A1 Functional advantages of cell-type heterogeneity in neural circuits

S and full research articles published in SLEEP, the official journal of the APSS. Sleep and sleep disorder scientific findings.

Background: The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. Objective: This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. Methods: A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. Results: Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: P=.045; LOAD: P=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: P=.005; LOAD: P=.01) Patients with AD showed the lower accuracy than NCs (EOAD: P=.004; LOAD: P=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. Conclusions: The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients’ ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

Objectives: In patients with schizophrenia, γ-band (30–70 Hz) auditory steady-state electroencephalogram responses (ASSR) are reduced in power and phase locking. Here, we examined whether γ-ASSR deficits are also present in a mouse model of schizophrenia, whose behavioural changes have shown schizophrenia-like endophenotypes. Methods: Electroencephalogram in frontal cortex and local field potential in primary auditory cortex were recorded in phospholipase C β1 (PLC-β1) null mice during auditory binaural click trains at different rates (20–50 Hz), and compared with wild-type littermates. Results: In mutant mice, the ASSR power was reduced at all tested rates. The phase locking in frontal cortex was reduced in the β band (20 Hz) but not in the γ band, whereas the phase locking in auditory cortex was reduced in the γ band. The cortico-cortical connectivity between frontal and auditory cortex was significantly reduced in mutant mice. Conclusions: The tested mouse model of schizophrenia showed impaired electrophysiological responses to auditory steady state stimulation, suggesting that it could be useful for preclinical studies of schizophrenia”.

θ-Band (4–12 Hz) activities in the frontal cortex have been thought to be a key mechanism of sustained attention and goal-related behaviors, forming a phase-coherent network with task-related sensory cortices for integrated neuronal ensembles. However, recent visual task studies found that selective attention attenuates stimulus-related θ power in the visual cortex, suggesting a functional dissociation of cortical θ oscillations. To investigate this contradictory behavior of cortical θ, a visual Go/No-Go task was performed with electroencephalogram (EEG) recording in C57BL/6J mice. During the No-Go period, transient θ oscillations were observed in both the frontal and visual cortices, but θ oscillations of the two areas were prominent in different trial epochs. By separating trial epochs based on subjects’ short-term performance, we found that frontal θ was prominent in good-performance epochs, while visual θ was prominent in bad-performance epochs, exhibiting a functional dissociation of cortical θ rhythms. Furthermore, the two θ rhythms also showed a heterogeneous pattern of phase-amplitude coupling with fast oscillations, reflecting their distinct architecture in underlying neuronal circuitry. Interestingly, in good-performance epochs, where visual θ was relatively weak, stronger fronto-visual long-range synchrony and shorter posterior-to-anterior temporal delay were found. These findings highlight a previously overlooked aspect of long-range synchrony between distinct oscillatory entities in the cerebral cortex and provide empirical evidence of a functional dissociation of cortical θ rhythms.