Rostromedial Prefrontal Cortex Research Articles

Effects of transcranial magnetic stimulation of the rostromedial prefrontal cortex in obsessive–compulsive disorder: a randomized clinical trial

Effects of transcranial magnetic stimulation of the rostromedial prefrontal cortex in obsessive–compulsive disorder: a randomized clinical trial

Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder

BackgroundBorderline personality disorder (BPD) is characterized by an elevated distress response to social exclusion (i.e., rejection distress), the neural mechanisms of which remain unclear. Functional magnetic resonance imaging studies of social exclusion have relied on the classic version of the Cyberball task, which is not optimized for functional magnetic resonance imaging. Our goal was to clarify the neural substrates of rejection distress in BPD using a modified version of Cyberball, which allowed us to dissociate the neural response to exclusion events from its modulation by exclusionary context. MethodsTwenty-three women with BPD and 22 healthy control participants completed a novel functional magnetic resonance imaging modification of Cyberball with 5 runs of varying exclusion probability and rated their rejection distress after each run. We tested group differences in the whole-brain response to exclusion events and in the parametric modulation of that response by rejection distress using mass univariate analysis. ResultsAlthough rejection distress was higher in participants with BPD (F1,40 = 5.25, p = .027, η2 = 0.12), both groups showed similar neural responses to exclusion events. However, as rejection distress increased, the rostromedial prefrontal cortex response to exclusion events decreased in the BPD group but not in control participants. Stronger modulation of the rostromedial prefrontal cortex response by rejection distress was associated with higher trait rejection expectation, r = −0.30, p = .050. ConclusionsHeightened rejection distress in BPD might stem from a failure to maintain or upregulate the activity of the rostromedial prefrontal cortex, a key node of the mentalization network. Inverse coupling between rejection distress and mentalization-related brain activity might contribute to heightened rejection expectation in BPD.

Resting-state functional connectivity predicts motor cortex stimulation-dependent pain relief in fibromyalgia syndrome patients

MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r = − 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.

Involvement of the Rostromedial Prefrontal Cortex in Human-Robot Interaction: fNIRS Evidence From a Robot-Assisted Motor Task.

Assistive exoskeleton robots are being widely applied in neurorehabilitation to improve upper-limb motor and somatosensory functions. During robot-assisted exercises, the central nervous system appears to highly attend to external information-processing (IP) to efficiently interact with robotic assistance. However, the neural mechanisms underlying this process remain unclear. The rostromedial prefrontal cortex (rmPFC) may be the core of the executive resource allocation that generates biases in the allocation of processing resources toward an external IP according to current behavioral demands. Here, we used functional near-infrared spectroscopy to investigate the cortical activation associated with executive resource allocation during a robot-assisted motor task. During data acquisition, participants performed a right-arm motor task using elbow flexion-extension movements in three different loading conditions: robotic assistive loading (ROB), resistive loading (RES), and non-loading (NON). Participants were asked to strive for kinematic consistency in their movements. A one-way repeated measures analysis of variance and general linear model-based methods were employed to examine task-related activity. We demonstrated that hemodynamic responses in the ventral and dorsal rmPFC were higher during ROB than during NON. Moreover, greater hemodynamic responses in the ventral rmPFC were observed during ROB than during RES. Increased activation in ventral and dorsal rmPFC subregions may be involved in the executive resource allocation that prioritizes external IP during human-robot interactions. In conclusion, these findings provide novel insights regarding the involvement of executive control during a robot-assisted motor task.

Manipulating Reward Sensitivity Using Reward Circuit–Targeted Transcranial Magnetic Stimulation

BackgroundThe reward circuit is important for motivation and learning, and dysregulations of the reward circuit are prominent in anhedonic depression. Noninvasive interventions that can selectively target the reward circuit may hold promise for the treatment of anhedonia. MethodsWe tested a novel transcranial magnetic stimulation intervention for modulating the reward circuit. A total of 35 healthy individuals participated in a crossover controlled study targeting the reward circuit or a control site with intermittent theta burst stimulation (iTBS), an excitatory form of transcranial magnetic stimulation. Individual reward circuit targets were defined based upon functional magnetic resonance imaging functional connectivity with the ventral striatum, yielding targets in the rostromedial prefrontal cortex (rmPFC). Reward circuit function was assessed at baseline using functional magnetic resonance imaging, and reward circuit modulation was assessed using an event-related potential referred to as the reward positivity, which has been shown to reliably track reward sensitivity, as well as individual differences in depression and risk for depression. ResultsRelative to control iTBS, rmPFC iTBS enhanced the reward positivity. This effect was moderated by reward function, suggesting greater enhancements in individuals with lower reward function. This effect was also moderated by rmPFC–ventral striatum connectivity insofar as iTBS reached the rmPFC, suggesting that efficacy relies jointly on the strength of the rmPFC–ventral striatum pathway and ability of transcranial magnetic stimulation to target the rmPFC. ConclusionsThese data suggest that the reward circuit can be modulated by rmPFC iTBS, and amenability to such modulations is related to measures of reward circuit function. This provides the first step toward a novel noninvasive treatment of disorders of the reward circuit.

