Biology subjects

Schall, J. D.

Publications and source records attributed to Schall, J. D..

At least 19 recordsLinked to original sources

bioRxiv2026

Visual cortical dynamics supporting predictable attentional capture

Visual behavior depends on the ability to prioritize relevant sensory information while filtering out distractions. Predictable sensory contexts enable more efficient behavior by altering sensory processing. Using laminar neurophysiology in macaque visual cortex measuring population spiking during a feature-based pop-out visual search task, we examined how predictable visual routines influence cortical columnar processing of sensory information. By manipulating predictability through attentional priming, we found improved behavioral performance with predictable stimulus arrays. These behavioral changes were supported by earlier neuronal attentional target selection driven by reduced variability in the sensory response to the predictable target stimulus and more homogeneous feedforward processing dynamics across the cortical column. More effective distractor suppression was driven by adapted feedforward processing of the more frequent distractor stimulus. Together, these changes implicate independent mechanisms for target enhancement and distractor suppression. Our results highlight how predictions from experience alter visual columnar processing to optimize attentional selection through streamlining feedforward signaling. HighlightsO_LIBoth target enhancement and distractor suppression are independently observable in visual cortex with different profiles of modulation as a function of predictability. C_LIO_LIPredictions produce stronger, more reliable feedforward responses to attention-capturing targets across the visual cortical layers. C_LIO_LIBetter distractor suppression with stimulus predictability is driven by adapted sensory representations, not top-down inhibition. C_LI SignificanceHow do predictions help determine what catches our attention? It is well known that when primates repeatedly perform visuomotor tasks, they become more proficient. Using neural recordings across the layers of the visual cortex, Groot et al. demonstrate that more efficient feedforward processing of sensory information contributes to improved visual behavior under predictable sensory conditions. These findings highlight the crucial role of predictions in proactively shaping sensory representations to facilitate efficient attentive behavior.

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bioRxiv2026

Overcoming the skull barrier for noninvasive transcranial functional ultrasound imaging in marmosets

Functional ultrasound (fUS) imaging enables high-resolution mapping of brain hemodynamics but is limited in primates by acoustic attenuation of the cranium. With topical application of ethylenediaminetetraacetic acid (EDTA), we were able to visualized cortical and deep vasculature in marmoset brains. We localized robust, stimulus-locked blood flow changes in cortical and subcortical regions contralateral to peripheral tactile stimulation. Beyond stimulus-evoked responses, resting-state cerebral blood flow also varied with the depth of isoflurane anesthesia. These findings advance translational ultrasound neuroimaging by offering a non-destructive alternative to a craniotomy.

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bioRxiv2025

Subanesthetic Ketamine Disrupts Predictive Signaling in the Prefrontal Cortex

Corollary discharge (CD) signals allow the brain to predict and suppress the sensory consequences of its own actions, providing stability to perception and thought. Disruption of these predictive mechanisms has long been hypothesized to contribute to the disorganization of experience in schizophrenia, yet direct circuit-level evidence has been lacking. Here, we show that ketamine, a dissociative N-methyl-D-aspartate receptor (NMDAR) antagonist, at subanesthetic doses, selectively disrupts CD signaling in the lateral prefrontal cortex (LPFC)--a region thought to be the seed of mental representations and one of the most affected areas in schizophrenia. We recorded activity from 1,342 neurons in LPFC areas 8a and 9/46 of macaques performing a visuospatial working-memory task in a virtual environment, before and after subanesthetic ketamine administration. Ketamine impaired performance and increased overall firing rates but markedly suppressed saccade-related responses carrying CD signals. This led to decreased discriminability of eye movement signals. This finding links two major ideas in neuroscience research: the role of disrupted glutamate signaling and the failure of the brains predictive models. It provides evidence for how these mechanisms may interact in the prefrontal cortex to disturb the sense of reality.

