Altered Resting-state Activity Research Articles

Altered Resting-State Activity and Connectivity in Late-Life Depression with Suicidal Ideation

Altered Resting-State Activity and Connectivity in Late-Life Depression with Suicidal Ideation

Functional MRI Derived Resting-State Alterations in Huntington’s Disease are Associated With the Distribution of Serotonergic and Dopaminergic Neurotransmitter Systems

Huntington’s disease (HD) is characterized by progressive striatal atrophy and widespread degeneration during the course of disease. Functionally, altered resting-state activity and connectivity in networks involving cortical, subcortical and cerebellar regions can be observed. The relationship of brain alterations in HD with specific neurotransmitter systems remains largely unknown.

Resting-State Functional Connectivity and Anxiety Predict Relapse in Remitted Late-Life Depression

<h3>Introduction</h3> Late-life depression (LLD) refers to depression occurring in older age and is associated with a multitude of psychosocial and biological factors, including conditions related to pathological aging, including cardiovascular and cerebrovascular diseases, and dementia. Relevant psychosocial factors comprise personality disorders, neuroticism, trauma and stress. Depending on the relative contribution of conditions related to pathological aging versus psychosocial factors, some patients may not respond to antidepressants and others may be prone to relapse even when they achieved initial remission on an antidepressant. The neural mechanisms related to recurrence of LLD are not clear. About 50% of individuals who have recovered from a first episode of depression will suffer from at least one additional episode. Therefore, identifying patients prone to relapse is important for developing tailored treatment regimens, preventing suicide, and reducing economic burdens and other morbidities. To understand the neural mechanisms related to relapse of depression, and identify neuroimaging markers to predict individuals who tend to relapse, we conducted a secondary data analysis on clinical and fMRI data collected from our NBOLD project. We hypothesized that, compared with individuals who did not relapse during a two-year clinical follow-up period, those who relapsed would show significantly altered resting-state activity patterns in core neural networks related to LLD including the default mode, executive control and salience networks. <h3>Methods</h3> The sample included 102 adults with LLD who were free of medication for at least two weeks before study enrollment. Depression severity was measured by MADRS and was assessed by a study psychiatrist at each study visit, which occurred frequently while the subject remained depressed and quarterly when remission was achieved. Among the enrolled participants, 52 (age range of 60 – 89) achieved depression remission after antidepressant treatment (MADRS< 8 for at least 2 months). We defined relapse as having a MADRS > 15 for at least two weeks. Individuals were classified as non-relapsed if they maintained a MADRS <13 after remission during the two follow-up years. Among the 52 LLD patients, 27 of them relapsed and 25 did not. We also measured trait and state anxiety and neuroticism using State-Trait Anxiety Inventory (STAI), NEO Personality Inventory (NEO PI). The neuroimaging data was collected from 3T Siemens Skyra scanner. The imaging parameters for T1-weighted images were: TR/TE=2200/2.8ms, flip angle=13^o, matrix = 256 × 256 × 169, voxelsize=1 × 1 × 1mm³. The 7-min resting-state fMRI data was collected using EPI sequence with FOV=240mm, flip angle=90^o, TR/TE=2000/31ms, matrix=64 × 64 × 34, voxelsize=3.8 × 3.8 × 3.75mm³. The resting-state fMRI data was preprocessed using the default protocol settings in Conn Toolbox version17f. The preprocessed data was entered to DPABI software for calculating the Amplitude of Low-Frequency Fluctuations (ALFF). Functional connectivity (FC) was done using Conn Toolbox version17f. Two sample t-tests were conducted to compare resting-state activity, ALFF, and FC to examine differences in ALFF and FC between relapsed and non-relapsed LLD groups (age and gender were controlled). Significance was set at p<0.05 with FDR correction for multiple comparisons. <h3>Results</h3> There were no significant differences between relapsed and non-relapsed groups in age, gender, state anxiety or neuroticism. Those who relapsed during the two-year follow-up had less severe depressive symptoms at baseline (mean (SD) MADRS=18.40(4.06) than those non-depressed group (mean (SD) MADRS=20.81(6.23) with p=0.001), whereas the relapsed group had higher STAI-trait anxiety than the non-relapsed group (p=0.04). Two-sample t-tests on FC showed that the relapsed group had a lower FC between the right parahippocampus and the superior and inferior parietal cortex. The relapsed group also had a reduced FC between the right globus pallidum and the right superior frontal gyrus. In addition, the relapsed group had significantly greater ALFF in the left amygdala and globus pallidum compared with the non-relapsed group; however, the significance was lost after controlling for depression severity and STAI-trait anxiety. <h3>Conclusions</h3> This is one of few studies that have examined clinical and neural characters in relapsed LLD. Lower FC between the right parahippocampus and the superior and inferior parietal cortex suggests a potential reduction in attention for memory. Low FC between the right globus pallidum and the right superior frontal gyrus may indicate reduced executive function in relapsed individuals. Importantly, the relapsed group also showed lower depressive symptoms yet higher trait anxiety. These results suggest that depression comorbid with anxiety might be an essential factor of relapse tendency. Future studies will examine whether the relapsed group also has lower executive function.

Learning to play badminton altered resting-state activity and functional connectivity of the cerebellar sub-regions in adults.

