Sharp-wave-ripple-associated activity in the medial prefrontal cortex supports spatial rule switching.

Previous studies have highlighted an important role for hippocampal sharp-wave ripples in spatial alternation learning, as well as in modulating activity in the medial prefrontal cortex (mPFC). However, the direct influence of hippocampal sharp-wave ripples on mPFC activity during spatial alternation learning has not been investigated. Here, we train Long Evans rats on a three-arm radial maze to perform a sequence of alternations. Three alternation sequences needed to be learned, and while learning a sequence, the activity in the mPFC was inhibited either directly following sharp-wave ripples in the hippocampus (on-time condition) or with a randomized delay (delayed condition). In the on-time condition, the behavioral performance is significantly worse compared to the same animals in the delayed inhibition condition, as measured by a lower correct alternation performance and more perseverative behavior. This indicates that the activity in the mPFC directly following hippocampal sharp-wave ripples is necessary for spatial rule switching.

Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. Individuals with AS display characteristic EEG patterns including high-amplitude rhythmic delta waves. Here, we sought to quantitatively explore EEG architecture in AS beyond known spectral power phenotypes. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS. Methods: We analyzed retrospective wake and sleep EEGs from children with AS (age 4-11) and age-matched neurotypical controls. We assessed long-range and short-range functional connectivity by measuring coherence across multiple frequencies during wake and sleep. We quantified sleep spindles using automated and manual approaches. Results: During wakefulness, children with AS showed enhanced long-range EEG coherence across a wide range of frequencies. During sleep, children with AS showed increased long-range EEG coherence specifically in the gamma band. EEGs from children with AS contained fewer sleep spindles, and these spindles were shorter in duration than their neurotypical counterparts. Conclusions: We demonstrate two quantitative readouts of dysregulated sleep composition in children with AS-gamma coherence and spindles-and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated in children with AS.

Microstructure of Strategic White Matter Tracts and Cognition in Memory Clinic Patients with Vascular Brain Injury.

BACKGROUND: White matter injury is an important factor for cognitive impairment in memory clinic patients. We determined the added value of diffusion tensor imaging (DTI) of strategic white matter tracts in explaining variance in cognition in memory clinic patients with vascular brain injury. METHODS: We included 159 patients. Conventional MRI markers (white matter hyperintensity volume, lacunes, nonlacunar infarcts, brain atrophy, and microbleeds), and fractional anisotropy and mean diffusivity (MD) of the whole brain white matter and of 18 white matter tracts were related to cognition using linear regression and Bayesian network analysis. RESULTS: On top of all conventional MRI markers combined, MD of the whole brain white matter explained an additional 3.4% (p = 0.014), 7.8% (p < 0.001), and 1.2% (p = 0.119) variance in executive functioning, speed, and memory, respectively. The Bayesian analyses of regional DTI measures identified strategic tracts for executive functioning (right superior longitudinal fasciculus), speed (left corticospinal tract), and memory (left uncinate fasciculus). MD within these tracts explained an additional 3.4% (p = 0.012), 3.8% (p = 0.007), and 2.1% (p = 0.041) variance in executive functioning, speed, and memory, respectively, on top of all conventional MRI and global DTI markers combined. CONCLUSION: In memory clinic patients with vascular brain injury, DTI of strategic white matter tracts has a significant added value in explaining variance in cognitive functioning.