Functional organization of the fusiform gyrus revealed with connectivity profiles

Within the object recognition‐related ventral visual stream, the human fusiform gyrus (FG), which topographically connects the striate cortex to the inferior temporal lobe, plays a pivotal role in high‐level visual/cognitive functions. However, though there are many previous investigations of distinct functional modules within the FG, the functional organization of the whole FG in its full functional heterogeneity has not yet been established. In the current study, a replicable functional organization of the FG based on distinct anatomical connectivity patterns was identified. The FG was parcellated into medial (FGm), lateral (FGl), and anterior (FGa) regions using diffusion tensor imaging. We validated the reasonability of such an organizational scheme from the perspective of resting‐state whole brain functional connectivity patterns and the involvement of functional subnetworks. We found corroborating support for these three distinct modules, and suggest that the FGm serves as a transition region that combines multiple stimuli, the FGl is responsible for categorical recognition, and the FGa is involved in semantic understanding. These findings support two organizational functional transitions of the ventral temporal gyrus, a posterior/anterior direction of visual/semantic processing, and a media/lateral direction of high‐level visual processing. Our results may facilitate a more detailed study of the human FG in the future. Hum Brain Mapp 37:3003–3016, 2016. © 2016 Wiley Periodicals, Inc .     

Longitudinal functional connectivity changes correlate with mood improvement after regular exercise in a dose‐dependent fashion

Exercise increases wellbeing and improves mood. It is however unclear how these mood changes relate to brain function. We conducted a randomized controlled trial investigating resting‐state modifications in healthy adults after an extended period of aerobic physical exercise and their relationship with mood improvements. We aimed to identify novel functional networks whose activity could provide a physiological counterpart to the mood‐related benefits of exercise. Thirty‐eight healthy sedentary volunteers were randomised to either the aerobic exercise group of the study or a control group. Participants in the exercise group attended aerobic sessions with a physiotherapist twice a week for 16 weeks. Resting‐state modifications using magnetic resonance imaging were assessed before and after the programme and related to mood changes. An unbiased approach using graph metrics and network‐based statistics was adopted. Exercise reduced mood disturbance and improved emotional wellbeing. It also induced a decrease in local efficiency in the parahippocampal lobe through strengthening of the functional connections from this structure to the supramarginal gyrus, precentral area, superior temporal gyrus and temporal pole. Changes in mood disturbance following exercise were correlated with those in connectivity between parahippocampal gyrus and superior temporal gyrus as well as with the amount of training. No changes were detected in the control group. In conclusion, connectivity from the parahippocampal gyrus to motor, sensory integration and mood regulation areas was strengthened through exercise. These functional changes might be related to the benefits of regular physical activity on mood.     

Recognition memory is associated with altered resting‐state functional connectivity in people at genetic risk for Alzheimer's disease

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50–80 years old), of which 20 carried the ε4 allele. All participants underwent resting‐state functional magnetic resonance imaging (fMRI), high‐resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting‐state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non‐carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non‐carriers between the PCC seed region and left‐hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting‐state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross‐links between DMN core areas and cortical areas involved in memory processing.     

Selectivity for mid‐level properties of faces and places in the fusiform face area and parahippocampal place area

Regions in the ventral visual pathway, such as the fusiform face area (FFA) and parahippocampal place area (PPA) are selective for images from specific object categories. Yet images from different object categories differ in their image properties. To investigate how these image properties are represented in the FFA and PPA, we compared neural responses to locally‐SCRAMBLED images (in which mid‐level, spatial properties are preserved) and globally‐SCRAMBLED images (in which mid‐level, spatial properties are not preserved). There was a greater response in the FFA and PPA to images from the preferred CATEGORY relative to their non‐preferred category for the scrambled conditions. However, there was a greater selectivity for locally‐scrambled compared to globally‐scrambled images. Next, we compared the magnitude of fMR‐adaptation to intact and scrambled images. fMR‐adaptation was evident to locally‐scrambled images from the preferred category. However, there was no adaptation to globally‐scrambled images from the preferred category. These results show that the selectivity to faces and places in the FFA and PPA is dependent on mid‐level properties of the image that are preserved by local‐scrambling.     

