IntroductionThe prefrontal cortex plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels, a marker of neuroaxonal damage.MethodsFifty two healthy middle-aged (...) adults from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power, two measures of cortical reactivity, were quantified after left prefrontal cortex stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe was used as a control stimulation condition.ResultsLocal reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education.ConclusionOur results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function. (shrink)

The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to (...) guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed. (shrink)

The ventromedial prefrontal cortex (VMPFC) is crucial for moral behavior, yet the mechanism through which the VMPFC promotes moral behavior remains unclear. In this article, we emphasize that moral choice is often intertemporal, requiring foregoing short-term gains in favor of future outcomes of larger value. We propose that the VMPFC may be necessary for mental time travel (MTT), a cognitive process enabling vivid preexperiencing of future outcomes. By providing anticipated outcomes that inform decisions, MTT may promote farsighted, moral (...) behaviors. (shrink)

A central debate in philosophy and neuroscience pertains to whether PFC activity plays an essential role in the neural basis of consciousness. Neuroimaging and electrophysiology studies have revealed that the contents of conscious perceptual experience can be successfully decoded from PFC activity, but these findings might be confounded by post- perceptual cognitive processes, such as thinking, reasoning, and decision-making, that are not necessary for con- sciousness. To clarify the involvement of the PFC in consciousness, we present a synthesis of research (...) that has used intracranial electrical stimulation (iES) for the causal modulation of neural activity in the human PFC. This research provides compelling evidence that iES of only certain prefrontal regions (i.e., orbitofrontal cortex and anterior cingu- late cortex) reliably perturbs conscious experience. Conversely, stimulation of anterolateral prefrontal sites, often con- sidered crucial in higher-order and global workspace theories of consciousness, seldom elicits any reportable alterations in consciousness. Furthermore, the wide variety of iES-elicited effects in the PFC (e.g., emotions, thoughts, and olfactory and visual hallucinations) exhibits no clear relation to the immediate environment. Therefore, there is no evidence for the kinds of alterations in ongoing perceptual experience that would be predicted by higher-order or global workspace theories. Nevertheless, effects in the orbitofrontal and anterior cingulate cortices suggest a specific role for these PFC subregions in supporting emotional aspects of conscious experience. Overall, this evidence presents a challenge for higher-order and global workspace theories, which commonly point to the PFC as the basis for con- scious perception based on correlative and possibly confounded information. (shrink)

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ (...) pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements. (shrink)

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex and the amygdala are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8–22 years participated in this study; each participant completed a computer-based food choice task and a (...) T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index and waist-to-height ratio. The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant’s self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary “self-control” was calculated as the proportion of trials where the individual chose the healthier food item over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions. We also found WHtR to be positively associated with the volume of the central nucleus region of the amygdala, after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity. (shrink)

The role of the prefrontal cortex is one of the most topical and important areas of research in contemporary neuropsychology. This cortical region appears to be linked with executive processes affecting many diverse areas of cognitive function. Working memory, information processing, behavioural organization, attention, judgement, and the ability to cope with novel experiences are just some of the diverse processes it affects. This book brings together contributions from some of the world's leading researchers on the prefrontal (...) class='Hi'>cortex. They discuss the many recent theoretical and technical advances in the field - for example in our understanding of the neural architecture of the prefrontal cortex, in the development of comparable texts of cognition in humans and other primates, in our understanding of the relationships between neuronal activity and behaviour, and in the increasing use of functional neuroimaging to identify different levels of organization within the prefrontal cortex. These important developments make this an ideal time to address the many questions and debates that have arisen about the role and functional organization of this area of the brain. One of the first books to be written on the subject, The Prefrontal Cortex is a state-of-the-art account of our knowledge of this exciting subject. It will be welcomed by all researchers and students in neuro- and cognitive psychology, and neuroscience. (shrink)

Is perceptual processing in dedicated sensory areas sufficient for conscious perception? Localists say ‘Yes—given some background conditions.’ Prefrontalists say ‘No: conscious perceptual experience requires the involvement of prefrontal structures.’ I review the evidence for prefrontalism. I start by presenting correlational evidence. In doing so, I answer the ‘report argument’, according to which the apparent involvement of the prefrontal cortex in consciousness stems from the requirement for reports. I then review causal evidence for prefrontalism and answer the ‘lesion (...) argument’, which purports to show that prefrontalism is wrong because lesions to the prefrontal cortex do not abolish consciousness. I conclude that multiple sources of evidence converge toward the view that the prefrontal cortex plays a significant role in consciousness. (shrink)

Training under high interference conditions through interleaved practice results in performance suppression during training but enhances long-term performance relative to repetitive practice involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent response using functional magnetic resonance imaging methodology resulting in mixed reports of prefrontal cortex recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy while (...) discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance. (shrink)

