Dissociable Neural Mechanisms Underlie the Effects of Attention on Visual Appearance and Response Bias.

A prominent theoretical framework spanning philosophy, psychology, and neuroscience holds that selective attention penetrates early stages of perceptual processing to alter the subjective visual experience of behaviorally relevant stimuli. For example, searching for a red apple at the grocery store might make the relevant color appear brighter and more saturated compared with seeing the exact same red apple while searching for a yellow banana. In contrast, recent proposals argue that data supporting attention-related changes in appearance reflect decision- and motor-level response biases without concurrent changes in perceptual experience. Here, we tested these accounts by evaluating attentional modulations of EEG responses recorded from male and female human subjects while they compared the perceived contrast of attended and unattended visual stimuli rendered at different levels of physical contrast. We found that attention enhanced the amplitude of the P1 component, an early evoked potential measured over visual cortex. A linking model based on signal detection theory suggests that response gain modulations of the P1 component track attention-induced changes in perceived contrast as measured with behavior. In contrast, attentional cues induced changes in the baseline amplitude of posterior alpha band oscillations (∼9-12 Hz), an effect that best accounts for cue-induced response biases, particularly when no stimuli are presented or when competing stimuli are similar and decisional uncertainty is high. The observation of dissociable neural markers that are linked to changes in subjective appearance and response bias supports a more unified theoretical account and demonstrates an approach to isolate subjective aspects of selective information processing.SIGNIFICANCE STATEMENT Does attention alter visual appearance, or does it simply induce response bias? In the present study, we examined these competing accounts using EEG and linking models based on signal detection theory. We found that response gain modulations of the visually evoked P1 component best accounted for attention-induced changes in visual appearance. In contrast, cue-induced baseline shifts in alpha band activity better explained response biases. Together, these results suggest that attention concurrently impacts visual appearance and response bias, and that these processes can be experimentally isolated.

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 between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.

Dissociation of Medial Frontal ß-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 ß-frequency band (15-29 Hz) of electroencephalogram (EEG). Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient ß-bursts over sensorimotor cortical areas before movement initiation and increased ß-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 (one male, one female) performing a saccade countermanding task. While we replicate the occurrence and modulation of ß-bursts associated with initiation and cancellation of saccades, we found that ß-bursts occur too infrequently to account for the observed stopping behavior. We also found ß-bursts were more common after errors, but their incidence was unrelated to response time (RT) adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of ß band functional significance.SIGNIFICANCE STATEMENT The finding of increased ß-bursting over medial frontal cortex with movement cancellation in humans is difficult to reconcile with the finding of modulation too late to contribute to movement cancellation in medial frontal cortex of macaque monkeys. To obtain comparable measurement scales, we recorded electroencephalogram (EEG) over medial frontal cortex of macaques performing a stop signal (countermanding) task. We replicated the occurrence and modulation of ß-bursts associated with the cancellation of movements, but we found that ß-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether ß-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.

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

Ca2+ spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+ spike-dependent gain and 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 overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+ and delayed-rectifier K+ conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (I h ), slow-inactivating 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, back-propagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking I h Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+ spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial 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 STATEMENT A minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.

Converging Evidence That Neural Plasticity Underlies Transcranial Direct-Current Stimulation.

It is not definitely known how direct-current stimulation causes its long-lasting effects. Here, we tested the hypothesis that the long time course of transcranial direct-current stimulation (tDCS) is because of the electrical field increasing the plasticity of the brain tissue. If this is the case, then we should see tDCS effects when humans need to encode information into long-term memory, but not at other times. We tested this hypothesis by delivering tDCS to the ventral visual stream of human participants during different tasks (i.e., recognition memory vs. visual search) and at different times during a memory task. We found that tDCS improved memory encoding, and the neural correlates thereof, but not retrieval. We also found that tDCS did not change the efficiency of information processing during visual search for a certain target object, a task that does not require the formation of new connections in the brain but instead relies on attention and object recognition mechanisms. Thus, our findings support the hypothesis that direct-current stimulation modulates brain activity by changing the underlying plasticity of the tissue.

Induced Forgetting Is the Result of True Forgetting, Not Shifts in Decision-making Thresholds.