Delineating functional segregations of the human middle temporal gyrus with resting‐state functional connectivity and coactivation patterns

Although the middle temporal gyrus (MTG) has been parcellated into subregions with distinguished anatomical connectivity patterns, whether the structural topography of MTG can inform functional segregations of this area remains largely unknown. Accumulating evidence suggests that the brain's underlying organization and function can be directly and effectively delineated with resting‐state functional connectivity (RSFC) by identifying putative functional boundaries between cortical areas. Here, RSFC profiles were used to explore functional segregations of the MTG and defined four subregions from anterior to posterior in two independent datasets, which showed a similar pattern with MTG parcellation scheme obtained using anatomical connectivity. The functional segregations of MTG were further supported by whole brain RSFC, coactivation, and specific RFSC, and coactivation mapping. Furthermore, the fingerprint with predefined 10 networks and functional characterizations of each subregion using meta‐analysis also identified functional distinction between subregions. The specific connectivity analysis and functional characterization indicated that the bilateral most anterior subregions mainly participated in social cognition and semantic processing; the ventral middle subregions were involved in social cognition in left hemisphere and auditory processing in right hemisphere; the bilateral ventro‐posterior subregions participated in action observation, whereas the left subregion was also involved in semantic processing; both of the dorsal subregions in superior temporal sulcus were involved in language, social cognition, and auditory processing. Taken together, our findings demonstrated MTG sharing similar structural and functional topographies and provide more detailed information about the functional organization of the MTG, which may facilitate future clinical and cognitive research on this area.     

Resting‐state functional MRI: Functional connectivity analysis of the visual cortex in primary open‐angle glaucoma patients

Purpose: To analyze functional connectivity (FC) of the visual cortex using resting‐state functional MRI in human primary open‐angle glaucoma (POAG) patients. Materials and Methods: Twenty‐two patients with known POAG and 22 age‐matched controls were included in this IRB‐approved study. Subjects were evaluated by 3 T MR using resting‐state blood oxygenation level dependent and three‐dimensional brain volume imaging (3D‐BRAVO) MRI. Data processing was performed with standard software. FC maps were generated from Brodmann areas (BA) 17/18/19/7 in a voxel‐wise fashion. Region of interest analysis was used to specifically examine FC among each pair of BA17/18/19/7. Results: Voxel‐wise analyses demonstrated decreased FC in the POAG group between the primary visual cortex (BA17) and the right inferior temporal, left fusiform, left middle occipital, right superior occipital, left postcentral, right precentral gyri, and anterior lobe of the left cerebellum. Increased FC was found between BA17 and the left cerebellum, right middle cerebellar peduncle, right middle frontal gyrus, and extra‐nuclear gyrus (P < 0.05). In terms of the higher visual cortices (BA18/19), positive FC was disappeared with the cerebellar vermis, right middle temporal, and right superior temporal gyri (P < 0.05). Negative FC was disappeared between BA18/19 and the right insular gyrus (P < 0.05). Region of interest analysis demonstrated no statistically significant differences in FC between the POAG patients relative to the controls (P > 0.05). Conclusion: Changes in FC of the visual cortex are found in patients with POAG. These include alterations in connectivity between the visual cortex and associative visual areas along with disrupted connectivity between the primary and higher visual areas. Hum Brain Mapp 34:2455–2463, 2013. © 2012 Wiley Periodicals, Inc.     

