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In this study, we merged methods from engineering control theory, machine learning, and human neuroimaging to critically test the putative role of the dorsal anterior cingulate cortex (dACC) in goal-directed performance monitoring during an emotion regulation task. Healthy adult participants (n=94) underwent cued-recall and re-experiencing of their responses to affective image stimuli with concurrent functional magnetic resonance imaging and psychophysiological response recording. During cued-recall/re-experiencing trials, participants engaged in explicit self-regulation of their momentary affective state to match a pre-defined affective goal state. Within these trials, neural decoding methods measured affect processing from fMRI BOLD signals across the orthogonal affective dimensions of valence and arousal. Participants’ affective brain states were independently validated via facial electromyography (valence) and electrodermal activity (arousal) responses. The decoded affective states were then used to contrast four computational models of performance monitoring (i.e., error, predicted response outcome, action-value, and conflict) by their relative abilities to explain emotion regulation task-related dACC activation. We found that the dACC most plausibly encodes action-value for both valence and arousal processing. We also confirmed that dACC activation directly encodes affective arousal and also likely encodes recruitment of attention and regulation resources. Beyond its contribution to improving our understanding of the roles that the dACC plays in emotion regulation, this study introduced a novel analytical framework through which affect processing and regulation may be functionally dissociated, thereby permitting mechanistic analysis of real-world emotion regulation strategies, e.g., distraction and reappraisal, which are widely employed in cognitive behavioral therapy to address clinical deficits in emotion regulation.

Background Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)—with its capability to improve neuronal function—may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC). Methods Eleven PWH (47–69 years old, 2 females, 100% African Americans, disease duration 16–36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2–3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1. Results Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test—Part B (TMT-B) to TMT—Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS. Conclusions Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p

Cognitive impairment is a common symptom in individuals with Multiple Sclerosis (MS), but meaningful, reliable biomarkers relating to cognitive decline have been elusive, making evaluation of the impact of therapeutics on cognitive function difficult. Here, we combine pathway-based MRI measures of structural and functional connectivity to construct a metric of functional decline in MS. The Structural and Functional Connectivity Index (SFCI) is proposed as a simple, z-scored metric of structural and functional connectivity, where changes in the metric have a simple statistical interpretation and may be suitable for use in clinical trials. Using data collected at six time points from a 2-year longitudinal study of 20 participants with MS and 9 age- and sex-matched healthy controls, we probe two common symptomatic domains, motor and cognitive function, by measuring structural and functional connectivity in the transcallosal motor pathway and posterior cingulum bundle. The SFCI is significantly lower in participants with MS compared to controls (p = 0.009) and shows a significant decrease over time in MS (p = 0.012). The change in SFCI over two years performed favorably compared to measures of brain parenchymal fraction and lesion volume, relating to follow-up measures of processing speed (r = 0.60, p = 0.005), verbal fluency (r = 0.57, p = 0.009), and score on the Multiple Sclerosis Functional Composite (r = 0.67, p = 0.003). These initial results show that the SFCI is a suitable metric for longitudinal evaluation of functional decline in MS.

Apathy is defined as reduction of goal-directed behaviors and a common nuisance syndrome of neurodegenerative and psychiatric disease. The underlying mechanism of apathy implicates changes of the front-striatal circuit, but its precise alteration is unclear for apathy in healthy aged people. The aim of our study is to investigate how the frontal-striatal circuit is changed in elderly with apathy using resting-state functional MRI. Eighteen subjects with apathy (7 female, 63.7 ± 3.0 years) and eighteen subjects without apathy (10 female, 64.8 ± 3.0 years) who underwent neuropsychological assessment and MRI measurement were recruited. We compared functional connectivity with/within the striatum between the apathy and non-apathy groups. The seed-to-voxel group analysis for functional connectivity between the striatum and other brain regions showed that the connectivity was decreased between the ventral rostral putamen and the right dorsal anterior cingulate cortex/supplementary motor area in the apathy group compared to the non-apathy group while the connectivity was increased between the dorsal caudate and the left sensorimotor area. Moreover, the ROI-to-ROI analysis within the striatum indicated reduction of functional connectivity between the ventral regions and dorsal regions of the striatum in the apathy group. Our findings suggest that the changes in functional connectivity balance among different frontal-striatum circuits contribute to apathy in elderly.

In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)–to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as “switched off” in generalized allodynia.

