Search

Background Enhanced memory for self-oriented information is known as the self-referential memory (SRM) effect. fMRI studies of the SRM effect have focused almost exclusively on encoding, revealing selective engagement of the medial prefrontal cortex (mPFC) during “self” relative to other processing conditions. Other critical areas for self-processing include ventrolateral prefrontal cortex (vlPFC), temporo-parietal junction (TPJ) and posterior cingulate/precuneus (PCC/PC). Previous behavioral studies show that individuals with schizophrenia fail to benefit from this memory boost. However, the neural correlates of this deficit, at either encoding or retrieval, are unknown. Methods Twenty individuals with schizophrenia and 16 healthy controls completed an event-related fMRI SRM paradigm. During encoding, trait adjectives were judged in terms of structural features (“case” condition), social desirability (“other” condition), or as self-referential (“self” condition). Participants then completed an unexpected recognition test (retrieval phase). We examined BOLD activation during both encoding and retrieval within mPFC, vlPFC, TPJ, and PCC/PC regions-of-interest (ROIs). Results During encoding, fMRI data indicated both groups had greater activation during the “self” relative to the “other” condition across ROIs. Controls showed this primarily in mPFC whereas patients showed this in PCC/PC. During retrieval, fMRI data indicated controls showed differentiation across ROIs between “self” and “other” conditions, but patients did not. Conclusions Results suggest regional differences in the neural processing of self-referential information in individuals with schizophrenia, perhaps because representation of the self is not as well established in patients relative to controls. The current study presents novel findings that add to the literature implicating impaired self-oriented processing in schizophrenia.

During the COVID-19 pandemic, people are at risk of developing disordered eating behaviors. The present study utilized resting-state functional magnetic resonance imaging (fMRI) to examine how trait self-control and its neural mechanisms predict overeating tendencies in young adults during the pandemic. Data on trait self-control, the amplitude of low-frequency fluctuation (ALFF), and resting-state functional connectivity (RSFC) were collected before COVID-19 (September 2019, T1), and data on overeating were collected during COVID-19 (February 2020, T2). Whole-brain regression analyses (N = 538) revealed that higher trait self-control was associated with higher ALFF in the right dorsolateral and ventrolateral prefrontal cortex (DLPFC, VLPFC) and the left anterior insula, and lower ALFF in the left fusiform gyrus and precuneus. With the DLPFC, fusiform gyrus and precuneus as seed regions, trait selfcontrol was associated with decreased connectivity of the orbitofrontal cortex, anterior cingulate cortex, temporal pole, and insula, and increased connectivity between the right VLPFC and anterior cerebellum. Longitudinal mediation models showed that trait self-control (T1) negatively predicted overeating (T2), and the mediating effects of the fusiform gyrus, DLPFC, and VLPFC were moderated by sex. The present study reveals that the brain networks for trait self-control are mainly involved in cognitive and executive control and incentive and emotional processing, demonstrating the longitudinal benefits of trait self-control in alleviating disordered eating behaviors during the pandemic. Sex differences in the neural substrates underlie this association. These finding may have implications of the interventions for behavioral maladjustment., Graphical abstract Image 1

The prefrontal cortex (PFC) plays a key role in the ability to pursue a particular goal in the face of competing alternatives, an ability that is fundamental to higher-order human behavior. Whether this region contributes to cognitive control through material-general mechanisms, or through hemispheric specialization of component abilities, remains unclear. Here we show that left or right ventrolateral PFC damage in humans leads to doubly dissociable deficits in two classic tests of interference control. Patients with damage centered on left ventrolateral prefrontal cortex had exaggerated interference effects in the color-word Stroop, but not the Eriksen flanker task, whereas patients with damage affecting right ventrolateral prefrontal cortex showed the opposite pattern. Thus, effective interference resolution requires either right or left lateral PFC, depending on the nature of the task. This finding supports a lateralized, material-specific account of cognitive control in humans.

The study of developmental disorders can provide a unique window into the role of domain-general cognitive abilities and neural systems in typical and atypical development. Mathematical disabilities (MD) are characterized by marked difficulty in mathematical cognition in the presence of preserved intelligence and verbal ability. Although studies of MD have most often focused on the role of core deficits in numerical processing, domain-general cognitive abilities, in particular working memory (WM), have also been implicated. Here we identify specific WM components that are impaired in children with MD and then examine their role in arithmetic problem solving. Compared to typically developing (TD) children, the MD group demonstrated lower arithmetic performance and lower visuo-spatial working memory (VSWM) scores with preserved abilities on the phonological and central executive components of WM. Whole brain analysis revealed that, during arithmetic problem solving, left posterior parietal cortex, bilateral dorsolateral and ventrolateral prefrontal cortex, cingulate gyrus and precuneus, and fusiform gyrus responses were positively correlated with VSWM ability in TD children, but not in the MD group. Additional analyses using a priori posterior parietal cortex regions previously implicated in WM tasks, demonstrated a convergent pattern of results during arithmetic problem solving. These results suggest that MD is characterized by a common locus of arithmetic and VSWM deficits at both the cognitive and functional neuroanatomical levels. Unlike TD children, children with MD do not use VSWM resources appropriately during arithmetic problem solving. This work advances our understanding of VSWM as an important domain-general cognitive process in both typical and atypical mathematical skill development.