Robust Estimation of Respiratory Variability Uncovers Correlates of Limbic Brain Activity and Transcutaneous Cervical Vagus Nerve Stimulation in the Context of Traumatic Stress.

Variations in respiration patterns are a characteristic response to distress due to underlying neurorespiratory couplings. Yet, no work to date has quantified respiration pattern variability (RPV) in the context of traumatic stress and studied its functional neural correlates - this analysis aims to address this gap. Fifty human subjects with prior traumatic experiences (24 with posttraumatic stress disorder (PTSD)) completed a ∼3-hr protocol involving personalized traumatic scripts and active/sham (double-blind) transcutaneous cervical vagus nerve stimulation (tcVNS). High-resolution positron emission tomography functional neuroimages, electrocardiogram (ECG), and respiratory effort (RSP) data were collected during the protocol. Supplementing the RSP signal with ECG-derived respiration for quality assessment and timing extraction, RPV metrics were quantified and analyzed. Specifically, correlation analyses were performed using neuroactivity in selected limbic regions, and responses to active and sham tcVNS were compared. The single-lag unscaled autocorrelation of respiration rate correlated negatively with left amygdala activity and positively with right rostromedial prefrontal cortex (rmPFC) activity for non-PTSD; it also correlated negatively with left and right insulae activity and positively with right rmPFC activity for PTSD. The single-lag unscaled autocorrelation of expiration time was greater following active stimulation for non-PTSD. Quantifying RPV is of demonstrable importance to assessing trauma-induced changes in neural function and tcVNS effects on respiratory physiology. This is the first demonstration of RPV's pertinence to traumatic stress- and tcVNS-induced neurorespiratory responses. The open-source processing pipeline elucidated herein uniquely includes both RSP and ECG-derived respiration signals for quality assessment, timing estimation, and RPV extraction.

Sex-specific alterations of cortical morphometry in treatment-naïve patients with major depressive disorder.

Major depressive disorder (MDD) shows sex differences in terms of incidence and symptoms, but the neurobiological basis underlying these sex differences remains to be clarified. High resolution T1-weighted Magnetic Resonance Imaging (MRI) scans were obtained from 123 non-comorbid treatment-naïve individuals with MDD and 81 age-, sex-, andhandedness-matched healthy controls (HCs). MRI data were preprocessed with FreeSurfer software and four cortical measures were extracted: cortical thickness (CT), surface area (SA), cortical volume (CV), and local gyrification index (LGI). We tested for both sex-specific and sex-nonspecific patterns of cortical anatomic alterations. Regardless of sex, individuals with MDD showed significantly higher LGI in posterior cortex relative to HCs. Significant sex-by-group interactions were observed, and subsequent post-hoc analyses revealed that female individuals with MDD showed significantly lower SA in left ventrolateral prefrontal cortex (vlPFC), lower CV in right rostromedial prefrontal cortex (rmPFC), and higher LGI in left visual cortex compared with sex-matched HCs, whereas the opposite patterns of significant effects were seen in male individuals with MDD relative to their sex-matched HCs. Thus, sex-nonspecific and specific morphometric differences from HCs were found in posterior cortex, while in PFC alterations were highly sex-specific early in the illness course. This may involve sex-specific alterations in brain development or processes related to illness onset. These findings highlight the presence and regional distribution of generalized as well as sex-specific alterations of brain neurobiology in MDD.

Neurocognitive Mechanism of Remote and Close Associations: An fMRI Study

Abstract Remote association is the ability to combine seemingly unrelated components into new concepts and is evaluated via the Remote Associates Test (RAT). The RAT has generally been used to examine brain activation during insight problem solving but not remote association. Moreover, little is known about the neural correlates of remote association and close association. To address this issue, we used the associative distance in the development of the RAT and designed remote associated items and close associated items. We collected brain images during observation of remote and close associated items from 30 adult participants and analyzed the activation of brain regions involved in remote and close associations. The results showed that processing of remote and close association occurred in the posterior cingulate cortex. After controlling for the influence of other associations, we found that the rostromedial prefrontal cortex, precuneus, and middle temporal gyrus were involved exclusively in remote association. These results showed that remote association has conjunctive and disjunctive neurocognitive mechanisms. Our results contribute to the understanding of the neurocognitive mechanisms of different associations and provide empirical support for the associative theory of creativity.

