Jia-Hong Gao

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age±s.d.=34.3±11.5 years) and 15 healthy comparison subjects (37.7±12.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P<0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex.

The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production (JATP)] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO2; i.e., index of aerobic metabolism), and lactate production (JLac; i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in JATP were small (12.2–16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %ΔJATP being linearly correlated with the percentage change in CMRO2 (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7–65.1%) and negatively correlated with the percentage change in CMRO2 (r = −0.64, P = 0.024), but positively correlated with %ΔJLac (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand.

Evaluation of MRI models in the measurement of CMRO2 and its relationship with CBF.

The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO2) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single‐compartment model (SCM) and the multicompartment model (MCM), were used to determine the relative changes in CMRO2 using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; α = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and α from measured δCBV and δCBF); and [3] MCM. The magnitude of relative changes in CMRO2 and the nonlinear relationship between CBF and CMRO2 obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO2 and determining the flow‐metabolism relationship. Magn Reson Med 60:380–389, 2008.

High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging

BACKGROUND AND PURPOSE: Although the prevalence of pineal cysts in autopsy series has been reported as being between 25% and 40%, MR studies have documented their frequency to range between 1.5% and 10.8%. The purpose of this high-resolution brain MR imaging study at 1.9T was to determine the prevalence of pineal cysts in healthy adults. MATERIALS AND METHODS: Brain MR images of 100 healthy young volunteers were randomly selected from our International Consortium for Brain Mapping project data base. Cysts were detected as circular areas of isointensity relative to CSF on both 3D gradient-echo T1-weighted and 2D fast spin-echo T2-weighted images. The inner diameters of all visualized pineal cysts were measured, and a criterion of 2.0 mm of the largest inner cross-sectional diameter was used to categorize cysts as being either small cystic changes (<2.0-mm diameter) or pineal cysts (>2.0-mm diameter). RESULTS: Twenty-three percent (23/100) of the volunteers had pineal cysts with a mean largest inner cross-sectional diameter of 4.3 mm (range, 2–14 mm); 13% (13/100) demonstrated cystic changes involving the pineal gland with the largest inner cross-sectional diameter of less than 2.0 mm. There was a slight female predominance. Two subjects with long-term follow-up scans showed no symptoms or changes in the size of their pineal cysts. CONCLUSION: On high-resolution MR imaging, the prevalence of pineal cysts was 23% in our healthy group of adults, which is consistent with previous autopsy studies. Long-term follow-up studies of 2 cases demonstrated the stability of the cysts.

Age-related differences in neural activities during risk taking as revealed by functional MRI

Previous research has clearly documented that risky decision making is different in young and older adults. Yet, there has been a relative dearth of research that seeks to understand such age-related changes in the neural activities associated with risk taking. To address this research issue, 21 men (12 young men, mean age 29.9 ± 6.2 years and 9 older men, mean age 65.2 ± 4.2 years) performed a risky-gains task while their brain activities were monitored by an fMRI scanner. The older adults, relative to their younger peers, presented with contralateral prefrontal activity, particularly at the orbitofrontal cortex. Furthermore, stronger activation of the right insula was observed for the older-aged participants compared to the younger-aged adults. The findings of this study are consistent with the a priori speculations established in accordance with the HAROLD model as well as previous findings. Findings of this study suggest that when making risky decisions, there may be possible neuropsychological mechanisms underlying the change in impulsive and risk-taking behaviors during the course of natural ageing.

APT‐weighted and NOE‐weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses

To investigate the saturation‐power dependence of amide proton transfer (APT)‐weighted and nuclear Overhauser enhancement‐weighted image contrasts in a rat glioma model at 4.7 T.

Sex-Related Differences in Neural Activity during Risk Taking: An fMRI Study

This study explored sex effects on the process of risk-taking. We observed that the female participants (n = 10) showed stronger activation in the right insula and bilateral orbitofrontal cortex (OFC) than did the male participants (n = 12) while they were performing in the Risky-Gains task. The female participants also showed stronger activations in the precentral, postcentral, and paracentral regions after receiving punishment feedback. In addition, the strength of neural activity in the insula correlated with the rate of risky behaviors for the female participants but not for the male participants. Similarly, the percent signal changes in the right OFC correlated negatively with the rate of selecting risky choices for the female group. These findings strongly suggest a sex-related influence modulating brain activity during risk-taking tasks. When taking the same level of risk, relative to men, women tend to engage in more neural processing involving the insula and the OFC to update and valuate possible uncertainty associated with risk-taking decision making. These results are consistent with the value-based decision-making model and offer insights into the possible neural mechanisms underlying the different risk-taking attitudes of men and women.

Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI

The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a newly calibrated single-compartment model (SCM) and a multi-compartment model (MCM) and was in agreement between these two models (P>0.5). The duration-varying delta CBF and delta CMRO(2) showed a negative correlation with time (r=-0.97, P<0.001); i.e., delta CBF declines while delta CMRO(2) increases during continuous stimulation. This study also illustrated that without properly calibrating the critical parameters employed in the SCM, an incorrect and even an opposite appearance of the flow-metabolism relationship during prolonged visual stimulation (positively linear coupling) can result. The time-dependent negative correlation between flow and metabolism demonstrated in this fMRI study is consistent with a previous PET observation and further supports the view that the increase in CBF is driven by factors other than oxygen demand and the energy demands will eventually require increased aerobic metabolism as stimulation continues.

Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury

For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness.

Physiologically evoked neuronal current MRI in a bloodless turtle brain: detectable or not?

Contradictory reports regarding the detection of neuronal currents have left the feasibility of neuronal current MRI (ncMRI) an open question. Most previous ncMRI studies in human subjects are suspect due to their inability to separate or eliminate hemodynamic effects. In this study, we used a bloodless turtle brain preparation that eliminates hemodynamic effects, to explore the feasibility of detecting visually-evoked ncMRI signals at 9.4 T. Intact turtle brains, with eyes attached, were dissected from the cranium and placed in artificial cerebral spinal fluid. Light flashes were delivered to the eyes to evoke neuronal activity. Local field potential (LFP) and MRI signals were measured in an interleaved fashion. Robust visually-evoked LFP signals were observed in turtle brains, but no significant signal changes synchronized with neuronal currents were found in the ncMRI images. In this study, detection thresholds of 0.1% and 0.1 degrees were set for MRI magnitude and phase signal changes, respectively. The absence of significant signal changes in the MRI images suggests that visually-evoked ncMRI signals in the turtle brain are below these detectable levels.