Distortion correction of functional MRI without reverse phase encoding scans or field maps.

Functional magnetic resonance images (fMRI) acquired using echo planar sequences typically suffer from spatial distortions due to susceptibility induced off-resonance fields, which may cause geometric mismatch with structural images and affect subsequent quantification and localization of brain function. State-of-the art distortion correction methods (for example, using FSL's topup or AFNI's 3dQwarp algorithms) require the collection of additional scans - either field maps or images with reverse phase encoding directions (i.e., blip-up/blip-down acquisitions) - to estimate and correct distortions. However, not all imaging protocols acquire these additional data and thus cannot take advantage of these post-acquisition corrections. In this study, we aim to enable state-of-the art processing of historical or limited datasets that do not include specific sequences for distortion correction by using only the acquired functional data and a single commonly acquired structural image. To achieve this, we synthesize an undistorted image with contrast similar to the fMRI data and use the non-distorted synthetic image as an anatomical target for distortion correction. We evaluate the efficacy of this approach, named SynBOLD-DisCo (Synthetic BOLD contrast for Distortion Correction), and show that this distortion correction process yields fMRI data that are geometrically similar to non-distorted structural images, with distortion correction virtually equivalent to acquisitions that do contain both blip-up/blip-down images. Our method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation and integration into existing fMRI preprocessing pipelines.

Periaqueductal gray matter and medial prefrontal cortex reflect negative prediction errors during differential conditioning.

Computational models of associative learning posit that negative prediction errors (PEs) arising from the omission of aversive outcomes weaken aversive Pavlovian associations during differential conditioning and extinction. It is possible that negative PEs may underlie exaggerated conditioned responses to the conditioned stimulus not paired with an aversitve outcome (CS-) during differential conditioning and to the conditioned stimulus originally paired with a aversive outcome (CS+) during extinction in patients with clinical anxiety disorders. Although previous research has demonstrated that manipulations of the periaqueductal gray matter (PAG) interfere with extinction learning in animals, the role of the PAG in processing negative PEs within the human brain is presently unclear. We set out to investigate how PAG responses and connectivity are impacted by negative PEs using ultra-high-field (7 T) functional magnetic resonance imaging and hierarchical Bayesian analysis. During differential conditioning, negative PEs were associated with larger responses within the lateral and dorsolateral PAG and increased connectivity between the dorsolateral PAG and medial areas of Brodmann area 9. Collectively, these results shed light on the association between activity within the PAG and medial prefrontal cortex and the omission of aversive outcomes during Pavlovian learning.

The Posterior Cingulate Cortex Reflects the Impact of Anxiety on Drift Rates During Cognitive Processing.

BACKGROUND: Generally, anxiety is thought to impair ongoing cognitive operations. Surprisingly, however, anxiety has been shown to improve performance during the Go/NoGo task. Understanding how anxiety can facilitate task performance may shed light on avenues to address the cognitive deficits commonly associated with anxiety. METHODS: A total of 39 participants (mean age ± SD = 27.5 ± 7.22 years; 18 women) performed a Go/NoGo task during periods of safety and periods of experimental anxiety, induced using the unpredictable delivery of aversive stimuli. Computational analysis and ultrahigh field (7T) functional magnetic resonance imaging were used to determine how induced anxiety affected computational processes and blood oxygen level-dependent responses during the task. RESULTS: Induced anxiety improved accuracy during the Go/NoGo task. Induced anxiety was associated with an amplified drift rate process, which is thought to reflect increased informational uptake. In addition, changes in drift rate during the anxiety condition were associated with enhanced blood oxygen level-dependent responses within the posterior cingulate cortex during Go trials. CONCLUSIONS: These results may reflect the impact of induced anxiety on the activity of neurons within the posterior cingulate cortex, whose activity patterns mimic the buildup of evidence accumulation. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within the posterior cingulate cortex.