Bilingual language experience, such as switching between languages, has been shown to shape both cognitive and neural mechanisms of non-linguistic cognitive control. However, the neural adaptations induced by language switching remain unclear. Using fMRI, the current study examined the impact of short-term language switching training on the neural network of domain-general cognitive control for unbalanced Chinese-English bilinguals. Effective connectivity maps were constructed by using the extended unified structural equation models (euSEM) within 10 common brain regions involved in both language control and domain-general cognitive control. Results showed that, the dorsal anterior cingulate cortex/pre-supplementary motor area (dACC/pre-SMA) lost connection from the right thalamus after training, suggesting that less neural connectivity was required to complete the same domain-general cognitive control task. These findings not only provide direct evidence for the modulation of language switching training on the neural interaction of domain-general cognitive control, but also have important implications for revealing the potential neurocognitive adaptation effects of specific bilingual language experiences.

Interrogation elicits anxiety in individuals under scrutiny regardless of their innocence, and thus, anxious responses to interrogation should be differentiated from deceptive behavior in practical lie detection settings. Despite its importance, not many empirical studies have yet been done to separate the effects of interrogation from the acts of lying or guilt state. The present fMRI study attempted to identify neural substrates of anxious responses under interrogation in either innocent or guilt contexts by developing a modified "Doubt" game. Participants in the guilt condition showed higher brain activations in the right central-executive network and bilateral basal ganglia. Regardless of the person's innocence, we observed higher activation of the salience, theory of mind and sensory-motor networks-areas associated with anxiety-related responses in the interrogative condition, compared to the waived conditions. We further explored two different types of anxious responses under interrogation-true detection anxiety in the guilty (true positive) and false detection anxiety in the innocent (false positive). Differential neural responses across these two conditions were captured at the caudate, thalamus, ventral anterior cingulate and ventromedial prefrontal cortex. We conclude that anxiety is a common neural response to interrogation, regardless of an individual's innocence, and that there are detectable differences in neural responses for true positive and false positive anxious responses under interrogation. The results of our study highlight a need to isolate complex cognitive processes involved in the deceptive acts from the emotional and regulatory responses to interrogation in lie detection schemes.

ObjectivesThe study aimed at determining the EEG correlates of concentration on either low or high-distressed tinnitus.MethodsSixty-seven patients (36 women, mean age = 50.34 ± 12.94 years) with chronic tinnitus were assigned to either a high (HD) or low (LD) tinnitus-related distress group based on THI results. All participants took part in the EEG study comprising two 3-4 min blocks of focusing on either tinnitus (Tinnitus Focus Condition, TFC) or the sensations from one's own body (Body Focus Condition, BFC). The absolute power and current density of 8 frequency bands in 7 clusters were compared between conditions and groups.ResultsThe most pronounced differences were found in the HD patients in the TFC, relative to the BFC, i.e. reduced power of frontally distributed low alpha (8-10 Hz) and posterior high alpha (10-12 Hz) as well as lower current density of 8-10 Hz rhythm over the right frontal/anterior cingulate cortex and higher middle beta (15-18 Hz) density in the precuneus. The HD, relative to LD patients, in both conditions, exhibited increased low beta (12-15 Hz) power over the left middle area and greater higher beta (15-25 Hz) power in the left posterior region.ConclusionsThe present study contrasted bioelectrical activity, acquired when concentrating on tinnitus with EEG data collected whilst patients focused on their body. Decreased alpha power and current density in the frontal/cingulate cortex when listening to bothersome tinnitus might reflect greater cortical arousal whereas increased beta power and density in the precuneus/posterior cingulate activity in this condition could be indicative for elevated tension or augmented cognitive/emotional processing of tinnitus sound. Enhanced beta rhythm in patients with high versus low tinnitus distress, observed independently of the study condition, may be due to greater self-focused attention or more active processing of sensations derived from the own body.

Background Chronic pain has been associated with alterations in brain structure and function that appear dependent on pain phenotype. Functional connectivity (FC) data on chronic back pain (CBP) is limited and based on heterogeneous pain populations. We hypothesize that failed back surgery syndrome (FBSS) patients being considered for spinal cord stimulation (SCS) therapy have altered resting state (RS) FC cross-network patterns that 1) specifically involve emotion and reward/aversion functions and 2) are related to pain scores. Methods RS functional MRI (fMRI) scans were obtained for 10 FBSS patients who are being considered for but who have not yet undergone implantation of a permanent SCS device and 12 healthy age-matched controls. Seven RS networks were analyzed including the striatum (STM). The Wilcoxon signed-rank test evaluated differences in cross-network FC strength (FCS). Differences in periaqueductal grey (PAG) FC were assessed with seed-based analysis. Results Cross-network FCS was decreased (p

