Age-Related Changes in the Neurophysiology of Language in Adults: Relationship to Regional Cortical Thinning and White Matter Microstructure

Abstract

Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18–33 years) and 10 middle-aged (42–64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250–350ms and in left inferior prefrontal cortex from 350–450ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250–350ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines.

Evoked Potentials and Memory/Cognition Tests Validate Brain Atrophy as Measured by 3T MRI (NeuroQuant) in Cognitively Impaired Patients

“…The higher the immediate memory, the lower the central atrophy. To our knowledge in this, the largest study utilizing 3T MRI and NeuroQuant, our results are in agreement with the literature [ 56 , 58 – 62 ].…”

“…In our current study, NeuroQuant measured hippocampal atrophy in individuals versus age-matched controls as normative percentile, so the effect of age upon hippocampal atrophy was not assessed. However, we did find age to be significantly correlated with small vessel ischemia (p < 0.0001) [ 55 ]; Reduced FA [diffusion imaging technique thought to reflect fiber density, axonal diameter, and white matter demyelination] in frontal lobes (p = 0.0134) [ 56 ] and bilateral atrophy (p = 0.0067) [ 57 ]. In terms of FA status we found a number of interesting correlations.…”

Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction

“…It was also found in older adults more than in younger adults during grammatically complex sentence reading [ 23 ] and speech perception [ 19 ]. Similarly, previous studies have also found age-related under-recruitment in lexical semantic processing [ 17 ], word recognition [ 47 ], and semantic coding [ 48 ]. Under-recruitment may reflect not enough resources [ 2 ] in older adults engaged in high demand tasks.…”

Neural changes associated with semantic processing in healthy aging despite intact behavioral performance

“…In a functional MRI study (fMRI), Stebbins et al (2002) found less activation in left prefrontal cortex in older adults relative to younger adults while they carried out a single-word semantic judgment task. Using magnetoencephalography (MEG), Kemmotsu et al (2012) compared young to middle-aged adults (mean age of 50 years-old) during single-word semantic judgment task, and reported that middle-aged adults recruited the inferior prefrontal region to a lesser extent than young adults. Thus, even when the impact of working memory load and syntactic demands was reduced by presenting single-words, patterns of prefrontal hypoactivation were still observed in older adults during semantic judgment, even though behavioral performance was equivalent across groups.…”