Use of Autogenous Tooth-Derived Mineralized Dentin Matrix in the Alveolar Ridge Preservation Technique: Clinical and Histologic Evaluation.

This study clinically and histologically evaluated the new bone formation and soft tissue changes when an autogenous tooth-derived mineralized dentin matrix (DDM) graft covered with a free gingival graft (FGG) was used for alveolar ridge preservation, as compared to spontaneous healing. Using a split-mouth protocol, 14 consecutive patients who required two extractions of a single-rooted tooth in the maxillary arch were enrolled. In each patient, one extraction site was treated with DDM and FGG (test group), while the other extraction site was covered with FGG and healed spontaneously (control group). In both test and control sites, implant placement was performed after a 16-week healing period. Compared to baseline (immediately after tooth extraction), both treatments yielded statistically significant differences in some clinical parameters and in the bone micro-architecture within the augmented sites. However, the use of DDM with the FGG created greater new vital bone formation, more newly formed bone, and fewer dimensional tissue changes than spontaneous healing with FGG.

Clinical characteristics and predictors of death among hospitalized patients infected with SARS-CoV-2 in Sicily, Italy: A retrospective observational study.

Since late December 2019, severe acute respiratory syndrome coronavirus 2 has spread across the world, which resulted in the World Health Organization declaring a global pandemic. Coronavirus disease 2019 (COVID-19) presents a highly variable spectrum with regard to the severity of illness. Most infected individuals exhibit a mild to moderate illness (81%); however, 14% have a serious disease and 5% develop severe acute respiratory distress syndrome (ARDS), requiring intensive care support. The mortality rate of COVID-19 continues to rise across the world. Data regarding predictors of mortality in patients with COVID 19 are still scarce but are being actively investigated. The present multicenter retrospective observational study provides a complete description of the demographic and clinical characteristics, comorbidities and laboratory abnormalities in a population of 421 hospitalized patients recruited across eight infectious disease units in Southern Italy (Sicily) with the aim of identifying the baseline characteristics predisposing COVID-19 patients to critical illness or death. In this study, older age, pre-existing comorbidities and certain changes in laboratory markers (such as neutrophilia, lymphocytopenia and increased C-reactive protein levels) at the time of admission were associated with a higher risk of mortality. Male sex, on the other hand, was not significantly associated with increased risk of mortality. Symptoms such as fatigue, older age, a number of co-pathologies and use of continuous positive airway pressure were the most significant contributors in the estimation of clinical prognosis. Further research is required to better characterize the epidemiological features of COVID-19, to understand the related predictors of death and to develop new effective therapeutic strategies.

Dynamic Time Warping Identifies Functionally Distinct fMRI Resting State Cortical Networks Specific to VTA and SNc: A Proof of Concept.

Functional connectivity (FC) is determined by similarity between functional magnetic resonance imaging (fMRI) signals from distinct brain regions. However, traditional FC analyses ignore temporal phase differences. Here, we addressed this limitation, using dynamic time warping (DTW) within a machine-learning framework, to study cortical FC patterns of 2 spatially adjacent but functionally distinct subcortical regions, namely Substantia Nigra Pars Compacta (SNc) and ventral tegmental area (VTA). We evaluate: 1) the influence of pair of brain regions considered, 2) the influence of warping window sizes, 3) the classification efficacy of DTW, and 4) the uniqueness of features identified. Whole brain 7 Tesla resting state fMRI scans from 81 healthy participants were used. FC between 2 subcortical regions of interests (ROIs) and 360 cortical parcels were computed using: 1) Pearson correlations (PCs), 2) dynamic time-warped PCs (DTW-PC). The separability of SNc-cortical and VTA-cortical network was validated on 40 participants and tested on the remaining 41, using a support vector machine (SVM). The SVM separated the SNc-cortical versus VTA-cortical network with 74.39 and 97.56% test accuracy using PC and DTW-PC, respectively. SVM-recursive feature elimination yielded 20 DTW-PC features that most strongly contributed to the separation of the networks and revealed novel VTA versus SNc preferential connections (P < 0.05, Bonferroni-Holm corrected).

