Field potential (FP) recording is an accessible means to capture the shifts in the activity of neuron populations. However, the spatial and composite nature of these signals has largely been ignored, at least until it became technically possible to separate activities from co-activated sources in different structures or those that overlap in a volume. The pathway-specificity of mesoscopic sources has provided an anatomical reference that facilitates transcending from theoretical analysis to the exploration of real brain structures. We review computational and experimental findings that indicate how prioritizing the spatial geometry and density of sources, as opposed to the distance to the
recording site, better defines the amplitudes and spatial reach of FPs. The role of geometry is enhanced by considering that zones of the active populations that act as sources or sinks of current may arrange differently respect to each other, and have different geometry and densities. Thus, observations that seem counterintuitive in the scheme of distance-based logic alone can now be explained. For example, geometric factors explain why some structures produce FPs and others do not, why different FP motifs generated in the same structure extend far while others remain local, why factors like the size of an active population or the strong synchronicity of its neurons may fail to
affect FPs, or why the rate of FP decay varies in different directions. These considerations are exemplified in large structures like the cortex and hippocampus, in which the role of geometrical elements and regional activation in shaping well-known FP oscillations generally go unnoticed. Discovering the geometry of the sources in play will decrease the risk of population or pathway misassignments based solely on the FP amplitude or temporal pattern., We thank Mark Sefton (BiomedRed) for editorial support. This work was supported by the Spanish Ministerio de Ciencia e Innovación (MICIN) grant PID2019-111587RB-I00, and the Agencia Estatal de Evaluación, Next Generation EU grant PDC2021-121103-I00 to O.H. Present addresses: D.T.: Instituto de Neurociencias de Alicante, UMH-CSIC, Sant Joan d'Alacant, Spain., Peer reviewed

Dietary polyphenols have beneficial effects in situations of impaired cognition in acute models of neurodegeneration. The possibility that they may have a direct effect on the electrical activity of neuronal populations has not been tested. We explored the electrophysiological action of protocatechuic acid (PCA) on CA1 pyramidal cells ex vivo and network activity in anesthetized female rats using pathway-specific field potential (FP) generators obtained from laminar FPs in cortex and hippocampus. Whole-cell recordings from CA1 pyramidal cells revealed increased synaptic potentials, particularly in response to basal dendritic excitation, while the associated evoked firing was significantly reduced. This counterintuitive result was attributed to a marked increase of the rheobase and voltage threshold, indicating a decreased ability to generate spikes in response to depolarizing current. Systemic administration of PCA only slightly altered the ongoing activity of some FP generators, although it produced a striking disengagement of infraslow activities between the cortex and hippocampus on a scale of minutes. To our knowledge, this is the first report showing the direct action of a dietary polyphenol on electrical activity, performing neuromodulatory roles at both the cellular and network levels., This work was supported by the Spanish Ministerio de Ciencia e Innovación (OH, PID2019-111587RB-I00, EM, PID2020-116327GB-100; MVMA and BB, PID2019-108851RB-C21; and MM, PRE2020-093312) and by the Agencia Estatal de Evaluación, Next Generation EU grant (PDC2021-121103-I00) to OH., Peer reviewed

The correlation dimension (CD) is a nonlinear measure of the complexity of invariant sets. First introduced for describing low-dimensional chaotic attractors, it has been later extended to the analysis of experimental electroencephalographic (EEG), magnetoencephalographic (MEG), and local field potential (LFP) recordings. However, its direct application to high-dimensional (dozens of signals) and high-definition (kHz sampling rate) 2HD data revealed a controversy in the results. We show that the need for an exponentially long data sample is the main difficulty in dealing with 2HD data. Then, we provide a novel method for estimating CD that enables orders of magnitude reduction of the required sample size. The approach decomposes raw data into statistically independent components and estimates the CD for each of them separately. In addition, the method allows ongoing insights into the interplay between the complexity of the contributing components, which can be related to different anatomical pathways and brain regions. The latter opens new approaches to a deeper interpretation of experimental data. Finally, we illustrate the method with synthetic data and LFPs recorded in the hippocampus of a rat., This work has been supported by the Spanish Ministry of Science and Innovation (Project No.PID2021-124047NB-I00), the Santander-UCM grant PR44/21-29927 to V.A.M., and the Next Generation EU grant PDC2021-121103-I00 to O.H., Peer reviewed

The role of interhemispheric connections along successive segments of cortico-hippocampal circuits is poorly understood. We aimed to obtain a global picture of spontaneous transfer of activity during non-theta states across several nodes of the bilateral circuit in anesthetized rats. Spatial discrimination techniques applied to bilateral laminar field potentials (FP) across the CA1/Dentate Gyrus provided simultaneous left and right readouts in five FP generators that reflect activity in specific hippocampal afferents and associative pathways. We used a battery of correlation and coherence analyses to extract complementary aspects at different time scales and frequency bands. FP generators exhibited varying bilateral correlation that was high in CA1 and low in the Dentate Gyrus. The submillisecond delays indicate coordination but not support for synaptic dependence of one side on another. The time and frequency characteristics of bilateral coupling were specific to each generator. The Schaffer generator was strongly bilaterally coherent for both sharp waves and gamma waves, although the latter maintained poor amplitude co-variation. The lacunosum-moleculare generator was composed of up to three spatially overlapping activities, and globally maintained high bilateral coherence for long but not short (gamma) waves. These two CA1 generators showed no ipsilateral relationship in any frequency band. In the Dentate Gyrus, strong bilateral coherence was observed only for input from the medial entorhinal areas, while those from the lateral entorhinal areas were largely asymmetric, for both alpha and gamma waves. Granger causality testing showed strong bidirectional relationships between all homonymous bilateral generators except the lateral entorhinal input and a local generator in the Dentate Gyrus. It also revealed few significant relationships between ipsilateral generators, most notably the anticipation of lateral entorhinal cortex toward all others. Thus, with the notable exception of the lateral entorhinal areas, there is a marked interhemispheric coherence primarily for slow envelopes of activity, but not for pulse-like gamma waves, except in the Schafer segment. The results are consistent with essentially different streams of activity entering from and returning to the cortex on each side, with slow waves reflecting times of increased activity exchange between hemispheres and fast waves generally reflecting ipsilateral processing., This work was supported by the Spanish Ministerio de Ciencia e Innovación (MICIN) grant PID2019-111587RB-I00, and the Agencia Estatal de Evaluación, Next Generation EU grant PDC2021-121103-I00 to OH. SH-R thanks support from Ministerio de Economía, Industria y Competitividad (MINECO) grant BES-2017-080752., Peer reviewed