Functional dissociation of the left and right fusiform gyrus in self-face recognition

It is well known that the fusiform gyrus is engaged in face perception, such as the processes of face familiarity and identity. However, the functional role of the fusiform gyrus in face processing related to high-level social cognition remains unclear. The current study assessed the functional role of individually defined fusiform face area (FFA) in the processing of self-face physical properties and self-face identity. We used functional magnetic resonance imaging to monitor neural responses to rapidly presented face stimuli drawn from morph continua between self-face (Morph 100%) and a gender-matched friend's face (Morph 0%) in a face recognition task. Contrasting Morph 100% versus Morph 60% that differed in self-face physical properties but were both recognized as the self uncovered neural activity sensitive to self-face physical properties in the left FFA. Contrasting Morphs 50% that were recognized as the self versus a friend on different trials revealed neural modulations associated with self-face identity in the right FFA. Moreover, the right FFA activity correlated with the frequency of recognizing Morphs 50% as the self. Our results provide evidence for functional dissociations of the left and right FFAs in the representations of self-face physical properties and self-face identity.     

Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Age‐related differences in practice‐dependent resting‐state functional connectivity related to motor sequence learning

Decreased neural plasticity is observed with healthy ageing in the primary sensorimotor (SM1) cortex thought to participate in motor learning and memory consolidation processes. In the present magnetoencephalography study, the post‐training reorganization of resting‐state functional connectivity (rsFC) and its relation with motor learning and early consolidation in 14 young (19–30 years) and 14 old (66–70 years) healthy participants were investigated. At the behavioral level, participants were trained on a motor sequence learning task then retested 20–30 min later for transient offline gains in performance. Using a sensorimotor seed‐based approach, rsFC relying on beta band power envelope correlation was estimated immediately before and 10 min after the learning episode. Post‐training changes in rsFC (from before to after learning) were correlated with motor learning performance and with the offline improvement in performance within the hour after learning. Young and old participants exhibited differential patterns of sensorimotor‐related rsFC, bearing specific relationships with motor learning and consolidation. Our findings suggest that rsFC changes following learning reflect the offline processing of the new motor skill and contribute to the early memory consolidation within the hour after learning. Furthermore, differences in post‐training changes in rsFC between young and old participants support the hypothesis that ageing modulates the neural circuits underlying the learning of a new motor skill and the early subsequent consolidation stages. Hum Brain Mapp 38:923–937, 2017. © 2016 Wiley Periodicals, Inc.     

Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting‐state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age‐, sex‐, and education‐matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non‐auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384–2397, 2017. © 2017 Wiley Periodicals, Inc.     

Functional characterization and differential coactivation patterns of two cytoarchitectonic visual areas on the human posterior fusiform gyrus

The ventral stream of the human extrastriate visual cortex shows a considerable functional heterogeneity from early visual processing (posterior) to higher, domain‐specific processing (anterior). The fusiform gyrus hosts several of those “high‐level” functional areas. We recently found a subdivision of the posterior fusiform gyrus on the microstructural level, that is, two distinct cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function, 2013). To gain a first insight in the function of these two areas, here we studied their behavioral involvement and coactivation patterns by means of meta‐analytic connectivity modeling based on the BrainMap database ( www.brainmap.org ), using probabilistic maps of these areas as seed regions. The coactivation patterns of the areas support the concept of a common involvement in a core network subserving different cognitive tasks, that is, object recognition, visual language perception, or visual attention. In addition, the analysis supports the previous cytoarchitectonic parcellation, indicating that FG1 appears as a transitional area between early and higher visual cortex and FG2 as a higher‐order one. The latter area is furthermore lateralized, as it shows strong relations to the visual language processing system in the left hemisphere, while its right side is stronger associated with face selective regions. These findings indicate that functional lateralization of area FG2 relies on a different pattern of connectivity rather than side‐specific cytoarchitectonic features. Hum Brain Mapp 35:2754–2767, 2014. © 2013 Wiley Periodicals, Inc .     