Moral judgments, whether delivered in ordinary experience or in the courtroom, depend on our ability to infer intentions. We forgive unintentional or accidental harms and condemn failed attempts to harm. Prior work demonstrates that patients with damage to the ventromedial prefrontal cortex deliver abnormal judgments in response to moral dilemmas and that these patients are especially impaired in triggering emotional responses to inferred or abstract events, as opposed to real or actual outcomes. We therefore predicted that VMPC patients (...) would deliver abnormal moral judgments of harmful intentions in the absence of harmful outcomes, as in failed attempts to harm. This prediction was confirmed in the current study: VMPC patients judged attempted harms, including attempted murder, as more morally permissible relative to controls. These results highlight the critical role of the VMPC in processing harmful intent for moral judgment. (shrink)

In this commentary, the formation of “pre-iconic” visual-prime persistence is described in the context of prime-specific, independent-component activation at prefrontal and posterior EEG-recording sites. Although this activity subserves neural systems that are near identical to those described by Ruchkin and colleagues, we consider priming to be a dynamic process, identified with patterns of coherence and temporal structure of very high precision.

Background: Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness.

Exposure Therapy (ET) has demonstrated its efficacy in the treatment of phobias, anxiety and Post-traumatic Stress Disorder (PTSD), however, it suffers a high drop-out rate because of too low or too high patient engagement in treatment. Virtual Reality Exposure Therapy (VRET) is comparably effective regarding symptom reduction and offers an alternative tool to facilitate engagement for avoidant participants. Neuroimaging studies have demonstrated that both ET and VRET normalize brain activity within a fear circuit. However, previous studies have employed brain imaging (...) technology which restricts people’s movement and hides their body, surroundings and therapist from view. This is at odds with the way engagement is typically controlled. We used a novel combination of neural imaging and VR technology—Functional Near-Infrared Spectroscopy (fNIRS) and Immersive Projection Technology (IPT), to avoid these limitations. Although there are a few studies that have investigated the effect of VRET on a brain function after the treatment, the present study utilized technologies which promote ecological validity to measure brain changes after VRET treatment. Furthermore, there are no studies that have measured brain activity within VRET session. In this study brain activity within the prefrontal cortex (PFC) was measured during three consecutive exposure sessions. N = 13 acrophobic volunteers were asked to walk on a virtual plank with a 6 m drop below. Changes in oxygenated (HbO) hemogl... (shrink)

Whether the prefrontal cortex is part of the neural substrates of consciousness is currently debated. Against prefrontal theories of consciousness, many have argued that neural activity in the prefrontal cortex does not correlate with consciousness but with subjective reports. We defend prefrontal theories of consciousness against this argument. We surmise that the requirement for reports is not a satisfying explanation of the difference in neural activity between conscious and unconscious trials, and that prefrontal (...) theories of consciousness come out of this debate unscathed. (shrink)

On the basis of neuroiinaging studies, Posner & Raichle summarily report that the prefrontal cortex is involved in executive functioning and attention. In contrast to that superficial view, we briefly describe a testable model of the kinds of representations that are stored in prefrontal cortex, which, when activated, are expressed via plans, actions, thematic knowledge, and schemas.

Many studies have discussed the neural basis of asset bubbles. They found that the dorsolateral prefrontal cortex (DLPFC) played an important role in bubble formation, but whether a causal relationship exists and the mechanism of the effect of the DLPFC on bubbles remains unsettled. Using transcranial direct current stimulation (tDCS), we modulated the activity of the DLPFC and investigated the causal relationship between the DLPFC and the asset bubble in the classical learning-to-forecast experiment. 126 subjects were randomly divided (...) into three groups and received different stimulations (left anodal/right cathodal, right anodal/left cathodal or sham stimulation) respectively. We also conducted a 2-back task before and after stimulation to measure changes in subjects’ cognitive abilities and explore in detail the cognitive mechanism of the effect of DLPFC stimulation on asset bubbles. Based on our results, we found that the bubble of the left anodal/right cathodal stimulation group was significantly smaller than that of the sham stimulation group. In the meantime, subjects performed significantly better in the 2-back task after left anodal/right cathodal stimulation but not right anodal/left cathodal or sham stimulation, which is consistent with their performance in the learning-to-forecast experiment, supporting the cognitive mechanism to some extent. Furthermore, we examined different forecasting rules across individuals and discovered that the left anodal/right cathodal stimulation group preferred the adaptive learning rule, while the sham and right anodal/left cathodal stimulation groups adopted a pure trend-following rule that tended to intensify market volatility aggressively. (shrink)

Trends in moral psychology largely support the role that emotion plays in moral cognition with human lesion studies offering the most compelling evidence to date. Specifically, data from ventromedial prefrontal cortex (vmPFC) patients on moral judgment tasks has suggested the necessity of having intact emotion to behave in morally appropriate ways. However, patients with vmPFC damage also have deficits in a variety of complex judgment and decision-making tasks, regardless of whether emotion is involved. This paper argues that a (...) basic information processing perspective of vmPFC functionality is a better interpretation of vmPFC patient deficits, specifically with the vmPFC being necessary for value assessment rather than being specific to emotion. (shrink)