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bioRxiv2025

Deep Brain Ultrasound Augments Human Attention

BackgroundDeep brain ultrasound offers a novel means of modulating human cognition by noninvasively targeting subcortical structures that were previously accessible only through invasive procedures. While decades of research have mapped cortical circuits of attention, the causal roles of deep hubs such as the basal ganglia and thalamus remain poorly understood in the healthy human brain. Objectives/HypothesisTo test whether low intensity transcranial ultrasound stimulation (TUS) of two nodes in the basal ganglia-thalamic network, the globus pallidus internus (GPi) and the pulvinar, causally alters visual attention. We hypothesized that TUS-induced modulations in attentional performance would be site specific, reflecting distinct circuit functions. ResultsAcross sessions, focal TUS accelerated reaction time in a visual search task, indicating augmented attention. Reaction time improvements were observed after stimulation relative to baseline. A dissociation emerged across sites: both GPi and pulvinar enhanced reaction times, but pulvinar yielded more robust benefits for target present trials at peripheral eccentricities, and improved search efficiency in the same trials. ConclusionsThese findings provide causal evidence that human attentional control can be steered at deep subcortical sites. TUS offers a practical approach for dissecting circuit level contributions to cognition and a potential noninvasive avenue for enhancing attention and other cognitive or affective functions.

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bioRxiv2025

Factorial variation of saccade vigor with dual decision processes

Canonical stochastic models of decision-making treats decision and action as independent and sequential processes. However, studies involving limb movements consistently show that movement duration and kinematics are influenced by the quality of evidence. We tested whether saccade velocity varies with the quality of evidence in monkeys performing a visual search GO/NOGO task in which singleton elongation cued the GO/NOGO stimulus-response rule and the location of a color singleton specified saccade endpoint. We factorially manipulated the efficiency of stimulus-response cue discrimination by varying the elongation of the singleton and the efficiency of singleton localization by varying the color similarity between the singleton and distractors. The effectiveness of the manipulations was revealed by the response times on correct trials that were separately modified by the singleton localizability and stimulus-response cue discriminability, by the incidence of localization and response selection errors with separately modified error response times. Saccade velocity was higher on correct relative to error trials and was inversely proportional to response time. Saccade velocity was separately modified by singleton localizability and stimulus-response cue discriminability. Distinct patterns of error rates and saccade velocity across monkeys indicated individual differences in decision-making strategies. These findings demonstrate that the process selecting endpoints can influence both the timing and dynamics of saccadic eye movements. Incorporating saccade vigor can provide valuable constraints on biologically plausible decision models and help address the persistent challenge of model mimicry.

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bioRxiv2025

A preparatory cranial potential for saccadic eye movements in macaque monkeys

Response preparation is accomplished by gradual accumulation in neural activity until a threshold is reached. In humans, such a preparatory signal, referred to as the lateralized readiness potential, can be observed in the EEG over sensorimotor cortical areas before execution of a voluntary movement. Although well-described for manual movements, less is known about preparatory EEG potentials for saccadic eye movements in humans and nonhuman primates. Hence, we describe a lateralized readiness potential over the frontolateral cortex in macaque monkeys. Homologous to humans, we observed lateralized electrical potentials ramping before the execution of both rewarded and non-rewarded contralateral saccades. This potential parallels the neural spiking of saccadic movement neurons in the frontal eye field, suggesting that it may offer a non-invasive correlate of intracortical spiking activity. However, unlike neural spiking in the frontal eye field, polarization in frontolateral channels did not distinguish between saccade generation and inhibition. These findings provide new insights into non-invasive electrophysiological signatures of saccadic preparation in nonhuman primates, highlighting the potential of EEG measures to bridge invasive neural recordings and non-invasive studies of eye movement control in humans.

