Biology subjects

Fabo, D.

Publications and source records attributed to Fabo, D..

12 recordsLinked to original sources

bioRxiv2026

Cortical isolation separates rhythmic synchrony from network integration in the human neocortex.

Human cortical activity reflects interactions between local recurrent circuits and distributed brain-wide inputs, but how these contributions shape cortical dynamics remains unclear. We compared oscillatory and single unit activity in laminar recordings from the same human cortical regions in eight patients across wakefulness, NREM sleep, and acute slices after surgical isolation. Gamma-band spike-field synchronization increased from wakefulness to sleep and isolated cortex, whereas population coupling, putative connectivity, network integration, and dynamical dimensionality declined. Laminar gamma sink-source organization persisted in isolation, indicating the presence of local gamma-generating mechanisms. Integration with histological data showed preserved tissue architecture, while neuronal density predicted population integration in vivo but not after isolation. Removing long-range inputs thus did not suppress cortical activity but shifted its organization toward stronger rhythmic coordination and reduced integration. Our findings suggest that neocortical microcircuits intrinsically generate coherent gamma activity, whereas network embedding supports the diverse, high-dimensional dynamics of the intact cortex.

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bioRxiv2026

Preserved functions with profound morphological reorganization in human organotypic cultures

Human organotypic slice cultures provide experimental access to adult human neuronal circuits ex vivo, yet it remains unclear whether these networks preserve function or undergo fundamental reorganization following the profound perturbation of slice preparation. Here, we combined extracellular population and single-unit electrophysiology, longitudinal calcium imaging, and quantitative histology to track the changes of human cortical slice cultures over several weeks in vitro. Early phases were marked by pronounced variability and instability, with reduced firing rates, increased burst propensity in principal cells, elevated discharge irregularity, and heterogeneous recruitment during population activity. These functional changes coincided with substantial structural remodeling, including considerable neuronal loss, disruption of laminar architecture, reactive gliosis, and selective vulnerability of inhibitory interneurons. Strikingly, despite this progressive structural degradation, neuronal activity did not diverge but instead converged. By the fourth week in culture, electrophysiological properties, cell-type-specific firing patterns, and population-event recruitment became stable and highly consistent across patients. Calcium imaging revealed persistent, spatially confined regions of synchronous activity, indicating the preservation of structured network dynamics. These events remained within physiological regimes and lacked features of epileptiform discharges. Thus, human neuronal circuits exhibit a robust capacity for self-organization, transitioning from heterogeneous, injury-driven dynamics to stable and homogeneous functional states. This dissociation between structural deterioration and functional convergence establishes human organotypic slice cultures as a reproducible and translationally relevant platform for studying human brain network dynamics ex vivo.

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bioRxiv2025

Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning

The brain must balance the automatic extraction of environmental regularities with top-down cognitive control, yet the causal neural mechanisms governing this interplay are debated. In particular, the hemispheric contributions of the dorsolateral prefrontal cortex (DLPFC) remain unresolved. Here, we applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to the left, right, or bilateral DLPFC in 95 healthy adults during a probabilistic sequence learning task. We found that inhibiting the right and bilateral DLPFC significantly enhanced statistical learning compared to sham stimulation, while the left DLPFC stimulation group remained similar to sham. Contrary to the hypothesis that this competition is mediated by the suppression of existing knowledge, episodic memory performance was unaffected across all stimulation groups. These findings challenge a direct episodic gating mechanism and suggest the DLPFCs influence on statistical learning is hemisphere-dependent. As an alternative, we propose that right DLPFC inhibition shifts cognitive processing toward a more exploratory information-sampling strategy, a view supported by our finding of significantly greater reaction time variability in the right and bilateral stimulation groups. Together, our results provide causal evidence for a right-lateralized suppressive influence of the DLPFC on unsupervised learning and suggest its modulatory role is linked to information processing style rather than direct competition with episodic memory systems.

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bioRxiv2024

Heartbeat related activity in the anterior thalamus differs between phasic and tonic REM sleep periods

Rapid eye movement (REM) sleep is a fundamental sleep state associated with diverse functions from elemental physiological processes to higher order neurocognitive functions. A growing body of research indicates that REM sleep with eye movements (phasic REM) differs from REM periods without ocular activity (tonic) in terms of spontaneous and evoked neural responses. Studies using auditory stimulation consistently observed enhanced evoked responses in tonic versus phasic REM, indicating that the external processing is largely diminished when the eyes move during REM sleep. Whereas exteroceptive processing during sleep is widely studies, investigation on interoception (the processing of bodily signals) during sleep is scarce, and limited to scalp electroencephalographic recordings. Here we studied interoceptive processing in a group of epileptic patients (N = 11) by measuring their heartbeat-related neural activity in the anterior nucleus of the thalamus (ANT) during phasic and tonic REM sleep and resting wakefulness. Evoked potentials and beta-low gamma spectral power locked to the heartbeat were significantly different in phasic REM compared to tonic REM and wakefulness. Heartbeat-related neural signals exhibited pronounced inter-trial phase synchronization at lower (7-20 Hz) oscillatory activity in all vigilance states, but reduced gamma synchronization at later time points in phasic REM only. Tonic REM and wakefulness did not show significant differences in heartbeat-related activity in the ANT. Our findings indicate that heartbeat-related neural activity is detectable at the level of the ANT, showing distinct signatures of interoceptive processing in phasic REM compared to tonic REM and wakefulness.

