Abstract
Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions –episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.
Highlights
Why do healthy older people decline in the efficiency of cognitive control, a cognitive function strongly dependent on PFC that includes working memory (WM), episodic memory, and reasoning [1,2]? Older people present something of a puzzle for understanding the relation between brain change and cognitive change
Higher fractional anisotropy (FA) in two PFC clusters were associated with better Letter Number Sequencing (LNS) performance: in the left body of the corpus callosum (98%, Juelich Histological Atlas) and in the left inferior fronto-occipital fasciculus (IFOF)/anterior thalamic radiation (45%/32%, JHU White-Matter Tractogaphy Atlas; Fig. 3B)
Peak signal intensities were found in the left body of the corpus callosum near the anterior intraparietal cortex (IPC; 96%, Juelich Histological Atlas, p,0.05; tfce corrected)
Summary
Older people present something of a puzzle for understanding the relation between brain change and cognitive change. They show a pattern of reduced PFC-dependent cognitive control in tandem with increased PFC activation [3]. We describe a novel approach for understanding white matter integrity in older adults by advancing the hypothesis that the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the organization of the PFC. Associations between white matter integrity and cognitive functions in older individuals can be informative about the neurocognitive organization of the PFC and about possible age-related changes in that organization
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