Neural mechanisms of object naming and word comprehension in primary progressive aphasia

Abstract

Primary progressive aphasia (PPA) is a neurodegenerative syndrome that causes a gradual atrophy of the left hemisphere language network, leading to impairments of object naming (anomia) and word comprehension. In 33 human subjects with PPA, object naming and word comprehension were explored with N400 potentials elicited by picture-word or picture-picture matching tasks. Two mechanisms of impairment were identified. In one group of patients, where the object name could be recognized but not retrieved during verbal naming, N400s in picture-word trials were also abnormal, revealing an associative basis for retrieval anomia. In these patients, a putative prephonological signal (i.e., lemma) evoked by the object picture appears to have become too weak to elicit retrieval, but not necessarily too weak to support the informationally less taxing process of recognition. A second group of PPA patients showed more severe naming deficits-the object name was neither verbalized nor recognized. Furthermore, nouns of the same category (but not those of other object categories) could not be identified as mismatches. This blurring of intracategory but not intercategory differentiation of word meaning was correlated with anterior temporal atrophy, predominantly in the left hemisphere, especially along the superior temporal gyrus. Although not part of the classic language network, this area appears critical for proceeding from generic to specific levels of word comprehension and object naming. N400 abnormalities emerged for lexical (picture-word) but not nonverbal (picture-picture) associations, supporting a dual-route rather than amodal organization of object concepts.

Figure 1.

Schematic of the ERP matching task. The task is based on a prime followed by a probe. The N400 was triggered by the probe and reflects the semantic discrepancy between the associations evoked by the prime and the identity of the probe. Primes in all trials were photographs of concrete objects presented for 800 ms. After a 200 ms interval (blank screen), the probe (object picture or written word) was presented for 800 ms. For picture–picture trials, the probe was another object photograph, and for picture–word trials, the probe was a written word. Matching primes were the written name of the object or (for picture–picture trials) another example picture of the same object. Mismatches were of two types: related mismatches came from the same category as the prime, and unrelated mismatches came from a different category. Participants responded by pressing one button for matches and another for mismatches. EEG was recorded from 32 scalp electrodes. Amplitude values from the 10 dorsal electrodes shown were used in inferential analyses of N400 effects.

Figure 2.

Naming, recognition, and categorization of objects used as primes. Several behavioral tasks were administered before the ERP recording session. In Picture Naming, patients were asked to name aloud each of the 48 experimental picture stimuli used as primes. In Word-to-Picture Pointing, patients were shown the written name of an object, one at a time, and asked to point to the corresponding picture in an array containing pictures of all 48 objects. In Word Categorization and Picture Categorization, they were then given 96 cards, each containing one of the 48 pictures or the corresponding 48 nouns, to sort into generic semantic categories (e.g., animals, tools, etc.). PPA-S patients showed pronounced impairments in Picture Naming and Word-to-Picture Pointing, suggesting that the anomia is based, at least in part, on the inability to recognize (or understand) the noun that denotes the specific object. The better performance in Word Categorization is likely to reflect a relative sparing of word comprehension at the more general categorical level than at the specific level required by the Word-to-Picture Pointing task. Error bars indicate SEM.

Figure 3.

ERP matching task results. A, ERPs in response to the three types of probes are shown from the vertex electrode (Cz). Controls showed more negative ERPs from 350 to 550 ms (i.e., N400) in response to both related and unrelated word and picture probes compared with matching probes, comprising an N400 mismatch effect. The N400 mismatch effect was significant in PPA-GL patients, but of smaller magnitude compared with controls. PPA-S patients showed an N400 mismatch effect for unrelated but not related word probes, suggesting a blurring of neural responses to nouns that denote objects within the same object category. In contrast, ERPs to picture probes were of equivalent amplitude in all three groups. B, N400 amplitudes corresponding to the waveforms in A are extracted from 350 to 550 ms after probe onset, averaged across the 10 dorsal electrodes used for interferential analyses. C, Controls and PPA-GL patients were highly accurate at the matching task. PPA-S patients showed distinctly worse performance on trials with matching as well as related word probes, showing further evidence of word recognition impairment and blurred distinctions between nouns that denote objects of the same category (i.e., the match and related mismatch). Error bars indicate SEM.

Figure 4.

Relationships between cortical thickness and ERPs. Structural MRI scans were available on 28 of the 33 PPA patients. A, The PPA group as a whole (19 PPA-GL and 9 PPA-S) showed peak atrophy in the temporoparietal junction (Wernicke's area), the inferior frontal gyrus (Broca's area), lateral and inferior temporal cortex, and the orbitofrontal area (A). Significance of thinning is displayed as log₁₀(p) values in yellow/red, thresholded by an FDR of p < 0.001 in each hemisphere [min/max log₁₀(p) values = 3.4/5.7, left hemisphere; 3.9/6.2, right hemisphere]. B, Compared with the PPA-GL group, the PPA-S group showed more severe atrophy throughout the anterior temporal lobe (min/max log₁₀(p) = 4.0/6.2). C, A relatedness index was calculated for picture–word trials by dividing the differential amplitude to a related mismatch (compared with a match) by the differential amplitude to an unrelated mismatch. With the exception of one PPA-GL patient, the PPA-S patients had the lower values of this index, reflecting their selective difficulty in differentiating words of the same object category. D, To clarify which part of the atrophy in A was most closely associated with the decline of the relatedness index, a correlation analysis was performed. The results showed significant correlations (p < 0.01) in the anterior part of the STG, and the TP. Both areas are more severely atrophied in PPA-S, which also has the lowest relatedness index and greatest difficulty in differentiating words of the same category. C also shows the quantitative basis of the correlation between decreased relatedness index and atrophy in the left anterior temporal area shaded in D. Abbreviations: B, Broca's area; FG, fusiform gyrus; ITG, inferior temporal gyrus; OFC, orbitofrontal cortex; PHG, perihippocampal gyrus; STG, superior temporal gyrus; TP, temporal pole; W, Wernicke's area.

Figure 5.

Responses to named and unnamed items in PPA-GL. A, Topographic plots of the N400 mismatch effect (responses to matched vs related and unrelated mismatched probes) from nine anomic PPA-GL patients. Red denotes a robust N400 effect, whereas yellow and green indicate low amplitude or absent responses. The plots show the widespread and selective absence of N400 to related and unrelated mismatches specifically for unnamed objects but only in the picture–word trials. B, Accuracy of performance during the ERP matching task according to naming success. PPA-GL patients show similar accuracy on both named and unnamed word and picture trials. The ERP abnormalities implicate associative failures in lexical access (or retrieval) even though the patients recognized (i.e., understood) the word that denoted the pictures they could not name. Error bars indicate SEM.