The yes-no reversal phenomenon in patients with primary progressive apraxia of speech

Abstract

Patients who have a yes-no reversal respond "yes" when they mean no and vice versa. The unintentional response can be made both verbally and with gestures (e.g., head shake or nod, thumbs up or down). Preliminary reports associate this phenomenon with 4-repeat tauopathies including primary progressive apraxia of speech (PPAOS), nonfluent/agrammatic primary progressive aphasia, and corticobasal syndrome; however, the significance and timing of this symptom relative to others are not well understood. Whereas some accounts associate yes-no reversals with other binary reversals (e.g., up/down, hot/cold) and attribute the reversals to disturbances of selection within the language system, others implicate more general inhibitory control processes. Here, we compared clinical and neuroimaging findings across 30 patients with PPAOS (apraxia of speech in the absence of aphasia), 15 of whom had a yes-no reversal complaint and 15 who did not. The two groups did not differ on any of the language or motor speech measures; however, patients who had the yes-no reversal received lower scores on the Frontal Assessment Battery and motor assessments. They also had greater hypometabolism in the left supplementary motor area and bilateral caudate nuclei on [¹⁸F]-fluorodeoxyglucose PET, but only the right caudate nucleus cluster survived correction for multiple comparisons. We interpret these results to suggest that the yes-no reversal phenomenon is associated with cognitive abilities that are supported by the frontostriatal network; more specifically, impaired response inhibition.

Keywords: Primary progressive apraxia of speech; Response inhibition; Yes–no reversal.

Figure 1.. Frontal Assessment Battery Subtest Scores.

YN+ patients (green) scored significantly lower than YN- patients (orange) on both the lexical fluency and Luria motor sequencing subtests. The maximum possible score per subtest is 3. Error bars show standard error of the mean. p-values based on Welch two-sample t-tests are indicated for significant results.

Figure 2.. Results of the voxel-level FDG-PET analysis.

Areas in yellow indicate relatively greater FDG uptake in the YN- group at the uncorrected p < .001 level. There were no significant clusters in the opposite comparison.