The present study employed functional magnetic resonance imaging (fMRI) to examine the characteristics of negative blood oxygen level-dependent (Negative BOLD) signals during motor execution. Subjects repeated extension and flexion of one of the following: the right hand, left hand, right ankle, or left ankle. Negative BOLD responses during hand movements were observed in the ipsilateral hemisphere of the hand primary sensorimotor area (SMI), medial frontal gyrus (MeFG), middle frontal gyrus (MFG), and superior frontal gyrus (SFG). Negative BOLD responses during foot movements were also noted in the bilateral hand SMI, MeFG, MFG, SFG, inferior frontal gyrus, middle temporal gyrus, parahippocampal gyrus, anterior cingulate cortex, cingulate gyrus (CG), fusiform gyrus, and precuneus. A conjunction analysis showed that portions of the MeFG and CG involving similar regions to those of the default mode network were commonly deactivated during voluntary movements of the right/left hand or foot. The present results suggest that three mechanisms are involved in the Negative BOLD responses observed during voluntary movements: (1) transcallosal inhibition from the contralateral to ipsilateral hemisphere in the SMI, (2) the deactivated neural network with several brain regions, and (3) the default mode network in the MeFG and CG.

Happiness, or Subjective Well-Being (SWB), is generally considered as a peaceful and satisfied state accompanied by consistent and optimistic mood. Due to its subjective and elusive nature, however, wellbeing has only been scarcely investigated in the neuroimaging literature. In this study, we investigated its neural substrates by characterizing two different perspectives: self- or other-concerned wellbeing. In the present study, 22 participants evaluated the subjective happiness (with button presses 1 to 4) to 3 categories (intra- and inter-personal and neutral) of pre-rated pictures in a slow event-related fMRI. Because wellbeing is constantly featured by pleasure feelings after self-inspection, we predict that happier conditions, featured by “intra-personal vs. neutral” and “inter-personal vs. neutral” conditions, should yield higher BOLD activities in overlapping reward- and self-related regions. Indeed, medial prefrontal (mPFC), pregenual ACC (pACC), precuneus and posterior cingulate cortex (PCC) were revealed both by General Linear Model (GLM) (categorical contrasts) and parametric modulations (correlations with rating 1-4s), specifically, more connectivity between nucleus accumbens (NAcc) and mPFC, via additional psychophysiological interaction, or PPI, analyses. More interestingly, GLM and multivariate searchlight analyses jointly reveal the subdivision of mPFC and the PCC/precuneus, with anterior mPFC and dorsal PCC/precuneus more for interpersonal, posterior mPFC and ventral PCC/precuneus more for intrapersonal, SWB, respectively. Taken together, these results are not only consistent with the “cortical midline hypothesis of the self”, but also extending the “spatial gradients of self-to-other-concerned processing” from mPFC to including both mPFC and PCC/precuneus, making them two “hubs” of self-to-other-concerned wellbeing network.

Introduction Early Huntington’s disease (HD) patients begin to show planning deficits even before motor alterations start to manifest. Generally, planning ability is associated with the functioning of anterior brain areas such as the medial prefrontal cortex. However, early HD neuropathology involves significant atrophy in the occipital and parietal cortex, suggesting that more posterior regions could also be involved in these planning deficits. Objective To identify brain regions associated with planning deficits in HD patients at an early clinical stage. Materials and methods Twenty-two HD-subjects genetically confirmed with incipient clinical manifestation and twenty healthy subjects were recruited. All participants underwent MRI T1 image acquisition as well as testing in the Stockings of Cambridge (SOC) task to measure planning ability. First, group comparison of SOC measures were performed. Then, correlation voxel-based morphometry analyses were done between gray matter degeneration and SOC performance in the HD group. Results Accuracy and efficiency planning scores correlated with gray matter density in right lingual gyrus, middle temporal gyrus, anterior cingulate gyrus, and paracingulate gyrus. Conclusions Our results suggest that planning deficits exhibited by early HD-subjects are related to occipital and temporal cortical degeneration in addition to the frontal areas deterioration.

How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory–related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level–dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.