Intracranial potentials are used as functional biomarkers of neural networks. As potentials spread away from the source populations, they become mixed in the recordings. In humans, interindividual differences in the gyral architecture of the cortex pose an additional challenge, as functional areas vary in location and extent. We used source separation techniques to disentangle mixing potentials obtained by exploratory deep arrays implanted in epileptic patients of either sex to gain access to the number, location, relative contribution, and dynamics of coactive sources. The unique spatial profiles of separated generators made it possible to discern dozens of independent cortical areas for each patient, whose stability maintained even during seizure, enabling the follow up of activity for days and across states. Through matching these profiles to MRI, we associated each with limited portions of sulci and gyri and determined the local or remote origin of the corresponding sources. We also plotted source-specific 3D coverage across arrays. In average, individual recording sites are contributed to by 3-5 local and distant generators from areas up to several centimeters apart. During seizure, 13-85% of generators were involved, and a few appeared anew. Significant bias in location assignment using raw potentials is revealed, including numerous false positives when determining the site of origin of a seizure. This is not amended by bipolar montage, which introduce additional errors of its own. In this way, source disentangling reveals the multisource nature and far intracranial spread of potentials in humans, while efficiently addressing patient-specific anatomofunctional cortical divergence., This work was supported by the Spanish Ministerio de Ciencia e Innovación (MICIN) grants PID2019-111587RB-I00, PID2022-137801NB-I00 (O.H.), and PID2021-127924NB-I00 (J.F.), the Agencia Estatal de Evaluación, Next Generation EU grant PDC2021-121103-I00 (O.H.), MCIN/AEI/10.13039/501100011033 (J.F.), and CSIC Interdisciplinary Thematic Platform - Cajal Blue Brain (PTI-BLUEBRAIN; Spain). We thank participants for their contributions to research, and Nick Guthrie for his helpful comments and excellent editorial assistance. AGN thanks Fundación Iniciativa para las Neurociencias (FINCE) for continuing support., Peer reviewed

The prevailing irregular pattern of field potentials is little used due to the uncertain origin and identity of the source populations. After recovering clean source-specific dynamics (field potential-generators) in multiple brain areas of anesthetized rats we explored if they contain temporal identity features and to what extent they remain upon blending in the volume (raw field potentials). Relevant factors and mechanisms were further explored through a feed-forward model of field potentials. Signals were characterized with a multivariate set of statistical, spectral and nonlinear measures and explored with machine-learning classifiers. Despite the strong variability of electrographic patterns, field potential generators exhibit unique temporal signatures that allow their discrimination. Signatures are contained in 1 to 5 s segments in any given brain region and are robust across groups of animals. In contrast, the spatial overlap of sources and the contribution by remote potentials cause indeterminacy of raw field potentials, making them approach a noisy behavior. The so revealed source-specific signatures contain spectral and nonlinear features, thus overcoming the traditional notion of waves and frequency bands. We propose that besides upstream dynamics cytoarchitectural factors of the source population contribute to these unique signatures. These findings pave the way to utilize the vast reserve of information contained in irregular field potentials., This work was supported by the Spanish Ministerio de Ciencia e Innovación (MICIN) under grants PID2022-137801NB-I00 (OH) and PID2021-124047NB-I00 (VAM), and the European Commission Next Generation EU under grants PDC2021-121103-I00 (Agencia Estatal de Evaluación) and EU 2020/2094-IASOMM24006 (CSIC's excellence programs) (OH). RMA is financed by a PhD fellowship PIPF-2023/SAL-GL-30443 from the Comunidad Autónoma de Madrid., Peer reviewed

The prevailing irregular pattern of field potentials is little used due to the uncertain origin and identity of the source populations. After recovering clean source-specific dynamics (field potential-generators) in multiple brain areas of anesthetized rats we explored if they contain temporal identity features and to what extent they remain upon blending in the volume (raw field potentials). Relevant factors and mechanisms were further explored through a feed-forward model of field potentials. Signals were characterized with a multivariate set of statistical, spectral and nonlinear measures and explored with machine-learning classifiers. Despite the strong variability of electrographic patterns, field potential generators exhibit unique temporal signatures that allow their discrimination. Signatures are contained in 1 to 5 s segments in any given brain region and are robust across groups of animals. In contrast, the spatial overlap of sources and the contribution by remote potentials cause indeterminacy of raw field potentials, making them approach a
noisy behavior. The so revealed source-specific signatures contain spectral and nonlinear features, thus overcoming the traditional notion of waves and frequency bands. We propose that besides upstream dynamics cytoarchitectural factors of the source population contribute to these unique signatures. These findings pave the way to utilize the vast reserve of information contained in irregular field potentials.