Keywords
1. Neural phase-amplitude coupling
2. Brain communication pathways
3. Hippocampus-to-prefrontal cortex signaling
4. Theta-gamma neural oscillations
5. Neural transmission directionality
The direction of neural signals within the brain has long been a subject of interest among neuroscientists, as it holds the key to understanding the complex orchestration of cognitive functions. In a ground-breaking study published in Scientific Reports, a team of researchers led by Nandi Bijurika and Mingzhou Ding, affiliated with the J. Crayton Pruitt Family Department of Biomedical Engineering at the University of Florida, detailed a novel application of phase-amplitude coupling (PAC) analysis that provides insights into the direction and strength of rhythmic neural transmission between disparate brain networks. This discovery carries substantial implications for the development of diagnostic and therapeutic approaches to neurological and psychiatric disorders.
Inter-Regional Phase-Amplitude Coupling (ir-PAC) as a Directional Indicator
PAC is a method of analyzing the statistical dependence between the phase of a low-frequency component of neural oscillations and the amplitude of a high-frequency component, within local field potentials (LFPs). Until recently, PAC had primarily been employed on single signal analyses. The study, DOI: 10.1038/s41598-019-43272-w, introduces the novel concept of ir-PAC, positing that PAC analysis can be applied to pairs of LFP signals from distinct regions to determine the directionality of neural communication. Transmembrane currents associated with action potentials add a broad-band component to the LFP in the high-gamma band (>60 Hz). Thus, examining the relationship between the amplitude of this high-gamma activity in one brain area and the phase of a low-frequency oscillation, such as the theta frequency (4-8 Hz), in another region could reveal the transmission direction from ‘sender’ to ‘receiver’. This innovative approach could revolutionize the way we comprehend the dynamic intercourse between different areas of the brain.
Theta-Band Communications Analysis: Hippocampus to Prefrontal Cortex (PFC) and Within the Hippocampus
The study’s hypothesis was put to the test by dissecting the long-range theta-band communication between the hippocampus and PFC as well as the theta-band short-range communications between the dentate gyrus (DG) and Ammon’s horn (CA1) within the hippocampus – a region critically involved in memory formation and spatial navigation. The known anatomical connections suggest unidirectional theta transmission from the hippocampus to the PFC and from the DG to the CA1, thus providing a ‘ground truth’ for assessing the proposed PAC-based method.
The researchers found that the amplitude of high-gamma oscillations in the hippocampus was significantly coupled to the PFC theta phase, but the reverse was not true. A similar relationship was observed between the DG and CA1, bolstering the hypothesis. Moreover, the correlation between DG high-gamma and CA1 theta PAC had significant congruence with Granger causality, a statistical measure used to predict the directionality of signal transfer between time series data. These converging lines of evidence support the promising utility of ir-PAC in inferring the flow of rhythmic neural activity.
Significance and Implications
The implications of these findings are vast. Not only do they offer a new lens through which neural circuit dynamics can be viewed, but they also pave the way for improvements in how neurological diseases are diagnosed and treated. Neurodegenerative conditions like Alzheimer’s disease and mental health disorders, including schizophrenia and depression, are often associated with disruptions in neural communication. Having the means to map the directional flow of neural signals could inform targeted interventions aimed at restoring the natural rhythms of brain circuitry.
Future Considerations and Research
As the exploration into ir-PAC in neural transmission continues, future research will likely delve into diversifying the frequency bands and regions of the brain under investigation. Additionally, there is the potential to correlate ir-PAC results with behavioral outcomes and to expand our understanding of how various patterns of neural activity align with cognitive and motor functions.
References
1. Bijurika, N., Swiatek, P., Kocsis, B., Ding, M. (2019). Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC). Sci Rep 9, 6933. https://doi.org/10.1038/s41598-019-43272-w
2. Buzsáki, G., Schomburg, E.W. (2015). What does gamma coherence tell us about inter-regional neural communication? Nat Neurosci 18, 484-489. https://doi.org/10.1038/nn.3952
3. Canolty, R.T., Knight, R.T. (2010). The functional role of cross-frequency coupling. Trends Cogn Sci 14, 506-515. https://doi.org/10.1016/j.tics.2010.09.001
4. Colgin, L.L., et al. (2009). Frequency of gamma oscillations routes flow of information in the hippocampus. Nature 462, 353-357. https://doi.org/10.1038/nature08573
5. Tort, A.B., Komorowski, R.W., Manns, J.R., Kopell, N.J., Eichenbaum, H. (2009). Theta-gamma coupling increases during the learning of item-context associations. Proc Natl Acad Sci USA 106, 20942-20947. https://doi.org/10.1073/pnas.0911331106
The study by Bijurika et al. holds the proverbial compass pointing toward the uncharted territories of brain function, a reminder that the brain’s communication highways are far from fully mapped. As we stand at the crux of translating laboratory breakthroughs into clinical applications, it’s paramount to continue supporting the untangling of the mind’s complex web of signals—a journey promising to unlock crucial gateways to comprehending and treating the human condition at its most intrinsic level.