High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts. Using a 14 T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100 µm×100 µm×200 µm resolution with a 2 s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust blood oxygen level-dependent (BOLD) responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 s prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous exposure of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.

Sleep cycles are defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Fractal or aperiodic neural activity is a well-established marker of arousal and sleep stages measured using electroencephalography. We introduce a new concept of ‘fractal cycles’ of sleep, defined as a time interval during which time series of fractal activity descend to their local minimum and ascend to the next local maximum. We assess correlations between fractal and classical (i.e. non-REM – REM) sleep cycle durations and study cycles with skipped REM sleep. The sample comprised 205 healthy adults, 21 children and adolescents and 111 patients with depression. We found that fractal and classical cycle durations (89±34 vs 90±25 min) correlated positively (r=0.5, p<0.001). Children and adolescents had shorter fractal cycles than young adults (76±34 vs 94±32 min). The fractal cycle algorithm detected cycles with skipped REM sleep in 91–98% of cases. Medicated patients with depression showed longer fractal cycles compared to their unmedicated state (107±51 vs 92±38 min) and age-matched controls (104±49 vs 88±31 min). In conclusion, fractal cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycles.