Metabolic modulation of synaptic failure and thalamocortical hypersynchronization with preserved consciousness in Glut1 deficiency.

Individuals with glucose transporter type I deficiency (G1D) habitually experience nutrient-responsive epilepsy associated with decreased brain glucose. However, the mechanistic association between blood glucose concentration and brain excitability in the context of G1D remains to be elucidated. Electroencephalography (EEG) in G1D individuals revealed nutrition time-dependent seizure oscillations often associated with preserved volition despite electrographic generalization and uniform average oscillation duration and periodicity, suggesting increased facilitation of an underlying neural loop circuit. Nonlinear EEG ictal source localization analysis and simultaneous EEG/functional magnetic resonance imaging converged on the thalamus-sensorimotor cortex as one potential circuit, and 18F-deoxyglucose positron emission tomography (18F-DG-PET) illustrated decreased glucose accumulation in this circuit. This pattern, reflected in a decreased thalamic to striatal 18F signal ratio, can aid with the PET imaging diagnosis of the disorder, whereas the absence of noticeable ictal behavioral changes challenges the postulated requirement for normal thalamocortical activity during consciousness. In G1D mice, 18F-DG-PET and mass spectrometry also revealed decreased brain glucose and glycogen, but preserved tricarboxylic acid cycle intermediates, indicating no overall energy metabolism failure. In brain slices from these animals, synaptic inhibition of cortical pyramidal neurons and thalamic relay neurons was decreased, and neuronal disinhibition was mitigated by metabolic sources of carbon; tonic-clonic seizures were also suppressed by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition. These results pose G1D as a thalamocortical synaptic disinhibition disease associated with increased glucose-dependent neuronal excitability, possibly in relation to reduced glycogen. Together with findings in other metabolic defects, inhibitory neuron dysfunction is emerging as a modulable mechanism of hyperexcitability.

The Color of Noise and Weak Stationarity at the NREM to REM Sleep Transition in Mild Cognitive Impaired Subjects.

In Older Adults (OAs), Electroencephalogram (EEG) slowing in frontal lobes and a diminished muscle atonia during Rapid Eye Movement sleep (REM) have each been effective tracers of Mild Cognitive Impairment (MCI), but this relationship remains to be explored by non-linear analysis. Likewise, data provided by EEG, EMG (Electromyogram) and EOG (Electrooculogram)-the three required sleep indicators-during the transition from REM to Non-REM (NREM) sleep have not been related jointly to MCI. Therefore, the main aim of the study was to explore, with results for Detrended Fluctuation Analysis (DFA) and multichannel DFA (mDFA), the Color of Noise (CN) at the NREM to REM transition in OAs with MCI vs. subjects with good performances. The comparisons for the transition from NREM to REM were made for each group at each cerebral area, taking bilateral derivations to evaluate interhemispheric coupling and anteroposterior and posterior networks. In addition, stationarity analysis was carried out to explore if the three markers distinguished between the groups. Neuropsi and the Mini-Mental State Examination (MMSE) were administered, as well as other geriatric tests. One night polysomnography was applied to 6 OAs with MCI (68.1 ± 3) and to 7 subjects without it (CTRL) (64.5 ± 9), and pre-REM and REM epochs were analyzed for each subject. Lower scores for attention, memory and executive funcions and a greater index of arousals during sleep were found for the MCI group. Results confirmed that EOGs constituted significant markers of MCI, increasing the CN for the MCI group in REM sleep. The CN of the EEG from the pre-REM to REM was higher for the MCI group vs. the opposite for the CTRL group at frontotemporal areas. Frontopolar interhemispheric scaling values also followed this trend as well as right anteroposterior networks. EMG Hurst values for both groups were lower than those for EEG and EOG. Stationarity analyses showed differences between stages in frontal areas and right and left EOGs for both groups. These results may demonstrate the breakdown of fractality of areas especially involved in executive functioning and the way weak stationarity analyses may help to distinguish between sleep stages in OAs.