Characterization of visual processing in temporomandibular disorders using functional magnetic resonance imaging.

BACKGROUND AND PURPOSE: Many patients with chronic pain report hypersensitivity not only to noxious stimuli, but also to other modalities including innocuous touch, sound, and light, possibly due to differences in the processing of these stimuli. The goal of this study was to characterize functional connectivity (FC) differences between subjects with temporomandibular disorders (TMD) and pain-free controls during a visual functional magnetic resonance imaging (fMRI) task that included an unpleasant, strobing visual stimulus. We hypothesized the TMD cohort would exhibit maladaptations in brain networks consistent with multisensory hypersensitivities observed in TMD patients. METHODS: This pilot study included 16 subjects, 10 with TMD and 6 pain-free controls. Clinical pain was characterized using self-reported questionnaires. Visual task-based fMRI data were collected on a 3T MR scanner and used to determine differences in FC via group independent component analysis. RESULTS: Compared to controls, subjects with TMD exhibited abnormally increased FC between the default mode network and lateral prefrontal areas involved in attention and executive function, and impaired FC between the frontoparietal network and higher order visual processing areas. CONCLUSIONS: The results indicate maladaptation of brain functional networks, likely due to deficits in multisensory integration, default mode network function, and visual attention and engendered by chronic pain mechanisms.

Selective blockade of rat brain T-type calcium channels provides insights on neurophysiological basis of arousal dependent resting state functional magnetic resonance imaging signals.

A number of studies point to slow (0.1-2 Hz) brain rhythms as the basis for the resting-state functional magnetic resonance imaging (rsfMRI) signal. Slow waves exist in the absence of stimulation, propagate across the cortex, and are strongly modulated by vigilance similar to large portions of the rsfMRI signal. However, it is not clear if slow rhythms serve as the basis of all neural activity reflected in rsfMRI signals, or just the vigilance-dependent components. The rsfMRI data exhibit quasi-periodic patterns (QPPs) that appear to increase in strength with decreasing vigilance and propagate across the brain similar to slow rhythms. These QPPs can complicate the estimation of functional connectivity (FC) via rsfMRI, either by existing as unmodeled signal or by inducing additional wide-spread correlation between voxel-time courses of functionally connected brain regions. In this study, we examined the relationship between cortical slow rhythms and the rsfMRI signal, using a well-established pharmacological model of slow wave suppression. Suppression of cortical slow rhythms led to significant reduction in the amplitude of QPPs but increased rsfMRI measures of intrinsic FC in rats. The results suggest that cortical slow rhythms serve as the basis of only the vigilance-dependent components (e.g., QPPs) of rsfMRI signals. Further attenuation of these non-specific signals enhances delineation of brain functional networks.

Reduced Interference and Serial Dependency Effects for Naming in Older but Not Younger Adults after 1 Hz rTMS of Right Pars Triangularis.

1 Hz repetitive transcranial magnetic stimulation (rTMS) was used to decrease excitability of right pars triangularis (R PTr) to determine whether increased R PTr activity during picture naming in older adults hampers word finding. We hypothesized that decreasing R PTr excitability would reduce interference with word finding, facilitating faster picture naming. 15 older and 16 younger adults received two rTMS sessions. In one, speech onset latencies for picture naming were measured after both sham and active R PTr stimulation. In the other session, sham and active stimulation of a control region, right pars opercularis (R POp), were administered before picture naming. Order of active vs. sham stimulation within session was counterbalanced. Younger adults showed no significant effects of stimulation. In older adults, a trend indicated that participants named pictures more quickly after active than sham R PTr stimulation. However, older adults also showed longer responses during R PTr than R POp sham stimulation. When order of active vs. sham stimulation was modeled, older adults receiving active stimulation first had significantly faster responding after active than sham R PTr stimulation and significantly faster responding after R PTr than R POp stimulation, consistent with experimental hypotheses. However, older adults receiving sham stimulation first showed no significant differences between conditions. Findings are best understood, based on previous studies, when the interaction between the excitatory effects of picture naming and the inhibitory effects of 1 Hz rTMS on R PTr is considered. Implications regarding right frontal activity in older adults and for design of future experiments are discussed.

