Intrinsic Functional Architecture Research Articles

Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest

Anticorrelation between the default and dorsal attention networks is a central feature of human functional brain organization. Hallmarks of aging include impaired default network modulation and declining medial temporal lobe (MTL) function. However, it remains unclear if this anticorrelation is preserved into older adulthood during task performance, or how this is related to the intrinsic architecture of the brain. We hypothesized that older adults would show reduced within- and increased between-network functional connectivity (FC) across the default and dorsal attention networks. To test this hypothesis, we examined the effects of aging on task-related and intrinsic FC using functional magnetic resonance imaging during an autobiographical planning task known to engage the default network and during rest, respectively, with young (n = 72) and older (n = 79) participants. The task-related FC analysis revealed reduced anticorrelation with aging. At rest, there was a robust double dissociation, with older adults showing a pattern of reduced within-network FC, but increased between-network FC, across both networks, relative to young adults. Moreover, older adults showed reduced intrinsic resting-state FC of the MTL with both networks suggesting a fractionation of the MTL memory system in healthy aging. These findings demonstrate age-related dedifferentiation among these competitive large-scale networks during both task and rest, consistent with the idea that age-related changes are associated with a breakdown in the intrinsic functional architecture within and among large-scale brain networks.

Intrinsic functional network architecture of human semantic processing: Modules and hubs

Semantic processing entails the activation of widely distributed brain areas across the temporal, parietal, and frontal lobes. To understand the functional structure of this semantic system, we examined its intrinsic functional connectivity pattern using a database of 146 participants. Focusing on areas consistently activated during semantic processing generated from a meta-analysis of 120 neuroimaging studies (Binder et al., 2009), we found that these regions were organized into three stable modules corresponding to the default mode network (Module DMN), the left perisylvian network (Module PSN), and the left frontoparietal network (Module FPN). These three dissociable modules were integrated by multiple connector hubs—the left angular gyrus (AG) and the left superior/middle frontal gyrus linking all three modules, the left anterior temporal lobe linking Modules DMN and PSN, the left posterior portion of dorsal intraparietal sulcus (IPS) linking Modules DMN and FPN, and the left posterior middle temporal gyrus (MTG) linking Modules PSN and FPN. Provincial hubs, which converge local information within each system, were also identified: the bilateral posterior cingulate cortices/precuneus, the bilateral border area of the posterior AG and the superior lateral occipital gyrus for Module DMN; the left supramarginal gyrus, the middle part of the left MTG and the left orbital inferior frontal gyrus (IFG) for Module FPN; and the left triangular IFG and the left IPS for Module FPN. A neuro-functional model for semantic processing was derived based on these findings, incorporating the interactions of memory, language, and control.

Task-switching Cost and Intrinsic Functional Connectivity in the Human Brain: Toward Understanding Individual Differences in Cognitive Flexibility.

The human ability to flexibly alternate between tasks (i.e., task-switching) represents a critical component of cognitive control. Many functional magnetic resonance imaging (fMRI) studies have explored the neural basis of the task-switching. However, no study to date has examined how individual differences in intrinsic functional architecture of the human brain are related to that of the task-switching. In the present study, we took 11 task-switching relevant areas from a meta-analysis study as the regions of interests (ROIs) and estimated their intrinsic functional connectivity (iFC) with the whole brain. This procedure was repeated for 32 healthy adults based upon their fMRI scans during resting-state (rfMRI) to investigate the correlations between switching cost and the iFC strength across these participants. This analysis found that switch cost was negatively correlated with a set of iFC involved ROIs including left inferior frontal junction, bilateral superior posterior parietal cortex, left precuneus, bilateral inferior parietal lobule, right middle frontal gyrus and bilateral middle occipital gyrus. These connectivity profiles represent an intrinsic functional architecture of task-switching where the left inferior frontal junction plays a hub role in this brain-behavior association. These findings are highly reproducible in another validation independent sample and provide a novel perspective for understanding the neural basis of individual differences in task-switching behaviors reflected in the intrinsic architecture of the human brain.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

BackgroundNeuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. MethodsWe compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8–14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). ResultsAt-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. ConclusionsChildren at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression.

Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility

Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum – VS, ventral tegmental area – VTA), motor (supplementary motor areas – SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex – mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex – lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex – dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control.

