Single-Neuron Correlates of Awareness during Attentional Blinks

A recent single-neuron study revealed an anatomical anterior-to-posterior gradient of awareness-related responses by ‘concept neurons’ in the human medial temporal lobe (MTL). Delayed and weaker responses were indicative of the failure of a stimulus to reach awareness, suggesting that reliable fast responses are a critical aspect of the neural mechanisms of consciousness

Single-Neuron Correlates of Awareness during Attentional Blinks

A recent single-neuron study revealed an anatomical anterior-to-posterior gradient of awareness-related responses by ‘concept neurons’ in the human medial temporal lobe (MTL). Delayed and weaker responses were indicative of the failure of a stimulus to reach awareness, suggesting that reliable fast responses are a critical aspect of the neural mechanisms of consciousness

Representations of Action Monitoring and Cognitive Control by Single Neurons in the Human Brain

Cognitive control arises whenever a prepotent and often automatic response needs to be overcome by another response. Control is usually effortful and relies on monitoring processes that detect when control is needed and/or when it failed. Control is one of the most important aspects of human behavior in everyday life and is a critical component of executive function. In a series of three empirical chapters, I present results from invasive single-neuron recordings from the frontal cortex of neurosurgical human patients while they perform tasks requiring cognitive control. I show that a substantial proportion of neurons in the pre-supplementary motor area (pre-SMA), and in the dorsal anterior cingulate cortex (dACC), signal response errors shortly after they occurred, but well before onset of feedback. Here I demonstrate that these error neurons signal self-detected errors and that they were separate from neurons signaling conflict. The response of error neurons correlated trial-by-trial with the simultaneously recorded intracranial error-related negativity (iERN), thereby establishing a single-neuron correlate of this important scalp potential. iERN-error neuron synchrony in dACC, but not pre-SMA, predicted whether post-error slowing, which is a measure of control, occurred or not. Spike-field coherence between action potentials and local field potentials in specific frequency bands, and latency differences between the different brain regions, suggest a mechanistic model whereby information relevant to control is passed between sectors of the medial frontal cortex. Multiplexing of different ex-post monitoring signals by individual neurons further documents that control relies on multiple sources of information, which can be dynamically routed in the brain depending on task demands. These findings provide the most complete set of single-neuron data on how errors and conflict signals at the single neuron level contribute to cognitive controls in humans. They provide a first-single neuron correlate of an extensively utilized scalp EEG potential. Together, this work provides a strong complement to investigations of this topic using fMRI in humans, and using electrophysiology in monkeys, and suggests specific future directions

Decision ambiguity is mediated by a late positive potential originating from cingulate cortex

People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction

Single-Neuron Correlates of Error Monitoring and Post-Error Adjustments in Human Medial Frontal Cortex

Humans can self-monitor errors without explicit feedback, resulting in behavioral adjustments on subsequent trials such as post-error slowing (PES). The error-related negativity (ERN) is a well-established macroscopic scalp EEG correlate of error self-monitoring, but its neural origins and relationship to PES remain unknown. We recorded in the frontal cortex of patients performing a Stroop task and found neurons that track self-monitored errors and error history in dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (pre-SMA). Both the intracranial ERN (iERN) and error neuron responses appeared first in pre-SMA, and ∼50 ms later in dACC. Error neuron responses were correlated with iERN amplitude on individual trials. In dACC, such error neuron-iERN synchrony and responses of error-history neurons predicted the magnitude of PES. These data reveal a human single-neuron correlate of the ERN and suggest that dACC synthesizes error information to recruit behavioral control through coordinated neural activity

Single-Neuron Correlates of Error Monitoring and Post-Error Adjustments in Human Medial Frontal Cortex

Humans can self-monitor errors without explicit feedback, resulting in behavioral adjustments on subsequent trials such as post-error slowing (PES). The error-related negativity (ERN) is a well-established macroscopic scalp EEG correlate of error self-monitoring, but its neural origins and relationship to PES remain unknown. We recorded in the frontal cortex of patients performing a Stroop task and found neurons that track self-monitored errors and error history in dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (pre-SMA). Both the intracranial ERN (iERN) and error neuron responses appeared first in pre-SMA, and ∼50 ms later in dACC. Error neuron responses were correlated with iERN amplitude on individual trials. In dACC, such error neuron-iERN synchrony and responses of error-history neurons predicted the magnitude of PES. These data reveal a human single-neuron correlate of the ERN and suggest that dACC synthesizes error information to recruit behavioral control through coordinated neural activity

Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization

Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design

Human Single Neuron Recordings

This chapter describes the history and current state-of-the-art techniques of recording from single neurons in humans. In collaboration with neurosurgeons and neurologists and while strictly adhering to ethical principles, this technique allows the study of cognitive processes in humans at the cellular level. We describe the settings within which single neuron data is commonly collected, ranging from epilepsy monitoring, deep brain stimulation surgery and brain-machine interface clinical trials. We further review technological advancement that allow simultaneous recordings of many neurons. The data collected offer unprecedented circuit-level insights into the neuronal bases of human cognition and build a bridge between animal and human neuroscience. We conclude by summarizing example findings that demonstrate the powerful scientific insights that can be revealed by human single neuron recordings