Cross-Frequency Coupling and Intelligent Neuromodulation

Abstract

Cross-frequency coupling (CFC) reflects (nonlinear) interactions between signals of different frequencies. Evidence from both patient and healthy participant studies suggests that CFC plays an essential role in neuronal computation, interregional interaction, and disease pathophysiology. The present review discusses methodological advances and challenges in the computation of CFC with particular emphasis on potential solutions to spurious coupling, inferring intrinsic rhythms in a targeted frequency band, and causal interferences. We specifically focus on the literature exploring CFC in the context of cognition/memory tasks, sleep, and neurological disorders, such as Alzheimer's disease, epilepsy, and Parkinson's disease. Furthermore, we highlight the implication of CFC in the context and for the optimization of invasive and noninvasive neuromodulation and rehabilitation. Mainly, CFC could support advancing the understanding of the neurophysiology of cognition and motor control, serve as a biomarker for disease symptoms, and leverage the optimization of therapeutic interventions, e.g., closed-loop brain stimulation. Despite the evident advantages of CFC as an investigative and translational tool in neuroscience, further methodological improvements are required to facilitate practical and correct use in cyborg and bionic systems in the field.

Beta–Gamma Phase-Amplitude Coupling as a Non-Invasive Biomarker for Parkinson’s Disease: Insights from Electroencephalography Studies

“…Neuromodulator approaches based on feedback from PAC modulation have been proposed as tools to quantify motor impairment in patients and to aid in therapy modulation by adjusting stimulation parameters [ 18 , 19 , 20 , 23 ]. This approach proposes the detection of changes in motor symptoms based on PAC increases, which would then lead to adjustments in stimulation, improving the efficacy of this technique [ 23 ]. A phase-targeted stimulation technique has been proposed as a promising method of modulating PAC increases in the motor cortex [ 19 ].…”

Flexible, ultrathin bioelectronic materials and devices for chronically stable neural interfaces

“…Promising and attractive applications of a neural interface range from neuroscience research, [1,2] brain-computer interfacing (BCI), [3,4] and body function reconstruction [5,6] to the diagnosis and treatment of neurological disorders. [7][8][9] Substantial efforts have been devoted to developing such platforms to facilitate the recording and modulation of the activity of neural systems, either at the level of individual neurons or across large areas and volumes of the brain. [10][11][12][13][14][15] Non-invasive devices, such as wearable electroencephalogram (EEG) arrays, can measure brain activity at a distance from the neural tissue with little risk, but suffer from signal distortion, low spatial resolution, and background noise due to the attenuating and low-pass filtering effect of the skull and scalp.…”

“…Promising and attractive applications of a neural interface range from neuroscience research, [1,2] brain‐computer interfacing (BCI), [3,4] and body function reconstruction [5,6] to the diagnosis and treatment of neurological disorders [7–9] . Substantial efforts have been devoted to developing such platforms to facilitate the recording and modulation of the activity of neural systems, either at the level of individual neurons or across large areas and volumes of the brain [10–15] .…”

Auditory cues modulate the short timescale dynamics of STN activity during stepping in Parkinson’s disease

“…Dynamic oscillatory activity within complex brain structures is believed to reflect both physiological and pathophysiological processes 7 . Recent studies of patients undergoing DBS surgery have revealed how synchronized oscillatory activity across the cortico-basal ganglia circuit can contribute to gait kinematics and motoric impairments in PD [8][9][10][11] . For example, it has been shown that excessive STN activity at beta frequencies (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), which is traditionally thought to be related to both bradykinesia and rigidity, can also precede paroxysmal episodes of freezing of gait (FOG).…”