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bioRxiv2024

Conflict neurons in cingulate cortex of macaques

Conflict--the magnitude of co-activation of mutually incompatible response processes--was proposed to explain how cognitive control is invoked (Botvinick et al. 2001) and continues to engage debate (Becker et al. 2024). Original observations consistent with this construct emphasized the primary contribution of cingulate cortex (CC) based on human functional imaging (Botvinick et al., 1999; Carter et al., 2000) and electroencephalogram (Yeung, Botvinick, & Cohen, 2004). In countermanding tasks conflict arises through co-activation of competing GO and STOP processes (Boucher et al. 2007; Schall & Boucher 2007; Sajad et al. 2022). Single neuron activity representing conflict has been described in the supplementary motor cortex of human epilepsy patients (Fu et al., 2019; Sheth et al., 2012) and of macaque monkeys (Sajad, Errington, & Schall, 2022; Stuphorn, Taylor, & Schall, 2000) and in human cingulate cortex (Fu et al., 2019; Sheth et al., 2012) but not in monkey cingulate cortex (Ebitz & Platt, 2015; Ito, Stuphorn, Brown, & Schall, 2003; Nakamura, Roesch, & Olson, 2005). This lack of homology generated debate about the utility of macaques for investigation of cognitive control (Cole et al. 2009; Schall & Emeric 2010). With higher-resolution, less-biased samples, we re-examined the presence of a conflict signal in cingulate cortex of monkeys. Neurons modulating specifically when response conflict was maximal were found in cingulate cortex-- more commonly in the dorsal than the ventral bank. However, such neurons were much more common in supplementary motor cortex. These data confirm the presence of a conflict signal in medial frontal cortex and demonstrate that it can be found in a small fraction of neurons in cingulate cortex. Further research is needed to determine if the weak response conflict signal in cingulate cortex is sufficient or negligible.

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bioRxiv2024

Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field (FEF) of two rhesus monkeys shifting gaze to a target while an isoeccentric distractor appeared either left or right of the target at various delays after target presentation. We found that the population level of pre-saccadic activity encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature towards the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved towards distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push-pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets. Significant StatementThis study not only advances our understanding of oculomotor function in dynamic environments but also has potential clinical relevance for diagnosing and understanding disorders characterized by abnormal saccade trajectories. Our research elucidates the neural mechanisms behind saccade trajectories that are not always linear due to the brains integration of multiple visual cues and/or motor plans. By analyzing the frontal eye field (FEF) activity in rhesus monkeys, we found that saccade directionality and timing are influenced by the interaction between FEF visual neurons representing target and distractor stimuli. The FEFs role extends beyond a winner-takes-all approach, incorporating saccade vector averaging computations that produce curved saccades. Furthermore, ipsilateral visual neurons encode distractor suppression that drives curvature away from the distractor.

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bioRxiv2023

Laminar architecture of visual responses in supplementary eye field of macaques

Previously, we have described the laminar organization of neurons in the supplementary eye field (SEF) that signal error, reward gain and loss, conflict, event timing, and goal maintenance. Here we describe the laminar organization of visually responsive neurons that were active during performance of a saccade stop-signal task. Nearly 40% of isolated neurons exhibited enhanced or suppressed responses to a visual target for a potential saccade, with the majority exhibiting enhanced activity and three-quarters with broad spikes. Visually responsive neurons were observed in all layers but were less common in layers 5 and 6. Response latencies were comparable to those reported previously, which are significantly later than those measured in occipital and temporal visual areas but overlapping those measured in cingulate cortex. Task-related visual response latency varied across cortical layers. Response latency was significantly earlier for neurons with narrow spikes. Neurons with task-related visual responses discharged until after saccade production. Around three-fifths of visually responsive neurons were most sensitive to the visual target appearing in one hemifield. Many neurons in layer 2 had ipsilateral receptive fields. Laminar current-source density aligned on visual target presentation revealed the earliest sink in layers 3 followed by a prolonged strong sink more superficially coupled with a weaker prolonged sink in layer 5 and a transient sink in layer 6. The current sink in layers 2 and 3 was stronger for ipsilateral stimuli. These findings reveal new details about visual processing in medial frontal cortex and complete the first catalogue of laminar organization of functional signals in a frontal lobe area.

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bioRxiv2023

Cortical Origin of Theta Error Signals

A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to account for error-related modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 PCs generate theta rhythmicity with random phase. Saccades synchronized the phase of this theta-rhythm, which was magnified on errors. Contributions from L5 PCs to the laminar current source density (CSD) observed in SEF were negligible. The CSD derived from L3 PCs could not explain the observed association between their error-related spiking modulation and scalp-EEG. Laminar CSD comprises multipolar components, with dipoles explaining ERN features, and quadrupoles reproducing those for Pe. The presence of monopoles indicates diffuse activation. These results provide the most advanced explanation of the cellular mechanisms generating the ERN.

