Specialization in the left prefrontal cortex for sentence comprehension

Using functional magnetic resonance imaging (fMRI), we examined cortical activation under syntactic decision tasks and a short-term memory task for sentences, focusing on essential properties of syntactic processing. By comparing activation in these tasks with a short-term memory task for word lists, we found that two regions in the left prefrontal cortex showed selective activation for syntactic processing: the dorsal prefrontal cortex (DPFC) and the inferior frontal gyrus (IFG). Moreover, the left DPFC showed more prominent activation under the short-term memory task for sentences than that for word lists, which cannot be explained by general cognitive factors such as task difficulty and verbal short-term memory. These results support the proposal of specialized systems for sentence comprehension in the left prefrontal cortex.     

The influences of task difficulty and response correctness on neural systems supporting fluid reasoning

This functional magnetic resonance imaging (fMRI) study examined neural contributions to managing task difficulty and response correctness during fluid reasoning. Previous studies investigate reasoning by independently varying visual complexity or task difficulty, or the specific domain. Under natural conditions these factors interact in a complex manner to support dynamic combinations of perceptual and conceptual processes. This study investigated fluid reasoning under circumstances that would represent the cognitive flexibility of real life decision-making. Results from a mixed effects analysis corrected for multiple comparisons indicate involvement of cortical and subcortical areas during fluid reasoning. A 2 × 2 ANOVA illustrates activity related to variances in task difficulty correlated with increased blood oxygenation level-dependent (BOLD)-signal in the left middle frontal gyrus (BA6). Activity related to response correctness correlated with increased BOLD-signal in a larger, distributed system including right middle frontal gyrus (BA6), right superior parietal lobule (BA7), left inferior parietal lobule (BA40), left lingual gyrus (BA19), and left cerebellum (Lobule VI). The dissociation of function in left BA 6 for task difficulty and right BA6 for response correctness and the involvement of a more diffuse network involving the left cerebellum in response correctness extends knowledge about contributions of classic motor and premotor areas supporting higher level cognition.     

Functional disconnection and compensation in mild cognitive impairment: evidence from DLPFC connectivity using resting-state fMRI

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in mild cognitive impairment (MCI) has given prominence to its importance in studies on the disconnection associated with MCI. The purpose of the current study was to examine the DLPFC functional connectivity patterns during rest in MCI patients and the impact of regional grey matter (GM) atrophy on the functional results. Structural and functional MRI data were collected from 14 MCI patients and 14 age, gender-matched healthy controls. We found that both the bilateral DLPFC showed reduced functional connectivity with the inferior parietal lobule (IPL), superior/medial frontal gyrus and sub-cortical regions (e.g., thalamus, putamen) in MCI patients when compared with healthy controls. Moreover, the DLPFC connectivity with the IPL and thalamus significantly correlated with the cognitive performance of patients as measured by mini-mental state examination (MMSE), clock drawing test (CDT), and California verbal learning test (CVLT) scores. When taking GM atrophy as covariates, these results were approximately consistent with those without correction, although there may be a decrease in the statistical power. These results suggest that the DLPFC disconnections may be the substrates of cognitive impairments in MCI patients. In addition, we also found enhanced functional connectivity between the left DLPFC and the right prefrontal cortex in MCI patients. This is consistent with previous findings of MCI-related increased activation during cognitive tasks, and may represent a compensatory mechanism in MCI patients. Together, the present study demonstrated the coexistence of functional disconnection and compensation in MCI patients using DLPFC functional connectivity analysis, and thus might provide insights into biological mechanism of the disease.     

The neural bases of cognitive conflict and control in moral judgment

Traditional theories of moral psychology emphasize reasoning and "higher cognition," while more recent work emphasizes the role of emotion. The present fMRI data support a theory of moral judgment according to which both "cognitive" and emotional processes play crucial and sometimes mutually competitive roles. The present results indicate that brain regions associated with abstract reasoning and cognitive control (including dorsolateral prefrontal cortex and anterior cingulate cortex) are recruited to resolve difficult personal moral dilemmas in which utilitarian values require "personal" moral violations, violations that have previously been associated with increased activity in emotion-related brain regions. Several regions of frontal and parietal cortex predict intertrial differences in moral judgment behavior, exhibiting greater activity for utilitarian judgments. We speculate that the controversy surrounding utilitarian moral philosophy reflects an underlying tension between competing subsystems in the brain.     