Emotional susceptibility trait modulates insula responses and functional connectivity in flavor processing

The present study aimed at investigating the relationship between Emotional Susceptibility (ES), an aspect of the personality trait Neuroticism, and individual differences in the neural responses in anterior insula to primary sensory stimuli colored by affective valence, i.e., distasting or pleasantly tasting oral stimuli. In addition, it was studied whether intrinsic functional connectivity patterns of brain regions characterized by such differential responses could be related to ES. To this purpose 25 female participants underwent functional magnetic resonance imaging scanning, while being involved in a flavor experiment. During the experiment, flavor stimuli were administered consisting of small amounts of liquid with a different affective valence: neutral, pleasant, unpleasant. The results showed that individual differences in ES trait predicted distinct neural activity patterns to the different stimulus conditions in a region of left anterior insula that a previous meta-analysis revealed to be linked with olfacto-gustatory processing. Specifically, low ES was associated with enhanced neural responses to both pleasant and unpleasant stimuli, compared to neutral stimuli. By contrast, high ES participants showed equally strong neural responses to all types of stimuli without differentiating between the neutral and affective stimuli. Finally, during a task-free state, high ES trait appeared also to be related to decreased intrinsic functional connectivity between left anterior insula and left cerebellum. Our findings show that individual differences in ES are associated with differential anterior insula responses to primary sensory (flavor) stimuli as well as to intrinsic functional cortico-cerebellar connectivity, the latter suggesting a basis in the brain intrinsic functional architecture of the regulation of emotional experiences.

Regional homogeneity changes in patients with primary insomnia.

The study aimed to explore the regional spontaneous activity changes in primary insomnia (PI) patients. Based on the resting-state fMRI datasets acquired from 59 PI patients and 47 healthy controls, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Relationships between abnormal ReHo values and the Pittsburgh Sleep Quality Index (PSQI), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were investigated with Pearson correlation analysis. In PI patients, we found increased ReHo in the left insula, right anterior cingulate gyrus, bilateral precentral gyrus and left cuneus, as well as decreased ReHo in the right middle cingulate cortex and left fusiform (p < 0.05, AlphaSim-corrected). We also found a significant positive correlation between increased ReHo in the left insula and SAS scores, decreased ReHo in the right middle cingulated cortex and SDS, SAS scores as well as a negative correlation between increased ReHo in the right precentral gyrus and SDS scores (p < 0.05). Our study found abnormal spontaneous activities in multiple brain regions, especially in emotion-related areas in PI patients. Alterative activities in these regions might contribute to an understanding the intrinsic functional architecture of insomnia and its clinical features. • Regional spontaneous activity changes were detected in PI patients. • Decreased or increased ReHo of some regions was identified in PI patients. • Significant correlations between mean ReHo and SDS scores were found.

Cortisol awakening response predicts intrinsic functional connectivity of the medial prefrontal cortex in the afternoon of the same day

Cortisol awakening response (CAR) is the cortisol secretory activity in the first 30–60min immediately after awakening in the morning. Alterations in CAR as a trait have been associated with changes in the brain structure and function. CAR also fluctuates over days. Little, however, is known about the relationship between CAR as a state and brain activity. Using resting-state functional magnetic resonance imaging (fMRI), we investigated whether the CAR predicts intrinsic functional connectivity (FC) of the brain in the afternoon of the same day. Data from forty-nine healthy participants were analyzed. Salivary cortisol levels were assessed immediately after awakening and 15, 30 and 60min after awakening, and resting-state fMRI data were obtained in the afternoon. Global FC strength (FCS) of each voxel was computed to provide a whole-brain characterization of intrinsic functional architecture. Correlation analysis was used to examine whether CAR predicts the intrinsic FC of core brain networks. We observed that the CAR was positively correlated with the FCS of the medial prefrontal cortex (mPFC). Further analysis revealed that higher CAR predicted stronger positive mPFC connectivity with regions in the default mode network. Our findings suggest that the HPA activity after awakening in the early morning may predict intrinsic functional connectivity of mPFC at rest in the afternoon of the same day.

Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments.

The influence of mild carbon dioxide on brain functional homotopy using resting-state fMRI.

Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS-fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory-motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease.