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bioRxiv2022

Cortical Contributions to Medial Frontal β-Bursts during Executive Control

EEG {beta}-bursts observed over the medial frontal cortex are claimed to mediate response inhibition despite their infrequent occurrence. The weak association with stopping behavior is supposed to be a by-product of the low signal-to-noise ratio of EEG recordings. We tested the premise that {beta}-bursts are more common within the cerebral cortex and more directly associated with response inhibition. We sampled simultaneously EEG and intracortical local field potentials (LFP) within the medial frontal cortex (MFC) of two macaque monkeys performing a response inhibition task. Intracortical {beta}-bursts were just as infrequent as those in EEG and did not parallel the likelihood of canceling a planned response. Cortical {beta}-bursts were more prevalent in upper layers but were not synchronized across a cortical column or with EEG {beta}-bursts. These findings contradict claims for a causal contribution of {beta}-bursts during response inhibition, provide important constraints for biophysical and cortical circuit models, and invite further considerations of {beta}-burst function in cognitive control.

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bioRxiv2022

Feedforward attentional selection in sensory cortex

Salient objects stand out (pop-out) from their surroundings, grabbing our attention. Whether this phenomenon is a consequence of bottom-up sensory processing or predicated on top-down influence is debated. We show that the neural computation of attentional pop-out is embedded in the earliest cortical sensory response, seemingly void of feedback from higher-level areas. We measured synaptic and spiking activity across cortical columns in mid-level area V4 of monkeys searching for an attention-grabbing stimulus. Indexed by reaction times and behavioral accuracy, attention was captured at variable times. This moment of attentional capture occurred within the earliest feedforward response, both in terms of timing and spatial location. Moreover, the magnitude of the earliest sensory response predicted reaction times. Crucially, errant attentional selection and consequent behavior was associated with errant selection in sensory cortex. Together, these findings demonstrate a dominant role for feedforward activation of sensory cortex for dictating attentional priority and subsequent behavior. In briefWhy do certain objects stand out from their surroundings and seemingly grab our attention? In this study, Westerberg et al. determine that attentional selection for salient objects in our environment is computed in sensory cortex as soon as sensory information arrives. HighlightsO_LIEarly sensory responses in V4 predict attentional selection and behavioral responses C_LIO_LIErrant attentional selection in sensory cortex precedes errant behavior C_LIO_LITonic modulation of sensory cortex can regulate attentional selection C_LI

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bioRxiv2022

Resolving the mesoscopic missing link: Biophysical modeling of EEG from cortical columns in primates

Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge from the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp. HighlightsO_LICognitive EEG production was accurately modeled from empirically measured cortical activity in awake macaques. C_LIO_LIV4 laminar activity plausibly generates the attention-related signal indexed by the EEG. C_LIO_LIModels demonstrate the importance of biophysical geometry in cognitive EEG production. C_LI

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bioRxiv2021

Laminar microcircuitry of visual cortex producing attention-associated electric fields

Cognitive operations are widely studied by measuring electric fields through EEG and ECoG. However, despite their widespread use, the component neural circuitry giving rise to these signals remains unknown. Specifically, the functional architecture of cortical columns which results in attention-associated electric fields has not been explored. Here we detail the laminar cortical circuitry underlying an attention-associated electric field often measured over posterior regions of the brain in humans and monkeys. First, we identified visual cortical area V4 as one plausible contributor to this attention-associated electric field through inverse modeling of cranial EEG in macaque monkeys performing a visual attention task. Next, we performed laminar neurophysiological recordings on the prelunate gyrus and identified the electric-field-producing dipoles as synaptic activity in distinct cortical layers of area V4. Specifically, activation in the extragranular layers of cortex resulted in the generation of the attention-associated dipole. Feature selectivity of a given cortical column determined the overall contribution to this electric field. Columns selective for the attended feature contributed more to the electric field than columns selective for a different feature. Lastly, the laminar profile of synaptic activity generated by V4 was sufficient to produce an attention-associated signal measurable outside of the column. These findings suggest that the top-down recipient cortical layers produce an attention-associated electric field capable of being measured extracranially and the relative contribution of each column depends upon the underlying functional architecture.