Neural mechanisms of transient and sustained cognitive control during task switching

A hybrid blocked and event-related functional magnetic resonance imaging (fMRI) study decomposed brain activity during task switching into sustained and transient components. Contrasting task-switching blocks against single-task blocks revealed sustained activation in right anterior prefrontal cortex (PFC). Contrasting task-switch trials against task-repeat and single-task trials revealed activation in left lateral PFC and left superior parietal cortex. In both sets of regions, activation dynamics were strongly modulated by trial-by-trial fluctuations in response speed. In addition, right anterior PFC activity selectively covaried with the magnitude of mixing cost (i.e., task-repeat versus single-task trial performance), and left superior parietal activity selectively covaried with the magnitude of the switching cost (i.e., task-switch versus task-repeat trial performance). These results indicate a functional double dissociation in brain regions supporting different components of cognitive control during task switching and suggest that both sustained and transient control processes mediate the behavioral performance costs of task switching.     

Default-Mode Network Changes in Huntington’s Disease: An Integrated MRI Study of Functional Connectivity and Morphometry

Previous MRI studies of functional connectivity in pre-symptomatic mutation carriers of Huntington’s disease (HD) have shown dysfunction of the Default-Mode Network (DMN). No data however are currently available on the DMN alterations in the symptomatic stages of the disease, which are characterized by cortical atrophy involving several DMN nodes. We assessed DMN integrity and its possible correlations with motor and cognitive symptoms in 26 symptomatic HD patients as compared to 22 normal volunteers, by analyzing resting state functional MRI data, using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Direct correlation with PC/PCC was decreased, without correlation with atrophy, in the ventral medial prefrontal cortex (including anterior cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the right inferior parietal cortex (mainly involving the angular gyrus). Negative correlations with PC/PCC were decreased bilaterally in the inferior parietal cortices, while a cluster in the right middle occipital gyrus presented increased correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex significantly correlated with the performance at the Stroop test (p = .0002). Widespread DMN changes, not correlating with the atrophy of the involved nodes, are present in symptomatic HD patients, and correlate with cognitive disturbances.     

Individual Differences in Brain Structure and Resting Brain Function Underlie Cognitive Styles: Evidence from the Embedded Figures Test

Cognitive styles can be characterized as individual differences in the way people perceive, think, solve problems, learn, and relate to others. Field dependence/independence (FDI) is an important and widely studied dimension of cognitive styles. Although functional imaging studies have investigated the brain activation of FDI cognitive styles, the combined structural and functional correlates with individual differences in a large sample have never been investigated. In the present study, we investigated the neural correlates of individual differences in FDI cognitive styles by analyzing the correlations between Embedded Figures Test (EFT) score and structural neuroimaging data [regional gray matter volume (rGMV) was assessed using voxel-based morphometry (VBM)] / functional neuroimaging data [resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF)] throughout the whole brain. Results showed that the increased rGMV in the left inferior parietal lobule (IPL) was associated with the EFT score, which might be the structural basis of effective local processing. Additionally, a significant positive correlation between ALFF and EFT score was found in the fronto-parietal network, including the left inferior parietal lobule (IPL) and the medial prefrontal cortex (mPFC). We speculated that the left IPL might be associated with superior feature identification, and mPFC might be related to cognitive inhibition of global processing bias. These results suggested that the underlying neuroanatomical and functional bases were linked to the individual differences in FDI cognitive styles and emphasized the important contribution of superior local processing ability and cognitive inhibition to field-independent style.     

Differential Contributions of Dorso-Ventral and Rostro-Caudal Prefrontal White Matter Tracts to Cognitive Control in Healthy Older Adults

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions –episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex''s role in semantic control and the dorsolateral prefrontal cortex''s role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.     

Levels of integration in cognitive control and sequence processing in the prefrontal cortex

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.     