Objective Aerobic fitness may be beneficial for neuroanatomical structure. However, few have investigated this in emerging adults while also accounting for potential sex differences. Here we examine aerobic fitness level, sex, and their interaction in relation to cortical thickness, surface area, and volume. Method Sixty-three young adults between the ages of 16–26 were balanced for sex and demonstrated a wide range of aerobic fitness levels. Exclusion criteria included left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal medical issues, prenatal alcohol/illicit drug exposure, or excessive substance use. Participants completed an MRI scan and a graded exercise test to volitional fatigue (VO2 max). Data analyses were run in Freesurfer and data was corrected for multiple comparisons with Monte Carlo simulations at .05. Results Males demonstrated higher VO2 values. Higher VO2 values were statistically independently related to thinner lateral occipital, superior parietal, cuneus, precuneus, and inferior parietal regions, smaller lateral occipital volume, and larger inferior parietal surface area. Compared to females, males had larger volume in rostral anterior cingulate, lateral occipital, and superior frontal regions, and greater surface area in fusiform, inferior parietal, rostral and caudal anterior cingulate, and superior parietal regions. VO2*Sex interactions revealed higher-fit females had higher inferior parietal, paracentral, and supramarginal surface area, while lower-fit males showed larger surface area in these same regions. Conclusions Individuals with higher aerobic fitness performance had thinner cortices, lower volume, and larger surface area in sensorimotor regions than lower fit individuals, perhaps suggesting earlier neuromaturation in higher fit individuals. Larger surface area was associated with higher-fit females and lower-fit males. Thus both sex and aerobic fitness are important in shaping brain health in emerging adults.

Episodic memory is the ability to learn, store and recall new information. The prefrontal cortex (PFC) is a crucial area engaged in this ability. Cognitive training has been demonstrated to improve episodic memory in adults and older subjects. However, there are no studies examining the effects of cognitive training on episodic memory encoding in typically developing children and adolescents. This study investigated the behavioral effects and neural correlates of semantic categorization strategy training in children and adolescents during verbal episodic memory encoding using functional magnetic resonance imaging (fMRI). Participants with age range: 7-18 years were scanned before and after semantic categorization training during encoding of word lists. Results showed improved memory performance in adolescents, but not in children. Deactivation of the anterior medial PFC/anterior cingulate and higher activation of the right anterior and lateral orbital gyri, right frontal pole and right middle frontal gyrus activation were found after training in adolescents when compared to children. These findings suggest different maturational paths of brain regions, especially in the PFC, and deactivation of default mode network areas, which are involved in successful memory and executive processes in the developing brain.

The link between anger and bodily states is readily apparent based on the autonomic and behavioral responses elicited. In everyday life angry people react in different ways, from being agitated with an increased heart rate to remaining silent or detached. Neuroimaging evidence supports the role of mid-posterior insula and midcingulate cortex/MCC as key nodes of a sensorimotor network that predominantly responds to salient stimuli, integration of interoceptive and autonomic information, as well as to awareness of bodily movements for coordinated motion. However, there is still a lack of clarity concerning how interindividual variability in bodily states reactions drives the connectivity within these key nodes in the sensorimotor network during anger processing. Therefore, we investigated whether individual differences in body-centered emotional experience, that is an active (inward prone) or inactive (outward prone) emotion-body connection disposition, would differently affect the information flow within these brain regions. Two groups of participants underwent fMRI scanning session watching video clips of actors performing simple actions with angry and joyful facial expressions. The whole-brain group-by-session interaction analysis showed that the bilateral insula and the right MCC were selectively activated by inward group during the angry session, whereas the outward group activated more the precuneus during the joyful session. Accordingly, dynamic causal modeling analyses (DCM) revealed an excitatory modulatory effect exerted by anger all over the insulae-MCC connectivity in the inward group, whereas in the outward group the modulatory effect exerted was inhibitory. Modeling the variability related to individual differences in body-centered emotional experience allowed to better explain to what extent subjective dispositions contributed to the insular activity and its connectivity. In addition, from the perspective of a hierarchical model of neurovisceral integration, these findings add knowledge to the multiple ways which the insula and MCC dynamically integrate affective and bodily aspects of the human experience.

We investigated whether negative feedback with information could benefit both behavioral and neural responses. Fifteen participants were scanned with functional magnetic resonance imaging (fMRI) while receiving various feedbacks in a novel perceptual task. Behavioral data showed that reaction times of task performance were faster after receiving negative informative feedback compared to negative confirmatory feedback. The fMRI analysis of the interaction contrast between feedback type (informative vs. confirmatory) and valence (negative vs. positive) showed greater activation in the ventrolateral prefrontal cortex (vlPFC) and the ventral striatum in response to negative informative compared to confirmatory feedback. The psychophysiological interactions (PPI) analyses showed that the vlPFC activation was positively correlated with the amygdala and the rostral cingulate zone (RCZ). The ventral striatum activation was negatively correlated with the dorsolateral prefrontal cortex (dlPFC). These results suggest that negative but informative feedback benefits subsequent performance and its primary function is to elicit positive prediction error (instructive signal) and to induce cognitive control to guide subsequent goal-directed behavior.