Neural Representation in mPFC Reveals Hidden Selfish Motivation in White Lies.

Identifying true motivation for Pareto lies, which are mutually beneficial for both the liar and others, can be challenging because different covert motivations can lead to identical overt behavior. In this study, we adopted a brain-fingerprinting approach, combining both univariate and multivariate analyses to estimate individual measures of selfish motivation in Pareto lies by the degree of multivoxel neural representation in the mPFC for Pareto lies conforming with those for selfish versus altruistic lies in human participants of either sex. An increase in selfish motivation for Pareto lies was associated with higher mean-level activity in both ventral and rostral mPFC. The former showed an increased pattern similarity to selfish lies, and the latter showed a decreased pattern similarity to altruistic lies. Higher ventral mPFC pattern similarity predicted faster response time in Pareto lies. Our findings demonstrated that hidden selfish motivation in white lies can be revealed by neural representation in the mPFC.SIGNIFICANCE STATEMENT True motivation for dishonesty serving both self and others cannot be accurately discerned from observed behaviors. Here we showed that fMRI combining both univariate and multivariate analyses can be effectively used to reveal hidden selfish motivation of Pareto lies serving both self and others. The present study suggests that selfish motivation for prosocial dishonesty is encoded primarily by increased activity of the ventromedial and the rostromedial prefrontal cortex, representing intuitive self-serving valuation and strategic switching of motivation depending on beneficiary of dishonesty, respectively.

Roles of the MPFC and insula in impression management under social observation.

People often engage in impression management by presenting themselves and others as socially desirable. However, specific behavioral manifestations and underlying neural mechanisms of impression management remain unknown. In this study, we investigated the neural mechanism of impression management during self- and friend-evaluation. Only participants assigned to the observation (OBS) group, not the control (CON) group, were informed that their responses would be monitored. They answered how well positive and negative trait adjectives described themselves or their friends. The behavioral results showed that the OBS group was more likely to reject negative traits for self-evaluation and to accept positive traits for friend-evaluation. An independent study revealed that demoting negative traits for oneself and promoting positive traits for a friend helps manage one’s impression. In parallel with the behavioral results, in the OBS vs the CON group, the rostromedial prefrontal cortex (rmPFC) and anterior insula (AI) activity showed a greater increase as the negativity of negatively valenced adjectives increased during self-evaluation and also showed a greater increase as the positivity of positively valenced adjectives increased during friend-evaluation. The present study suggests that rmPFC and AI are critically involved in impression management, promoting socially desirable target evaluations under social observation.

Interaction of irritability and anxiety on emotional responding and emotion regulation: a functional MRI study.

Irritability and anxiety frequently co-occur in pediatric populations. Studies separately looking at the neural correlates of these symptoms have identified engagement of similar neural systems - particularly those implicated in emotional processing. Both irritability and anxiety can be considered negative valence emotional states that might relate to emotion dysregulation. However, previous work has not examined the neural responding during the performance of an emotion regulation task as a function of interaction between irritability and anxiety simultaneously. This fMRI study involved 155 participants (90 with significant psychopathologies and 92 male) who performed the Affective Stroop Task, designed to engage emotion regulation as a function of task demands. The Affective Reactivity Index (ARI) was used to index irritability and the Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to index anxiety. Levels of irritability, but not anxiety, was positively correlated with responses to visual images within the right rostro-medial prefrontal cortex and left anterior cingulate cortex during view trials. The second region of ventral anterior cingulate cortex showed a condition-by-emotion-by-ARI score-by-SCARED score interaction. Specifically, anxiety level was significantly correlated with a decreased differential BOLD response to negative relative to neutral view trials but only in the presence of relatively high irritability. Atypical maintenance of emotional stimuli within the rostro-medial prefrontal cortex may exacerbate the difficulties faced by adolescents with irritability. Moreover, increased anxiety combined with significant irritability may disrupt an automatic emotional conflict-based form of emotion regulation that is particularly associated with the ventral anterior cingulate cortex.

Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease.

Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE. Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization. We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08-1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (P=0.03). Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.

