Human Medial Frontal Cortex Research Articles

Neural dynamics underlying minute-timescale persistent behavior in the human brain.

The ability to pursue long-term goals relies on a representations of task context that can both be maintained over long periods of time and switched flexibly when goals change. Little is known about the neural substrate for such minute-scale maintenance of task sets. Utilizing recordings in neurosurgical patients, we examined how groups of neurons in the human medial frontal cortex and hippocampus represent task contexts. When cued explicitly, task context was encoded in both brain areas and changed rapidly at task boundaries. Hippocampus exhibited a temporally dynamic code with fast decorrelation over time, preventing cross-temporal generalization. Medial frontal cortex exhibited a static code that decorrelated slowly, allowing generalization across minutes of time. When task context needed to be inferred as a latent variable, hippocampus encoded task context with a static code. These findings reveal two possible regimes for encoding minute-scale task-context representations that were engaged differently based on task demands.

Neurophysiological mechanisms of error monitoring in human and non-human primates.

Performance monitoring is an important executive function that allows us to gain insight into our own behaviour. This remarkable ability relies on the frontal cortex, and its impairment is an aspect of many psychiatric diseases. In recent years, recordings from the macaque and human medial frontal cortex have offered a detailed understanding of the neurophysiological substrate that underlies performance monitoring. Here we review the discovery of single-neuron correlates of error monitoring, a key aspect of performance monitoring, in both species. These neurons are the generators of the error-related negativity, which is a non-invasive biomarker that indexes error detection. We evaluate a set of tasks that allows the synergistic elucidation of the mechanisms of cognitive control across the two species, consider differences in brain anatomy and testing conditions across species, and describe the clinical relevance of these findings for understanding psychopathology. Last, we integrate the body of experimental facts into a theoretical framework that offers a new perspective on how error signals are computed in both species and makes novel, testable predictions.

The geometry of domain-general performance monitoring in the human medial frontal cortex.

Controlling behavior to flexibly achieve desired goals depends on the ability to monitor one's own performance. It is unknown how performance monitoring can be both flexible, to support different tasks, and specialized, to perform each task well. We recorded single neurons in the human medial frontal cortex while subjects performed two tasks that involve three types of cognitive conflict. Neurons encoding conflict probability, conflict, and error in one or both tasks were intermixed, forming a representational geometry that simultaneously allowed task specialization and generalization. Neurons encoding conflict retrospectively served to update internal estimates of conflict probability. Population representations of conflict were compositional. These findings reveal how representations of evaluative signals can be both abstract and task-specific and suggest a neuronal mechanism for estimating control demand.

The Geometry of Domain-General Performance Monitoring in the Human Medial Frontal Cortex

Flexibly controlling behavior to achieve a desired goal depends on the ability to monitor one’s own performance. A key open question is how performance monitoring can be both flexible to support multiple tasks and specialized to support specific tasks. We characterized performance monitoring representations by recording single neurons in the human medial frontal cortex (MFC). Subjects performed two tasks that involve three types of cognitive conflict. Neurons encoding error, conflict and predicted control demand in one or both tasks coexisted in the same population. Collectively, they gave rise to a representational geometry that simultaneously allowed task specialization and generalization. Representations of conflicts were compositional. Neurons encoding conflict retrospectively served to update estimates of control demand as predicted by a Bayesian model. These findings reveal how the MFC representation of evaluative signals are both abstract and specific, suggesting a mechanism for computing and maintaining control demand estimates across trials and tasks.

Divergence of rodent and primate medial frontal cortex functional connectivity

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.

Flexible recruitment of memory-based choice representations by the human medial frontal cortex.

Decision-making in complex environments relies on flexibly using prior experience. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe, but it remains unknown how these structures implement selective memory retrieval. We recorded single neurons in the MFC, amygdala, and hippocampus while human subjects switched between making recognition memory-based and categorization-based decisions. The MFC rapidly implemented changing task demands by using different subspaces of neural activity and by representing the currently relevant task goal. Choices requiring memory retrieval selectively engaged phase-locking of MFC neurons to amygdala and hippocampus field potentials, thereby enabling the routing of memories. These findings reveal a mechanism for flexibly and selectively engaging memory retrieval and show that memory-based choices are preferentially represented in the frontal cortex when required.