Resting‐state functional connectivity of the human hypothalamus

The hypothalamus is of enormous importance for multiple bodily functions such as energy homeostasis. Especially, rodent studies have greatly contributed to our understanding how specific hypothalamic subregions integrate peripheral and central signals into the brain to control food intake. In humans, however, the neural circuitry of the hypothalamus, with its different subregions, has not been delineated. Hence, the aim of this study was to map the hypothalamus network using resting‐state functional connectivity (FC) analyses from the medial hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal‐weight adults (n = 49). Furthermore, in a separate sample, we examined differences within the LH and MH networks between healthy normal‐weight (n = 25) versus overweight/obese adults (n = 23). FC patterns from the LH and MH revealed significant connections to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior cingulum and temporal brain regions. However, our analysis revealed subtler distinctions within hypothalamic subregions. The LH was functionally stronger connected to the dorsal striatum, anterior cingulum, and frontal operculum, while the MH showed stronger functional connections to the nucleus accumbens and medial orbitofrontal cortex. Furthermore, overweight/obese participants revealed heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH network. Our results indicate that the MH and LH network are tapped into different parts of the dopaminergic circuitry of the brain, potentially modulating food reward based on the functional connections to the ventral and dorsal striatum, respectively. In obese adults, FC changes were observed in the MH network. Hum Brain Mapp 35:6088–6096, 2014. © 2014 Wiley Periodicals, Inc.     

Functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain

During rest, multiple cortical brain regions are functionally linked forming resting‐state networks. This high level of functional connectivity within resting‐state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting‐state functional magnetic resonance imaging time‐series with diffusion tensor imaging scans. Nine consistently found functionally linked resting‐state networks were retrieved from the resting‐state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting‐state networks. Our results show that well‐known anatomical white matter tracts interconnect at least eight of the nine commonly found resting‐state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal‐frontal networks. Our results suggest that the functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Altered resting‐state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross‐sectional and machine learning study

Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain–gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting‐state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula‐left dorsolateral prefrontal cortex (dlPFC) and habenula‐periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula‐right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula‐thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = ?.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula‐dlPFC, habenula‐thalamus, and habenula‐PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.     

Isoflurane induces dose‐dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture

Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting‐state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting‐state investigations. Dose‐dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose‐specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness. Hum Brain Mapp 35:5754–5775, 2014. © 2014 Wiley Periodicals, Inc.     

Reduced resting‐state functional connectivity and sleep impairment in abstinent male alcohol‐dependent patients

Alcohol dependence is associated with poor sleep quality, which has both been implicated with thalamocortical circuits function. To identify the possible roles of these circuits in the alcohol‐sleep association, we investigated the volume of both left and right thalamus and corresponding resting‐state functional connectivity (RSFC) differences between 15 alcohol‐dependent patients (AD) and 15 healthy controls (HC) male participants. The neuroimaging findings were then correlated with clinical variables, that is, Alcohol Use Disorders Identification Test (AUDIT) and Pittsburgh Sleep Quality Index (PSQI). Additionally, mediation analysis was carried out to test whether the thalamocortical RSFC mediates the relationship between drinking behavior and sleep impairments in AD when applicable. We observed a significant positive correlation between AUDIT score and PSQI score in AD. Compared with HC, AD showed reduced RSFC between the left thalamus and medial prefrontal cortex (mPFC), orbitofrontal cortex, anterior cingulate cortex (ACC), and right caudate. We also observed a negative correlation between RSFC of the left thalamus–mPFC and PSQI score in AD. More importantly, the left thalamus–mPFC RSFC strength mediated the relationship between AUDIT score and PSQI score in AD. No significant difference was detected in the normalized volume of both left and right thalamus, and volumes were not significantly correlated with clinical variables. Our results demonstrate that AD show abnormal interactions within thalamocortical circuits in association with drinking behaviors and sleep impairments. It is hoped that our study focusing on thalamocortical circuits could provide new information on potential novel therapeutic targets for treatment of sleep impairment in alcohol‐dependent patients.     

Individual and sex‐related differences in pain and relief responsiveness are associated with differences in resting‐state functional networks in healthy volunteers

Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex‐related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting‐state network. In men, pain measures correlated with increased connectivity within the visual resting‐state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions.     

Resting‐state functional connectivity and motor imagery brain activation

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting‐state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting‐state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel‐matched correlation between the individual MI parameter estimates and seed‐based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter‐individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847–3857, 2016. © 2016 Wiley Periodicals, Inc.