Intrinsic Connectivity Contrast Research Articles

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r = - 0.53, p = .0006) and anxiety (r = - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r = - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r = - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r = - 0.52, p = .001; r = - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r = - 0.50, p = .001). Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI.

Brain connectivity patterns associated with individual differences in the access to experience-near personal semantics: a resting-state fMRI study

It has been proposed that a continuum of specificity exists between episodic and semantic autobiographical memory. Personal semantics have been theorized to situate intermediately on this continuum, with more “experience-near” personal semantics (enPS) closer to the episodic end. We used individual differences in behavior as a model to investigate brain networks associated with the access to episodic autobiographical (EAM) and enPS information, assessing the relation between performance in the EAM and enPS conditions of the Autobiographical Fluency Task (AFT) and intrinsic brain connectivity. Results of an intrinsic connectivity contrast analysis showed that the global connectivity of two clusters in the left and right posterior cingulate cortex (PCC) was predicted by performance in the enPS conditions. Moreover, enPS scores predicted the connectivity strength of the right PCC with the bilateral anterior hippocampus (aHC), anterior middle temporal gyrus (aMTG) and medial orbitofrontal cortex, and the left aMTG and PCC. enPS scores also predicted the connectivity strength of the left PCC with the bilateral HC and MTG. The network highlighted involves parts of the core and of the dorsal medial subsystems of the Default Mode Network, in line with the proposal that enPS represents an intermediate entity between episodic and semantic memory.

Reduced Cortico-Cortical Resting-State Connectivity in Sensory Systems Related to Bodily Pain in Juvenile Fibromyalgia.

Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain. Whole-brain voxel-wise rsFC alterations were assessed using the intrinsic connectivity contrast, a measure of node centrality at each voxel, and seed-based analyses for interpretability. We studied the relationship between rsFC alterations in somatosensory systems and the location and extension of bodily pain. Adolescents with JFM had voxel-wise rsFC reductions in the paracentral lobule (PCL)/primary somatosensory cortex (S1) (T=4.89, family-wise error corrected p-value (pFWE)< 0.001) and left midcingulate cortex (T=4.67, pFWE=0.043). Post hoc analyses revealed reduced rsFC spanning major cortical sensory hubs (T > 4.4, pFWE < 0.030). Cortico-cortical rsFC reductions within PCL/S1 in JFM occurred in locations innervated by bodily areas where the pain was most frequent (F=3.15; positive false discovery rate=0.029) and predicted widespread pain (T > 4.4, pFWE < 0.045). Conversely, adolescents with JFM had increases in PCL/S1-thalamus (T=4.75, pFWE=0.046) and PCL/S1-anterior insula rsFC (T=5.13, pFWE=0.039). Reduced cortico-cortical sensory integration involving PCL/S1 and spanning the sensory systems may underly critical pain sensory features in youth with JFM. Reduced sensory integration is paralleled by augmented cross-talk between sensory and affective/salience-processing regions, potentially indicating a shift toward more affectively colored sensory experiences to the detriment of specific sensory discrimination.

The changes of intrinsic connectivity contrast in young smokers.

Previous studies demonstrated that reward circuit plays an important role in smoking. The differences of functional and structural connectivity were found among several brain regions such as thalamus and frontal lobe. However, few studies focused on functional connectivity (FC) in whole-brain voxel level of young smokers. In this study, intrinsic connectivity contrast (ICC) was used to perform voxel-based whole-brain analyses in 55 young smokers and 55 matched non-smokers to identify brain regions with significant group differences. ICC results showed that the connectivity of young smokers in medial frontal cortex (MedFC), supramarginal gyrus anterior division left (L_aSMG), central opercular cortex left (L_CO) and middle frontal gyrus left (L_MidFG) showed a significantly lower trend compared with the non-smokers. The seed-based FC analysis about MedFC indicated that young smokers showed reduced connectivity between the MedFC and left hippocampus, left amygdala compared to non-smokers. Correlation analysis showed that the ICC of MedFC in young smokers was significantly negatively correlated with Fagerstrom test for nicotine dependence (FTND) and Questionnaire on Smoking Urges (QSU). The FC between the MedFC and left hippocampus, left amygdala was significantly negatively correlated with Pack_years. The mediation analysis indicated that ICC of MedFC completely mediated FTND and QSU of young smokers. The results suggest that nicotine accumulation may affect the communication of the frontal lobe with the whole brain to some extent, leading to changes in smoking cravings. The above research also provides in-depth insights into the mechanism of adolescent smoking addiction and related intervention treatment.