Altered Network Topologies and Hub Organization in Adults with Autism: A Resting-State fMRI Study

Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of “hubness” in several nodes (e.g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC.     

A Longitudinal Study of Atrophy in Amnestic Mild Cognitive Impairment and Normal Aging Revealed by Cortical Thickness

In recent years, amnestic mild cognitive impairment (aMCI) has attracted significant attention as an indicator of high risk for Alzheimer''s disease. An understanding of the pathology of aMCI may benefit the development of effective clinical treatments for dementia. In this work, we measured the cortical thickness of 109 aMCI subjects and 99 normal controls (NC) twice over two years. The longitudinal changes and the cross-sectional differences between the two types of participants were explored using the vertex thickness values. The thickness of the cortex in aMCI was found significantly reduced in both longitudinal and between-group comparisons, mainly in the temporal lobe, superolateral parietal lobe and some regions of the frontal cortices. Compared to NC, the aMCI showed a significantly high atrophy rate in the left lateral temporal lobe and left parahippocampal gyrus over two years. Additionally, a significant positive correlation between brain atrophy and the decline of Mini-Mental State Examination (MMSE) scores was also found in the left superior and left middle temporal gyrus in aMCI. These findings demonstrated specific longitudinal spatial patterns of cortical atrophy in aMCI and NC. The higher atrophy rate in aMCI might be responsible for the accelerated functional decline in the aMCI progression process.     

Distinct neurocognitive strategies for comprehensions of human and artificial intelligence

Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence.     

The effect of tryptophan depletion on brain activation measured by functional magnetic resonance imaging during the Stroop test in healthy subjects

We investigated the role of serotonin in cognitive activation of the frontal cortex. The serotonergic system was affected by the administration of an amino acids mixture without tryptophan (tryptophan depletion). In a placebo-controlled double-blind cross-over study with 20 healthy volunteers, we tested the hypothesis that a tryptophan (serotonin) decrease affects the activation of prefrontal cortex by the Stroop test. Cognitive brain activation was evaluated by functional magnetic resonance imaging (fMRI). Tryptophan depletion decreased the plasma tryptophan level up to 90 % for five hours after the tryptophan-free drink had been consumed when compared with the same mixture with tryptophan (p?0.0001). Tryptophan depletion did not affect the Stroop test performance. We compared fMRI activation in both conditions (tryptophan depletion and placebo) with plasma tryptophan levels as the covariates. The tryptophan depletion increased the activation (fMRI signal) in the bilateral mediofrontal cortex, anterior cingulate and left dorsolateral prefrontal cortex. The present findings allow the postulate that serotonergic medial forebrain and cingulum bundle pathways play a role in the activity of cortical structures involved in Stroop test processing.     

Evaluation of Resting State Networks in Patients with Gliomas: Connectivity Changes in the Unaffected Side and Its Relation to Cognitive Function

In this study, we investigated changes in resting state networks (RSNs) in patients with gliomas located in the left hemisphere and its relation to cognitive function. We hypothesized that long distance connection, especially between hemispheres, would be affected by the presence of the tumor. We further hypothesized that these changes would correlate with, or reflect cognitive changes observed in patients with gliomas. Resting state functional MRI datasets from 12 patients and 12 healthy controls were used in the analysis. The tumor’s effect on three well-known RSNs including the default mode network (DMN), executive control network (ECN), and salience network (SN) identified using independent component analysis were investigated using dual regression analysis. Scores of neuropsychometric testing (WAIS-III and WMS-R) were also compared. Compared to the healthy control group, the patient group showed significant decrease in functional connectivity in the right angular gyrus/inferior parietal lobe of the ventral DMN and in the dorsolateral prefrontal cortex of the left ECN, whereas a significant increase in connectivity in the right ECN was observed in the right parietal lobe. Changes in connectivity in the right ECN correlated with spatial memory, while that on the left ECN correlated with attention. Connectivity changes in the ventral DMN correlated with attention, working memory, full IQ, and verbal IQ measures. Although the tumors were localized in the left side of the brain, changes in connectivity were observed in the contralateral side. Moreover, these changes correlated with some aspects of cognitive function indicating that patients with gliomas may undergo cognitive changes even in the absence of or before the onset of major symptoms. Evaluation of resting state networks could be helpful in advancing our hodological understanding of brain function in glioma cases.     