Induced forgetting occurs when accessing an item in memory appears to harm memory representations of categorically related items. However, it is possible that the actual memory representations are unharmed. Instead, people may just change how they make decisions. Specifically, signal detection theory suggests this apparent forgetting may be due to participants shifting their decision criterion. Here, we used behavioral and electrophysiological measures to determine whether induced forgetting is truly due to changes in how items are represented or simply due to a shifting criterion. Participants' behavior and brain activity showed that induced forgetting was due to changes in the strength of the underlying representations, weighing against a criterion shift explanation of induced forgetting.

Stimulus-induced Alpha Suppression Tracks the Difficulty of Attentional Selection, Not Visual Working Memory Storage.

Human alpha-band activity (8-12 Hz) has been proposed to index a variety of mechanisms during visual processing. Here, we distinguished between an account in which alpha suppression indexes selective attention versus an account in which it indexes subsequent working memory storage. We manipulated two aspects of the visual stimuli that perceptual attention is believed to mitigate before working memory storage: the potential interference from distractors and the size of the focus of attention. We found that the magnitude of alpha-band suppression tracked both of these aspects of the visual arrays. Thus, alpha-band activity after stimulus onset is clearly related to how the visual system deploys perceptual attention and appears to be distinct from mechanisms that store target representations in working memory.

α-Band activity tracks a two-dimensional spotlight of attention during spatial working memory maintenance.

Covert spatial attention is thought to facilitate the maintenance of locations in working memory, and EEG α-band activity (8-12 Hz) is proposed to track the focus of covert attention. Recent work has shown that multivariate patterns of α-band activity track the polar angle of remembered locations relative to fixation. However, a defining feature of covert spatial attention is that it facilitates processing in a specific region of the visual field, and prior work has not determined whether patterns of α-band activity track the two-dimensional (2-D) coordinates of remembered stimuli within a visual hemifield or are instead maximally sensitive to the polar angle of remembered locations around fixation. Here, we used a lateralized spatial estimation task, in which observers remembered the location of one or two target dots presented to one side of fixation, to test this question. By applying a linear discriminant classifier to the topography of α-band activity, we found that we were able to decode the location of remembered stimuli. Critically, model comparison revealed that the pattern of classifier choices observed across remembered positions was best explained by a model assuming that α-band activity tracks the 2-D coordinates of remembered locations rather than a model assuming that α-band activity tracks the polar angle of remembered locations relative to fixation. These results support the hypothesis that this α-band activity is involved in the spotlight of attention, and arises from mid- to lower-level visual areas involved in maintaining spatial locations in working memory.NEW & NOTEWORTHY A substantial body of work has shown that patterns of EEG α-band activity track the angular coordinates of attended and remembered stimuli around fixation, but whether these patterns track the two-dimensional coordinates of stimuli presented within a visual hemifield remains an open question. Here, we demonstrate that α-band activity tracks the two-dimensional coordinates of remembered stimuli within a hemifield, showing that α-band activity reflects a spotlight of attention focused on locations maintained in working memory.

Performance Monitoring during Visual Priming.

Repetitive performance of single-feature (efficient or pop-out) visual search improves RTs and accuracy. This phenomenon, known as priming of pop-out, has been demonstrated in both humans and macaque monkeys. We investigated the relationship between performance monitoring and priming of pop-out. Neuronal activity in the supplementary eye field (SEF) contributes to performance monitoring and to the generation of performance monitoring signals in the EEG. To determine whether priming depends on performance monitoring, we investigated spiking activity in SEF as well as the concurrent EEG of two monkeys performing a priming of pop-out task. We found that SEF spiking did not modulate with priming. Surprisingly, concurrent EEG did covary with priming. Together, these results suggest that performance monitoring contributes to priming of pop-out. However, this performance monitoring seems not mediated by SEF. This dissociation suggests that EEG indices of performance monitoring arise from multiple, functionally distinct neural generators.

Visual working memory buffers information retrieved from visual long-term memory.

Human memory is thought to consist of long-term storage and short-term storage mechanisms, the latter known as working memory. Although it has long been assumed that information retrieved from long-term memory is represented in working memory, we lack neural evidence for this and need neural measures that allow us to watch this retrieval into working memory unfold with high temporal resolution. Here, we show that human electrophysiology can be used to track information as it is brought back into working memory during retrieval from long-term memory. Specifically, we found that the retrieval of information from long-term memory was limited to just a few simple objects' worth of information at once, and elicited a pattern of neurophysiological activity similar to that observed when people encode new information into working memory. Our findings suggest that working memory is where information is buffered when being retrieved from long-term memory and reconcile current theories of memory retrieval with classic notions about the memory mechanisms involved.