Emotion regulation ability varies in relation to intrinsic functional brain architecture.

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture.

Widespread correlation patterns of fMRI signal across visual cortex reflect eccentricity organization.

The human visual system can be divided into over two-dozen distinct areas, each of which contains a topographic map of the visual field. A fundamental question in vision neuroscience is how the visual system integrates information from the environment across different areas. Using neuroimaging, we investigated the spatial pattern of correlated BOLD signal across eight visual areas on data collected during rest conditions and during naturalistic movie viewing. The correlation pattern between areas reflected the underlying receptive field organization with higher correlations between cortical sites containing overlapping representations of visual space. In addition, the correlation pattern reflected the underlying widespread eccentricity organization of visual cortex, in which the highest correlations were observed for cortical sites with iso-eccentricity representations including regions with non-overlapping representations of visual space. This eccentricity-based correlation pattern appears to be part of an intrinsic functional architecture that supports the integration of information across functionally specialized visual areas.

Impaired consciousness is linked to changes in effective connectivity of the posterior cingulate cortex within the default mode network

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness.We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness.The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness.These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex.

Increased interhemispheric functional connectivity in college students with non-clinical depressive symptoms in resting state

The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains unclear. Interhemispheric functional connectivity has been suggested as one of the most robust characteristics of brain’s intrinsic functional architecture. Here, we investigated the functional connectivity between homotopic points in the brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We performed VMHC analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who were enrolled from a sample of 1105 college students. We found increased VMHCs in the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated that VMHC values in the posterior cerebellum lobes could use to differente nCDSs from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs indicate a possible compensatory mechanism involved in the pathophysiology of nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable biomarker for identifying nCDSs.

Resting-State fMRI in MS: General Concepts and Brief Overview of Its Application.

Brain functional connectivity (FC) is defined as the coherence in the activity between cerebral areas under a task or in the resting-state (RS). By applying functional magnetic resonance imaging (fMRI), RS FC shows several patterns which define RS brain networks (RSNs) involved in specific functions, because brain function is known to depend not only on the activity within individual regions, but also on the functional interaction of different areas across the whole brain. Region-of-interest analysis and independent component analysis are the two most commonly applied methods for RS investigation. Multiple sclerosis (MS) is characterized by multiple lesions mainly affecting the white matter, determining both structural and functional disconnection between various areas of the central nervous system. The study of RS FC in MS is mainly aimed at understanding alterations in the intrinsic functional architecture of the brain and their role in disease progression and clinical impairment. In this paper, we will examine the results obtained by the application of RS fMRI in different multiple sclerosis (MS) phenotypes and the correlations of FC changes with clinical features in this pathology. The knowledge of RS FC changes may represent a substantial step forward in the MS research field, both for clinical and therapeutic purposes.

Resting-state anticorrelations between medial and lateral prefrontal cortex: Association with working memory, aging, and individual differences

We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex (DLPFC), a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of WM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity.

Altered brain spontaneous activity and connectivity network in irritable bowel syndrome patients: A resting-state fMRI study

ObjectiveWe aimed to provide additional evidence that brain functional alterations induced by IBS are not limited to local changes but also express at a level of functional integration within related brain regions involved in processing of visceral afferent information and somatic pain. MethodsWith fMRI data acquired from 21 IBS and healthy control (HC) subjects. We investigated the amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) to reveal the changes of the brain spontaneous activity and the interaction among different related regions. ResultsIBS patients showed decreased ALFF values in the left superior frontal gyrus, right hippocampus, right middle frontal gyrus, bilateral postcentral, and right superior temporal pole, while increased ALFF values in the left median cingulate and left calcarine. There was significant correlation between ALFF values in the altered regions and duration of disease in IBS. FC analysis revealed the increased connectivity between cingulate and frontal cortex in IBS. ConclusionsOur findings could provide both regional and brain connectivity spontaneous neuronal activity properties in IBS. SignificanceOur study may lead to a better understanding of intrinsic functional architecture of brain activity in IBS and highlight the potential for using the ALFF and FC metrics as a disease biomarker.