Prevalence of Early Childhood Caries in Southern Italy: An Epidemiological Study.

The purpose of this study was to assess the prevalence of Early Childhood Caries (ECC) and oral habits among preschool children from a southern Italian cohort. The survey population consisted of 300 subjects randomly selected among children attending two kindergartens in Catania, Italy. The prevalence of ECC and oral habits were clinically evaluated. During the clinical evaluation, the oral hygiene of children was also assessed. Parents were also interviewed using a brief and simple online questionnaire aimed at investigating eating and oral hygiene habits. The selected sample age ranged between 3 and 5 years. The prevalence of ECC was 9.34%, and the most affected teeth were primary molars. Moreover, the prevalence of oral habits was 44.66%. Only two-thirds of the sample brush their teeth at least once per day. The prevalence of ECC among Sicilian children (9.33%) seems suitable with the rest of the country. The results of the present study evidenced that oral habits showed a high prevalence among preschool children. The level of oral hygiene among preschool children is still not sufficient.

Highly accelerated submillimeter resolution 3D GRASE with controlled T2 blurring in T2 -weighted functional MRI at 7 Tesla: A feasibility study.

PURPOSE: To achieve highly accelerated submillimeter resolution T2 -weighted functional MRI at 7T by developing a three-dimensional gradient and spin echo imaging (GRASE) with inner-volume selection and variable flip angles (VFA). METHODS: GRASE imaging has disadvantages in that (a) k-space modulation causes T2 blurring by limiting the number of slices and (b) a VFA scheme results in partial success with substantial SNR loss. In this work, accelerated GRASE with controlled T2 blurring is developed to improve a point spread function (PSF) and temporal signal-to-noise ratio (tSNR) with a large number of slices. To this end, the VFA scheme is designed by minimizing a trade-off between SNR and blurring for functional sensitivity, and a new GRASE-optimized random encoding, which takes into account the complex signal decays of T2 and T2∗ weightings, is proposed by achieving incoherent aliasing for constrained reconstruction. Numerical and experimental studies were performed to validate the effectiveness of the proposed method over regular and VFA GRASE (R- and V-GRASE). RESULTS: The proposed method, while achieving 0.8 mm isotropic resolution, functional MRI compared to R- and V-GRASE improves the spatial extent of the excited volume up to 36 slices with 52%-68% full width at half maximum (FWHM) reduction in PSF but approximately 2- to 3-fold mean tSNR improvement, thus resulting in higher BOLD activations. CONCLUSIONS: We successfully demonstrated the feasibility of the proposed method in T2 -weighted functional MRI. The proposed method is especially promising for cortical layer-specific functional MRI.

Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.

BACKGROUND: The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex. AIMS: The thalamus is a heterogeneous structure, and the present study sought to clarify how the intrinsic connections of thalamic sub-regions are differentially impacted by acute dopamine transporter blockade. METHODS: Sixty healthy volunteers were orally administered either 20 mg of methylphenidate (N = 29) or placebo (N = 31) in a double-blind, randomized, between-subject design. Multi-echo fMRI was used to assess intrinsic functional connectivity of sub-regions of the thalamus during a resting state scan. An N-back working-memory paradigm provided a measure of cognitive performance. RESULTS: Acute methylphenidate significantly reduced connectivity of the lateral prefrontal cortex with the motor and somatosensory sub-regions of the thalamus and reduced connectivity with the parietal and visual sub-regions at a trend level. Connectivity with the premotor, prefrontal, and temporal sub-regions was not impacted. The intrinsic connectivity between the thalamus and the lateral prefrontal cortex was not associated with working-memory performance. CONCLUSIONS: Methylphenidate decreases functional connections between the lateral prefrontal cortex and thalamus broadly, while sparing intrinsic connectivity with thalamic sub-regions involved with working-memory and language related processes. Collectively, our results suggest that the dopamine transporter regulates functional connections between the prefrontal cortex and non-cognitive areas of the thalamus.