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bioRxiv2021

Cortical Microcircuitry of Executive Control and Source of Associated Event-Related Potentials

Medial frontal cortex enables executive control by monitoring relevant information and using it to adapt behavior. In macaques performing a saccade countermanding (stop-signal) task, we recorded EEG over and neural spiking across all layers of the supplementary eye field (SEF). We report the laminar organization of concurrently activated neurons monitoring the conflict between incompatible responses and the timing of events serving goal maintenance and executive control. We also show their relation to coincident event-related potentials (ERP). Neurons signaling response conflict were largely broad-spiking found across all layers. Neurons signaling the interval until specific task events were largely broad-spiking neurons concentrated in L3 and L5. Neurons predicting the duration of control and sustaining the task goal until the release of operant control were a mix of narrow- and broad-spiking neurons confined to L2/3. We complement these results with the first report of a monkey homologue of the N2/P3 ERP complex associated with response inhibition. N2 polarization varied with error likelihood and P3 polarization varied with the duration of expected control. The amplitude of the N2 and P3 were predicted by the spike rate of different classes of neurons located in L2/3 but not L5/6. These findings reveal important, new features of the cortical microcircuitry supporting executive control and producing associated ERP.

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bioRxiv2020

Dissociation of Medial Frontal β-Bursts and Executive Control

The neural mechanisms of executive and motor control concern both basic researchers and clinicians. In human studies, preparation and cancellation of movements are accompanied by changes in the {beta}-frequency band (15-29 Hz) of EEG. Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient {beta}-bursts over sensorimotor cortical areas before movement initiation and increased {beta}-bursting over medial frontal areas with movement cancellation. This modulation has been interpreted as contributing to the trial-by-trial control of behavior. We performed identical analyses of EEG recorded over the frontal lobe of macaque monkeys performing a saccade countermanding task. Whilst, we replicate the occurrence and modulation of {beta}-bursts associated with initiation and cancellation of saccades, we found that {beta}-bursts occur too infrequently to account for the observed stopping behavior. We also found {beta}-bursts were more common after errors, but their incidence was unrelated to response time adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of {beta}-band functional significance.

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bioRxiv2020

Express saccades during a countermanding task

Express saccades are unusually short latency, visually guided saccadic eye movements. They are most commonly observed when the fixation spot disappears at a consistent, short interval before a target spot appears at a repeated location. The saccade countermanding task includes no fixation-target gap, variable target presentation times, and the requirement to withhold saccades on some trials. These testing conditions should discourage production of express saccades. However, two macaque monkeys performing the saccade countermanding task produced consistent, multimodal distributions of saccadic latencies. These distributions consisted of a longer mode extending from 200 ms to as much as 600 ms after target presentation and another consistently less than 100 ms after target presentation. Simulations revealed that by varying express saccade production, monkeys could earn more reward. If express saccades were not rewarded, they were rarely produced. The distinct mechanisms producing express and longer saccade latencies were revealed further by the influence of regularities in the duration of the fixation interval preceding target presentation on saccade latency. Temporal expectancy systematically affected the latencies of regular but not of express saccades. This study highlights that cognitive control can integrate information across trials and strategically elicit intermittent very short latency saccades to acquire more reward.

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bioRxiv2020

A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation

Ca2+ spikes initiated in the apical dendrites of layer-5 pyramidal cells (PC) underlie nonlinear dynamic changes in the gain of cellular response, which is critical for top-down cognitive control. Detailed models with several compartments and dozens of ionic channels have been proposed to account for this Ca2+ spike-dependent gain with its associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We present a minimal 2-compartment biophysical model, overcoming these limitations. In our model, a basal-dendritic/somatic compartment included typical Na+ and K+ conductances, while an apical-dendritic/trunk compartment included persistent Na+, hyperpolarization-activated cation (Ih), slow inactivation K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer-5 PC synaptic integration: linear frequency-current relationships, backpropagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking Ih. Simulating 1,000 synchronized layer-5 PCs, we reproduced the current source density patterns evoked by Ca2+-spikes both with and without Ih current. Thus, a 2-compartment model with five non-classic ionic currents in the apical-dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials such as the error-related negativity. Significance StatementA tractable model of layer-5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. This minimal model enables new multi-scale investigations of microcircuit functions with associated current flows measured by intracranial local field potentials. It thus establishes a foundation for the future computational evaluation of scalp electroencephalogram signatures imprinted by Ca2+ spikes in pyramidal cells, a phenomenon underlying many brain cognitive processes.

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