A comprehensive data-driven analysis framework for detecting impairments in brain function networks with resting state fMRI in HIV-infected individuals on cART.

Central nervous system (CNS) sequelae continue to be common in HIV-infected individuals despite combination antiretroviral therapy (cART). These sequelae include HIV-associated neurocognitive disorder (HAND) and virologic persistence in the CNS. Resting state functional magnetic resonance imaging (rsfMRI) is a widely used tool to examine the integrity of brain function and pathology. In this study, we examined 16 HIV-positive (HIV+) subjects and 12 age, sex, and race matched HIV seronegative controls (HIV-) whole-brain high-resolution rsfMRI along with a battery of neurocognitive tests. A comprehensive data-driven analysis of rsfMRI revealed impaired functional connectivity, with very large effect sizes in executive function, language, and multisensory processing networks in HIV+ subjects. These results indicate the potential of high-resolution rsfMRI in combination with advanced data analysis techniques to yield biomarkers of neural impairment in HIV.

A method to mitigate spatio-temporally varying task-correlated motion artifacts from overt-speech fMRI paradigms in aphasia.

Quantifying accurate functional magnetic resonance imaging (fMRI) activation maps can be dampened by spatio-temporally varying task-correlated motion (TCM) artifacts in certain task paradigms (e.g., overt speech). Such real-world tasks are relevant to characterize longitudinal brain reorganization poststroke, and removal of TCM artifacts is vital for improved clinical interpretation and translation. In this study, we developed a novel independent component analysis (ICA)-based approach to denoise spatio-temporally varying TCM artifacts in 14 persons with aphasia who participated in an overt language fMRI paradigm. We compared the new methodology with other existing approaches such as "standard" volume registration, nonselective motion correction ICA packages (i.e., AROMA), and combining the novel approach with AROMA. Results show that the proposed methodology outperforms other approaches in removing TCM-related false positive activity (i.e., improved detectability power) with high spatial specificity. The proposed method was also effective in maintaining a balance between removal of TCM-related trial-by-trial variability and signal retention. Finally, we show that the TCM artifact is related to clinical metrics, such as speech fluency and aphasia severity, and the implication of TCM denoising on such relationship is also discussed. Overall, our work suggests that routine bulkhead motion based denoising packages cannot effectively account for spatio-temporally varying TCM. Further, the proposed TCM denoising approach requires a one-time front-end effort to hand label and train the classifiers that can be cost-effectively utilized to denoise large clinical data sets.

Correcting Task fMRI Signals for Variability in Baseline CBF Improves BOLD-Behavior Relationships: A Feasibility Study in an Aging Model.

Blood Oxygen Level Dependent (BOLD) functional MRI is a complex neurovascular signal whose magnitude depends on baseline physiological factors such as cerebral blood flow (CBF). Because baseline CBF varies across the brain and is altered with aging, the interpretation of stand-alone aging-related BOLD changes can be misleading. The primary objective of this study was to develop a methodology that combines task fMRI and arterial spin labeling (ASL) techniques to sensitize task-induced BOLD activity by covarying out the baseline physiology (i.e., CBF) in an aging model. We recruited 11 younger and 13 older healthy participants who underwent ASL and an overt language fMRI task (semantic category member generation). We measured in-scanner language performance to investigate the effect of BOLD sensitization on BOLD-behavior relationships. The results demonstrate that our correction approach is effective at enhancing the specificity and sensitivity of the BOLD signal in both groups. In addition, the correction strengthens the statistical association between task BOLD activity and behavioral performance. Although CBF has inherent age dependence, our results show that retaining the age factor within CBF aides in greater sensitization of task fMRI signals. From a cognitive standpoint, compared to young adults, the older participants showed a delayed domain-general language-related task activity possibly due to compromised vessel compliance. Further, assessment of functional evolution of corrected BOLD activity revealed biphasic BOLD dynamics in both groups where BOLD deactivation may reflect greater semantic demand or increased premium on domain general executive functioning in response to task difficulty. Although it was promising to note that the predictability of behavior using the proposed methodology outperforms other methodologies (i.e., no correction and normalization by division), and provides moderate stability and adequate power, further work with a larger cohort and other task designs is necessary to improve the stability of predicting associated behavior. In summary, we recommend correction of task fMRI signals by covarying out baseline CBF especially when comparing groups with different neurovascular properties. Given that ASL and BOLD fMRI are well established and widely employed techniques, our proposed multi-modal methodology can be readily implemented into data processing pipelines to obtain more accurate BOLD activation maps.

Examining fMRI time-series entropy as a marker for brain E/I balance with pharmacological neuromodulation in a non-human primate translational model.

Recently, there has been a lot of interest in the neuroimaging community in exploring fMRI time-series measures of local neuronal activity and excitation/inhibition (E/I) balance in the brain. In this preliminary study we probed the sensitivity of widely used sample entropy (SE) measure at multiple scales to controlled alteration of the brain's E/I balance in non-human primates (NHPs) with a well-characterized sub-anesthetic ketamine infusion fMRI model. We found that SE failed to detect the expected changes in E/I balance induced by ketamine. Subsequently, noticing that the complexity in the time series contributing SE could be dominated by non-neuronal noise in this experimental setting, we developed a new time-series measure called restricted sample entropy (RSE) by restricting SE estimations to regular portions of the fMRI time-series. RSE was able to adequately reflect the increased excitatory activity engendered by disinhibition of glutamergic neurons, through sub-anesthetic ketamine infusion. These results show that RSE is potentially a powerful tool for examining local neural activity, E/I balance, and alterations in brain state.

Internally Guided Lower Limb Movement Recruits Compensatory Cerebellar Activity in People With Parkinson's Disease.

Background: Externally guided (EG) and internally guided (IG) movements are postulated to recruit two parallel neural circuits, in which motor cortical neurons interact with either the cerebellum or striatum via distinct thalamic nuclei. Research suggests EG movements rely more heavily on the cerebello-thalamo-cortical circuit, whereas IG movements rely more on the striato-pallido-thalamo-cortical circuit (1). Because Parkinson's (PD) involves striatal dysfunction, individuals with PD have difficulty generating IG movements (2). Objectives: Determine whether individuals with PD would employ a compensatory mechanism favoring the cerebellum over the striatum during IG lower limb movements. Methods: 22 older adults with mild-moderate PD, who had abstained at least 12 h from anti-PD medications, and 19 age-matched controls performed EG and IG rhythmic foot-tapping during functional magnetic resonance imaging. Participants with PD tapped with their right (more affected) foot. External guidance was paced by a researcher tapping participants' ipsilateral 3rd metacarpal in a pattern with 0.5 to 1 s intervals, while internal guidance was based on pre-scan training in the same pattern. BOLD activation was compared between tasks (EG vs. IG) and groups (PD vs. control). Results: Both groups recruited the putamen and cerebellar regions. The PD group demonstrated less activation in the striatum and motor cortex than controls. A task (EG vs. IG) by group (PD vs. control) interaction was observed in the cerebellum with increased activation for the IG condition in the PD group. Conclusions: These findings support the hypothesized compensatory shift in which the dysfunctional striatum is assisted by the less affected cerebellum to accomplish IG lower limb movement in individuals with mild-moderate PD. These findings are of relevance for temporal gait dysfunction and freezing of gait problems frequently noted in many people with PD and may have implications for future therapeutic application.

Effects of ketamine treatment on cocaine-induced reinstatement and disruption of functional connectivity in unanesthetized rhesus monkeys.

RATIONALE: Substance use disorders are characterized by a loss of executive control over reward-based decision-making, and disruption of fronto-striatal connectivity has been implicated in this process. Sub-anesthetic ketamine has recently been shown to bolster fronto-striatal connectivity in drug-naïve subjects. OBJECTIVES: The influence of ketamine treatment was examined on the disruptive effects of cocaine on functional connectivity (FC) and on cocaine-seeking behavior in female rhesus monkeys. METHODS: Three female rhesus were trained for unanesthetized MRI scanning. Each received three drug-naïve/abstinent pharmacological MRI scans with acute injections of saline, cocaine (0.3 mg/kg i.v.), and cocaine (0.3 mg/kg i.v.) 48-h after a ketamine treatment (low dose = 0.345 mg/kg bolus + 0.256 mg/kg/h for 1 h; i.v.), and a fourth scan with saline injection following 2 months of daily cocaine self-administration. A separate cohort of five rhesus (4 female), all with extensive histories of cocaine exposure, underwent reinstatement testing 48 h after ketamine (or vehicle) treatment. Two sub-anesthetic doses were tested: low dose and high dose = 0.69 mg/kg + 0.512 mg/kg/h for 1 h. RESULTS: Ketamine treatment attenuated the effects of cocaine on both global and fronto-striatal FC in drug-naïve/abstinent subjects. Two months of daily cocaine self-administration led to prolonged disruption of both global and fronto-striatal FC. Cocaine-seeking behavior during reinstatement was reduced following ketamine treatment at the low dose, but not high dose. CONCLUSION: These findings illustrate the disruptive effects of cocaine on functional connectivity and provide evidence for the potential efficacy of ketamine as a treatment for stimulant use disorder.

Exploring brain mechanisms underlying Gulf War Illness with group ICA based analysis of fMRI resting state networks.

Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW illness (GWI), which is characterized by multiple deficits in cognitive, affective, sensory and nociception domains. In this study we employed resting state fMRI (rsfMRI) to map impairments in brain function in GWI with advanced network analysis. RsfMRI data was obtained from 60 GWI veterans and 30 age-matched military controls. Group independent component analysis (GICA) was conducted to probe the functional connectivity networks in all 90 subjects. GICA revealed impaired functional connectivity (FC) in GWI veterans between a number of brain function networks consistent with their self-reported symptoms. GWI veterans exhibited impaired FC between language networks, and sensory input networks of all modalities as well as motor output networks. GWI veterans also exhibited impaired FC between different sensory perception and motor networks, and between different networks in the sensorimotor domain. These FC impairments provide putative mechanism of central nervous system dysfunction in GWI.

Effects of a 12-Week Aerobic Spin Intervention on Resting State Networks in Previously Sedentary Older Adults.

Objective: We have previously demonstrated that aerobic exercise improves upper extremity motor function concurrent with changes in motor cortical activity using task-based functional magnetic resonance imaging (fMRI). However, it is currently unknown how a 12-week aerobic exercise intervention affects resting-state functional connectivity (rsFC) in motor networks. Previous work has shown that over a 6-month or 1-year exercise intervention, older individuals show increased resting state connectivity of the default mode network and the sensorimotor network (Voss et al., 2010b; Flodin et al., 2017). However, the effects of shorter-term 12-week exercise interventions on functional connectivity have received less attention. Method: Thirty-seven sedentary right-handed older adults were randomized to either a 12-week aerobic, spin cycling exercise group or a 12-week balance-toning exercise group. Resting state functional magnetic resonance images were acquired in sessions PRE/POST interventions. We applied seed-based correlation analysis to left and right primary motor cortices (L-M1 and R-M1) and anterior default mode network (aDMN) to test changes in rsFC between groups after the intervention. In addition, we performed a regression analysis predicting connectivity changes PRE/POST intervention across all participants as a function of time spent in aerobic training zone regardless of group assignment. Results: Seeding from L-M1, we found that participants in the cycling group had a greater PRE/POST change in rsFC in aDMN as compared to the balance group. When accounting for time in aerobic HR zone, we found increased heart rate workload was positively associated with increased change of rsFC between motor networks and aDMN. Interestingly, L-M1 to aDMN connectivity changes were also related to motor behavior changes in both groups. Respective of M1 laterality, comparisons of all participants from PRE to POST showed a reduction in the extent of bilateral M1 connectivity after the interventions with increased connectivity in dominant M1. Conclusion: A 12-week physical activity intervention can change rsFC between primary motor regions and default mode network areas, which may be associated with improved motor performance. The decrease in connectivity between L-M1 and R-M1 post-intervention may represent a functional consolidation to the dominant M1. Topic Areas: Neuroimaging, Aging.

Task-residual functional connectivity of language and attention networks.

Functional connectivity using task-residual data capitalizes on remaining variance after mean task-related signal is removed from a time series. The degree of network specificity in language and attention domains featured by task-residual and resting-state data types were compared. Functional connectivity based on task-residual data evidenced stronger laterality of the language and attention connections and thus greater network specificity compared to resting-state functional connectivity of the same connections. Covariance between network nodes of task-residuals may thus reflect the degree to which two regions are coordinated in their specific activity, rather than a general shared co-activation. Task-residual functional connectivity provides complementary data to that of resting-state, emphasizing network relationships during task engagement.

Accounting for Non-Gaussian Sources of Spatial Correlation in Parametric Functional Magnetic Resonance Imaging Paradigms I: Revisiting Cluster-Based Inferences.

In a recent study, Eklund et al. employed resting-state functional magnetic resonance imaging data as a surrogate for null functional magnetic resonance imaging (fMRI) datasets and posited that cluster-wise family-wise error (FWE) rate-corrected inferences made by using parametric statistical methods in fMRI studies over the past two decades may have been invalid, particularly for cluster defining thresholds less stringent than p < 0.001; this was principally because the spatial autocorrelation functions (sACF) of fMRI data had been modeled incorrectly to follow a Gaussian form, whereas empirical data suggested otherwise. Here, we show that accounting for non-Gaussian signal components such as those arising from resting-state neural activity as well as physiological responses and motion artifacts in the null fMRI datasets yields first- and second-level general linear model analysis residuals with nearly uniform and Gaussian sACF. Further comparison with nonparametric permutation tests indicates that cluster-based FWE corrected inferences made with Gaussian spatial noise approximations are valid.

Accounting for Non-Gaussian Sources of Spatial Correlation in Parametric Functional Magnetic Resonance Imaging Paradigms II: A Method to Obtain First-Level Analysis Residuals with Uniform and Gaussian Spatial Autocorrelation Function and Independent and Identically Distributed Time-Series.

In a recent study Eklund et al. have shown that cluster-wise family-wise error (FWE) rate-corrected inferences made in parametric statistical method-based functional magnetic resonance imaging (fMRI) studies over the past couple of decades may have been invalid, particularly for cluster defining thresholds less stringent than p < 0.001; principally because the spatial autocorrelation functions (sACFs) of fMRI data had been modeled incorrectly to follow a Gaussian form, whereas empirical data suggest otherwise. Hence, the residuals from general linear model (GLM)-based fMRI activation estimates in these studies may not have possessed a homogenously Gaussian sACF. Here we propose a method based on the assumption that heterogeneity and non-Gaussianity of the sACF of the first-level GLM analysis residuals, as well as temporal autocorrelations in the first-level voxel residual time-series, are caused by unmodeled MRI signal from neuronal and physiological processes as well as motion and other artifacts, which can be approximated by appropriate decompositions of the first-level residuals with principal component analysis (PCA), and removed. We show that application of this method yields GLM residuals with significantly reduced spatial correlation, nearly Gaussian sACF and uniform spatial smoothness across the brain, thereby allowing valid cluster-based FWE-corrected inferences based on assumption of Gaussian spatial noise. We further show that application of this method renders the voxel time-series of first-level GLM residuals independent, and identically distributed across time (which is a necessary condition for appropriate voxel-level GLM inference), without having to fit ad hoc stochastic colored noise models. Furthermore, the detection power of individual subject brain activation analysis is enhanced. This method will be especially useful for case studies, which rely on first-level GLM analysis inferences.

Ketamine-induced changes in connectivity of functional brain networks in awake female nonhuman primates: a translational functional imaging model.