The visual color-word Stroop task is widely used in clinical and research settings as a measure of cognitive control. Numerous neuroimaging studies have used color-word Stroop tasks to investigate the neural resources supporting cognitive control, but to our knowledge all have used unimodal (typically visual) Stroop paradigms. Thus, it is possible that this classic measure of cognitive control is not capturing the resources involved in multisensory cognitive control. The audiovisual integration and crossmodal correspondence literatures identify regions sensitive to congruency of auditory and visual stimuli, but it is unclear how these regions relate to the unimodal cognitive control literature. In this study we aimed to identify brain regions engaged by crossmodal cognitive control during an audiovisual color-word Stroop task, and how they relate to previous unimodal Stroop and audiovisual integration findings. First, we replicated previous behavioral audiovisual Stroop findings in an fMRI-adapted audiovisual Stroop paradigm: incongruent visual information increased reaction time towards an auditory stimulus and congruent visual information decreased reaction time. Second, we investigated the brain regions supporting cognitive control during an audiovisual color-word Stroop task using fMRI. Similar to unimodal cognitive control tasks, a left superior parietal region exhibited an interference effect of visual information on the auditory stimulus. This superior parietal region was also identified using a standard audiovisual integration localizing procedure, indicating that audiovisual integration resources are sensitive to cognitive control demands. Facilitation of the auditory stimulus by congruent visual information was found in posterior superior temporal cortex, including in the posterior STS which has been found to support audiovisual integration. The dorsal anterior cingulate cortex, often implicated in unimodal Stroop tasks, was not modulated by the audiovisual Stroop task. Overall the findings indicate that an audiovisual color-word Stroop task engages overlapping resources with audiovisual integration and overlapping but distinct resources compared to unimodal Stroop tasks.

Somatostatin-expressing (SOM+), inhibitory interneurons represent a heterogeneous group of cells and given their remarkable diversity, classification of SOM+ interneurons remains a challenging task. Electrophysiological, morphological and neurochemical classes of SOM+ interneurons have been proposed in the past but it remains unclear as to what extent these classes are congruent. We performed whole-cell patch-clamp recordings from 127 GFP-labeled SOM+ interneurons ('GIN') of the superficial cingulate cortex with subsequent biocytin-filling and immunocytochemical labeling. Principal component analysis followed by k-means clustering predicted two putative subtypes of SOM+ interneurons, which we designated as group I and group II GIN. A key finding of our study is the fact that these electrophysiologically and morphologically distinct groups of SOM+ interneurons can be correlated with two neurochemical subtypes of SOM+ interneurons described recently in our laboratory. In particular, all SOM+ interneurons expressing calbindin but no calretinin could be classified as group I GIN, whereas all but one neuropeptide Y- and calretinin-positive interneurons were found in group II.

The neurobiology of sexual preference is often discussed in terms of cerebral sex dimorphism. Yet, our knowledge about possible cerebral differences between homosexual men (HoM), heterosexual men (HeM) and heterosexual women (HeW) are extremely limited. In the present MRI study, we addressed this issue investigating measures of cerebral anatomy and function, which were previously reported to show sex difference. Specifically, we asked whether there were any signs of sex atypical cerebral dimorphism among HoM, if these were widely distributed (providing substrate for more general ‘female’ behavioral characteristics among HoM), or restricted to networks involved in self-referential sexual arousal. Cortical thickness (Cth), surface area (SA), subcortical structural volumes, and resting state functional connectivity were compared between 30 (HoM), 35 (HeM) and 38 (HeW). HoM displayed a significantly thicker anterior cingulate cortex (ACC), precuneus, and the left occipito-temporal cortex compared to both control groups. These differences seemed coordinated, since HoM also displayed stronger cortico-cortical covariations between these regions. Furthermore, functional connections within the default mode network, which mediates self- referential processing, and includes the ACC and precuneus were significantly weaker in HoM than HeM and HeW, whereas their functional connectivity between the thalamus and hypothalamus (important nodes for sexual behavior) was stronger. In addition to these singular features, HoM displayed ‘female’ characteristics, with a similar Cth in the left superior parietal and cuneus cortices as HeW, but different from HeM. These data suggest both singular and sex atypical features and motivate further investigations of cerebral midline structures in relation to male homosexuality.