Ventrolateral prefrontal cortex (VLPFC) has long been linked to language production, but the precise mechanisms are still being elucidated. Using neuropsychological case studies, we explored possible sub-specialization within this region for different linguistic and executive functions. Frontal patients with different lesion profiles completed two sequencing tasks, which were hypothesized to engage partially overlapping components. The multi-word priming task tested the sequencing of co-activated representations and the overriding of primed word orders. The sequence reproduction task tested the sequencing of co-activated representations, but did not employ a priming manipulation. We compared patients' performance on the two tasks to that of healthy, age-matched controls. Results are partially consistent with an anterior–posterior gradient of cognitive control within lateral prefrontal cortex ( Koechlin & Summerfield, 2007 ). However, we also found a stimulus-specific pattern, which suggests that sub-specialization might be contingent on type of representation as well as type of control signal. Isolating such components functionally and anatomically might lead to a better understanding of language production deficits in aphasia.

Impulsivity has been associated with several psychiatric disorders including drug addiction and gambling. Impulsive subjects typically have a preference for short-term over long-term rewards and make risky choices. This study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-rated impulsivity and venturesomeness during tasks involving delayed and risky choice. A broader sampling approach was taken by recruiting participants with behaviors that have been linked to impulsivity (gambling N=15, and recreational drug use N=10) and those without these behaviors (N=9). Selection between delayed or probabilistic rewards was associated with activation in fronto-parietal regions in line with previous research. When selecting between delayed rewards, activity within the pregenual anterior cingulate cortex and ventrolateral prefrontal cortex correlated positively with impulsivity scores while activity within the orbitofrontal cortex, subgenual anterior cingulate cortex and caudate correlated positively with venturesomeness scores. Selection between probabilistic rewards revealed no correlation between scores and regional activations. The results from this study provide targets for future research investigating the neural substrates of impulsivity. They also provide targets for the further investigation into the pathophysiology of addiction and impulse-control disorders.

The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs’ capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. FMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation.

While the role of left prefrontal cortex in reasoning tasks has long been recognized, the role of right prefrontal cortex remains unclear. One patient study [Goel, V., Tierney, M., Sheesley, L., Bartolo, A., Vartanian, O., & Grafman, J. (2007). Hemispheric specialization in human prefrontal cortex for resolving certain and uncertain inferences. Cerebral Cortex, 17(10), 2245-2250] has suggested that right prefrontal cortex plays an essential role in resolving indeterminate relations. To test this hypothesis, and to identify the involvement of specific regions within right prefrontal cortex we scanned 17 normal volunteers with fMRI while they engaged in a transitive inference task involving determinate and indeterminate relations. The results show a nice crossover interaction such that, right ventrolateral prefrontal cortex (BA 47) is selectively activated by the processing of indeterminate trials with no belief-bias cues, while left lateral prefrontal cortex (BA 45) is selectively activated by the processing of indeterminate trials containing belief-bias cues. These results are not only consistent with, but also amplify, the lesion data by identifying specific regions within right and left prefrontal cortex.

A considerable body of evidence supports the notion that cerebellar lesions lead to neuropsychological deficits, including impairments in working-memory, executive tasks and verbal fluency. Studies employing functional magnetic resonance imaging (fMRI) and anatomical tracing in primates provide evidence for a cortico-cerebellar circuitry as the functional substrate of working-memory. The present fMRI study explores the activation pattern during an n-back working-memory task in patients with an isolated cerebellar infarct. To determine each patient's cognitive impairment, neuropsychological tests of working-memory and attention were carried out. We conducted fMRI in nine patients and nine healthy age-matched controls while they performed a 2-back task in a blocked-design. In both groups we found bilateral activations in a widespread cortico-cerebellar network, consisting of the ventrolateral prefrontal cortex (BA 44, 45), dorsolateral prefrontal cortex (BA 9, 46), parietal cortex (BA 7, 40), pre-supplementary motor area (BA 6) anterior cingulate (BA 32). Relative to healthy controls, patients with isolated cerebellar infarcts demonstrated significantly more pronounced BOLD-activations in the precuneus and the angular gyrus during the 2-back task. The significant increase in activation in the posterior parietal areas of the cerebellar patients could be attributed to a compensatory recruitment to maintain task performance. We conclude that cerebellar lesions affect remote cortical regions that are part of a putative cortico-cerebellar network.