Common and Distinct Functional Connectivity of the Orbitofrontal Cortex in Depression and Schizophrenia.

Schizophrenia and depression are psychiatric disorders with overlapping clinical and biological features. This study aimed to identify common and distinct neuropathological mechanisms in schizophrenia and depression patients using resting-state functional magnetic resonance imaging (fMRI). The study included 28 patients with depression (DEP), 29 patients with schizophrenia (SCH), and 30 healthy control subjects (HC). Intrinsic connectivity contrast (ICC) was used to identify functional connectivity (FC) changes at the whole-brain level, and significant ICC differences were found in the bilateral orbitofrontal cortex (OFC) across all three groups. Further seed-based FC analysis indicated that compared to the DEP and HC groups, the FC between bilateral OFC and medial prefrontal cortex (MPFC), right anterior insula, and right middle frontal gyrus were significantly lower in the SCH group. Additionally, the FC between right OFC and left thalamus was decreased in both patient groups compared to the HC group. Correlation analysis showed that the FC between OFC and MPFC was positively correlated with cognitive function in the SCH group. These findings suggest that OFC connectivity plays a critical role in the pathophysiology of schizophrenia and depression and may provide new insights into the potential neural mechanisms underlying these two disorders.

Distinct hemodynamic and functional connectivity features of fatigue in clinically isolated syndrome and multiple sclerosis: accounting for the confounding effect of concurrent depression symptoms

PurposeThis study aims to identify common and distinct hemodynamic and functional connectivity (FC) features for self-rated fatigue and depression symptoms in patients with clinically isolated syndrome (CIS) and relapsing–remitting multiple sclerosis (RR-MS).MethodsTwenty-four CIS, 29 RR-MS patients, and 39 healthy volunteers were examined using resting-state fMRI (rs-fMRI) to obtain whole-brain maps of (i) hemodynamic response patterns (through time shift analysis), (ii) FC (via intrinsic connectivity contrast maps), and (iii) coupling between hemodynamic response patterns and FC. Each regional map was correlated with fatigue scores, controlling for depression, and with depression scores, controlling for fatigue.ResultsIn CIS patients, the severity of fatigue was associated with accelerated hemodynamic response in the insula, hyperconnectivity of the superior frontal gyrus, and evidence of reduced hemodynamics–FC coupling in the left amygdala. In contrast, depression severity was associated with accelerated hemodynamic response in the right limbic temporal pole, hypoconnectivity of the anterior cingulate gyrus, and increased hemodynamics–FC coupling in the left amygdala. In RR-MS patients, fatigue was associated with accelerated hemodynamic response in the insula and medial superior frontal cortex, increased functional role of the left amygdala, and hypoconnectivity of the dorsal orbitofrontal cortex, while depression symptom severity was linked to delayed hemodynamic response in the medial superior frontal gyrus; hypoconnectivity of the insula, ventromedial thalamus, dorsolateral prefrontal cortex, and posterior cingulate; and decreased hemodynamics–FC coupling of the medial orbitofrontal cortex.ConclusionThere are distinct FC and hemodynamic responses, as well as different magnitude and topography of hemodynamic connectivity coupling, associated with fatigue and depression in early and later stages of MS.

Resting State Functional Connectivity is Associated With Treatment Response in Major Depression: A Real World Study

IntroductionMajor depressive disorder (MDD) is largely considered the most prevalent psychiatric disorder worldwide. Despite its domineering presence, effective treatment for many individuals remains elusive. Investigation into relevant biological markers, specifically neuroimaging correlates, of MDD and treatment response have gained traction in recent years; however, findings are still inconsistent.ObjectivesIn this study, we aimed to investigate the resting state functional connectivity patterns associated with treatment response in MDD inpatients in a real world setting.MethodsForty-three inpatients suffering from a major depressive episode were recruited from the psychiatric ward at IRCCS San Raffaele Hospital in Milan, Italy. Symptom severity was assessed via the 21-item Hamilton Depression Rating Scale (HDRS). The percentage of decrease in HDRS scores from admission to discharge was then calculated with the formula [(HDRS admission – HDRS discharge) * 100] / HDRS admission. All patients underwent a 3T MRI scan within one week of admission to acquire resting-state fMRI images, which included 200 sequential T2*-weighted volumes. Images were preprocessed using the CONN toolbox, running within Statistical Parametric Mapping (SPM 12). Preprocessing was performed according to a standard pipeline. A voxel-wise metric, intrinsic connectivity contrast (ICC), was implemented to explore the global resting state functional connectivity (rs-FC) patterns associated with treatment response. ICC-derived maps were then entered in the second-level analyses to examine the effect of the percentage of HDRS decrease, including age, sex, admission HDRS score, duration of hospitalization, and antidepressant dose equivalents as nuisance covariates.ResultsWe found that the percentage of HDRS decrease after treatment predicted rs-FC. ICC analysis identified 2 clusters where changes in HDRS scores were significantly associated with rs-FC, with increased connectivity in the supramarginal gyrus (pFDR = 0.002) and decreased connectivity in the amygdala and parahippocampal gyrus (pFDR = 0.047).ConclusionsOur results suggest that altered connectivity of the supramarginal gyrus, amygdala and parahippocampal gyrus is related to antidepressant treatment response. Given that these brain areas are implicated in emotional processing and mood, it is conceivable that a better integrity of brain connectivity may facilitate treatment response in major depression.Disclosure of InterestNone Declared