Lag in maturation of the brain's intrinsic functional architecture in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood, and there is great interest in understanding its neurobiological basis. A prominent neurodevelopmental hypothesis proposes that ADHD involves a lag in brain maturation. Previous work has found support for this hypothesis, but examinations have been limited to structural features of the brain (e.g., gray matter volume or cortical thickness). More recently, a growing body of work demonstrates that the brain is functionally organized into a number of large-scale networks, and the connections within and between these networks exhibit characteristic patterns of maturation. In this study, we investigated whether individuals with ADHD (age 7.2-21.8 y) exhibit a lag in maturation of the brain's developing functional architecture. Using connectomic methods applied to a large, multisite dataset of resting state scans, we quantified the effect of maturation and the effect of ADHD at more than 400,000 connections throughout the cortex. We found significant and specific maturational lag in connections within default mode network (DMN) and in DMN interconnections with two task positive networks (TPNs): frontoparietal network and ventral attention network. In particular, lag was observed within the midline core of the DMN, as well as in DMN connections with right lateralized prefrontal regions (in frontoparietal network) and anterior insula (in ventral attention network). Current models of the pathophysiology of attention dysfunction in ADHD emphasize altered DMN-TPN interactions. Our finding of maturational lag specifically in connections within and between these networks suggests a developmental etiology for the deficits proposed in these models.

Hyper-coupling between working memory task-evoked activations and amplitude of spontaneous fluctuations in first-episode schizophrenia

Working memory (WM) deficit is an important component of impaired cognition in schizophrenia. However, between-studies inconsistencies as to the specific functional substrate imply that inter-individual variability (IIV) in the WM performance is associated with IIV in brain activity in schizophrenia. To examine the neural substrate of this WM IIV, we studied whether the neural mechanisms that underlie individual differences in WM capacity are the same in schizophrenia patients and healthy people. We correlated the IIV of the task-evoked brain activity and task performance during an n-back WM task with the IIV of the moment-to-moment variability in intrinsic resting-state activity, as measured by the amplitude of low-frequency fluctuations (ALFFs) and further compared this relationship between 17 patients with first-episode schizophrenia (FES) and 18 healthy controls. Between-group comparisons of the correlation patterns indicated aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in the FES patients, but no significant changes were detected in any single measurement of these three characteristics. Specifically, we found increased positive ALFF-WM activation correlations in the bilateral lateral prefrontal cortices, posterior parietal cortices and fusiform gyri in the FES patients. We also observed significant increases in positive ALFF-WM performance correlations in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper-coupling between the ALFF and fMRI measures during a WM task may indicate that it was difficult for the patients to detach themselves from one state to transition to another and suggests that the inefficient cortical function in schizophrenia stems from the intrinsic functional architecture of the brain.

A correspondence between individual differences in the brain's intrinsic functional architecture and the content and form of self-generated thoughts.

Although neural activity often reflects the processing of external inputs, intrinsic fluctuations in activity have been observed throughout the brain. These may relate to patterns of self-generated thought that can occur while not performing goal-driven tasks. To understand the relationship between self-generated mental activity and intrinsic neural fluctuations, we developed the New York Cognition Questionnaire (NYC-Q) to assess the content and form of an individual's experiences during the acquisition of resting-state fMRI data. The data were collected as a part of the Nathan Kline Rockland Enhanced sample. We decomposed NYC-Q scores using exploratory factor analysis and found that self-reported thoughts clustered into distinct dimensions of content (future related, past related, positive, negative, and social) and form (words, images, and specificity). We used these components to perform an individual difference analysis exploring how differences in the types of self-generated thoughts relate to whole brain measures of intrinsic brain activity (fractional amplitude of low frequency fluctuations, regional homogeneity, and degree centrality). We found patterns of self-generated thoughts related to changes that were distributed across a wide range of cortical areas. For example, individuals who reported greater imagery exhibited greater low frequency fluctuations in a region of perigenual cingulate cortex, a region that is known to participate in the so-called default-mode network. We also found certain forms of thought were associated with other areas, such as primary visual cortex, the insula, and the cerebellum. For example, individuals who reported greater future thought exhibited less homogeneous neural fluctuations in a region of lateral occipital cortex, a result that is consistent with the claim that particular types of self-generated thought depend on processes that are decoupled from sensory processes. These data provide evidence that self-generated thought is a heterogeneous category of experience and that studying its content can be helpful in understanding brain dynamics.