Morphometry of Left Frontal and Temporal Poles Predicts Analogical Reasoning Abilities.

Analogical reasoning is critical for making inferences and adapting to novelty. It can be studied experimentally using tasks that require creating similarities between situations or concepts, i.e., when their constituent elements share a similar organization or structure. Brain correlates of analogical reasoning have mostly been explored using functional imaging that has highlighted the involvement of the left rostrolateral prefrontal cortex (rlPFC) in healthy subjects. However, whether inter-individual variability in analogical reasoning ability in a healthy adult population is related to differences in brain architecture is unknown. We investigated this question by employing linear regression models of performance in analogy tasks and voxel-based morphometry in 54 healthy subjects. Our results revealed that the ability to reason by analogy was associated with structural variability in the left rlPFC and the anterior part of the inferolateral temporal cortex. Tractography of diffusion-weighted images suggested that these 2 regions have a different set of connections but may exchange information via the arcuate fasciculus. These results suggest that enhanced integrative and semantic abilities supported by structural variation in these areas (or their connectivity) may lead to more efficient analogical reasoning.

Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval.

Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom-up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi-voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto-parietal control network across tasks, its coupling with other cortical areas varied in a task-dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain-general role for left RLPFC in monitoring and/or integrating task-relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations.

fNIRS analysis of rostral prefrontal cortex activity and perception of inspiratory loads.

It is well-established that the brainstem is responsible for the automatic control of breathing, however, cortical areas control perception and conscious breathing. This study investigated activity in the prefrontal cortex (PFC) during breathing difficulty using functional near-infrared spectroscopy (fNIRS). It was hypothesized that extrinsic inspiratory loads will elicit regional changes in PFC activity and increased perception ratings, as a function of load magnitude and type. Participants were exposed to varying magnitudes of resistive (R) and pressure threshold (PT) inspiratory loads to increase breathing effort. Perception ratings of breathing effort and load magnitude were positively correlated (p < 0.05). PT loads were rated more effortful than R loads (p < 0.05). Differences in perceived effort were a function of inspiratory pressure-time-product (PTP) and inspiratory work of breathing (WoB). PFC activity increased with the largest PT load (p < 0.01), suggesting that the PFC is involved in processing respiratory stimuli. The results support the hypothesis that the PFC is an element of the neural network mediating effortful breathing perception.

Relation between frontal pole volumes and cognitive insight in Schizophrenia.

OBJECTIVE: Cognitive insight comprising self-reflection and self-certainty is an important determinant of functional outcomes in Schizophrenia. The neural correlates of cognitive insight in Schizophrenia are underexamined. The frontal pole (FP) is implicated in metacognitive function in healthy individuals, but its role is not well examined in Schizophrenia. We had earlier reported the relationship between Frontal pole volumes and cognitive insight in a small sample of only male patients. Hence, we studied this relationship in an independent sample of schizophrenia patients and healthy controls. METHODS: We examined 41 healthy volunteers (HV) and 57 patients with Schizophrenia (SCZ). We used a previously validated manual morphometric method to perform FP parcellation on images obtained from a 3 T scanner and calculated the volumes. Cognitive insight was measured using Beck's Cognitive insight scale (BCIS). To assess the relationship between FP volumes and BCIS scores, multiple linear regression analyses were performed. RESULTS: In the overall sample, age, years of education, and intracranial volume were significant predictors of BCIS scores. Within the SCZ group, age and left FP volume were significant predictors of BCIS composite scores and age, ICV for BCIS-self certainty. There was no significant relationship between age and FP volumes in either SCZ or HV group. DISCUSSION: The current study in an independent sample further supports the critical role of the frontal pole in cognitive insight, earlier reported by us. As cognitive insight has a vital role in functional outcome, our findings have potential clinical implications.

Evidence that the frontal pole has a significant role in the pathophysiology of schizophrenia.