Reduced Resting-State Connectivity in Sensory Regions in Juvenile Fibromyalgia

Juvenile fibromyalgia (JFM) is a chronic pain condition affecting predominantly female adolescents. Although JFM pathophysiology has not been addressed, a study found reduced resting-state functional connectivity (rs-FC) in the primary somatosensory system of children with chronic pain. This finding concurs with rs-FC reductions in somatosensory areas described in adults with fibromyalgia. In adults, such rs-FC alterations extended beyond the somatosensory domain and implicated other sensory modalities (3), which may suggest that fibromyalgia patients experience a weakening of sensory integration. Whether this phenomenon replicates in JFM remains to be elucidated. This research aimed to evaluate rs-FC alterations in adolescents with JFM for the first time. We evaluated 37 female adolescents with JFM and 43 matched controls. All participants underwent a resting-state functional magnetic resonance imaging examination. Using an Intrinsic Connectivity Contrast approach, we computed whole-brain, voxel-wise rs-FC and assessed between-group differences via t-tests. Significant clusters were used as seeds of interest in post-hoc seed-to-voxel analyses. The statistical threshold of all analyses was set at family-wise error-corrected p<.05. Compared to controls, JFM patients had decreased whole-brain rs-FC in the primary somatosensory cortex (SI) and the midcingulate cortex, involved in pain processing and response selection. Seed-to-voxel analyses revealed that JFM patients had reduced rs-FC within these regions and between the midcingulate cortex and the bilateral supplementary motor area, posterior insula and parietal operculum (SII), and auditory cortices, thus, areas mediating somatomotor and sensory processing. In contrast, JFM participants showed increased rs-FC between SI and the thalamus, potentially reflecting increased coupling between subcortical and cortical relays of nociceptive processing, and between SI and the ventral anterior insula, involved in affective and visceral processing. Our findings suggest an overall reduction of cortico-cortical integration of sensory signal and an augmented cross-talk between primary sensory and affective-visceral processing regions in adolescents with JFM. This work was funded by NIH/NIAMS Grants R01 AR074795 and P30 AR076316.

Converging evidence of impaired brain function in systemic lupus erythematosus: changes in perfusion dynamics and intrinsic functional connectivity.

Τhe study examined changes in hemodynamics and functional connectivity in patients with systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations. Participants were 44 patients with neuropsychiatric SLE (NPSLE), 20 SLE patients without such manifestations (non-NPSLE), and 35 healthy controls. Resting-state functional MRI (rs-fMRI) was used to obtain whole-brain maps of (a) perfusion dynamics derived through time shift analysis (TSA), (b) regional functional connectivity (intrinsic connectivity contrast (ICC) coefficients), and (c) hemodynamic-connectivity coupling. Group differences were assessed through independent samples t-tests, and correlations of rs-fMRI indices with clinical variables and neuropsychological test scores were, also, computed. Compared to HC, NPSLE patients demonstrated intrinsic hypoconnectivity of anterior Default Mode Network (DMN) and hyperconnectivity of posterior DMN components. These changes were paralleled by elevated hemodynamic lag. In NPSLE, cognitive performance was positively related to higher intrinsic connectivity in these regions, and to higher connectivity-hemodynamic coupling in posterior DMN components. Uncoupling between hemodynamics and connectivity in the posterior DMN was associated with worse task performance. Non-NPSLE patients displayed hyperconnectivity in posterior DMN and sensorimotor regions paralleled by relatively increased hemodynamic lag. Adaptation of regional brain function to hemodynamic changes in NPSLE may involve locally decreased or locally increased intrinsic connectivity (which can be beneficial for cognitive function). This process may also involve elevated coupling of hemodynamics with functional connectivity (beneficial for cognitive performance) or uncoupling, which may be detrimental for the cognitive skills of NPSLE patients.

