Search bioRxiv⌕ Search

Biology subjects

Ben-Haim, S.

Publications and source records attributed to Ben-Haim, S..

7 recordsLinked to original sources
bioRxiv2026

Simulated field potentials capture multiple simultaneous processes underlying human temporal attention

Essential cognitive processes like attention, memory, and decision-making require the brain to perform many operations simultaneously. Disentangling the neural mechanisms underlying these processes is challenging because they often unfold concurrently with similar dynamics. In auditory temporal expectation, these mechanisms include the accumulation of incoming sensory information in the auditory cortex interacting with cortical signals biasing activity in anticipation of future stimuli. Here, we leverage invasive human field potential recordings from participants performing a subjective temporal expectation task. Rather than relying on traditional neuroimaging methods that average or transform neural responses, we instead simulate each trial's predicted field potential, based on known field potential physiology combined with components of established cognitive theories of the temporal expectation task: sensory input, top-down bias, and sensory anticipation. Our predicted field potentials strongly correlate with neural activity in auditory regions and in regions associated with auditory temporal perception, including the parietal, temporal, and prefrontal cortices. By differentiating individual cognitive mechanisms through simulation, we identify neural signatures of attentional bias and anticipatory sensory activity across multiple cortical regions that predict trial-by-trial perceptual accuracy and confidence.

neuroscience↗
bioRxiv2026

Adaptive Charge Modulation Enables Focal, Selective Spinal Cord Stimulation

Clinical neuromodulation primarily employs near-field low frequency electrical stimulation to activate neurons in the immediate vicinity of the electrode. We introduce Adaptive Charge Modulation (ACM), a spatiotemporal, charge-balanced stimulation strategy that focuses activation at deep tissue sites distant from the stimulating contacts. We apply ACM to stimulate deep regions of the spinal cord, distant from dorsal root entry zones which are preferentially activated during low frequency stimulation (LFS). ACM applies multipolar, biphasic rectangular pulses to exceed activation thresholds in deeper neuronal populations, with reduced surface activation, potentially due to high-frequency suppression of neural activity. In epidural spinal cord stimulation in rats, ACM achieved single-muscle selectivity among fourteen monitored muscles with minimal co-activation of other muscles. Using simultaneous, high spatiotemporal resolution, 2,112-channel brain-spine recordings, we characterized the response latencies and pathways consistent with focal recruitment at depth. We observed chronic stability of the electrode and ACM in freely behaving animals over 68 days post-implantation. By enabling focal activation with epidural surface electrodes, ACM may expand the reach and precision of neuromodulation and neural interfaces.

bioengineering↗
bioRxiv2024

The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma

Whether an individual is a biological female or male affects cancer risk, but the responsible mechanisms and cell types remain obscure. Glioblastoma multiforme (GBM) is a male-biased cancer that is highly aggressive, and resistant to treatment, with poor patient survival. Dismal prognoses in GBM are due in part to the specialized immune system of the brain, consisting largely of microglia, which regulate GBM development and progression. We hypothesized that microglia function differently in females and males and thereby contribute to the observed male bias in GBM. We sorted TAM-MGs (tumor-associated macrophages - microglia) from human GBMs and low-grade gliomas and performed bulk transcriptomic and epigenomic assays to identify sex-biased gene expression. We used published single-cell transcriptomic data from human GBMs to predict sex-biased TAM-MG interactions with other cell types. We found that female and male TAM-MGs mount different inflammatory responses, with female TAM-MGs displaying stronger interferon signaling and cytotoxic T-cell interactions that should enhance anti-tumor immunity in GBM. We validated these sex-differential inflammatory responses experimentally, and determined that genes on the sex chromosomes, specifically those expressed by Xi (the "inactive" X chromosome), drive these differences. Together, our results suggest that sex-differential TAM-MG inflammatory responses contribute to the higher incidence and mortality of GBM in males.

genomics↗
bioRxiv2021

Gene regulatory networks underlying human microglia maturation

The fetal period is a critical time for brain development, characterized by neurogenesis, neural migration, and synaptogenesis1-3. Microglia, the tissue resident macrophages of the brain, are observed as early as the fourth week of gestation4 and are thought to engage in a variety of processes essential for brain development and homeostasis5-11. Conversely, microglia phenotypes are highly regulated by the brain environment12-14. Mechanisms by which human brain development influences the maturation of microglia and microglia potential contribution to neurodevelopmental disorders remain poorly understood. Here, we performed transcriptomic analysis of human fetal and postnatal microglia and corresponding cortical tissue to define age-specific brain environmental factors that may drive microglia phenotypes. Comparative analysis of open chromatin profiles using bulk and single-cell methods in conjunction with a new computational approach that integrates epigenomic and single-cell RNA-seq data allowed decoding of cellular heterogeneity with inference of subtype- and development stage-specific transcriptional regulators. Interrogation of in vivo and in vitro iPSC-derived microglia models provides evidence for roles of putative instructive signals and downstream gene regulatory networks which establish human-specific fetal and postnatal microglia gene expression programs and potentially contribute to neurodevelopmental disorders.

genomics↗
bioRxiv2021

Widespread ripples synchronize human cortical activity

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such binding of different components of mental events into unified representations occurs is unknown. The binding-bysynchrony theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ( ripples) occur in the hippocampus and cortex, and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ~70ms duration 90Hz ripples often couple (within {+/-}500ms), co-occur ([≥]25ms overlap), and crucially, phase-lock (have consistent phase-lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phaselocking increases with more cortical sites co-rippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase-lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical co-ripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and co-ripples increase high-frequency correlations between areas, suggesting synchronized unit-spiking facilitating information exchange. Co-occurrence, phasesynchrony, and high-frequency correlation are maintained with little decrement over very long distances (25cm). Hippocampo-cortico-cortical co-ripples appear to possess the essential properties necessary to support binding-by-synchrony during memory retrieval, and perhaps generally in cognition. Significance StatementDifferent elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called ripples, but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres, and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing, and phase-synchronize with little decay between locations separated by up to 25cm, enabling long-distance integration. Indeed, co-rippling sites have increased correlation of very high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.

neuroscience↗
bioRxiv2019

Microscale physiological events on the human cortical surface detected with PEDOT:PSS Electrodes

Despite ongoing advancements in our understanding of the local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their intermediate microscale local circuit dynamics. Here, we utilized ultrahigh density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper layers of the grey matter. They were also observed in rodents, non-human primates, and semi-chronic recordings in humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that with the proper combination of high resolution microelectrodes and analytic techniques it is possible to capture neuronal dynamics that lay between somatic action potentials and aggregate population activity and that understanding these intermediate microscale dynamics may reveal important details of the full circuit behavior in human cognition.

neuroscience↗