reduced gray matter volumes in svPPA patients’ anterior temporal lobes, views from top to bottom: lateral, medial, ventral (thresholded at p<0.05 with family-wise error [FWE] correction, cluster threshold of 100 voxels).

Stimulus-locked (0 ms = stimulus onset) within-group analyses of task-related changes in oscillatory power.

(a) Rendering of the results in the high-gamma band for both controls (healthy controls [HC], upper row) and patients (semantic variant primary progressive aphasia [svPPA], lower row). Cold color = more desynchronization (vs. baseline). Warm color = more synchronization (vs. baseline). (c-e) Same as in (a) but for the low-gamma, beta, alpha, and theta band, respectively. Within-group analyses were performed, with no additional smoothing, on normalized reconstructions using statistical nonparametric mapping (SnPM one-sample, two-tailed t-test against baseline).

Stimulus-locked (0 ms = stimulus onset) between-group analyses of changes in oscillatory power.

Rendering of the results in the high-gamma (a), low-gamma (b), beta (c), alpha (d), and theta (e) bands. Purple color = more synchronization in semantic variant primary progressive aphasia (svPPA) (vs. healthy controls [HC]). Brown color = less synchronization in svPPA (vs. HC). Table 2 summarizes the temporal windows, peaks of local maxima, and t-values of all clusters isolated by the direct comparison of the two cohorts. Between-group analyses were performed, with no additional smoothing, on normalized reconstructions using statistical nonparametric mapping (SnPM two-sample, two-tailed t-test).

Results of the region of interest post hoc analysis.

Three regions-of-interest (ROIs) of 20 mm radius were centered on the occipital pole (OCC, Montreal Neurological Institute [MNI]: −10, –94, −16), left ventral occipito-temporal cortex (VOT, MNI: −50, –52, −20), and left ATL (MNI: −30, –6, −40). Pink color represents healthy controls data, light blue svPPA patients. Shaded areas indicate the standard deviation around the group average (i.e., solid line).

Results of the post hoc regions of interest analysis of power changes.

Full time-frequency plot of power changes in two representative voxels centered in the peak of activation (as per group results, Montreal Neurological Institute [MNI]: −34.8, –93.9, 2.7) and on the occipital pole (OCC, MNI: −10, –94, −16).

Tables

Table 1
Demographics and neuropsychological profiles.

Healthy controls and semantic variant of primary progressive aphasia (svPPA) patients, native English speakers, were matched for age, gender, and education. Scores shown are mean (standard deviation). * Indicates values significantly different from controls (p<0.05). MMSE = Mini-Mental State Exam; CDR = Clinical Dementia Rating; PPVT = Picture Vocabulary Test; WAB = Western Aphasia Battery; VOSP = Visual Object and Space Perception Battery.

ControlssvPPA
Demographic
N1818
Age, mean (SD)70.7 ± 6.567.1 ± 6.2
Education, mean (SD)17.5 ± 1.817.9 ± 3.2
Gender, n female129
Handedness, n right1515
MMSE (max. 30)29.0 ± 1.624.5 ± 3.8*
CDR score0.03 ± 0.10.7 ± 0.4*
CDR box score0.3 ± 1.24.0 ± 2.6*
Language production
Boston (object) naming test (15)14.7 ± 0.65.4 ± 3.7*
Phonemic (D-letter) fluency15.7 ± 5.89.1 ± 4.3*
Semantic (animal) fluency23.4 ± 3.99.3 ± 4.1*
Language comprehension
PPVT (max. 16)9.4 ± 3.2
WAB auditory word recognition (60)56.5 ± 4.2
WAB sequential command (100)70.7 ± 14.3
Digit span forwards7.1 ± 1.16.4 ± 1.2
Reading
Arizona reading total (max. 36)35.6 ± 0.530.5 ± 3.7*
Regular high-frequency words (9)9 ± 0.08.8 ± 0.4
Regular low-frequency words (9)8.9 ± 0.28.3 ± 1.2
Irregular high-frequency words (9)8.9 ± 0.37.7 ± 0.6
Irregular low-frequency words (9)8.8 ± 0.45.7 ± 2.3
Pseudowords (18)15.8 ± 2.715.2 ± 2.2
Spelling
Arizona spelling total (max. 20)18.1 ± 1.613.1 ± 4.0*
Regular high-frequency words (5)5 ± 0.04.4 ± 0.9
Regular low-frequency words (5)4.5 ± 0.64.1 ± 0.8
Irregular high-frequency words (5)4.1 ± 0.92.1 ± 1.6
Irregular low-frequency words (5)4.5 ± 0.52.6 ± 1.6
Pseudowords (10)8.8 ± 1.38.1 ± 2.6
Famous faces – spontaneous naming (max. 16)12.4 ± 3.42.9 ± 2.4*
Famous faces – face recognition (max 20)18.4 ± 2.012.8 ± 6.5*
Famous faces short triplets, pictures (max. 10)8.9 ± 1.06.6 ± 2.4
Famous faces short triplets, words (max. 10)9.7 ± 0.67.0 ± 2.0
Working memory/executive functions
Digit span backwards5.4 ± 1.14.5 ± 1.6*
Modified trials (total time)25.3 ± 13.641.9 ± 23.1*
Modified trials (# of correct lines)13.2 ± 3.213.2 ± 3.3
Design fluency (# of correct designs)11.7 ± 3.07.1 ± 3.4*
Visuospatial function
Benson figure copy (17)15.7 ± 0.715.3 ± 1.0
VOSP number location (30)9.3 ± 0.99.0 ± 1.5
Visual memory
Benson figure recall (17)12.1 ± 2.47.1 ± 4.9*
Table 2
Local maxima in Montreal Neurological Institute (MNI) coordinates.

