BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent

This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at ∼50 mg/dL); in the other, plasma glucose was maintained at euglycemic levels (∼100 mg/dL). During scans subjects were presented with sentences of contrasting syntactic (embedding vs. conjunction) and semantic (reversibility vs. irreversibility) load. Semantic factors dominated the overall load effects on both performance (p < 0.001) and BOLD response (p < 0.01, corrected). Differential BOLD signal was observed in frontal, temporal, temporo-parietal and medio-temporal regions. Hypoglycemia and syntactic factors significantly impacted performance (p = 0.002) and BOLD response (p < 0.01, corrected) in the reversible clause conditions, more extensively in reversible-embedded than in reversible-conjoined clauses. Hypoglycemia resulted in a robust decrease in performance on reversible clauses and exerted attenuating effects on BOLD unselectively across cortical circuits.The dominance of reversibility in all measures underscores the distinction between the syntactic and semantic contrasts. The syntactic is based in a quantitative difference in algorithms interpreting embedded and conjoined structures. We suggest that the semantic is based in a qualitative difference between algorithmic mapping of arguments in reversible clauses and heuristic linking in irreversible clauses. Because heuristics drastically reduce resource demand, the operations they support would resist the load-dependent cognitive consequences of hypoglycemia.

► Performance and BOLD response varies with syntactic and semantic processing load.
► Hypoglycemia attenuates response proportional to load.
► Reversible arguments consistently contribute to processing load more than clause embedding.
► Heuristic mapping of irreversible clauses accounts for highly accurate processing across conditions.
► Allow for available glucose in models of load-sensitive BOLD response mechanisms.