TABLE 3.

Summary of neurodegeneration-related criticality literature.

Study	Study Population	Modality	Analysis	Main Findings
Stam et al., 2005	24 adults with AD, 19 non-demented adults with subjective memory complaints	EEG during eyes-closed resting state	DFA	• Study examined mean synchronization in different frequency bands. Mean EEG synchronization and spontaneous fluctuations of synchronization were lower in AD in upper alpha and beta bands compared to non-AD patients. Mean synchronization level and DFA exponents were correlated to MMSE score. Both patients and controls showed scale-free patterns of synchronization fluctuations, extending to up to 10 s. • AD patients may have brain electrical pattern consistent with SOC but exhibit decreased processing speed from decreased fluctuations of synchronization.
Montez et al., 2009	19 adults with early-stage AD, 16 age-matched controls	MEG during eyes-closed resting state	DFA, burst statistics	• Using criticality-based “avalanche analysis,” study found that AD patients had a strongly reduced incidence of alpha-band oscillation bursts over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1–25 s). • Study suggested that criticality-related measurements of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.
Hohlefeld et al., 2012	10 adults with idiopathic PD	LFP from bilaterally implanted electrodes from STN DBS	DFA	• Study examined LRTC of the amplitude envelope of LFPs recorded from subthalamic nucleus, both on and off of levodopa. “On levodopa” state was characterized by stronger LRTC (up to 50 s) than the “off” state in beta and high-frequency oscillations. • Weaker LRTC in off state might indicate limited information processing in dopamine-depleted basal ganglia. Study suggests LRTC may serve as possible biomarker of pathological neuronal processes in PD.
Ruiz et al., 2014	1 adult with severe idiopathic PD, treated with STN DBS	Inter-onset interval (time between note onset of two subsequent notes) while playing piano, with STN DBS both on and off	DFA, spectral density	• Study investigated temporal deviations during skilled piano performance of a non-professional pianist with severe PD treated with STN DBS. In tremor-affected right hand, timing fluctuations of the performance exhibited random correlations while off DBS. When DBS was on, LRTC increased along with general motor improvement. • The authors remark that the presence of LRTC and 1/f laws in performance (improved by DBS) can be related to the brain operating near criticality.
Vyšata et al., 2014	110 adults with moderate-to-severe AD, 110 healthy controls	EEG during resting-state	Power-law estimation, spectral density	• Study evaluated power-law exponents for power-law distribution of EEG spectrogram from patients with AD compared to healthy controls. Power-law exponent was found to be a specific marker of AD in the frontal EEG channels. Authors suggest that loss of functional connectivity may explain these differences in power-law exponents. Clinical utility of power-law exponent of spectrogram would require repeating the study on patients with mild cognitive impairment or early stages of AD.
West et al., 2016	12 adults with PD who received bilateral STN DBS	LFP while on and off dopaminergic medications	Spectral density, signal coherence, DFA	• Study examined LFPs from PD patients undergoing STN DBS surgery, on and off of dopaminergic medications. Authors demonstrated up-modulation of alpha-theta (5−12 Hz) band power with L-DOPA treatment, whilst low beta band power (15−20 Hz) band-power was suppressed. Using DFA adapted to phase synchrony (DFA-PS), study found LRTC in phase dynamics of coupled left and right STN region for low beta band. Low beta band DFA-PS scaling exponent magnitude for interhemispheric pairs was positively correlated with PD symptom severity in the off-medication state. Findings suggested that the more severe the motor impairment, the closer the subthalamic network was to onset of synchronization, implying shift of network toward supercritical regime.

AD, Alzheimer’s disease; PD, Parkinson’s disease; STN DBS, subthalamic nucleus deep brain stimulation; MMSE, Mini-Mental Status Examination; LFP, local field potential.