Striatal responsiveness to reward under threat-of-shock and working memory load: A preliminary study.

INTRODUCTION: Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute stressor (threat-of-shock) to modulate motivational and hedonic processes in healthy adults. MATERIALS AND METHODS: A reward task, involving stress with unpredictable mild electric shocks, was conducted in 23 healthy adults aged 20-37 (mean age: 24.7 ± 0.9; 14 females) during functional magnetic resonance imaging (fMRI). Manipulation included the use of (a) monetary reward for reinforcement, (b) threat-of-shock as the stressor, and (c) a spatial working memory task with two levels of difficulty (low and high load) for cognitive load. Reward-related activation was investigated in a priori three regions of interest, the nucleus accumbens (NAcc), caudate nucleus, and putamen. RESULTS: During anticipation, threat-of-shock or cognitive load did not affect striatal responsiveness to reward. Anticipated reward increased activation in the ventral and dorsal striatum. During feedback delivery, both threat-of-shock and cognitive effort modulated striatal activation. Higher working memory load blunted NAcc responsiveness to reward delivery, while stress strengthened caudate nucleus reactivity regardless reinforcement or load. CONCLUSIONS: These findings provide initial evidence that both stress and cognitive load modulate striatal responsiveness during feedback delivery but not during anticipation in healthy adults. Of clinical importance, sustained stress exposure might go along with dysregulated arousal, increasing therefore the risk for the development of maladaptive incentive-triggered motivation. This study brings new insight that might help to build a framework to understand common stress-related disorders, given that these psychiatric disorders involve disturbances of the reward system, cognitive deficits, and abnormal stress reactivity.

Resting-state connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in clinical anxiety

Background: The central nucleus of the amygdala and bed nucleus of the stria terminalis are involved primarily in phasic and sustained aversive states. Although both structures have been implicated in pathological anxiety, few studies with a clinical population have specifically focused on them, partly because of their small size. Previous work in our group used high-resolution imaging to map the restingstate functional connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in healthy subjects at 7 T, confirming and extending structural findings in humans and animals, while providing additional insight into cortical connectivity that is potentially unique to humans. Methods: In the current follow-up study, we contrasted resting-state functional connectivity in the bed nucleus of the stria terminalis and central nucleus of the amygdala at 7 T between healthy volunteers (n = 30) and patients with generalized and/or social anxiety disorder (n = 30). Results: Results revealed significant voxel-level group differences. Compared with healthy volunteers, patients showed stronger resting-state functional connectivity between the central nucleus of the amygdala and the lateral orbitofrontal cortex and superior temporal sulcus. They also showed weaker resting-state functional connectivity between the bed nucleus of the stria terminalis and the dorsolateral prefrontal cortex and occipital cortex. Limitations: These findings depart from a previous report of resting-state functional connectivity in the central nucleus of the amygdala and bed nucleus of the stria terminalis under sustained threat of shock in healthy volunteers. Conclusion: This study provides functional MRI proxies of the functional dissociation of the bed nucleus of the stria terminalis and central nucleus of the amygdala, and suggests that resting-state functional connectivity of key structures in the processing of defensive responses do not recapitulate changes related to induced state anxiety. Future work needs to replicate and further probe the clinical significance of these findings.

Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma.

OBJECTIVE: The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH). METHODS: Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed. RESULTS: In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred. SIGNIFICANCE: For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom from seizures by 45% compared to conventional ablation, regardless of hamartoma size or anatomical classification. This technique showed the same or reduced morbidity (0%) compared to recent non-rs-fMRI-guided SLA studies with as high as 20% permanent significant morbidity.

Statistical power comparisons at 3T and 7T with a GO / NOGO task.

