Distinct neural substrates of affective distress and communicative disability in head and neck cancer: a cross-sectional 18F-FDG PET study

BackgroundHead and neck cancer (HNC) uniquely threatens communication through its impact on voice and speech. The neural systems linking depressive symptoms with perceived voice handicap remain poorly characterized. We examined whether these symptom domains show dissociable associations with regional brain glucose metabolism. MethodsWe conducted a cross-sectional 18FFDG-PET study in 63 HNC patients following diagnosis. Regional cerebral glucose metabolism (standardized uptake value ratios) was quantified in five a priori regions of interest: Brocas area, Wernickes area, bilateral insula, and bilateral hippocampus. Depressive symptoms (Zung Self-Rating Depression Scale, SDS) and perceived voice handicap (Voice Handicap Index, VHI) were assessed. Spearman correlations with false discovery rate correction, partial correlations, and unique variance analyses were performed. Brain-behavior associations were examined using Spearman correlations with FDR correction. ResultsDepression and perceived voice handicap were strongly correlated ({rho} = 0.64, p < 0.001) and exhibited partially dissociable metabolic correlates. Depressive symptom severity was associated with reduced metabolism in Brocas area ({rho} = -0.31, p_FDR = 0.041) and higher metabolism in the left insula ({rho} = 0.36, p_FDR = 0.039), with graded insular elevation in moderate-severe depression (+14%, p = 0.008). Voice handicap was associated with reduced hippocampal metabolism ({rho} = -0.34, p = 0.016 after covariate adjustment) in exploratory analyses. ConclusionsDepression and voice handicap in HNC arise from partially independent neurobiological processes despite their clinical co-occurrence. This dissociation supports parallel rather than hierarchical supportive care pathways. Routine clinical imaging can be leveraged to generate testable hypotheses for psychosomatic and rehabilitation research. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/26352637v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@174642org.highwire.dtl.DTLVardef@5c750org.highwire.dtl.DTLVardef@1607b27org.highwire.dtl.DTLVardef@1355ef9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Depressive symptoms were associated with reduced Brocas area metabolism and elevated left insula metabolism, consistent with limbic-cortical dysregulation. Perceived voice handicap was uniquely associated with reduced bilateral hippocampal metabolism, implicating contextual memory and adaptation processes. Arrows indicate direction of association. C_FIG