Stability or Plasticity? - A Hierarchical Allostatic Regulation Model of Medial Prefrontal Cortex Function for Social Valuation.

The medial prefrontal cortex (mPFC) has long been recognized as the key component of the neurocircuitry involved in various social as well as non-social behaviors, however, little is known regarding the organizing principle of distinctive subregions in the mPFC that integrates a wide range of mPFC functions. The present study proposes a hierarchical model of mPFC functionality, where three functionally dissociable subregions, namely, the ventromedial prefrontal cortex (vmPFC), rostromedial prefrontal cortex (rmPFC), and dorsomedial prefrontal cortex (dmPFC), are differentially involved in computing values of decision-making. According to this model, the mPFC subregions interact with each other in such a way that more dorsal regions utilize additional external sensory information from environment to predict and prevent conflicts occurring in more ventral regions tuned to internal bodily signals, thereby exerting the hierarchically organized allostatic regulatory control over homeostatic reflexes. This model also emphasizes the role of the thalamic reticular nucleus (TRN) in arbitrating the transitions between different thalamo-cortical loops, detecting conflicts between competing options for decision-making, and in shifting flexibly between decision modes. The hierarchical architecture of the mPFC working in conjunction with the TRN may play a key role in adjusting the internal (bodily) needs to suit the constraints of external (environmental) variables better, thus effectively addressing the stability-plasticity dilemma.

Default Mode Network Connectivity and Social Dysfunction in Major Depressive Disorder

Though social functioning is often hampered in Major Depressive Disorder (MDD), we lack a complete and integrated understanding of the underlying neurobiology. Connectional disturbances in the brain’s Default Mode Network (DMN) might be an associated factor, as they could relate to suboptimal social processing. DMN connectional integrity, however, has not been explicitly studied in relation to social dysfunctioning in MDD patients. Applying Independent Component Analysis and Dual Regression on resting-state fMRI data, we explored DMN intrinsic functional connectivity in relation to social dysfunctioning (i.e. composite of loneliness, social disability, small social network) among 74 MDD patients (66.2% female, Mean age = 36.9, SD = 11.9). Categorical analyses examined whether DMN connectivity differs between high and low social dysfunctioning MDD groups, dimensional analyses studied linear associations between social dysfunction and DMN connectivity across MDD patients. Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used for statistical thresholding and multiple comparisons correction (P < 0.05). The analyses cautiously linked greater social dysfunctioning among MDD patients to diminished DMN connectivity, specifically within the rostromedial prefrontal cortex and posterior superior frontal gyrus. These preliminary findings pinpoint DMN connectional alterations as potentially germane to social dysfunction in MDD, and may as such improve our understanding of the underlying neurobiology.

Alcohol use disorder and cannabis use disorder symptomatology in adolescents are differentially related to dysfunction in brain regions supporting face processing

Despite extensive behavioral evidence of impairments in face processing and expression recognition in adults with alcohol or cannabis use disorders (AUD/CUD), neuroimaging findings have been inconsistent. Moreover, relatively little work has examined the relationship of AUD or CUD symptoms with face or expression processing within adolescents. Given the high prevalence of alcohol and cannabis use during adolescence, understanding how these usage behaviors interact with neural mechanisms supporting face and expression processing could have important implications for youth social and emotional functioning. In this study, adolescents (N = 104) responded to morphed fearful and happy expressions during fMRI and their level of AUD and/or CUD symptoms were related to the BOLD response data. We found that AUD and CUD symptom severity were both negatively related to responses to faces generally. However, whereas this relationship was shown for AUD within ventromedial prefrontal cortex and lingual gyrus, it was shown for CUD within rostromedial prefrontal cortex including anterior cingulate cortex. Additionally, AUD symptom levels were associated with differential responses within medial temporal pole and inferior parietal lobule as a function of expression. These results have potential implications for understanding the social and emotional functioning of adolescents with AUD and CUD symptoms.

Development of MPFC function mediates shifts in self-protective behavior provoked by social feedback

How do people protect themselves in response to negative social feedback from others? How does such a self-protective system develop and affect social decisions? Here, using a novel reciprocal artwork evaluation task, we demonstrate that youths show self-protective bias based on current negative social evaluation, whereas into early adulthood, individuals show self-protective bias based on accumulated evidence of negative social evaluation. While the ventromedial prefrontal cortex (VMPFC) mediates self-defensive behavior based on both current and accumulated feedback, the rostromedial prefrontal cortex (RMPFC) exclusively mediates self-defensive behavior based on longer feedback history. Further analysis using a reinforcement learning model suggests that RMPFC extending into VMPFC, together with posterior parietal cortex (PPC), contribute to age-related increases in self-protection bias with deep feedback integration by computing the discrepancy between current feedback and previously estimated value of self-protection. These findings indicate that the development of RMPFC function is critical for sophisticated self-protective decisions.

