Altered Baseline Brain Activity Research Articles

High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel invivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology.

Altered baseline brain activity differentiates regional mechanisms subserving biological and psychological alterations in obese men.

Obesity as a chronic disease is a major factor for insulin resistance and Type 2 diabetes, which has become a global health problem. In the present study, we used resting state functional MRI to investigate the amplitude of low frequency fluctuations of spontaneous signal during both hunger and satiety states in 20 lean and 20 obese males. We found that, before food intake, obese men had significantly greater baseline activity in the precuneus and lesser activity in dorsal anterior cingulate cortex (dACC) relative to lean subjects. Furthermore, after food intake, obese males had significantly lesser activity in dACC than lean males. We further found a significant positive correlation between precuneus activation and hunger ratings before food intake, while dACC activity was negatively correlated with plasma insulin levels before and after food intake. These results indicated that both precuneus and dACC may play an important role in eating behavior. While precuneus rather seemed to mediate subjective satiety, dACC levels rather reflected indirect measures of glucose utilization.

Altered baseline brain activity in experts measured by amplitude of low frequency fluctuations (ALFF): a resting state fMRI study using expertise model of acupuncturists.

It is well established that expertise modulates evoked brain activity in response to specific stimuli. Recently, researchers have begun to investigate how expertise influences the resting brain. Among these studies, most focused on the connectivity features within/across regions, i.e., connectivity patterns/strength. However, little concern has been given to a more fundamental issue whether or not expertise modulates baseline brain activity. We investigated this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as the metric of brain activity and a novel expertise model, i.e., acupuncturists, due to their robust proficiency in tactile perception and emotion regulation. After the psychophysical and behavioral expertise screening procedure, 23 acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results explicated higher ALFF for acupuncturists in the left ventral medial prefrontal cortex (VMPFC) and the contralateral hand representation of the primary somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF of VMPFC was negatively correlated with the outcomes of the emotion regulation task (corrected for multiple comparisons). We suggest that our study may reveal a novel connection between the neuroplasticity mechanism and resting state activity, which would upgrade our understanding of the central mechanism of learning. Furthermore, by showing that expertise can affect the baseline brain activity as indicated by ALFF, our findings may have profound implication for functional neuroimaging studies especially those involving expert models, in that difference in baseline brain activity may either smear the spatial pattern of activations for task data or introduce biased results into connectivity-based analysis for resting data.

Disrupted neural activity in unilateral vascular pulsatile tinnitus patients in the early stage of disease: evidence from resting-state fMRI.

Numerous studies have shown that neurological changes are important findings of tinnitus patients. Previous studies on tinnitus have indicated that patients with pulsatile tinnitus (PT) often show altered baseline brain activity in the resting state. This study used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in spontaneous brain activity among patients with unilateral pulsatile tinnitus in the early stage of disease (less than forty-eight months) and determined the relationship of these changes with clinical data. The PT patients (n=34) and matched normal control subjects (n=34) were enrolled in this study. Spontaneous brain activity was revealed by the regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values. Compared with normal controls, the patients with PT had significantly increased ReHo and ALFF in the posterior cingulate cortex, right inferior parietal lobule (IPL) and right cerebellum posterior lobe. The PT group showed increased ReHo in the posterior cingulate cortex (PCC), precuneus, right IPL, right superior frontal gyrus, some occipital areas and part of the right cerebellum posterior lobe. For ALFF, the increased clusters were in the PCC and precuneus and in some areas of the cerebellum posterior lobe, bilateral IPL and inferior frontal gyrus (IFG). Increased PT duration was correlated with increased ALFF in the bilateral inferior frontal gyrus (IFG) and precuneus. An increased THI score was correlated with ReHo and ALFF values in the precuneus. Taken together, the combined study of ReHo and ALFF measurements may yield a more comprehensive neurological pathophysiology framework for PT patients in the early stage of the disease.

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI.

ObjectiveWe hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD.MethodsWe investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed.ResultsOur findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus.ConclusionThese results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.

Altered baseline brain activity in children with bipolar disorder during mania state: a resting-state study

BackgroundPrevious functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain’s total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients.MethodsEighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores.ResultsCompared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD.ConclusionThe abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients.

Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting-state FMRI study.

Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.

Altered baseline brain activity in type 2 diabetes: A resting-state fMRI study

This study aims to investigate whether altered baseline brain activity exists in type 2 diabetes mellitus (T2DM) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and whether abnormal neural activity in the middle temporal gyrus (MTG) is correlated with cognitive function. T2DM patients (n=28) were compared with nondiabetic age-, sex-, and education-matched control subjects (n=29) using rs-fMRI. We computed the amplitude of low-frequency fluctuations (ALFF) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between rs-fMRI information and clinical data. Compared with healthy controls, T2DM patients had significantly decreased ALFF values in the bilateral middle temporal gyrus, left fusiform gyrus, left middle occipital gyrus, right inferior occipital gyrus; and increased ALFF values in both the bilateral cerebellum posterior lobe and right cerebellum culmen. Moreover, we found an inverse correlation between the ALFF values in the MTG and both the HbA1c (r=-0.451, p=0.016) and the score of Trail Making Test-B (r=-0.420, p=0.026) in the patient group. On the other hand, C-peptide level and pancreatic β-cell function had a positive correlation (r=0.429, p=0.023; r=0.453, p=0.016, respectively) with the ALFF value in the middle temporal gyrus. The present study confirms that T2DM patients have altered ALFF in many brain regions, which is associated with poor neurocognitive performances, severity of consistent hyperglycemic state and impaired β-cell function. ALFF disturbance in MTG may play a central role in cognitive decline associated with T2DM and serve as reference for future clinical diagnosis.

Altered Baseline Brain Activity with 72 h of Simulated Microgravity – Initial Evidence from Resting-State fMRI

To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a −6° head down tilt (HDT). A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a −6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm3 (13 voxels), which corresponded with the corrected threshold of P<0.05 determined by AlphaSim). Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment.

Altered baseline brain activity in children with TS revealed by resting-state functional MRI

Altered baseline brain activity in children with TS revealed by resting-state functional MRI

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01–0.08 Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0 ± 1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, left sensorimotor cortex, and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.