One of the most pressing questions concerning singular demonstrative mental contents is what makes their content singular: that is to say, what makes it the case that individual objects are the representata of these mental states. Many philosophers have required sophisticated intellectual capacities for singular content to be possible, such as the possession of an elaborate scheme of space and time. A more recent reaction to this strategy proposes to account for singular content solely on the basis of empirical models (...) of visual processing. We believe both sides make good points, and offer an intermediate way of looking into singular content. Our suggestion is that singular content may be traced to psychological capacities to form flexible, abstract representations in the prefrontal cortex. This allows them to be sustained for increasingly longer periods of time and extrapolated beyond the context of perception, thus going beyond lowlevel sensory representations while also falling short of more sophisticated intellectual abilities. (shrink)

The human self model suggests that the construct of self involves functions such as agency, body-centered spatial perspectivity, and long-term unity. Vogeley, Kurthen, Falkai, and Maieret (1999) suggest that agency is subserved by the prefrontal cortex and other association areas of the cortex, spatial perspectivity by the prefrontal cortex and the parietal lobes, and long-term unity by the prefrontal cortex and the temporal lobes and that all of these functions are impaired in schizophrenia. (...) Exploring the connections between the prefrontal cortex and the construct of self, the present article extends the application of the self model to autism. It suggests that in contrast to schizophrenia, agency and spatial perspectivity are probably preserved in autism, but that, similarly to schizophrenia, long-term unity is probably impaired. This hypothesis is compatible with a model of neuropsychological dysfunction in autism in a neural network including parts of the prefrontal cortex, the temporal lobes, and the cerebellum. (shrink)

Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns (...) of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. (shrink)

The role of prefrontal cortex (PFC) in influencing creative thinking has been investigated by many researchers who, while succeeding in proving an effective involvement of PFC, reported suggestive but sometimes conflicting results. In order to better understand the relationships between creative thinking and brain activation in a more specific area of the PFC, we explored the role of dorsolateral PFC. We devised an experimental protocol using transcranial direct-current stimulation (tDCS). The study was based on a 3 (kind of (...) stimulation: anodal vs. cathodal vs. sham) X 2 (priming: divergent vs. convergent) design. Forty-five healthy adults were randomly assigned to one stimulation condition. Participants’ creativity skills were assessed using the Product Improvement subtest from the Torrance Tests of Creative Thinking. After 20 minutes of tDCS stimulation, participants were presented with visual images of common objects. Half of the participants were instructed to visualize themselves using the object in an unusual way (divergent priming), whereas the other half were asked to visualize themselves while using the object in a common way (convergent priming). Priming was aimed at inducing participants to adopt different attitudes toward the creative task. Afterwards, participants were asked to describe all of the possible uses of the objects that were presented. Participants’ physiological activation was recorded using a biofeedback equipment. Results showed a significant effect of anodal stimulation that enhanced creative performance, but only after divergent priming. Participants showed lower skin temperature values after cathodal stimulation, a findings which is coherent with studies reporting that, when a task is not creative or creative thinking is not prompted, people show lower levels of arousal. The involvement of dorsolateral PFC in creativity has been supported, presumably in association to shift of attention modulated by priming. (shrink)

The Fist-Edge-Palm task, a manual hand task, has been used to detect frontal dysfunctions in clinical situations: its performance failures are observed in various prefrontal cortex -related disorders, including schizophrenia. However, previous imaging studies reported that the performance of the FEP task activated motor-related areas, but not the PFC. Here, we aimed to investigate the relationships between the performance of the FEP task and PFC functions. Hemodynamic activity in the PFC, including the dorsolateral PFC and frontal pole, was (...) recorded. Healthy young subjects performed the FEP task as well as a palm tapping task three times. The subjects also completed a Wisconsin Card Sorting Test and Schizotypal Personality Scale questionnaire. We found that hemodynamic activity in the PFC increased in the first trial of the FEP task but decreased considerably in the second and third trials compared to the PT task. The number of performance errors in the FEP task also decreased in the second and third trials. Error reduction in the FEP task between the first and second trials was negatively correlated with schizotypal trait and the number of perseveration errors in the WCST. Furthermore, changes in the PFC hemodynamic activity between the first and second trials were positively correlated with error reduction in the FEP task between the first and second trials, and negatively correlated with the number of perseveration errors in the WCST. These results suggest that learning in the FEP task requires PFC activation, which is negatively associated with perseveration errors in the WCST. The results further suggest that the FEP task, in conjunction with near-infrared spectroscopy, may be useful as a diagnostic method for various disorders with PFC dysfunction. (shrink)

The tension between focusing on species similarities versus species differences (phylogenetic versus adaptationist approaches) recurs in discussions about the nature of neural connectivity and organization following brain expansion. Whereas Striedter suggests a primary role for response inhibition, other possibilities include dense recurrent connectivity loops. Computer simulations and brain imaging technologies are crucial in better understanding actual neuronal connectivity patterns.