Dynamical Representation of Dominance Relationships in the Human Rostromedial Prefrontal Cortex

Humans and other primates have evolved the ability to represent their status in the group's social hierarchy, which is essential for avoiding harm and accessing resources. Yet it remains unclear how the human brain learns dominance status and adjusts behavior accordingly during dynamic social interactions. Here we address this issue with a combination of fMRI and transcranial direct current stimulation (tDCS). In a first fMRI experiment, participants learned an implicit dominance hierarchy while playing a competitive game against three opponents of different skills. Neural activity in the rostromedial PFC (rmPFC) dynamically tracked and updated the dominance status of the opponents, whereas the ventromedial PFC and ventral striatum reacted specifically to competitive victories and defeats. In a second experiment, we applied anodal tDCS over the rmPFC to enhance neural excitability while subjects performed a similar competitive task. The stimulation enhanced the relative weight of victories over defeats in learning social dominance relationships and exacerbated the influence of one's own dominance over competitive strategies. Importantly, these tDCS effects were specific to trials in which subjects learned about dominance relationships, as they were not present for control choices associated with monetary incentives but no competitive feedback. Taken together, our findings elucidate the role of rmPFC computations in dominance learning and unravel a fundamental mechanism that governs the emergence and maintenance of social dominance relationships in humans.

Observational learning computations in neurons of the human anterior cingulate cortex.

When learning from direct experience, neurons in the primate brain have been shown to encode a teaching signal used by algorithms in artificial intelligence: the reward prediction error (PE)—the difference between how rewarding an event is, and how rewarding it was expected to be. However, in humans and other species learning often takes place by observing other individuals. Here, we show that, when humans observe other players in a card game, neurons in their rostral anterior cingulate cortex (rACC) encode both the expected value of an observed choice, and the PE after the outcome was revealed. Notably, during the same task neurons recorded in the amygdala (AMY) and the rostromedial prefrontal cortex (rmPFC) do not exhibit this type of encoding. Our results suggest that humans learn by observing others, at least in part through the encoding of observational PEs in single neurons in the rACC.

A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits.

The way in which brains generate working memories (those used for the transient processing and storage of newly acquired information) is still an intriguing question. Here, we report that the firing activities of neurons located in the rostromedial prefrontal cortex recorded in alert behaving rabbits are controlled by a dynamic oscillator. This oscillator generated firing frequencies in a variable band of 3-12 Hz depending on the conditioned stimulus-unconditioned stimulus intervals (1 s, 500 ms, 250 ms) selected for classical eyeblink conditioning of behaving rabbits. Shorter (50 ms) and longer (2 s) intervals failed to activate the oscillator and prevented the acquisition of conditioned eyelid responses. This is an unexpected mechanism to generate sustained firing activities in neural circuits generating working memories.

Encoding of Prospective Tasks in the Human Prefrontal Cortex under Varying Task Loads

Successful realization of planned actions requires the brain to encode intentions over delays. Previous research has indicated that several regions in the rostral or anterior prefrontal cortex (PFC) encode delayed intentions. However, different processes may encode the same future task depending on task load during the delay. This difference may depend on the computational resources available when the delay is occupied with an ongoing task and when it is task-free. Here we directly investigated and compared the representation of delayed intentions in the human brain in the presence and absence of ongoing task load during the delay. We acquired fMRI data in combination with an event-based prospective memory design where human subjects remembered to perform the same future tasks over occupied and task-free delays. We used time-resolved multivoxel pattern classification and found that: (1) rostrolateral PFC (BA 46) encoded the delayed intention during both delay types; (2) rostromedial PFC (BA 10) encoded the intentions during occupied delays; whereas (3) a variety of more posterior regions, including the anterior cingulate cortex (BA 24), the supplementary motor area (BA 6), and the precuneus, encoded intentions during task-free delays. Overall, the medial PFC encoded delayed intentions more rostrally in the presence of an ongoing delay task and more caudally in its absence. Thus, rostromedial PFC may play a specialized role in the encoding of prospective memory that depends on higher computational demands (e.g., given higher task load during the delay). In contrast, the rostrolateral PFC is a more general area that encodes future intentions regardless of task load.