Left parietal involvement in motion sickness susceptibility revealed by multimodal magnetic resonance imaging.

Susceptibility to motion sickness varies greatly across individuals. However, the neural mechanisms underlying this susceptibility remain largely unclear. To address this gap, the current study aimed to identify the neural correlates of motion sickness susceptibility using multimodal MRI. First, we compared resting‐state functional connectivity between healthy individuals who were highly susceptible to motion sickness (N = 36) and age/sex‐matched controls who showed low susceptibility (N = 36). Seed‐based analysis revealed between‐group differences in functional connectivity of core vestibular regions in the left posterior Sylvian fissure. A data‐driven approach using intrinsic connectivity contrast found greater network centrality of the left intraparietal sulcus in high‐ rather than in low‐susceptible individuals. Moreover, exploratory structural connectivity analysis uncovered an association between motion sickness susceptibility and white matter integrity in the left inferior fronto‐occipital fasciculus. Taken together, our data indicate left parietal involvement in motion sickness susceptibility.

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study

ObjectiveTo examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).MethodsResting-state fMRI (rs-fMRI) was performed...

Evidence of Age-Related Hemodynamic and Functional Connectivity Impairment: A Resting State fMRI Study.

Purpose: To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging.Methods: Sixty-four healthy adults (28 men) aged 23–79 years (mean 45.0, SD = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL).Results: Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices (p < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex (p < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex.Conclusion: Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions—most of them part of DMN and salience networks—while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age.

Aging Impacts the Overall Connectivity Strength of Regions Critical for Information Transfer Among Brain Networks.

Recent studies have demonstrated that connector hubs, regions considered critical for the flow of information across neural systems, are mostly involved in neurodegenerative dementia. Considering that aging can significantly affect the brain’s intrinsic connectivity, identifying aging’s impact on these regions’ overall connection strength is important to differentiate changes associated with healthy aging from neurodegenerative disorders. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of 175 healthy volunteers aging from 21 to 86 years old, we computed an intrinsic connectivity contrast (ICC) metric, which quantifies a region’s overall connectivity strength, for whole brain, short-range, and long-range connections and examined age-related changes of this metric over the adult lifespan. We have identified a limited number of hub regions with ICC values that showed significant negative relationship with age. These include the medial precentral/midcingulate gyri and insula with both their short-range and long-range (and thus whole-brain) ICC values negatively associated with age, and the angular, middle frontal, and posterior cingulate gyri with their long-range ICC values mainly involved. Seed-based connectivity analyses further confirmed that these regions are connector hubs with connectivity profile that strongly overlapped with multiple large-scale brain networks. General cognitive performance was not associated with these hubs’ ICC values. These findings suggest that even healthy aging could negatively impact the efficiency of regions critical for facilitating information transfer among different functional brain networks. The extent of the regions involved, however, was limited.

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. To this end we combined categorical and dimensional disorder models with a fully data-driven intrinsic network-level analysis (intrinsic connectivity contrast, ICC) to resting-state fMRI data acquired in 108 individuals (n = 35 and n = 38 unmedicated patients with first-episode GAD, MDD, respectively, and n = 35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers.

Resting-state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta-analysis.

One of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta-analysis, we analyze the current role of rs-fMRI in identifying the SOZ for presurgical planning for patients with drug-resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization. A literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs-fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta-analysis was performed to analyze how ground truth compares to rs-fMRI in SOZ localization. The odds ratio comparing ground truth to rs-fMRI was 2.63 (95% confidence interval = 0.66-10.56). Average concordance of rs-fMRI SOZ localization compared with ground truth localization across studies was 71.3%. In the hunt for less invasive presurgical planning for epilepsy surgery, rs-fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs-fMRI with ICA. We believe that rs-fMRI could be a step forward in this search. Further investigation comparing rs-fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods.