The field of cognitive neuroscience is weighing evidence about whether to move from standard field strength to ultra-high field (UHF). The present study contributes to the evidence by comparing a cognitive neuroscience paradigm at 3 Tesla (3T) and 7 Tesla (7T). The goal was to test and demonstrate the practical effects of field strength on a standard GO/NOGO task using accessible preprocessing and analysis tools. Two independent matched healthy samples (N = 31 each) were analyzed at 3T and 7T. Results show gains at 7T in statistical strength, the detection of smaller effects and group-level power. With an increased availability of UHF scanners, these gains may be exploited by cognitive neuroscientists and other neuroimaging researchers to develop more efficient or comprehensive experimental designs and, given the same sample size, achieve greater statistical power at 7T.

Extended amygdala connectivity changes during sustained shock anticipation.

The bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) of the extended amygdala are small, anatomically interconnected brain regions. They are thought to mediate responses to sustained, unpredictable threat stimuli and phasic, predictable threat stimuli, respectively. They perform these operations largely through their interconnected networks. In two previous studies, we mapped and contrasted the resting functional connectivity networks of the BNST and CeA at 7 Tesla with high resolution. This follow-up study investigates the changes in functional connectivity of these structures during sustained anticipation of electric shock. Results show that the BNST and CeA become less strongly coupled with the ventromedial prefrontal cortex (vmPFC), cingulate, and nucleus accumbens in shock threat relative to a safety condition. In addition, the CeA becomes more strongly coupled with the thalamus under threat. An exploratory, whole-brain connectivity analysis reveals that, although the BNST/CeA exhibits generally decreased connectivity, many other cortical regions demonstrate greater coupling under threat than safety. Understanding the differential network structures of these two regions and how they contribute to processing under threat will help elucidate the building blocks of the anxious state.

Intrinsic functional connectivity of the central extended amygdala.

The central extended amygdala (EAc)-including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)-plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordinated activity of distributed neural circuits, the functional architecture of the EAc network and the degree to which the BST and the Ce show distinct patterns of functional connectivity is unclear. Here, we used a novel combination of imaging approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community-dwelling adults. Multiband imaging, high-precision registration techniques, and spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and showcase image registration techniques that are likely to be useful for researchers working with "deidentified" neuroimaging data.

Intrinsic functional connectivity of the central nucleus of the amygdala and bed nucleus of the stria terminalis.

The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST.

Threat of shock increases excitability and connectivity of the intraparietal sulcus.

Anxiety disorders affect approximately 1 in 5 (18%) Americans within a given 1 year period, placing a substantial burden on the national health care system. Therefore, there is a critical need to understand the neural mechanisms mediating anxiety symptoms. We used unbiased, multimodal, data-driven, whole-brain measures of neural activity (magnetoencephalography) and connectivity (fMRI) to identify the regions of the brain that contribute most prominently to sustained anxiety. We report that a single brain region, the intraparietal sulcus (IPS), shows both elevated neural activity and global brain connectivity during threat. The IPS plays a key role in attention orienting and may contribute to the hypervigilance that is a common symptom of pathological anxiety. Hyperactivation of this region during elevated state anxiety may account for the paradoxical facilitation of performance on tasks that require an external focus of attention, and impairment of performance on tasks that require an internal focus of attention.

Anxiety Patients Show Reduced Working Memory Related dlPFC Activation During Safety and Threat.

BACKGROUND: Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these deficits reflect threat-related processes or symptoms of the disorder. Here, we distinguish between these hypotheses by determining the effect of shock threat versus safety on the neural substrates of WM performance in anxiety patients and healthy controls. METHODS: Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N-back WM task during periods of safety and threat of shock. We recorded blood-oxygen-level dependent (BOLD) activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load-related BOLD activation. RESULTS: Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load-related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load-related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat. CONCLUSIONS: This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat.

Resting state connectivity of the human habenula at ultra-high field.

The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.