The Contralateral Delay Activity Tracks the Sequential Loading of Objects into Visual Working Memory, Unlike Lateralized Alpha Oscillations.

Visual working memory temporarily represents a continuous stream of task-relevant objects as we move through our environment performing tasks. Previous work has identified candidate neural mechanisms of visual working memory storage; however, we do not know which of these mechanisms enable the storage of objects as we sequentially encounter them in our environment. Here, we measured the contralateral delay activity (CDA) and lateralized alpha oscillations as human subjects were shown a series of objects that they needed to remember. The amplitude of CDA increased following the presentation of each to-be-remembered object, reaching asymptote at about three to four objects. In contrast, the concurrently measured lateralized alpha power remained constant with each additional object. Our results suggest that the CDA indexes the storage of objects in visual working memory, whereas lateralized alpha suppression indexes the focusing of attention on the to-be-remembered objects.

Electrophysiological and behavioral evidence for attentional up-regulation, but not down-regulation, when encoding pictures into long-term memory.

Visual long-term memory allows us to store a virtually infinite amount of visual information (Brady, Konkle, Alvarez, & Oliva in Proceedings of the National Academy of Sciences of the United States of America, 105(38), 14325-14329, 2008; Standing in Quarterly Journal of Experimental Psychology, 25(2), 207-222, 1973). However, our ability to encode new visual information fluctuates from moment to moment. In Experiment 1, we tested the hypothesis that we have voluntary control over these periodic fluctuations in our ability to encode representations into visual long-term memory using a precueing paradigm combined with behavioral and electrophysiological indices of memory encoding. We found that visual memory encoding can be up-regulated, but it was much more difficult, if not impossible, to down-regulate encoding on a trial-by-trial basis. In Experiment 2, we tested the hypothesis that voluntary up-regulation of visual memory encoding for an item incurs a cost to memory encoding of other items by manipulating the cueing probability. Here, we found that, although the cueing benefit was constant for both low (20%) and high (50%) cueing probabilities, the benefit in the high cueing probability condition came with the overall impairment of memory encoding. Taken together, our findings demonstrate that top-down control of visual long-term memory encoding may be primarily to prioritize certain memories, but this prioritization has a cost and should not be overused to avoid its negative consequences.

Enhancing long-term memory with stimulation tunes visual attention in one trial.

Scientists have long proposed that memory representations control the mechanisms of attention that focus processing on the task-relevant objects in our visual field. Modern theories specifically propose that we rely on working memory to store the object representations that provide top-down control over attentional selection. Here, we show that the tuning of perceptual attention can be sharply accelerated after 20 min of noninvasive brain stimulation over medial-frontal cortex. Contrary to prevailing theories of attention, these improvements did not appear to be caused by changes in the nature of the working memory representations of the search targets. Instead, improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory. We found that this pattern of effects was reliably observed when we stimulated medial-frontal cortex, but when we stimulated posterior parietal cortex, we found that stimulation directly affected the perceptual processing of the search array elements, not the memory representations providing top-down control. Our findings appear to challenge dominant theories of attention by demonstrating that changes in the storage of target representations in long-term memory may underlie rapid changes in the efficiency with which humans can find targets in arrays of objects.

Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain.

Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.

Medial-Frontal Stimulation Enhances Learning in Schizophrenia by Restoring Prediction Error Signaling.