Electroencephalographic evidence for a reinforcement learning advantage during motor skill acquisition

The feedback that we receive shapes how we learn. Previous research has demonstrated that quantitative feedback results in better performance than qualitative feedback. However, the data supporting a quantitative feedback advantage are not conclusive and further little work has been done to examine the mechanistic neural differences that underlie the relative benefits of quantitative and qualitative feedback. To address these issues, participants learned a simple motor task in quantitative and qualitative feedback conditions while electroencephalographic (EEG) data were recorded. We found that participants were more accurate and had a larger neural response – the feedback related negativity - when qualitative feedback was provided. Our data suggest that qualitative feedback is more advantageous than quantitative feedback during the early stages of skill acquisition. Additionally, our findings support previous work suggesting that a reinforcement learning system within the human medial-frontal cortex plays a key role in motor skill acquisition.

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 ∼50ms 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.

Variations of cingulate sulcal organization and link with cognitive performance

The sulcal morphology of the human medial frontal cortex has received marked interest because of (1) its remarkable link with the functional organization of this region, and (2) observations that deviations from ‘normal’ sulcal morphological variability correlate with the prevalence of some psychiatric disorders, cognitive abilities, or personality traits. Unfortunately, background studies on environmental or genetic factors influencing the ontogenesis of the sulcal organization in this region are critically lacking. We analysed the sulcal morphological organization in this region in twins and non-twin siblings, as well as in control subjects for a total of 599 subjects from the Human Connectome Project. The data first confirm significant biases in the presence of paracingulate sulci in left vs right hemispheres in the whole population (twin: p < 2.4.10−9; non-twin: p < 2.10−6) demonstrating a clear general laterality in human subjects. Second, measures of similarity between siblings and estimations of heritability suggest significant environmental factors, in particular in-womb environment, and weak additive genetic factors influencing the presence of a paracingulate sulcus. Finally, we found that relationships between sulcal organization and performance in cognitive, motor, and affective tests depend on the twin status (Twins versus Non-twins). These results provide important new insights to the issue of the significance of sulcal organization in the human medial frontal cortex.

Older adults display diminished error processing and response in a continuous tracking task.

Advancing age is often accompanied by a decline in motor control that results in a decreased ability to successfully perform motor tasks. While there are multiple factors that contribute to age-related deficits in motor control, one unexplored possibility is that age-related deficits in our ability to evaluate motor output result in an increase in motor errors. In line with this, previous work from our laboratory demonstrated that motor errors evoked an error-related negativity (ERN)-a component of the human ERP associated with error evaluation originating within the human medial-frontal cortex. In the present study, we examined whether or not deficits in the medial-frontal error evaluation system contribute to age-related deficits in motor control. Two groups of participants (young, old) performed a computer-based tracking task that paralleled driving while EEG data were recorded. Our results show that older adults committed more behavioral errors than young adults during performance of the tracking task. An analysis of our ERP data revealed that the amplitude of the ERN was reduced in older adults relative to young adults following motor errors. Our results make an important extension from previous work demonstrating age-related reductions in the ERN during performance of cognitive tasks. Importantly, our results imply the possibility of understanding motor deficits in older age.

Persistently active neurons in human medial frontal and medial temporal lobe support working memory.

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.

We are more selfish than we think: The endowment effect and reward processing within the human medial-frontal cortex.

Perceived ownership has been shown to impact a variety of cognitive processes: attention, memory, and--more recently--reward processing. In the present experiment we examined whether or not perceived ownership would interact with the construct of value-the relative worth of an object. Participants completed a simple gambling game in which they gambled either for themselves or for another while electroencephalographic data were recorded. In a key manipulation, gambles for oneself or for another were for either small or large rewards. We tested the hypothesis that value affects the neural response to self-gamble outcomes, but not other-gamble outcomes. Our experimental data revealed that while participants learned the correct response option for both self and other gambles, the reward positivity evoked by wins was impacted by value only when gambling for oneself. Importantly, our findings provide additional evidence for a self-ownership bias in cognitive processing and further demonstrate the insensitivity of the medial-frontal reward system to gambles for another.

Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization.

The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2-4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex using relatively unbiased data-driven methods. This approach revealed three distinct zones that differed substantially in function, each of which were further subdivided into 2-4 smaller subregions that showed additional functional variation. Each individual region was recruited by multiple psychological states, suggesting subregions of medial frontal cortex are functionally heterogeneous.