Different regions of the cortex have been implicated in the pathophysiology of schizophrenia. Recently published data suggested there are many more changes in gene expression in the frontal pole (Brodmann's Area (BA) 10) compared to the dorsolateral prefrontal cortex (BA 9) and the anterior cingulate cortex (BA 33) from patients with schizophrenia. These data argued that the frontal pole is significantly affected by the pathophysiology of schizophrenia. The frontal pole is a region necessary for higher cognitive functions and is highly interconnected with many other brain regions. In this review we summarise the growing body of evidence to support the hypothesis that a dysfunctional frontal pole, due at least in part to its widespread effects on brain function, is making an important contribution to the pathophysiology of schizophrenia. We detail the many structural, cellular and molecular abnormalities in the frontal pole from people with schizophrenia and present findings that argue the symptoms of schizophrenia are closely linked to dysfunction in this critical brain region.

Medio-lateral functional dissociation of the rostral prefrontal cortex with focal/non-focal cues during a prospective memory task.

The rostral prefrontal cortex (rPFC) is crucial in prospective memory (PM) behavior. Several functional magnetic resonance imaging studies showed that its medial (mrPFC) and lateral (lrPFC) portions dissociate during PM tasks. In light of the Multiprocess theory (McDaniel and Einstein 2000), here we tested whether the two portions of the rPFC are dissociable by modulating strategic vs. spontaneous processes during a PM task. We investigated these two processes by means of a 2 × 2 experimental design in which focal vs. non-focal conditions were modulated by varying the conjoint nature of the ongoing task (i.e., lexical decision vs. syllable matching) and the PM cue (words vs. syllables). Using the two portions of the rPFC as regions of interest, we found an effect of the non-focal condition in the lrPFC and, conversely, an effect of the focal condition in the mrPFC. In the whole-brain analysis we found an effect of the non-focal condition in the bilateral intraparietal sulcus, the bilateral middle frontal gyrus, the supplementary motor areas and the vermis of the cerebellum, whereas we found an effect of the focal condition in the ventromedial PFC. Overall, our results show that different brain regions are involved when multiple processes underlying PM behavior are modulated.

Regional gray matter volume mediates the relationship between maternal emotional warmth and gratitude.

Researchers have examined how parenting behavior influences individuals' brain structure and behavioral development, primarily among people who have experienced maltreatment. However, information relating to the anatomical structure associated with the parenting behavior in young healthy individuals who have not experienced maltreatment is scant. Gratitude is an important aspect of human sociality. Both the extent to which parenting behavior influences gratitude and the neural basis of the relationship between parenting behavior and gratitude are unclear. Thus, in the present study, the primary aim was to use voxel-based morphometry (VBM) to investigate the neuroanatomical basis of parenting behavior in young healthy participants. The results showed a significant negative correlation between the maternal emotional warmth and both the dorsal medial prefrontal cortex (dmPFC) and the lateral rostral prefrontal cortex. Then, we used mediation analysis to investigate the neural basis of the relationship between parenting behavior and gratitude. The results revealed that the volume of the lateral rostral prefrontal cortex mediates the relationship between the maternal emotional warmth and gratitude. Together, these findings suggest that the family environment, specifically parenting behavior, might be associated with the gray matter volume of brain structure. Further, the lateral rostral prefrontal cortex might have an important role in the relationship between the maternal emotional warmth and gratitude.

Transcranial Magnetic Stimulation Reveals Executive Control Dissociation in the Rostral Prefrontal Cortex.

Although previous studies have shown that the rostral prefrontal cortex (rPFC) plays a crucial role in executive tasks, the various functions of the rPFC in the humans are still understudied. Here we used transcranial magnetic stimulation (TMS) with continuous theta burst stimulation (cTBS) to interfere with the executive control functions of the right rostrolateral PFC (RLPFC) or the right rostromedial PFC (RMPFC). Subjects performed a task-switching paradigm, which included spatial detection (SD), prospective memory (PM) and working memory (WM) tasks, after cTBS. The performance of 18 healthy volunteers was evaluated on different days after cTBS over the right RLPFC, the right RMPFC, and the vertex (serving as a control site). The application of cTBS over the RLPFC significantly increased the switching costs (SCs) of the error rates (ERs) when switching to the PM task, while RMPFC-cTBS decreased SCs of ERs when switching to the WM task, compared with the control vertex site. These findings provide evidence for a differential role of the RLPFC and the RMPFC in executive functions, with a specific involvement of the RLPFC and the RMPFC in PM, and WM, respectively.

