IntroductionThe earliest changes in the brain due to Alzheimer’s disease are associated with the neural networks related to memory function. We investigated changes in functional and structural connectivity among regions that support memory function in prodromal Alzheimer’s disease, i.e., during the mild cognitive impairment (MCI) stage.MethodsTwenty-three older healthy controls and 25 adults with MCI underwent multimodal MRI scanning. Limbic white matter tracts–the fornix, parahippocampal cingulum, retrosplenial cingulum, subgenual cingulum and uncinate fasciculus–were reconstructed in ExploreDTI using constrained spherical deconvolution-based tractography. Using a network-of-interest approach, resting-state functional connectivity time-series correlations among sub-parcellations of the default mode and limbic networks, the hippocampus and the thalamus were calculated in Conn.AnalysisControlling for age, education, and gender between group linear regressions of five diffusion-weighted measures and of resting state connectivity measures were performed per hemisphere. FDR-corrections were performed within each class of measures. Correlations of within-network Fisher Z-transformed correlation coefficients and the mean diffusivity per tract were performed. Whole-brain graph theory measures of cluster coefficient and average path length were inspecting using the resting state data.Results & conclusionMCI-related changes in white matter structure were found in the fornix, left parahippocampal cingulum, left retrosplenial cingulum and left subgenual cingulum. Functional connectivity decreases were observed in the MCI group within the DMN-a sub-network, between the hippocampus and sub-areas -a and -c of the DMN, between DMN-c and DMN-a, and, in the right hemisphere only between DMN-c and both the thalamus and limbic-a. No relationships between white matter tract ‘integrity’ (mean diffusivity) and within sub-network functional connectivity were found. Graph theory revealed that changes in the MCI group was mostly restricted to diminished between-neighbour connections of the hippocampi and of nodes within DMN-a and DMN-b.

A consensus has emerged that the cerebellum makes important contributions to a spectrum of linguistic processes, but that the psychobiology of these contributions remains enigmatic (Mariën et al., Cerebellum 13(3):386-410, 2014). One aspect of this enigma arises from the fact that, although the language-dominant left cerebral hemisphere is connected to the right cerebellum, distinctive contributions of the left cerebellar hemisphere have been documented (Murdoch and Whelan, Folia Phoniatr Logop 59:184-9, 2007), but remain poorly understood. Here, we report that neurodisruption of the left and right cerebellar hemispheres have opposite effects on associative word priming in a lexical decision task. Reaction time was measured for decisions on whether a target letter string constituted a word (e.g. bread) or, with equal probability, a pronounceable non-word (e.g. dreab). A prime word was presented for 150 ms before the target and could either, and with equal probability, be related (e.g. BUTTER) or unrelated (TRACTOR). Associative word priming was computed as the reduction in lexical decision RT on trials with related primes. Left cerebellar hemisphere continuous theta-burst transcranial magnetic stimulation (TMS) decreased, and right hemisphere stimulation increased, priming. The results suggest that the cerebellum contributes to predictive sequential processing, in this case language, through an opponent process mechanism coordinated by both cerebellar hemispheres.

Prism adaptation (PA) after-effects are assessed using tests that measure changes in sensorimotor systems. After-effects on pointing without feedback to a visual target (open loop pointing -OLP) are traditionally described as being larger than those measured by straight ahead pointing (SAP) with eyes closed, and the difference between them is attributed to a shift in visual localisation. However, neither differences between OLP and SAP, nor shifts in perceptual judgement of visual straight ahead (VSA), are consistently reported. Moreover, since very few studies have directly recorded direction of gaze, an effect of PA on the state estimate of gaze direction has not been reliably documented. The current research aimed to isolate the effects of PA on state estimates of eye position. We measured sensorimotor aftereffects through common (OLP, SAP, and VSA) measures, and also recorded eye position and additional after-effect measures to interrogate changes to the oculomotor system and how these might relate to other measures of sensorimotor change. To ascertain if PA's effects on estimates of eye position could be attributed to eye muscle potentiation, we compared the effects of PA to sustained gaze deviation without adaptation. PA induced no effect on visual straight-ahead and no change in direction of gaze, when measured while positioning a target, looking straight ahead in the dark, or looking toward the passively positioned and occluded unexposed hand. We also found that after-effects measured by SAP with the eyes open were larger than SAP with the eyes closed and equal to those observed with OLP. The findings challenge the concept that total adaptation after-effect is a direct sum of arm proprioceptive and visual after-effects as conventionally measured, and suggest that the oculomotor system is altered by prism adaptation only in interaction with an arm motor command when vision is available. Highlights• No evidence of a shift of visual straight-ahead or of gaze direction following prism adaptation.• Active arm movement under the availability of vision produced largest after-effect.• Findings challenge the concept of linear additivity of arm proprioceptive and visual after-effects of prism adaptation.

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