Learning, working memory, and intelligence revisited

Based on early findings showing low correlations between intelligence test scores and learning on laboratory tasks, psychologists typically have dismissed the role of learning in intelligence and emphasized the role of working memory instead. In 2006, however, B.A. Williams developed a verbal learning task inspired by three-term reinforcement contingencies and reported unexpectedly high correlations between this task and Raven's Advanced Progressive Matrices (RAPM) scores [Williams, B.A., Pearlberg, S.L., 2006. Learning of three-term contingencies correlates with Raven scores, but not with measures of cognitive processing. Intelligence 34, 177-191]. The present study replicated this finding: Performance on the three-term learning task explained almost 25% of the variance in RAPM scores. Adding complex verbal working memory span, measured using the operation span task, did not improve prediction. Notably, this was not due to a lack of correlation between complex working memory span and RAPM scores. Rather, it occurred because most of the variance captured by the complex working memory span was already accounted for by the three-term learning task. Taken together with the findings of Williams and Pearlberg, the present results make a strong case for the role of learning in performance on intelligence tests.     

Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial

Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

Neural activity in the human brain relating to uncertainty and arousal during anticipation

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.     

Structural Interactions within the Default Mode Network Identified by Bayesian Network Analysis in Alzheimer’s Disease

Alzheimer’s disease (AD) is a well-known neurodegenerative disease that is associated with dramatic morphological abnormalities. The default mode network (DMN) is one of the most frequently studied resting-state networks. However, less is known about specific structural dependency or interactions among brain regions within the DMN in AD. In this study, we performed a Bayesian network (BN) analysis based on regional grey matter volumes to identify differences in structural interactions among core DMN regions in structural MRI data from 80 AD patients and 101 normal controls (NC). Compared to NC, the structural interactions between the medial prefrontal cortex (mPFC) and other brain regions, including the left inferior parietal cortex (IPC), the left inferior temporal cortex (ITC) and the right hippocampus (HP), were significantly reduced in the AD group. In addition, the AD group showed prominent increases in structural interactions from the left ITC to the left HP, the left HP to the right ITC, the right HP to the right ITC, and the right IPC to the posterior cingulate cortex (PCC). The BN models significantly distinguished AD patients from NC with 87.12% specificity and 81.25% sensitivity. We then used the derived BN models to examine the replicability and stability of AD-associated BN models in an independent dataset and the results indicated discriminability with 83.64% specificity and 80.49% sensitivity. The results revealed that the BN analysis was effective for characterising regional structure interactions and the AD-related BN models could be considered as valid and predictive structural brain biomarker models for AD. Therefore, our study can assist in further understanding the pathological mechanism of AD, based on the view of the structural network, and may provide new insights into classification and clinical application in the study of AD in the future.     

Creating abstract topographic representations: Implications for coding,learning and reasoning

Topographic maps are a fundamental and ubiquitous feature of the sensory and motor regions of the brain. There is less evidence for the existence of conventional topographic maps in associational areas of the brain such as the prefrontal cortex and parietal cortex. The existence of topographically arranged anatomical projections is far more widespread and occurs in associational regions of the brain as well as sensory and motor regions: this points to a more widespread existence of topographically organised maps within associational cortex than currently recognised. Indeed, there is increasing evidence that abstract topographic representations may also occur in these regions. For example, a topographic mnemonic map of visual space has been described in the dorsolateral prefrontal cortex and topographically arranged visuospatial attentional signals have been described in parietal association cortex. This article explores how abstract representations might be extracted from sensory topographic representations and subsequently code abstract information. Finally a simple model is presented that shows how abstract topographic representations could be integrated with other information within the brain to solve problems or form abstract associations. The model uses correlative firing to detect associations between different types of stimuli. It is flexible because it can produce correlations between information represented in a topographic or non-topographic coordinate system. It is proposed that a similar process could be used in high-level cognitive operations such as learning and reasoning.