Resting State Functional Connectivity Signatures of MRgFUS Vim Thalamotomy in Parkinson's Disease: A Preliminary Study

Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI “connectomic” analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson's disease who underwent MRgFUS. We tested whether rs-FC between tremor-related areas was modulated by MRgFUS at 1 and 3 months post-operatively, and whether such changes correlated with individual clinical outcomes assessed by the MDS-UPDRS-III sub items for tremor. Significant increase in FC was detected within bilateral primary motor (M1) cortices, as well as between bilateral M1 and crossed primary somatosensory cortices, and also between pallidum and the dentate nucleus of the untreated hemisphere. Correlation between disease duration and FC increase at 3 months was found between the putamen of both cerebral hemispheres and the Lobe VI of both cerebellar hemispheres, as well as between the Lobe VI of untreated cerebellar hemisphere with bilateral supplementary motor area (SMA). Drop-points value of MDS-UPDRS at 3 months correlated with post-treatment decrease in FC, between the anterior cingulate cortex and bilateral SMA, as well as between the Lobe VI of treated cerebellar hemisphere and the interpositus nucleus of untreated cerebellum. Tremor improvement at 3 months, expressed as percentage of intra-subject MDS-UPDRS changes, correlated with FC decrease between bilateral occipital fusiform gyrus and crossed Lobe VI and Vermis VI. Good responders (≥50% of baseline tremor improvement) showed reduced FC between bilateral SMA, between the interpositus nucleus of untreated cerebellum and the Lobe VI of treated cerebellum, as well as between the untreated SMA and the contralateral putamen. Good responders were characterized at baseline by crossed hypoconnectivity between bilateral putamen and M1, as well as between the putamen of the treated hemisphere and the contralateral SMA. We conclude that MRgFUS can effectively modulate brain FC within the tremor network. Such changes are associated with clinical outcome. The shifting mode of integration among the constituents of this network is, therefore, susceptible to external redirection despite the chronic nature of PD.

Imbalance between default mode and sensorimotor connectivity is associated with perseverative thinking in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is highly heterogeneous. Although perseverative negative thinking (PT) is a feature of OCD, little is known about its neural mechanisms or relationship to clinical heterogeneity in the disorder. In a sample of 85 OCD patients, we investigated the relationships between self-reported PT, clinical symptom subtypes, and resting-state functional connectivity measures of local and global connectivity. Results indicated that PT scores were highly variable within the OCD sample, with greater PT relating to higher severity of the “unacceptable thoughts” symptom dimension. PT was positively related to local connectivity in subgenual anterior cingulate cortex (ACC), pregenual ACC, and the temporal poles—areas that are part of, or closely linked to, the default mode network (DMN)—and negatively related to local connectivity in sensorimotor cortex. While the majority of patients showed higher local connectivity strengths in sensorimotor compared to DMN regions, OCD patients with higher PT scores had less of an imbalance between sensorimotor and DMN connectivity than those with lower PT scores, with healthy controls exhibiting an intermediate pattern. Clinically, this imbalance was related to both the “unacceptable thoughts” and “symmetry/not-just-right-experiences” symptom dimensions, but in opposite directions. These effects remained significant after accounting for variance related to psychiatric comorbidity and medication use in the OCD sample, and no significant relationships were found between PT and global connectivity. These data indicate that PT is related to symptom and neural variability in OCD. Future work may wish to target this circuity when developing personalized interventions for patients with these symptoms.

Weaker connectivity in resting state networks is associated with disinhibited eating in older adults

Background/objectives Obesity affects more than forty percent of adults over the age of sixty. Aberrant eating styles such as disinhibition have been associated with the engagement of brain networks underlying executive functioning, attentional control, and interoception. However, these effects have been exclusively studied in young samples overlooking those most at risk of obesity related harm. Methods Here we assessed associations between resting-state functional connectivity and disinhibited eating (using the Three Factor Eating Questionnaire) in twenty-one younger (aged 19–34 years, BMI range: 18–31) and twenty older (aged 60–73 years, BMI range: 19–32) adults matched for BMI. The Alternative Healthy Eating Index was used to quantify diet quality. Results Older, compared to younger, individuals reported lower levels of disinhibited eating, consumed a healthier diet, and had weaker connectivity in the frontoparietal (FPN) and default mode (DMN) networks. In addition, associations between functional connectivity and eating behaviour differed between the two age groups. In older adults, disinhibited eating was associated with weaker connectivity in the FPN and DMN––effects that were absent in the younger sample. Importantly, these effects could not be explained by differences in habitual diet. Conclusions These findings point to a change in interoceptive signalling as part of the ageing process, which may contribute to behavioural changes in energy intake, and highlight the importance of studying this under researched population.

Transdiagnostic phenotypes of compulsive behavior and associations with psychological, cognitive, and neurobiological affective processing

Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous sample of community-based individuals (N = 45; 18–45 years; 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger samples are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.

Resting-State Functional Connectivity in the Dorsal Attention Network Relates to Behavioral Performance in Spatial Attention Tasks and May Show Task-Related Adaptation

Between-subject variability in cognitive performance has been related to inter-individual differences in functional brain networks. Targeting the dorsal attention network (DAN) we questioned (i) whether resting-state functional connectivity (FC) within the DAN can predict individual performance in spatial attention tasks and (ii) whether there is short-term adaptation of DAN-FC in response to task engagement. Twenty-seven participants first underwent resting-state fMRI (PRE run), they subsequently performed different tasks of spatial attention [including visual search (VS)] and immediately afterwards received another rs-fMRI (POST run). Intra- and inter-hemispheric FC between core hubs of the DAN, bilateral intraparietal sulcus (IPS) and frontal eye field (FEF), was analyzed and compared between PRE and POST. Furthermore, we investigated rs-fMRI-behavior correlations between the DAN-FC in PRE/POST and task performance parameters. The absolute DAN-FC did not change from PRE to POST. However, different significant rs-fMRI-behavior correlations were revealed for intra-/inter-hemispheric connections in the PRE and POST run. The stronger the FC between left FEF and IPS before task engagement, the better was the learning effect (improvement of reaction times) in VS (r = 0.521, p = 0.024). And the faster the VS (mean RT), the stronger was the FC between right FEF and IPS after task engagement (r = −0.502, p = 0.032). To conclude, DAN-FC relates to the individual performance in spatial attention tasks supporting the view of functional brain networks as priors for cognitive ability. Despite a high inter- and intra-individual stability of DAN-FC, the change of FC-behavior correlations after task performance possibly indicates task-related adaptation of the DAN, underlining that behavioral experiences may shape intrinsic brain activity. However, spontaneous state fluctuations of the DAN-FC over time cannot be fully ruled out as an alternative explanation.

Disrupting The Resting State: Meta-Analytic Evidence That Mindfulness Training Alters Default Mode Network Connectivity

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to structurally-equivalent programs, with the hypothesis that that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of standardized mindfulness-based interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = .162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

Relationships between Diffusion Tensor Imaging and Resting State Functional Connectivity in Patients with Schizophrenia and Healthy Controls: A Preliminary Study

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects and acquired resting state fMRI and diffusion tensor imaging. The Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) was used to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal components analysis. Nine of 28 possible region pairs showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS values correlated with several aspects of the Positive and Negative Syndrome Scale, positively with those involving inwardly directed psychopathology, and negatively with those involving external psychopathology. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.