The neural mechanisms underlying visual perceptual learning (VPL) have typically been studied by examining changes in task-related brain activation after training. However, the relationship between post-task "offline" processes and VPL remains unclear. The present study examined this question by obtaining resting-state functional magnetic resonance imaging (fMRI) scans of human brains before and after a task-fMRI session involving visual perceptual training. During the task-fMRI session, participants performed a motion coherence discrimination task in which they judged the direction of moving dots with a coherence level that varied between trials (20, 40, and 80%). We found that stimulus-induced activation increased with motion coherence in the middle temporal cortex (MT+), a feature-specific region representing visual motion. On the other hand, stimulus-induced activation decreased with motion coherence in the dorsal anterior cingulate cortex (dACC) and bilateral insula, regions involved in decision making under perceptual ambiguity. Moreover, by comparing pre-task and post-task rest periods, we revealed that resting-state functional connectivity (rs-FC) with the MT+ was significantly increased after training in widespread cortical regions including the bilateral sensorimotor and temporal cortices. In contrast, rs-FC with the MT+ was significantly decreased in subcortical regions including the thalamus and putamen. Importantly, the training-induced change in rs-FC was observed only with the MT+, but not with the dACC or insula. Thus, our findings suggest that perceptual training induces plastic changes in offline functional connectivity specifically in brain regions representing the trained visual feature, emphasising the distinct roles of feature-representation regions and decision-related regions in VPL.

Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

Serotonin (5-HT) brain architecture appears to be implicated in normal personality traits as supported by genetic associations and studies using molecular brain imaging. However, so far, no studies have addressed potential contributions to variation in normal personality traits from in vivo serotonin 4 receptor (5-HT4R) brain availability, which has recently become possible to image with Positron Emission Tomography (PET). This is particularly relevant since availability of 5-HT4R has been shown to adapt to synaptic levels of 5-HT and thus offers information about serotonergic tone in the healthy brain. In 69 healthy participants (18 females), the associations between personality traits assessed with the five-factor NEO Personality Inventory-Revised (NEO PI-R) and regional cerebral 5-HT4R binding in neocortex, amygdala, hippocampus, and anterior cingulate cortex (ACC) were investigated using linear regression models. The associations between each of the five personality traits and a latent variable construct of global 5-HT4R levels were also evaluated using latent variable structural equation models. We found no significant associations between the five NEO personality traits and regional 5-HT4R binding (all p-values > .17) or the latent construct of global 5-HT4R levels (all p-values > .37). Our findings indicate that NEO personality traits and 5-HT4R are not related in healthy participants. Under the assumption that global 5-HT4R levels index 5-HT tone, our data also suggest that 5-HT tone per se is not directly implicated in normal personality traits.

Objective: \ud Time-based prospective memory (PM), remembering to do something at a particular\ud moment in the future, is considered to depend upon self-initiated strategic monitoring,\ud involving a retrieval mode (sustained maintenance of the intention) plus target checking\ud (intermittent time checks). The present experiment was designed to explore what brain\ud regions and brain activity are associated with these components of strategic monitoring in\ud time-based PM tasks.\ud Method: \ud 24 participants were asked to reset a clock every four minutes, while performing a foreground\ud ongoing word categorisation task. EEG activity was recorded and data were decomposed\ud into source-resolved activity using Independent Component Analysis. Common brain\ud regions across participants, associated with retrieval mode and target checking, were found\ud using Measure Projection Analysis.\ud Results: \ud Participants decreased their performance on the ongoing task when concurrently performed\ud with the time-based PM task, reflecting an active retrieval mode that relied on withdrawal of\ud limited resources from the ongoing task. Brain activity, with its source in or near the anterior\ud cingulate cortex (ACC), showed changes associated with an active retrieval mode including\ud greater negative ERP deflections, decreased theta synchronization, and increased alpha\ud suppression for events locked to the ongoing task while maintaining a time-based intention.\ud Activity in the ACC was also associated with time-checks and found consistently across participants;\ud however, we did not find an association with time perception processing per se.\ud Conclusion: \ud The involvement of the ACC in both aspects of time-based PM monitoring may be related to\ud different functions that have been attributed to it: strategic control of attention during the\ud retrieval mode (distributing attentional resources between the ongoing task and the timebased\ud task) and anticipatory/decision making processing associated with clock-checks.

Contains fulltext : 169889.pdf (Publisher’s version ) (Open Access) Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study's small sample size, potential clinical benefits need to be further investigated in future studies. TRIAL REGISTRATION: ISRCTN12390961.

Background & aims Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain–gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. Methods Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. Results The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. Conclusions Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

The relationship between impulsivity and cognitive control is still unknown. We hypothesized that trait impulsivity would differentially correlate with specific cognitive control processes. Trait impulsivity was measured by the Barratt Impulsiveness Scale, which assesses motor, attention, and non-planning impulsiveness components. Cognitive control was measured by a hybrid-designed Stroop task, which distinguishes proactive and reactive control. Thirty-three participants performed the Stroop task while they were scanned by functional magnetic resonance imaging. Proactive and reactive control involved increased activity in the fronto-parietal network, and brain activity was associated with impulsivity scores. Specifically, higher motor impulsiveness was associated with a larger proactive control effect in the inferior parietal lobule and a smaller reactive control effect in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate contex. Higher attention impulsivity was associated with a smaller proactive control effect in the right DLPFC. Such a correlation pattern suggests that impulsivity trait components are attributable to different cognitive control subsystems.