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bioRxiv2021

The sleep EEG envelope: a novel, neuronal firing-based human biomarker

Sleep EEG reflects instantaneous voltage differences relative to a reference, while its spectrum reflects the degree to which it is comprised of oscillations at various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations at specific frequencies, and its spectrum reflects the rhythmicity of the occurrence of these oscillations. The ordinary sleep EEG and its spectrum have been extensively studied and its individual stability and relationship to various demographic characteristics, psychological traits and pathologies is well known. In contrast, the envelope spectrum has not been extensively studied before. In two studies, we explored the generating mechanisms and utility of studying the envelope of the sleep EEG. First, we used human invasive data from cortex-penetrating microelectrodes and subdural grids to demonstrate that the sleep EEG envelope spectrum reflects local neuronal firing. Second, we used a large database of healthy volunteers to demonstrate that the scalp EEG envelope spectrum is highly stable within individuals, especially in NREM sleep, and that it is affected by age and sex. Multivariate models based on a learning algorithm could predict both age (r=0.6) and sex (r=0.5) with considerable accuracy from the EEG envelope spectrum. With age, oscillations characteristically shifted from a 4-5 second rhythm to higher rhythms. The envelope spectrum was not associated with general cognitive ability (IQ). Our results demonstrate that the sleep envelope spectrum is a promising, neuronal firing-based biomarker of various demographic and disease-related phenotypes.

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bioRxiv2021

Thalamic activity during scalp slow waves in humans

Slow waves are major pacemakers of NREM sleep oscillations. While slow waves themselves are mainly generated by cortical neurons, it is not clear what role thalamic activity plays in the generation of some oscillations grouped by slow waves, and to what extent thalamic activity during slow waves is itself driven by corticothalamic inputs. To address this question, we simultaneously recorded both scalp EEG and local field potentials from six thalamic nuclei (bilateral anterior, mediodorsal and ventral anterior) in fifteen epileptic patients (age-range: 17-64 years, 7 females) undergoing Deep Brain Stimulation Protocol and assessed the temporal evolution of thalamic activity relative to scalp slow waves using time-frequency analysis. We found that thalamic activity in all six nuclei during scalp slow waves is highly similar to what is observed on the scalp itself. Slow wave downstates are characterized by delta, theta and alpha activity and followed by beta, high sigma and low sigma activity during subsequent upstates. Gamma activity in the thalamus is not significantly grouped by slow waves. Theta and alpha activity appeared first on the scalp, but sigma activity appeared first in the thalamus. These effects were largely independent from the scalp region in which SWs were detected and the precise identity of thalamic nuclei. Our results indicate that while small thalamocortical neuron assemblies may initiate cortical oscillations, especially in the sleep spindle range, the large-scale neuronal activity in the thalamus which is detected by field potentials is principally driven by global cortical activity, and thus it is highly similar to what is observed on the scalp.

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bioRxiv2021

Sleep spindles, ripples, and interictal epileptiform discharges in the human anterior and mediodorsal thalamus

Sleep spindles are major oscillatory components of Non-Rapid Eye Movement (NREM) sleep, reflecting hyperpolarization-rebound sequences of thalamocortical neurons, the inhibition of which is caused by the NREM-dependent activation of GABAergic neurons in the reticular thalamic nucleus. Reports suggest a link between sleep spindles and several forms of interictal epileptic discharges (IEDs) which are considered as expressions of pathological off-line neural plasticity in the central nervous system. Here we investigated the relationship between thalamic sleep spindles, IEDs and ripples in the anterior and mediodorsal nuclei (ANT and MD) of epilepsy patients. Whole-night LFP from the ANT and MD were co-registered with scalp EEG/polysomnography by using externalized leads in 15 epilepsy patients undergoing Deep Brain Stimulation protocol. Slow ([~]12 Hz) and fast ([~]14 Hz) sleep spindles were present in the human ANT and MD. Roughly, one third of thalamic sleep spindles were associated with IEDs or ripples. Both IED- and ripple-associated spindles were longer than pure spindles. IED-associated thalamic sleep spindles were characterized by broadband increase in thalamic and cortical activity, both below and above the spindle frequency range, whereas ripple-associated thalamic spindles exceeded pure spindles in terms of 80-200 Hz thalamic, but not cortical activity as indicated by time-frequency analysis. These result show that thalamic spindles coupled with IEDs are reflected at the scalp slow and beta-gamma oscillation as well. IED density during sleep spindles in the MD, but not in the ANT was identified as correlates of years spent with epilepsy, whereas no signs of pathological processes were correlated with measures of ripple and spindle association. Furthermore, the density of ripple-associated sleep spindles in the ANT showed a positive correlation with general intelligence. Our findings indicate the complex and multifaceted role of the human thalamus in sleep spindle-related physiological and pathological neural plasticity.

