Modularity and granularity across the language network-A primary progressive aphasia perspective.

Tests of grammar, repetition and semantics were administered to 62 prospectively enrolled right-handed participants with primary progressive aphasia (PPA). Structural brain images were obtained at the time of testing. Regression analyses uncovered 3 clearly delineated non-overlapping left hemisphere clusters where cortical thinning (atrophy) was significantly correlated with impaired performance. A morphosyntactic cluster associated with the grammaticality of sentence construction was located predominantly within the middle and inferior frontal gyri; a phonolexical cluster associated with language repetition was located in the temporoparietal junction; a lexicosemantic cluster associated with object naming and single word comprehension was located within the middle and anterior parts of the temporal lobe and extended into insular, orbitofrontal, and mediotemporal cortices. Commonality analyses were undertaken to explore whether these three clusters were as modular as indicated by the regression analyses or whether some underlying functional granularity could be uncovered. Modularity was defined as the exclusive association of an anatomical cluster with a single type of language task whereas granularity was defined as the association of a single anatomical cluster with more than one type of language task. The commonality analyses revealed a predominantly modular organization with quantitatively minor instances of inter-cluster granularity. The results also reconfirmed previous work on PPA which had shown that Wernicke's area is not essential for word comprehension, that naming impairments can be based either on deficits of lexical retrieval or word comprehension, and that the essential substrates of word comprehension encompass much wider areas of the temporal lobe than the temporal pole. The anatomy of the language network has traditionally been explored through patients with focal cerebrovascular accidents and experiments based on functional activation. Investigations on PPA are showing that focal neurodegenerations can add new perspectives to existing models of the language network.

Word comprehension in temporal cortex and Wernicke area: A PPA perspective.

OBJECTIVE: To explore atrophy-deficit correlations of word comprehension and repetition in temporoparietal cortices encompassing the Wernicke area, based on patients with primary progressive aphasia (PPA). METHODS: Cortical thickness in regions within and outside the classical Wernicke area, measured by FreeSurfer, was correlated with repetition and single word comprehension scores in 73 right-handed patients at mild to moderate stages of PPA. RESULTS: Atrophy in the Wernicke area was correlated with repetition (r = 0.42, p = 0.001) but not single word comprehension (r = -0.072, p = 0.553). Correlations with word comprehension were confined to more anterior parts of the temporal lobe, especially its anterior third (r = 0.60, p < 0.001). A single case with postmortem autopsy illustrated preservation of word comprehension but not repetition 6 months prior to death despite nearly 50% loss of cortical volume and severe neurofibrillary degeneration in core components of the Wernicke area. CONCLUSIONS: Temporoparietal cortices containing the Wernicke area are critical for language repetition. Contrary to the formulations of classic aphasiology, their role in word and sentence comprehension is ancillary rather than critical. Thus, the Wernicke area is not sufficient to sustain word comprehension if the anterior temporal lobe is damaged. Traditional models of the role of the Wernicke area in comprehension are based almost entirely on patients with cerebrovascular lesions. Such lesions also cause deep white matter destruction and acute network diaschisis, whereas progressive neurodegenerative diseases associated with PPA do not. Conceptualizations of the Wernicke area that appear to conflict, therefore, can be reconciled by considering the hodologic and physiologic differences of the underlying lesions.