Tools of the trade: estimating time-varying connectivity patterns from fMRI data

Given the dynamic nature of the brain, there has always been a motivation to move beyond ‘static’ functional connectivity, which characterizes functional interactions over an extended period of time. Progress in data acquisition and advances in analytical neuroimaging methods now allow us to assess the whole brain’s dynamic functional connectivity (dFC) and its network-based analog, dynamic functional network connectivity at the macroscale (mm) using fMRI. This has resulted in the rapid growth of analytical approaches, some of which are very complex, requiring technical expertise that could daunt researchers and neuroscientists. Meanwhile, making real progress toward understanding the association between brain dynamism and brain disorders can only be achieved through research conducted by domain experts, such as neuroscientists and psychiatrists. This article aims to provide a gentle introduction to the application of dFC. We first explain what dFC is and the circumstances under which it can be used. Next, we review two major categories of analytical approaches to capture dFC. We discuss caveats and considerations in dFC analysis. Finally, we walk readers through an openly accessible toolbox to capture dFC properties and briefly review some of the dynamic metrics calculated using this toolbox.     

Resistant Hypertension

Resistant hypertension is defined as a blood pressure that remains above goal despite the concurrent use of optimal doses of three antihypertensive agents of different classes, ideally including a diuretic. Resistant hypertension has become increasingly common in hypertensive populations around the world. In recent years there has been increased recognition and characterization of patients with resistant hypertension, and over the past year there have been several important developments in lifestyle, pharmacologic, and nonpharmacologic interventions. Although sodium restriction and adherence remain the foundation of treatment for resistant hypertension, many new pharmacologic approaches and innovative surgical interventions highlight a new and developing field for the treatment of resistant hypertension. Despite these recent advances, management of resistant hypertension remains a challenge and there continues to be a need for novel and improved therapeutic strategies.     

Antipsychotic dose and diminished neural modulation: a multi-site fMRI study

Background

The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.

Methods

Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.

Results

Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t₇₇ = 2.01, P = 0.048).

Conclusion

The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.     

Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder

Rationale

Nicotinic acetylcholine receptors (nAChRs) are a critical component of the cholinergic system of neurotransmission in the brain that modulates important physiological processes such as reward, cognition, and mood. Abnormalities in this system are accordingly implicated in multiple psychiatric illnesses, including addiction, schizophrenia, and mood disorders. There is significantly increased tobacco use, and therefore nicotine intake, in patient populations, and pharmacological agents that act on various nicotinic receptor subtypes ameliorate clinical features of these disorders. Better understanding of the molecular mechanisms underlying cholinergic dysfunction in psychiatric disease will permit more targeted design of novel therapeutic agents.

Results

The objective of this review is to describe the multiple cellular pathways through which chronic nicotine exposure regulates nAChR expression, and to juxtapose these mechanisms with evidence for altered expression of high-affinity nAChRs in human psychiatric illness. Here, we summarize multiple studies from pre-clinical animal models to human in vivo imaging and post-mortem experiments demonstrating changes in nAChR regulation and expression in psychiatric illness.

Conclusions

We conclude that a mechanistic explanation of nAChR abnormalities in psychiatric illness will arise from a fuller understanding of normal nAChR trafficking, along with the detailed study of human tissue, perhaps using novel biotechnological advances, such as induced pluripotent stem cells.     

Early onset amyloid lesions lead to severe neuritic abnormalities and local, but not global neuron loss in APPPS1 transgenic mice

APPPS1 transgenic mice develop amyloid-β 42 (Aβ42)-driven early-onset cerebral β-amyloidosis. Stereological analysis of neocortical neuron number in groups of 2-, 10-, and 17-month-old APPPS1 mice did not reveal any changes compared with wild-type control animals despite massive amyloid-β (Aβ) load and disrupted cytoarchitecture. However, in subregions with high neuron density such as the granule cell layer of the dentate gyrus, modest but significant neuron loss was found, reminiscent of findings in previously published mouse models with late onset cerebral β-amyloidosis and predominant amyloid-β 40 (Aβ40) expression.     

Cardiac geometry and function in diabetic or prediabetic adolescents and young adults: the Strong Heart Study

OBJECTIVE

The aim of this study was to evaluate whether diabetes (DM) and impaired fasting glucose (IFG) were associated with early alterations in left ventricular geometry and function in a large population of adolescents and young adults independently of major confounders.

RESEARCH DESIGN AND METHODS

We analyzed echocardiographic data of 1,624 14- to 39-year-old participants (mean age 26.6 ± 7.7 years; 57% female) without prevalent cardiovascular disease from the fourth Strong Heart Study examination; 179 (11%) participants had DM and 299 (18%) had IFG.

RESULTS

Participants with DM and IFG were older and more often obese and hypertensive than participants with normal fasting glucose (NFG) (all P < 0.05). After adjustment for age, sex, systolic blood pressure, and body fat, diabetic and IFG participants had higher left ventricular mass index than those with NFG (41.5 ± 8.7 and 39.6 ± 9.2 vs. 35.6 ± 7.8 g/m^2.7) and reduced stress-corrected midwall shortening (98 ± 8.6 and 99 ± 7.5 vs. 101 ± 8.5%; all P < 0.05). The prevalence of left ventricular hypertrophy was higher in DM (20%) and IFG (17%) than in NFG participants (12%; P < 0.05). Compared with the other groups, DM was also associated with higher prevalence of inappropriate left ventricular mass, concentric geometry, and more diastolic abnormalities independently of covariates (all P < 0.05).

CONCLUSIONS

In a population of adolescents and young adults, DM is independently associated with early unfavorable cardiovascular phenotype characterized by increased left ventricular mass, concentric geometry, and early preclinical systolic and diastolic dysfunction; early cardiovascular alterations are also present in participants with prediabetes.The prevalence of obesity and type 2 diabetes (DM) in youth has increased dramatically in the last decade, especially in minority populations (1,2). Early onset of type 2 DM is associated with increased risk of cardiovascular complications compared with usual onset of the disease (3). Part of the increased cardiovascular risk might be related to a direct adverse effect of DM on the heart, independently of coronary artery disease, that has been documented in adults (4–6). However, the impact of DM and prediabetes on cardiac geometry and function in youth has not been extensively characterized in large population-based samples. It is unknown whether in the youth there is an independent influence of DM on cardiovascular phenotype. Accordingly, the current study was undertaken to evaluate whether DM and prediabetes, as measured by impaired fasting glucose (IFG), are associated with cardiac alterations independently of major confounders in a population-based sample of adolescents and young adults.