Previous studies have shown that sport experts are different from novices in functions and structures of the cerebellar sub-regions and the functional connectivity (FC) associated with the cerebellum, suggesting the role of the cerebellum on motor skill learning (MSL). However, the manipulation of individuals with different motor skills fails to exclude the effects of innate talents. In addition, individuals with higher motor skills often start with the MSL in their young ages. It is still unclear whether the effects regarding the cerebellum would be shown at one’s adult age. The present study was to directly alter individuals’ motor skills to investigate whether MSL (taking learning to play badminton as an example) in adulthood influences resting-state activity in the cerebellum. To this end, young adults without ball training experience were recruited as participants and were assigned randomly into the experimental group and the control group. Participants in the experimental group were asked to attend a badminton training course for 12 weeks, while the control group did not regularly attend any ball sports during this period. Resting-state functional magnetic resonance imaging (fMRI) was recorded before and after the training. Results showed that compared to the control group, the experimental group had smaller amplitude of low-frequency fluctuation (ALFF) in right cerebellar hemispheric VI and left VIII after training. For the experimental group, right hemispheric VIII had a stronger FC with left hemispheric IV-V, cerebellar vermal IX, left middle cingulate gyrus and right hippocampus after training. Taken together, these findings suggested that MSL, at least learning to play badminton in adulthood, reduces resting-state activity in different sub-regions in the cerebellum but increases FC between sub-regions of the cerebellum as well as between sub-regions of the cerebellum and cerebral cortices (e.g., middle cingulate cortex and hippocampus).

Decreased Resting-State Activity in the Precuneus Is Associated With Depressive Episodes in Recurrent Depression.

To investigate alterations in resting-state spontaneous brain activity in patients with major depressive disorder (MDD) experiencing multiple episodes. Between May 2007 and September 2014, 24 recurrent and 22 remitted patients diagnosed with MDD with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and 69 healthy controls matched for age, sex, and educational level participated in this study. Among them, 1 healthy control was excluded due to excessive head motion. The fractional amplitude of low-frequency fluctuation (fALFF) was assessed for all recruited subjects during the completion of resting-state functional magnetic resonance imaging. Relationships between fALFF and clinical measurements, including number of depressive episodes and illness duration, were examined. Compared to patients with remitted MDD and to healthy controls, patients with recurrent MDD exhibited decreased fALFF in the right posterior insula and right precuneus and increased fALFF in the left ventral anterior cingulate cortex. Decreased fALFF in the right precuneus and increased fALFF in the right middle insula were correlated with the number of depressive episodes in the recurrent MDD groups (r = -0.75, P < .01 and r = 0.78, P < .01, respectively) and remitted MDD groups (r = -0.63, P < .01 and r = 0.41, P = .03, respectively). In addition to regions in the default mode network (DMN) and salience network, the altered resting-state activity in the middle temporal and visual cortices was also identified. Altered resting-state activity was observed across several neural networks in patients with recurrent MDD. Consistent with the emerging theory that altered DMN activity is a risk factor for depression relapses, the association between reduced fALFF in the right precuneus and number of depressive episodes supports the role of the DMN in the pathology of recurrent depression.

Regional homogeneity and resting state functional connectivity: Associations with exposure to early life stress

Early life stress (ELS) confers risk for psychiatric illness. Previous literature suggests ELS is associated with decreased resting-state functional connectivity (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity in this population. This study investigated whether ELS-exposed individuals demonstrate resting-state activity patterns similar to those found in PTSD. Twenty-seven adults (14 with at least moderate ELS), who were medication-free and without psychiatric or medical illness, underwent MRI scans during two 4-minute rest periods. Resting-state activity was examined using regional homogeneity (ReHo), which estimates regional activation patterns through indices of localized concordance. ReHo values were compared between groups, followed by rs-FC analyses utilizing ReHo-localized areas as seeds to identify other involved regions. Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were inversely correlated with ELS severity. Secondary analyses revealed decreased rs-FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus, cerebellum and caudate in ELS subjects. These findings indicate that ELS is associated with altered resting-state activity and connectivity in brain regions involved in trauma-related psychiatric disorders. Future studies are needed to evaluate whether these associations represent potential imaging biomarkers of stress exposure.

Altered resting-state activity in seasonal affective disorder.

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD.

Nicotine effects on default mode network during resting state

The default mode network (DMN), one of several resting-state networks (RSN) in the brain, is thought to be involved in self-referential thought, awareness, and episodic memories. Nicotine improves cognitive performance, in part by improving attention. Nicotinic agonists have been shown to decrease activity in regions within DMN and increase activity in regions involved in visual attention during effortful processing of external stimuli. It is unknown if these pharmacological effects also occur in the absence of effortful processing. This study aims to determine if nicotine suppresses activity in default mode and enhances activity in extra-striate RSNs in the absence of an external visual task. Within-subject, single-blinded, counterbalanced study of 19 non-smoking subjects who had resting functional MRI scans after 7 mg nicotine or placebo patch. Group independent component analysis was performed. The DMN component was identified by spatial correlation with a reference DMN mask. A visual attention component was identified by spatial correlation with an extra-striate mask. Analyses were conducted using statistical parametric mapping. Nicotine was associated with decreased activity in regions within the DMN and increased activity in extra-striate regions. Suppression of DMN and enhancement of extra-striate resting-state activity in the absence of visual stimuli or effortful processing suggest that nicotine's cognitive effects may involve a shift in activity from networks that process internal to those that process external information. This is a potential mechanism by which cholinergic agonists may have a beneficial effect in diseases associated with altered resting-state activity.