Relational association of disparate semantic concepts can strengthen encoding of episodes. Previous research has shown that the left medial temporal lobe (MTL) and the left prefrontal cortex (PFC) are the primary brain regions activated during both verbal encoding and the association of disparate semantic concepts. In the current functional magnetic resonance imaging (fMRI) study, our goal was to compare the coordinated response of the left MTL and left PFC when disparate semantic associations are strongly encoded compared to when they are weakly encoded. To achieve this goal, subjects were scanned while creating sentences based on a presented pair of words, and were asked to free-recall these sentences at a later time. Half the word pairs were semantically unrelated, and half were semantically related. Analysis of relatedness activations (unrelated-related contrast) suggested that the PFC was active whether or not the items were free-recalled, and increased activation of the MTL was required to promote encoding. Analyses of coordination of relatedness activations comparing free-recalled items to not free-recalled items showed an increase in left MTL-left PFC coordination for relatedness activations on free-recalled items. These results suggest that formation of relational semantic associations that lead to strongly encoded episodes requires increased coordination of the left MTL-left PFC neural pathway.

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Brocaamp;lsquo;s and Wernicke//!--MFG_und-- //amp;am p;lsquo; s areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.

Previously, in a simple probability-matching experiment with two split-brain patients that involved having the participant predict which of two events will happen on the next trial, we found that the left hemisphere tended to look for patterns and match the frequency of previous occurrences but not the right hemisphere [Wolford, G., Miller, M. B., & Gazzaniga, M. S. (2000). The left hemisphere's role in hypothesis formation. Journal of Neuroscience, 20(RC64), 1-4]. In this study, we examined those findings in normal subjects using fMRI. Subjects alternated between blocks of trials in which they predicted the location of a stimulus and those in which they detected the location of a stimulus. Previous investigators using similar paradigms reported mostly right hemisphere activations, including activations in the right dorsolateral and ventrolateral prefrontal cortex, the medial prefrontal cortex, and the right lateral parietal lobe. We also found mostly right hemisphere activations, but we found that some of the activations in the dorsolateral prefrontal and parietal cortices were sensitive to individual differences in the tendency to look for patterns in random sequences. Further, we found that, by controlling for the working memory component of the predicting task, all brain activations in the normal brain associated with looking for patterns were related to the task demands of working memory processes underlying probability matching and predicting.

We studied the neural activation associated with anticipations of emotional pictures using functional magnetic resonance imaging (fMRI) by directly comparing certain with uncertain anticipation conditions. While being scanned with fMRI, healthy participants ( n = 18) were cued to anticipate and then perceive emotional stimuli having predictable (i.e., certain) emotional valences (i.e., positive and negative), given a preceding cue, as well as cued stimuli of uncertain valence (positive or negative). During anticipation of pictures with certain negative valence, activities of supracallosal anterior cingulate cortex, ventrolateral prefrontal cortex, insula, and amygdala were enhanced relative activity levels that for the uncertain emotional anticipation condition. This result suggests that these brain regions are involved in anticipation of negative images, and that their activity levels may be enhanced by the certainty of anticipation. Furthermore, the supracallosal anterior cingulate cortex showed functional connectivity with the insula, prefrontal cortex, and occipital cortex during the certain negative anticipation. These findings are consistent with an interpretation that top-down modulation, arising from anterior brain regions, is engaged in certain negative anticipation within the occipital cortex. It is thought that the limbic system involving the amygdala, ACC, and insula, engaged emotional processes, and that the input system involving the visual cortex entered an idling state.

The ventrolateral prefrontal cortex (vlPFC) has been implicated in studies of both executive and social functions. Recent meta-analyses suggest that vlPFC plays an important but little understood role in Theory of Mind (ToM). Converging neuropsychological and functional Magnetic Resonance Imaging (fMRI) evidence suggests that this may reflect inhibition of self-perspective. The present study adapted an extensively published ToM localizer to evaluate the role of vlPFC in inhibition of self-perspective. The classic false belief, false photograph vignettes that comprise the localizer were modified to generate high and low salience of self-perspective. Using a factorial design, the present study identified a behavioural and neural cost associated with having a highly salient self-perspective that was incongruent with the representational content. Importantly, vlPFC only differentiated between high versus low salience of self-perspective when representing mental state content. No difference was identified for non-mental representation. This result suggests that different control processes are required to represent competing mental and non-mental content.