Posterror learning, associated with medial-frontal cortical recruitment in healthy subjects, is compromised in neuropsychiatric disorders. Here we report novel evidence for the mechanisms underlying learning dysfunctions in schizophrenia. We show that, by noninvasively passing direct current through human medial-frontal cortex, we could enhance the event-related potential related to learning from mistakes (i.e., the error-related negativity), a putative index of prediction error signaling in the brain. Following this causal manipulation of brain activity, the patients learned a new task at a rate that was indistinguishable from healthy individuals. Moreover, the severity of delusions interacted with the efficacy of the stimulation to improve learning. Our results demonstrate a causal link between disrupted prediction error signaling and inefficient learning in schizophrenia. These findings also demonstrate the feasibility of nonpharmacological interventions to address cognitive deficits in neuropsychiatric disorders. SIGNIFICANCE STATEMENT: When there is a difference between what we expect to happen and what we actually experience, our brains generate a prediction error signal, so that we can map stimuli to responses and predict outcomes accurately. Theories of schizophrenia implicate abnormal prediction error signaling in the cognitive deficits of the disorder. Here, we combine noninvasive brain stimulation with large-scale electrophysiological recordings to establish a causal link between faulty prediction error signaling and learning deficits in schizophrenia. We show that it is possible to improve learning rate, as well as the neural signature of prediction error signaling, in patients to a level quantitatively indistinguishable from that of healthy subjects. The results provide mechanistic insight into schizophrenia pathophysiology and suggest a future therapy for this condition.

Distinct neural mechanisms for spatially lateralized and spatially global visual working memory representations.

Visual working memory (VWM) allows humans to actively maintain a limited amount of information. Whereas previous electrophysiological studies have found that lateralized event-related potentials (ERPs) track the maintenance of information in VWM, recent imaging experiments have shown that spatially global representations can be read out using the activity across the visual cortex. The goal of the present study was to determine whether both lateralized and spatially global electrophysiological signatures coexist. We first show that it is possible to simultaneously measure lateralized ERPs that track the number of items held in VWM from one visual hemfield and parietooccipital α (8-12 Hz) power over both hemispheres indexing spatially global VWM representations. Next, we replicated our findings and went on to show that this bilateral parietooccipital α power as well as the contralaterally biased ERP correlate of VWM carries a signal that can be used to decode the identity of the representations stored in VWM. Our findings not only unify observations across electrophysiology and imaging techniques but also suggest that ERPs and α-band oscillations index different neural mechanisms that map on to lateralized and spatially global representations, respectively.

Attention's Accelerator.

How do people get attention to operate at peak efficiency in high-pressure situations? We tested the hypothesis that the general mechanism that allows this is the maintenance of multiple target representations in working and long-term memory. We recorded subjects' event-related potentials (ERPs) indexing the working memory and long-term memory representations used to control attention while performing visual search. We found that subjects used both types of memories to control attention when they performed the visual search task with a large reward at stake, or when they were cued to respond as fast as possible. However, under normal circumstances, one type of target memory was sufficient for slower task performance. The use of multiple types of memory representations appears to provide converging top-down control of attention, allowing people to step on the attentional accelerator in a variety of high-pressure situations.

Causal control of medial-frontal cortex governs electrophysiological and behavioral indices of performance monitoring and learning.

Adaptive human behavior depends on the capacity to adjust cognitive processing after an error. Here we show that transcranial direct current stimulation of medial-frontal cortex provides causal control over the electrophysiological responses of the human brain to errors and feedback. Using one direction of current flow, we eliminated performance-monitoring activity, reduced behavioral adjustments after an error, and slowed learning. By reversing the current flow in the same subjects, we enhanced performance-monitoring activity, increased behavioral adjustments after an error, and sped learning. These beneficial effects fundamentally improved cognition for nearly 5 h after 20 min of noninvasive stimulation. The stimulation selectively influenced the potentials indexing error and feedback processing without changing potentials indexing mechanisms of perceptual or response processing. Our findings demonstrate that the functioning of mechanisms of cognitive control and learning can be up- or down-regulated using noninvasive stimulation of medial-frontal cortex in the human brain.

Microcircuitry of agranular frontal cortex: testing the generality of the canonical cortical microcircuit.

We investigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single- or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways.

Predicting and Improving Recognition Memory Using Multiple Electrophysiological Signals in Real Time.

Although people are capable of storing a virtually infinite amount of information in memory, their ability to encode new information is far from perfect. The quality of encoding varies from moment to moment and renders some memories more accessible than others. Here, we were able to forecast the likelihood that a given item will be later recognized by monitoring two dissociable fluctuations of the electroencephalogram during encoding. Next, we identified individual items that were poorly encoded, using our electrophysiological measures in real time, and we successfully improved the efficacy of learning by having participants restudy these items. Thus, our memory forecasts using multiple electrophysiological signals demonstrate the feasibility and the effectiveness of using real-time monitoring of the moment-to-moment fluctuations of the quality of memory encoding to improve learning.