Purpose Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Methods Study participants consisted of 34 children with AS (2-12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2-11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. Results In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. Conclusion The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

OBJECTIVE To reveal the brain functional changes of nicotine addicts compared with those of non-smokers and explore the objective biomarker for nicotine dependence evaluation. METHODS A total of 14 smokers and 11 non-smoking controls were recruited for this study. Resting-state functional magnetic resonance imaging and regional homogeneity (ReHo) were applied in the neural activity analysis. Two-sample t-test was performed to examine the voxel-wise difference between the smokers and the controls. Correlation analysis between the ReHo values and the Fagerstrom Test for Nicotine Dependence (FTND) scores were performed to explore the biomarkers for the clinical characteristics of smokers. RESULTS The ReHo values from the right superior frontal gyrus of the Brodmann's area (BA) 9 to the right middle frontal gyrus and the ReHo value from the left and right precuneus (BA 23) to the left and right middle cingulum gyrus were lower in the smokers than in the non-smokers. The ReHo value in the precuneus (BA 23) was significantly and positively correlated with the FTND score of smokers. CONCLUSION The ReHo values in the right superior frontal gyrus and left precuneus can be used to separate the smokers from the non-smokers. In particular, the left precuneus is a potential neuroimaging biomarker for nicotine addicts.

The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition.

In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABAA signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia.

In recent years, several studies have indicated that healthy older adults exhibit a reduction in task-unrelated thoughts compared to young adults. However, much less is known regarding age-related differences in time spent engaging in stimulus-independent thoughts or in their neural correlates in the absence of an ongoing task. In the current study, we collected functional magnetic resonance imaging (fMRI) data while 29 young (mean age = 22y) and 22 older (mean age = 70y) adults underwent experience sampling in the absence of an ongoing task (i.e., at "rest"). Although both age groups reported spending a similar amount of time engaged in stimulus-independent thoughts, older adults rated their thoughts as more present-oriented (rather than atemporal) and more novel. Moreover, controlling for these age-related differences in content, we found that experiencing stimulus-independent thoughts was associated with increased posterior cingulate and left angular gyrus activation across age groups compared to exhibiting an external focus of attention. When experiencing stimulus-independent thoughts, younger adults engaged medial and left lateral prefrontal cortex as well as left superior temporal gyrus to a greater degree than older adults. Taken together, our results suggest that, in the absence of an ongoing task, although young and older adults spend a similar amount of time engaging in stimulus-independent thoughts, the content and neural correlates of these thoughts differ with age.

Little is known about disorder-specific biomarkers of bipolar disorder (BD) and major depressive disorder (MDD). Our aim was to determine a neural substrate that could be used to distinguish BD from MDD. Our study included a BD group (10 patients with BD, 10 first-degree relatives (FDRs) of individuals with BD), MDD group (17 patients with MDD, 17 FDRs of individuals with MDD), and 27 healthy individuals. Structural and functional brain abnormalities were evaluated by voxel-based morphometry and a trail making test (TMT), respectively. The BD group showed a significant main effect of diagnosis in the gray matter (GM) volume of the anterior cingulate cortex (ACC; p = 0.01) and left insula (p < 0.01). FDRs of individuals with BD showed significantly smaller left ACC GM volume than healthy subjects (p < 0.01), and patients with BD showed significantly smaller ACC (p < 0.01) and left insular GM volume (p < 0.01) than healthy subjects. The MDD group showed a tendency toward a main effect of diagnosis in the right and left insular GM volume. The BD group showed a significantly inverse correlation between the left insular GM volume and TMT-A scores (p < 0.05). Our results suggest that the ACC volume could be a distinct endophenotype of BD, while the insular volume could be a shared BD and MDD endophenotype. Moreover, the insula could be associated with cognitive decline and poor outcome in BD.

Neurocognitive decline, including deficits in motor learning, occurs in the presymptomatic phase of Huntington's disease (HD) and precedes the onset of motor symptoms. Findings from recent neuroimaging studies have linked these deficits to alterations in fronto-striatal and fronto-parietal brain networks. However, little is known about the temporal dynamics of these networks when subjects approach phenoconversion. Here, 10 subjects with presymptomatic HD were scanned with 15O-labeled water at baseline and again 1.5 years later while performing a motor sequence learning task and a kinematically matched control task. Spatial covariance analysis was utilized to characterize patterns of change in learning-related neural activation occurring over time in these individuals. Pattern expression was compared to corresponding values in 10 age-matched healthy control subjects. Spatial covariance analysis revealed significant longitudinal changes in the expression of a specific learning-related activation pattern characterized by increasing activity in the right orbitofrontal cortex, with concurrent reductions in the right medial prefrontal and posterior cingulate regions, the left insula, left precuneus, and left cerebellum. Changes in the expression of this pattern over time correlated with baseline measurements of disease burden and learning performance. The network changes were accompanied by modest improvement in learning performance that took place concurrently in the gene carriers. The presence of increased network activity in the setting of stable task performance is consistent with a discrete compensatory mechanism. The findings suggest that this effect is most pronounced in the late presymptomatic phase of HD, as subjects approach clinical onset.