Time window, MNI coordinates, p- and t-value of the local maxima of the different magnetoencephalographic (MEG) whole brain contrasts performed. The spatiotemporal distribution of these clusters at four exemplar time points can be appreciated in Figure 3.

Time windowLocal maxima
t-test svPPA vs. HCmsMNI [x,y,z]p-valuet-value
Theta band [3–7 Hz]
Left lingual gyrus0–212−10.0 –100.0 −10.00.0053.7More ERD in svPPA
Left lingual gyrus412–612−8.5 –100.0 −8.10.0053.1More ERD in svPPA
Right medial and superior frontal gyrus187–38718.6 61.4 –14.70.001−3.92Less ERS in svPPA
Alpha band [8–12 Hz]
Right precentral gyrus212–61245.0 –15.0 40.00.0013.4More ERD in svPPA
Left middle temporal gyrus287–362−59.8 –41.6 −1.00.0052.8More ERD in svPPA
Bilateral medial and orbital frontal gyrus462–612−6.2 34.3 –24.90.0015.1More ERS in svPPA
Beta band [12–30 Hz]
Left cingulate cortex0–62−6.2–30.3 43.30.0052.9More ERS in svPPA
Right medial frontal gyrus137–2627.8 56.8 11.70.0013.6More ERS in svPPA
Left middle temporal gyrus237–362−65.0 –20.0 −5.00.001−3.4Less ERD in svPPA
Left superior frontal gyrus587–612−21.8 46.7 45.70.005−3.1Less ERD in svPPA
Low-gamma band [30–55 Hz]
Left lingual gyrus62–612−10.1–98.4 −8.90.0014.2More ERS in svPPA
Left inferior occipital gyrus362–612−34.8 –93.9 2.70.0014.1More ERS in svPPA
Right lingual gyrus212–43718.2 –89.1 8.30.0053.4More ERS in svPPA
Right medial frontal gyrus212–4129.3 63.0 2.20.0013.7Less ERD in svPPA
Left superior frontal gyrus262–462−3.8 62.8 14.00.0053.6Less ERD in svPPA
High-gamma band [63–117 Hz]
Left superior frontal gyrus62–137−36.5 26.6 48.80.0013.4More ERS in svPPA
Left superior temporal gyrus62–287−48.2 –22.3 13.30.0053More ERS in svPPA
Left parahippocampal gyrus212–312−15.5 –27.1 −6.50.0013.3More ERS in svPPA
Right medial frontal gyrus287–33713.2 70.7 0.60.0053.2More ERS in svPPA
Left superior frontal gyrus287–612−22 68.4 140.0013.6More ERS in svPPA
Right superior frontal gyrus462–61243.9 54.7 17.20.0013.9More ERS in svPPA
Table 3
Psycholinguistic characteristics of the stimuli.

Stimuli consisted of 70 colored drawings illustrating living items (n = 36) or nonliving items (n = 34). Length, imaginability, concreteness, and familiarity (norm) were extracted from the Medical Research Council (MRC) Psycholinguistic Database searching for the most common label for each item. Similarly, frequency was extracted from the Corpus of Contemporary American English (COCA). Category agreement, category prototypicality, and familiarity (quest.) were assessed with a behavioral study on separate age-matched healthy controls. As a proxy for visual complexity, we used Shannon entropy as computed with Scikit-Image. Values shown are mean (standard deviation). * Indicate values significantly different between the two categories (two-tailed t-test, p<0.05).

Living itemsNonliving items
N3634
ExamplesFish, flowerScissors, train
Frequency (log)3.69 (0.54)3.96 (0.65)
Length (# of letters)5.29 (1.58)5.61 (1.84)
Imageability613.19 (19.62)596.43 (28.08)*
Familiarity (norm)498.26 (69.32)547.96 (45.82)*
Familiarity (quest.)6.15 (0.32)6.67 (0.21)*
Concreteness608.27 (16.26)599.10 (25.94)
Category agreement96.86 (4.07)99.18 (1.20)*
Category prototypicality6.24 (0.52)6.47 (0.32)*
Visual complexity3.04 (0.84)3.13 (0.96)

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