Frontopolar Resource Allocation in Human and Nonhuman Primates.

A recent report suggested that monkey frontopolar cortex (FPC) is vital for the reallocation of cognitive resources among potential goals in complex underspecified situations. These findings nicely complement evidence from human neuroimaging and patient studies, leading to a common conceptual framework of FPC function across species.

Impact of childhood emotional abuse on neocortical neurometabolites and complex emotional processing in patients with generalized anxiety disorder.

BACKGROUND: The rostral prefrontal cortex (RPFC) is involved in reflective thought processes such as self-knowledge and person perception. We hypothesized that childhood emotional abuse, which is disruptive of emotional regulation, would differentially impact neurometabolite concentrations of the RPFC, and related neocortical areas, in adults with generalized anxiety disorder (GAD) versus healthy controls. METHODS: GAD patients (n=16; females=11) and medically healthy volunteers (n=16; F=10) were assessed using the Childhood Trauma Questionnaire (CTQ), specifically the emotional abuse category. Proton magnetic resonance spectroscopy imaging examined 3 regions of interest (ROI) from the most rostral slice from the Duyn et al. (1993) multivoxel imaging modality: rostral prefrontal cortex (BA 10,9), premotor cortex (BA 6,8) and secondary somatosensory and associated parietal cortex (BA 5,7). Metabolites included N-acetyl-aspartate, creatine, and choline. RESULTS: GAD patients reported higher emotional abuse scores versus controls. An omnibus general linear model including 3 ROI, 3 metabolites, and laterality as dependent variables revealed a significant diagnosis by CTQ emotional abuse score interactive effect. In controls, all 3 ROI for all 3 metabolites on both sides demonstrated a significant inverse relationship with emotional abuse scores; none were significant in GAD patients. LIMITATIONS: A major limitation is the uneven distribution of emotional abuse scores between the controls and GAD patients, with GAD patients reporting higher scores. CONCLUSION: Unlike controls, GAD patients appear compromised in forming a molecular representation reflective of magnitude of childhood emotional abuse. The neurometabolites in GAD patients appear non-aligned to childhood emotional abuse, suggesting potential consequences for normative "theory of mind" processes and emotional function in certain anxiety disorders.

Endogenous-cue prospective memory involving incremental updating of working memory: an fMRI study.

INTRODUCTION: Prospective memory paradigms are conventionally classified on the basis of event-, time-, or activity-based intention retrieval. In the vast majority of such paradigms, intention retrieval is provoked by some kind of external event. However, prospective memory retrieval cues that prompt intention retrieval in everyday life are commonly endogenous, i.e., linked to a specific imagined retrieval context. We describe herein a novel prospective memory paradigm wherein the endogenous cue is generated by incremental updating of working memory, and investigated the hemodynamic correlates of this task. METHODS: Eighteen healthy adult volunteers underwent functional magnetic resonance imaging while they performed a prospective memory task where the delayed intention was triggered by an endogenous cue generated by incremental updating of working memory. Working memory and ongoing task control conditions were also administered. RESULTS: The 'endogenous-cue prospective memory condition' with incremental working memory updating was associated with maximum activations in the right rostral prefrontal cortex, and additional activations in the brain regions that constitute the bilateral fronto-parietal network, central and dorsal salience networks as well as cerebellum. In the working memory control condition, maximal activations were noted in the left dorsal anterior insula. CONCLUSIONS: Activation of the bilateral dorsal anterior insula, a component of the central salience network, was found to be unique to this 'endogenous-cue prospective memory task' in comparison to previously reported exogenous- and endogenous-cue prospective memory tasks without incremental working memory updating. Thus, the findings of the present study highlight the important role played by the dorsal anterior insula in incremental working memory updating that is integral to our endogenous-cue prospective memory task.