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal.

The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has increasingly become a focus of epigenetic studies. Despite advances, the number of known miRNAs with a consistent expression response during epileptogenesis is still small. Addressing this situation requires additional miRNA profiling studies coupled to detailed individual expression analyses. Here, we perform a miRNA microarray analysis of the hippocampus of Wistar rats 24 hours after intra-hippocampal pilocarpine-induced Status Epilepticus (H-PILO SE). We identified 73 miRNAs that undergo significant changes, of which 36 were up-regulated and 37 were down-regulated. To validate, we selected 5 of these (10a-5p, 128a-3p, 196b-5p, 352 and 324-3p) for RT-qPCR analysis. Our results confirmed that miR-352 and 196b-5p levels were significantly higher and miR-128a-3p levels were significantly lower in the hippocampus of H-PILO SE rats. We also evaluated whether the 3 miRNAs show a dysregulated hippocampal expression at three time periods (0h, 24h and chronic phase) after systemic pilocarpine-induced status epilepticus (S-PILO SE). We demonstrate that miR-128a-3p transcripts are significantly reduced at all time points compared to the naive group. Moreover, miR-196b-5p was significantly higher only at 24h post-SE, while miR-352 transcripts were significantly up-regulated after 24h and in chronic phase (epileptic) rats. Finally, when we compared hippocampi of epileptic and non-epileptic humans, we observed that transcript levels of miRNAs show similar trends to the animal models. In summary, we successfully identified two novel dysregulated miRNAs (196b-5p and 352) and confirmed miR-128a-3p downregulation in SE-induced epileptogenesis. Further functional assays are required to understand the role of these miRNAs in MTLE pathogenesis.

Anterior cingulate cortex (ACC) and striatum are part of the emotional neural circuitry implicated in major depressive disorder (MDD). Music is often used for emotion regulation, and pleasurable music listening activates the dopaminergic system in the brain, including the ACC. The present study uses functional MRI (fMRI) and an emotional nonmusical and musical stimuli paradigm to examine how neural processing of emotionally provocative auditory stimuli is altered within the ACC and striatum in depression.Nineteen MDD and 20 never-depressed (ND) control participants listened to standardized positive and negative emotional musical and nonmusical stimuli during fMRI scanning and gave subjective ratings of valence and arousal following scanning.ND participants exhibited greater activation to positive versus negative stimuli in ventral ACC. When compared with ND participants, MDD participants showed a different pattern of activation in ACC. In the rostral part of the ACC, ND participants showed greater activation for positive information, while MDD participants showed greater activation to negative information. In dorsal ACC, the pattern of activation distinguished between the types of stimuli, with ND participants showing greater activation to music compared to nonmusical stimuli, while MDD participants showed greater activation to nonmusical stimuli, with the greatest response to negative nonmusical stimuli. No group differences were found in striatum.These results suggest that people with depression may process emotional auditory stimuli differently based on both the type of stimulation and the emotional content of that stimulation. This raises the possibility that music may be useful in retraining ACC function, potentially leading to more effective and targeted treatments.

When not engaged in the moment, we often spontaneously represent people, places and events that are not present in the environment. Although this capacity has been linked to the default mode network (DMN), it remains unclear how interactions between the nodes of this network give rise to particular mental experiences during spontaneous thought. One hypothesis is that the core of the DMN integrates information from medial and lateral temporal lobe memory systems, which represent different aspects of knowledge. Individual differences in the connectivity between temporal lobe regions and the default mode network core would then predict differences in the content and form of people's spontaneous thoughts. This study tested this hypothesis by examining the relationship between seed-based functional connectivity and the contents of spontaneous thought recorded in a laboratory study several days later. Variations in connectivity from both medial and lateral temporal lobe regions was associated with different patterns of spontaneous thought and these effects converged on an overlapping region in the posterior cingulate cortex. We propose that the posterior core of the DMN acts as a representational hub that integrates information represented in medial and lateral temporal lobe and this process is important in determining the content and form of spontaneous thought.