An Echo of Consciousness: Brain Function During Preferred Music

Background: Given its emotional and autobiographical properties, music appears as a potential aid in diagnostic assessment and therapeutics in patients with disorders of consciousness (DOCs). Several studies have shown boosting effects on behavior and brain functioning when patients were exposed to (their preferred) music. Objective: The aim of this study was to investigate if these effects on the brain's spontaneous activity are dependent on the level of consciousness. Methods: Nine postcomatose patients and eight healthy control subjects were assessed using functional magnetic resonance imaging in two conditions: rest (without stimulation) and music. All patients presented at least an auditory startle, thereby suggesting the presence of residual auditory function. A gradient of consciousness (from unresponsive wakefulness syndrome to healthy subjects) was formulated to evaluate consciousness-level-dependent increases in brain activity and connectivity. Network-based functional connectivity assessed auditory, default-mode, frontoparietal, and music-evoked emotion networks. Furthermore, exploratory voxel-to-voxel analyses were performed at the whole brain level using intrinsic connectivity contrast and (fractional) amplitude of low-frequency fluctuations. Results: Stronger consciousness-level-dependent increases within network-to-voxel analysis of connectivity were found in the frontoparietal network with the precuneus during music stimulation compared with rest. Voxel-to-voxel analyses showed stronger increases of intrinsic connectivity in the music condition compared with rest in regions previously related to music processing. There were consistently more regions with increased connectivity during the main effect of music compared with rest. These increases of connectivity during music were observed in brain regions involved in consciousness, language, emotion, and memory processing. Conclusions: Our results show that music seems to trigger more substantial connectivity changes compared with rest, pointing toward the potential ability of music to stimulate patients' brain function. Further research should focus on effects of music in general, its specific acoustical features, and the effects of simple auditory stimuli, as well as the possible therapeutic and diagnostic effects of music in well-controlled clinical trials. Impact statement Due to its emotional and autobiographical properties, music is a particularly salient stimulus. A few studies using musical stimuli have shown promising results in terms of behavioral responsiveness in patients with disorders of consciousness (Magee, 2005; Raglio et al., 2014; Verger et al., 2014). Our study confirms the presence of a beneficial effect of music on brain connectivity in these severely brain-injured patients, which moreover seems to be dependent on the level of consciousness. Our findings therefore strengthen the hypothesis that music could play a role from a diagnostic and therapeutic standpoint in this population, paving the way for future well-controlled clinical trials.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging.

Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Altered Resting Functional Connectivity Is Related to Cognitive Outcome in Males With Moderate-Severe Traumatic Brain Injury.

TBI results in significant cognitive impairments and in altered brain functional connectivity. However, no studies explored so far, the relationship between global functional connectivity and cognitive outcome in chronic moderate-severe TBI. This proof of principle study employed the intrinsic connectivity contrast, an objective voxel-based metric of global functional connectivity, in a small sample of chronic moderate-severe TBI participants and a group of healthy controls matched on gender (males), age, and education. Cognitive tests assessing executive functions, verbal memory, visual memory, attention/organization, and cognitive reserve were administered. Group differences in terms of global functional connectivity maps were assessed and the association between performance on the cognitive measures and global functional connectivity was examined. Next, we investigated the spatial extent of functional connectivity in the brain regions found to be associated with cognitive performance, using traditional seed-based analyses. Global functional connectivity of the TBI group was altered, compared to the controls. Moreover, the strength of global functional connectivity in affected brain areas was associated with cognitive outcome. These findings indicate that impaired global functional connectivity is a significant consequence of TBI suggesting that cognitive impairments following TBI may be partly attributed to altered functional connectivity between brain areas involved in the specific cognitive functions.

Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis-dependent males.

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral-dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two-step approach to: (a) precisely map striatal alterations using a novel, data-driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis-dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

Age of Insomnia Onset Correlates with a Reversal of Default Mode Network and Supplementary Motor Cortex Connectivity.

Insomnia might occur as result of increased cognitive and physiological arousal caused by acute or long acting stressors and associated cognitive rumination. This might lead to alterations in brain connectivity patterns as those captured by functional connectivity fMRI analysis, leading to potential insight about primary insomnia (PI) pathophysiology as well as the impact of long-term exposure to sleep deprivation. We investigated changes of voxel-wise connectivity patterns in a sample of 17 drug-naïve PI patients and 17 age-gender matched healthy controls, as well as the relationship between brain connectivity and age of onset, illness duration, and severity. Results showed a significant increase in resting-state functional connectivity of the bilateral visual cortex in PI patients, associated with decreased connectivity between the visual cortex and bilateral temporal pole. Regression with clinical scores originally unveiled a pattern of increased local connectivity as measured by intrinsic connectivity contrast (ICC), specifically resembling the default mode network (DMN). Additionally, age of onset was found to be correlated with the connectivity of supplementary motor area (SMA), and the strength of DMN←→SMA connectivity was significantly correlated with both age of onset (R2 = 41%) and disease duration (R2 = 21%). Chronic sleep deprivation, but most importantly early insomnia onset, seems to have a significant disruptive effect over the physiological negative correlation between DMN and SMA, a well-known fMRI marker of attention performance in humans. This suggests the need for more in-depth investigations on the prevention and treatment of connectivity changes and associated cognitive and psychological deficits in PI patients.