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bioRxiv2021

The timescale and magnitude of aperiodic activity decreases with cortical depth in humans, macaques and mice

Cortical dynamics obey a 1/f power law, exhibiting an exponential decay of spectral power with increasing frequency. The slope and offset of this 1/f decay reflect the timescale and magnitude of aperiodic neural activity, respectively. These properties are tightly linked to cellular and circuit mechanisms (e.g. excitation:inhibition balance and firing rates) as well as cognitive processes (e.g. perception, memory, and state). However, the physiology underlying the 1/f power law in cortical dynamics is not well understood. Here, we compared laminar recordings from human, macaque and mouse cortex to evaluate how 1/f aperiodic dynamics vary across cortical layers and species. We report that 1/f slope is steepest in superficial layers and flattest in deep layers in each species. Additionally, the magnitude of this 1/f decay is greatest in superficial cortex and decreases with depth. We could account for both of these findings with a simple model in which superficial cortical transmembrane currents had longer time constants and greater densities than those in deeper layers. Together, our results provide novel insight into the organization of cortical dynamics, suggesting that the amplitude and time constant of local currents control circuit processing as a function of laminar depth. This may represent a general mechanism to facilitate appropriate integration of fast sensory inputs (infragranular) with slow feedback-type inputs (supragranular) across cortical areas and species.

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bioRxiv2019

The laminar profile of sleep spindles in humans

Sleep spindles are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IME electrodes within cortical layers was confirmed using postsurgical histological reconstructions. Many micro-domain spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. Macro-domain spindles sufficiently large to be detected on the ECoG were in contrast usually accompanied by IME spindles. Neither micro-domain nor macro-domain spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and subjects. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes.

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bioRxiv2019

Intracortical dynamics underlying repetitive stimulation predicts changes in network connectivity

Targeted stimulation can be used to modulate the activity of brain networks. Previously we demonstrated that direct electrical stimulation produces predictable post-stimulation changes in brain excitability. However, understanding the neural dynamics during stimulation and its relationship to post-stimulation effects is limited but critical for treatment optimization. Here, we applied 10Hz direct electrical stimulation across several cortical regions in 14 patients implanted with intracranial electrodes for seizure monitoring. The stimulation train was characterized by a consistent increase in high gamma (70-170Hz) power. Immediately post-train, low-frequency (1-8Hz) power increased, resulting in an evoked response that was highly correlated with the neural response during stimulation. Using two measures of network connectivity, cortico-cortical evoked potentials (indexing effective connectivity) and theta coherence (indexing functional connectivity), we found a stronger response to stimulation in regions that were highly connected to the stimulation site. In these regions, repeated cycles of stimulation trains and rest progressively altered the stimulation response. Finally, after just 2 minutes (10%) of repetitive stimulation, we were able to predict post-stimulation connectivity changes with high discriminability. Taken together, this work reveals a relationship between stimulation dynamics and post-stimulation connectivity changes in humans. Thus, measuring neural activity during stimulation can inform future plasticity-inducing protocols.

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bioRxiv2017

Superficial Slow Rhythms Integrate Cortical Processing in Humans

The neocortex is composed of six anatomically and physiologically specialized layers. It has been proposed that integration of activity across cortical areas is mediated anatomically by associative connections terminating in superficial layers, and physiologically by slow cortical rhythms. However, the means through which neocortical anatomy and physiology interact to coordinate neural activity remains obscure. Using laminar microelectrode arrays in 19 human participants, we found that most EEG activity is below 10-Hz (delta/theta) and generated by superficial cortical layers during both wakefulness and sleep. Cortical surface grid, grid-laminar, and dual-laminar recordings demonstrate that these slow rhythms are synchronous within upper layers across broad cortical areas. The phase of this superficial slow activity is reset by infrequent stimuli and coupled to the amplitude of faster oscillations and neuronal firing across all layers. These findings support a primary role of superficial slow rhythms in generating the EEG and integrating cortical activity.

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bioRxiv2017

The Generation and Propagation of the Human Alpha Rhythm

IntroductionThe alpha rhythm (7-13 Hz) is the longest studied brain oscillation and has been theorized to play a key role in cognition. Still, substantial uncertainty remains over its physiology. In this study, we used micro and macro electrodes in patients undergoing surgery for epilepsy to measure the intracortical and thalamic generators of the human alpha rhythm. We first found that alpha propagates from higher-order anterosuperior cortex towards the lower-order occipital poles, consistent with alpha effecting top-down processing. This cortical alpha drives thalamic alpha, reversing prevailing theories of a thalamic alpha pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortex, contravening the popular conception of alpha as an infragranular rhythm. Together, these results demonstrate that the alpha rhythm reflects short-range supragranular feedback which propagates from higher-order to lower order cortex and cortex to thalamus. These physiological insights explain how alpha could mediate feedback throughout the thalamocortical system.

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