The scarcity heuristic impacts reward processing within the medial-frontal cortex.

Objects that are rare are often perceived to be inherently more valuable than objects that are abundant - a bias brought about in part by the scarcity heuristic. In the present study, we sought to test whether perception of rarity impacted reward evaluation within the human medial-frontal cortex. Here, participants played a gambling game in which they flipped rare and abundant 'cards' on a computer screen to win financial rewards while electroencephalographic data were recorded. Unbeknownst to participants, reward outcome and frequency was random and equivalent for both rare and abundant cards; thus, only a perception of scarcity was true. Analysis of the electroencephalographic data indicated that the P300 component of the event-related brain potential differed in amplitude for wins and losses following the selection of rare cards, but not following the selection of abundant cards. Importantly, then, we found that the perception of card rarity impacted reward processing even though reward feedback was independent of and subsequent to card selection. Our data indicate a top-down influence of the scarcity heuristic on reward evaluation, and specifically the processing of reward magnitude, within the human medial-frontal cortex.

The impact of cognitive load on reward evaluation

The neural systems that afford our ability to evaluate rewards and punishments are impacted by a variety of external factors. Here, we demonstrate that increased cognitive load reduces the functional efficacy of a reward processing system within the human medial–frontal cortex. In our paradigm, two groups of participants used performance feedback to estimate the exact duration of one second while electroencephalographic (EEG) data was recorded. Prior to performing the time estimation task, both groups were instructed to keep their eyes still and avoid blinking in line with well established EEG protocol. However, during performance of the time-estimation task, one of the two groups was provided with trial-to-trial-feedback about their performance on the time-estimation task and their eye movements to induce a higher level of cognitive load relative to participants in the other group who were solely provided with feedback about the accuracy of their temporal estimates. In line with previous work, we found that the higher level of cognitive load reduced the amplitude of the feedback-related negativity, a component of the human event-related brain potential associated with reward evaluation within the medial–frontal cortex. Importantly, our results provide further support that increased cognitive load reduces the functional efficacy of a neural system associated with reward processing.

Watch out! Medial frontal cortex is activated by cues signaling potential changes in response demands

The human medial frontal cortex and especially the anterior cingulate cortex (ACC) have been implicated in several aspects of performance monitoring. We examined event-related EEG during a general process of controlling attention by using a novel paradigm to elicit a medial frontal negativity (MFN) to stimuli that indicate potential changes in future response demands. Independent components analysis revealed that the latent factors that accounted for MFN activity to such changes also accounted for activity associated with the error-related negativity and the NoGo inhibitory N2. Given that the medial frontal activation to these changes varied reliably across subjects simply as a function of potential need to alter responses in the absence of error commission and response inhibition, we propose that the underlying basis for medial frontal activation in situations demanding ongoing monitoring of performance involves an increase in attention control, a factor common to all MFN paradigms.

Genetic sculpture of fine-grained human cortical regionalization

Genetic sculpture of fine-grained human cortical regionalization

Updating Expected Action Outcome in the Medial Frontal Cortex Involves an Evaluation of Error Type

Forming expectations about the outcome of an action is an important prerequisite for action control and reinforcement learning in the human brain. The medial frontal cortex (MFC) has been shown to play an important role in the representation of outcome expectations, particularly when an update of expected outcome becomes necessary because an error is detected. However, error detection alone is not always sufficient to compute expected outcome because errors can occur in various ways and different types of errors may be associated with different outcomes. In the present study, we therefore investigate whether updating expected outcome in the human MFC is based on an evaluation of error type. Our approach was to consider an electrophysiological correlate of MFC activity on errors, the error-related negativity (Ne/ERN), in a task in which two types of errors could occur. Because the two error types were associated with different amounts of monetary loss, updating expected outcomes on error trials required an evaluation of error type. Our data revealed a pattern of Ne/ERN amplitudes that closely mirrored the amount of monetary loss associated with each error type, suggesting that outcome expectations are updated based on an evaluation of error type. We propose that this is achieved by a proactive evaluation process that anticipates error types by continuously monitoring error sources or by dynamically representing possible response-outcome relations.

The organization of dorsal frontal cortex in humans and macaques.

The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for "new" regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed.

Perceptual learning and decision making in human medial frontal cortex

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