RATIONALE: There is a significant interest in the NMDA-receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. Pharmacological MRI in awake nonhuman primates provides a highly translational model for studying the brain network dynamics involved in producing these drug effects. OBJECTIVE: The present study evaluated ketamine-induced changes in functional connectivity (FC) in awake rhesus monkeys. The effects of ketamine after pretreatment with the antipsychotic drug risperidone were also examined. METHODS: Functional MRI scans were conducted in four awake adult female rhesus monkeys during sub-anesthetic i.v. infusions of ketamine (0.345 mg/kg bolus followed by 0.256 mg kg-1 h-1 constant infusion) with and without risperidone pretreatment (0.06 mg/kg). A 10-min window of stable BOLD signal was used to compare FC between baseline and drug conditions. FC was assessed in specific regions of interest using seed-based cross-correlation analysis. RESULTS: Ketamine infusion induced extensive changes in FC. In particular, FC to the dorsolateral prefrontal cortex (dlPFC) was increased in several cortical and subcortical regions. Pretreatment with risperidone largely attenuated ketamine-induced changes in FC. CONCLUSIONS: The results are highly consistent with similar human imaging studies showing ketamine-induced changes in FC, as well as a significant attenuation of these changes when ketamine infusion is preceded by pretreatment with risperidone. The extensive increases shown in FC to the dlPFC are consistent with the idea that disinhibition of the dlPFC may be a key driver of the antidepressant and psychotomimetic effects of ketamine.

Ketamine-induced brain activation in awake female nonhuman primates: a translational functional imaging model.

RATIONALE: There is significant interest in the NMDA receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. OBJECTIVE: The present study extends the successful development of an apparatus and methodology to conduct pharmacological MRI studies in awake rhesus monkeys in order to evaluate the CNS effects of ketamine. METHODS: Functional MRI scans were conducted in four awake adult female rhesus monkeys during sub-anesthetic intravenous (i.v.) infusions of ketamine (0.345 mg/kg bolus followed by 0.256 mg/kg/h constant infusion) with and without risperidone pretreatment (0.06 mg/kg). Statistical parametric maps of ketamine-induced blood oxygenation level-dependent (BOLD) activation were obtained with appropriate general linear regression models (GLMs) incorporating motion and hemodynamics of ketamine infusion. RESULTS: Ketamine infusion induced and sustained robust BOLD activation in a number of cortical and subcortical regions, including the thalamus, cingulate gyrus, and supplementary motor area. Pretreatment with the antipsychotic drug risperidone markedly blunted ketamine-induced activation in many brain areas. CONCLUSIONS: The results are remarkably similar to human imaging studies showing ketamine-induced BOLD activation in many of the same brain areas, and pretreatment with risperidone or another antipsychotic blunting the ketamine response to a similar extent. The strong concordance of the functional imaging data in humans with these results from nonhuman primates highlights the translational value of the model and provides an excellent avenue for future research examining the CNS effects of ketamine. This model may also be a useful tool for evaluating the efficacy of novel antipsychotic drugs.

Resting-state fMRI reveals enhanced functional connectivity in spatial navigation networks after transcranial direct current stimulation.

A number of studies have established that transcranial direct current stimulation (tDCS) modulates cortical excitability. We previously demonstrated polarity dependent changes in parietal lobe blood oxygen level dependent (BOLD) fMRI in a group of young adults during a spatial navigation task [15]. Here we used resting state functional connectivity (rsFC) to examine whether analogous changes were also evident during the resting state. Participants were randomized to either a parietal-anodal, frontal-cathodal (P+F-) or the opposite montage (P-F+) and received 20min of tDCS (2mA) before undergoing resting-state fMRI. rsFC was evaluated between the groups by placing a seed in the medial superior parietal lobule (mSPL), which was under the target electrode. rsFC between the mSPL and a number of other areas involved in spatial navigation, scene processing, and sensorimotor processing was significantly higher in the P+F- than the P-F+ group. Thus, the modulatory effects of tDCS were evident during rest and suggest that stimulation primes not just the underlying neocortex but an extended network that can be recruited as necessary during active task performance.

Word-finding impairment in veterans of the 1991 Persian Gulf War.

