Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Resting-state fMRI activity predicts unsupervised learning and memory in an immersive virtual reality environment

In the real world, learning often proceeds in an unsupervised manner without explicit instructions or feedback. In this study, we employed an experimental paradigm in which subjects explored an immersive virtual reality environment on each of two days. On day 1, subjects implicitly learned the location of 39 objects in an unsupervised fashion. On day 2, the locations of some of the objects were changed, and object location recall performance was assessed and found to vary across subjects. As prior work had shown that functional magnetic resonance imaging (fMRI) measures of resting-state brain activity can predict various measures of brain performance across individuals, we examined whether resting-state fMRI measures could be used to predict object location recall performance. We found a significant correlation between performance and the variability of the resting-state fMRI signal in the basal ganglia, hippocampus, amygdala, thalamus, insula, and regions in the frontal and temporal lobes, regions important for spatial exploration, learning, memory, and decision making. In addition, performance was significantly correlated with resting-state fMRI connectivity between the left caudate and the right fusiform gyrus, lateral occipital complex, and superior temporal gyrus. Given the basal ganglia's role in exploration, these findings suggest that tighter integration of the brain systems responsible for exploration and visuospatial processing may be critical for learning in a complex environment

Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. Thus, we sought to identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These RSNM targets were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region ( sgACC-derived targets ). The TBI-D cohort was also randomized to receive active (n = 9) or sham (n = 4) rTMS to RSNM targets with 20 daily sessions of sequential high-frequency left-sided stimulation and low-frequency right-sided stimulation. We found that the group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were thus identified based on DAN anti-correlation and DMN correlation. These RSNM targets showed greater test-retest reliability than sgACC-derived targets. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was also stronger and more reliable for RSNM-derived targets than for sgACC-derived targets. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment also led to increased connectivity within and between the stimulation sites, the sgACC, and the DMN. Overall, these results suggest that RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes

Resting-state anticorrelations between medial and lateral prefrontal cortex: Association with working memory, aging, and individual differences

We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex (DLPFC), a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of WM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity.National Institutes of Health (U.S.) (National Institute on Aging Grant R21 AG030770)National Institutes of Health (U.S.) (Grant T32 GM007484)Barbara J. Weedon Fund Fellowshi

Beyond fingerprinting: Choosing predictive connectomes over reliable connectomes

Recent years have seen a surge of research on variability in functional brain connectivity within and between individuals, with encouraging progress toward understanding the consequences of this variability for cognition and behavior. At the same time, well-founded concerns over rigor and reproducibility in psychology and neuroscience have led many to question whether functional connectivity is sufficiently reliable, and call for methods to improve its reliability. The thesis of this opinion piece is that when studying variability in functional connectivity—both across individuals and within individuals over time—we should use behavior prediction as our benchmark rather than optimize reliability for its own sake. We discuss theoretical and empirical evidence to compel this perspective, both when the goal is to study stable, trait-level differences between people, as well as when the goal is to study state-related changes within individuals. We hope that this piece will be useful to the neuroimaging community as we continue efforts to characterize inter- and intra-subject variability in brain function and build predictive models with an eye toward eventual real-world applications

A rede padrão de repouso parece preservada intrinsecamente mas sua conectividade funcional extrínseca pode estar comprometida em usuários de crack-cocaína

O Defalut Mode Network (DMN) parace estar afetado na dependência química. Conectividade funcional reduzida foi descrita em usuários de psicoestimulantes (cocaína, nicotina e cafeína) e também em dependentes de drogas depressoras (álcool, heroína, opioides de prescrição), porém nenhum estudo investigou a conectividade funcional do DMN em dependentes de crack até então. Neste estudo, usuários de crack em abstinência por no mínimo 4 semanas e pareados por idade com controles não usuários foram submetidos a exames de imagem por Ressonância Magnética funcional adquiridos quando em repouso e com os olhos fechados (rs-fMRI) em aparelhos de 1,5T e 3,0T. Após o pré-processamento dos dados, DMN foram definidos por análise de componentes independentes (Independent Component Analysis ICA) e por análise de correlação seed based, por regiões de interesse (ROIs) no Córtex Cingulado Anterior ventral (vACC) e no Córtex Cingulado Posterior (PCC). A conectividade funcional global do DMN não foi diferente entre os usuários de crack e os controles não usuários pareados por idade nos estudos de rs-fMRI adquiridos em ambos os scanners. A análise seed based evidenciou maior negatividade da conectividade entre o vACC e o lóbulo parietal superior esquerdo quando comparado aos controles pareados por idade (p < 0,0322). Não foram encontradas diferenças entre os grupos na conectividade funcional entre o PCC e outras regiões cerebrais. Assim, a conectividade funcional total do DMN analisada por ICA foi encontrada preservada nos dependentes de crack em abstinência. Quando uma análise de correlação seed based foi aplicada buscando-se por uma conectividade funcional métrica simples entre regiões cerebrais específicas, uma maior negatividade foi encontrada entre a região frontal medial e a região cerebral posterior, sugerindo que embora o DMN global não esteja afetado uma conectividade funcional seletiva pode estar comprometida na dependência do crack. Palavras-chave: Cocaína Crack. Dependência. Transtornos Relacionados ao Uso de Substâncias. Imagem por Ressonância Magnética. IRMf

The Effect of Circadian Rhythms on BOLD Dynamics and Effective Connectivity

Masteroppgave i psykologiMAPSYK360INTL-KMDINTL-MNMAPS-PSYKINTL-PSYKINTL-MEDINTL-JUSINTL-SVINTL-H

Investigating the role of the central and the peripheral benzodiazepine receptor on stress and anxiety related parameters

Anxiety disorders belong to the most prevalent mental disorders worldwide implying a high burden of illness. Due to their complexity and variety of underlying dysfunctions, it remains a challenging task to find optimum pharmacological treatment. Benzodiazepines, which modulate the GABAA or central benzodiazepine receptor, are among the most frequently used substances in this field. However, they hold several side effects, especially at longer application. In the search for alternatives, substances that target the translocator protein (TSPO), also known as peripheral benzodiazepine receptor, yield promising candidates. Within the present work, we aimed to compare the effects of a benzodiazepine and a TSPO ligand, which further binds to GABAA receptors, on stress and anxiety related parameters. Within a randomized clinical trial, 60 healthy male subjects received either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine or placebo for a period of five days. We applied the Trier Social Stress Test in Virtual Reality, the NPU Threat Test, resting-state functional imaging, and the Continuous Performance Test and assessed self-reports, physiological parameters, salivary and blood markers, objective performance parameters as well as changes of functional brain connectivity. While alprazolam blunted the response of the HPA axis to acute psychosocial stress, etifoxine increased expression of TSPO independent of additional external stimulation. There were no effects of the medication on subjective or physiological measures of the stress response. Neither alprazolam nor etifoxine had an impact on the anxiety-related startle reflex, while etifoxine attenuated the fear-potentiated startle on day 1 of treatment. Alprazolam increased functional neuronal connectivity within and between several resting- state networks. In neither group, there was strong impairment of alertness or any serious adverse event or study dropout. When focusing on symptoms related to sedation, there were more reports from subjects that had received alprazolam. The present work revealed different effects of the applied substances on molecular, physiological and neuronal markers of stress and anxiety. Thereby, especially the strength with which the GABAergic system is affected seems to play an important role, while the involvement of TSPO might be rather specific and dependent on the respective pathological state