Approximately one quarter of 1991 Persian Gulf War Veterans experience cognitive and physiological sequelae that continue to be unexplained by known medical or psychological conditions. Difficulty coming up with words and names, familiar before the war, is a hallmark of the illness. Three Gulf War Syndrome subtypes have been identified and linked to specific war-time chemical exposures. The most functionally impaired veterans belong to the Gulf War Syndrome 2 (Syndrome 2) group, for which subcortical damage due to toxic nerve gas exposure is the suspected cause. Subcortical damage is often associated with specific complex language impairments, and Syndrome 2 veterans have demonstrated poorer vocabulary relative to controls. 11 Syndrome 1, 16 Syndrome 2, 9 Syndrome 3, and 14 age-matched veteran controls from the Seabees Naval Construction Battalion were compared across three measures of complex language. Additionally, functional magnetic resonance imaging (fMRI) was collected during a covert category generation task, and whole-brain functional activity was compared between groups. Results demonstrated that Syndrome 2 veterans performed significantly worse on letter and category fluency relative to Syndrome 1 veterans and controls. They also exhibited reduced activity in the thalamus, putamen, and amygdala, and increased activity in the right hippocampus relative to controls. Syndrome 1 and Syndrome 3 groups tended to show similar, although smaller, differences than the Syndrome 2 group. Hence, these results further demonstrate specific impairments in complex language as well as subcortical and hippocampal involvement in Syndrome 2 veterans. Further research is required to determine the extent of language impairments in this population and the significance of altered neurologic activity in the aforementioned brain regions with the purpose of better characterizing the Gulf War Syndromes.

A shift in perspective: Decentering through mindful attention to imagined stressful events.

Ruminative thoughts about a stressful event can seem subjectively real, as if the imagined event were happening in the moment. One possibility is that this subjective realism results from simulating the self as engaged in the stressful event (immersion). If so, then the process of decentering--disengaging the self from the event--should reduce the subjective realism associated with immersion, and therefore perceived stressfulness. To assess this account of decentering, we taught non-meditators a strategy for disengaging from imagined events, simply viewing these events as transient mental states (mindful attention). In a subsequent neuroimaging session, participants imagined stressful and non-stressful events, while either immersing themselves or adopting mindful attention. In conjunction analyses, mindful attention down-regulated the processing of stressful events relative to baseline, whereas immersion up-regulated their processing. In direct contrasts between mindful attention and immersion, mindful attention showed greater activity in brain areas associated with perspective shifting and effortful attention, whereas immersion showed greater activity in areas associated with self-processing and visceral states. These results suggest that mindful attention produces decentering by disengaging embodied senses of self from imagined situations so that affect does not develop.

Hubs of Anticorrelation in High-Resolution Resting-State Functional Connectivity Network Architecture.

A major focus of brain research recently has been to map the resting-state functional connectivity (rsFC) network architecture of the normal brain and pathology through functional magnetic resonance imaging. However, the phenomenon of anticorrelations in resting-state signals between different brain regions has not been adequately examined. The preponderance of studies on resting-state fMRI (rsFMRI) have either ignored anticorrelations in rsFC networks or adopted methods in data analysis, which have rendered anticorrelations in rsFC networks uninterpretable. The few studies that have examined anticorrelations in rsFC networks using conventional methods have found anticorrelations to be weak in strength and not very reproducible across subjects. Anticorrelations in rsFC network architecture could reflect mechanisms that subserve a number of important brain processes. In this preliminary study, we examined the properties of anticorrelated rsFC networks by systematically focusing on negative cross-correlation coefficients (CCs) among rsFMRI voxel time series across the brain with graph theory-based network analysis. A number of methods were implemented to enhance the neuronal specificity of resting-state functional connections that yield negative CCs, although at the cost of decreased sensitivity. Hubs of anticorrelation were seen in a number of cortical and subcortical brain regions. Examination of the anticorrelation maps of these hubs indicated that negative CCs in rsFC network architecture highlight a number of regulatory interactions between brain networks and regions, including reciprocal modulations, suppression, inhibition, and neurofeedback.