Yantao Zuo

Synchronized delta oscillations correlate with the resting-state functional MRI signal

Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in α-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the γ bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the δ band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain.

Effects of quitting smoking on EEG activation and attention last for more than 31 days and are more severe with stress, dependence, DRD2 A1 allele, and depressive traits

Changes in physiology and attentional performance associated with smoking abstinence were characterized in 67 female smokers during low-stress and high-stress conditions. Abstinence was associated with decreases in cognitive performance, heart rate, and electroencephalographic (EEG) activation but with no change in serum estradiol or progesterone. Effects of quitting showed no tendency to resolve across the 31 days of abstinence. EEG deactivation and heart rate slowing were greater during a math task (high stress) than during relaxation (low stress). Individuals high in trait depression or nicotine dependence or with at least one dopamine D(2) receptor A1 allele experienced greater EEG deactivation following abstinence, especially in the right hemisphere during the stressful task. Thus, findings support the situation x trait adaptive response model of abstinence effects and emphasize the value of multiple dependent measures when characterizing abstinence responses.

Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats

Previous studies have demonstrated that electrical stimulation of the vagus nerve (VNS) delivered at a moderate intensity following a learning experience enhances memory in laboratory rats and human subjects, while VNS at lower or higher intensities has little or no effect. This finding suggests that VNS may affect memory processes by modulating neural plasticity in brain structures associated with memory storage such as the hippocampus. To test this hypothesis, the present study investigated the modulatory effect of VNS on the development of long-term potentiation (LTP) in the dentate gyrus of freely-moving rats. Rats receiving 0.4 mA VNS showed enhanced potentiation of the population spike amplitude for at least 24 h after tetanus relative to the sham-stimulation group. In contrast, no such effect was observed with 0.2 mA VNS. Stimulation at 0.8 mA had a short-term effect and tended to enhance early LTP, but to a lesser extent than did 0.4 mA. The 0.4 mA stimulation was the same intensity that was previously shown to enhance retention performance in an inhibitory avoidance task. These findings suggest that the neural mechanisms underlying the mnemonic effect of VNS may involve modulating synaptic plasticity in the hippocampus. These data also suggest that neural activity in the vagus nerve, occurring as a result of changes in peripheral state, is an important mechanism by which emotional experiences and arousal can enhance the storage of memories of those experiences.

Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets

Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

Quantifying the blood oxygenation level dependent effect in cerebral blood volume-weighted functional MRI at 9.4T.

In cerebral blood volume (CBV)‐weighted functional MRI (fMRI) employing superparamagnetic contrast agent, iron dose and blood oxygenation level dependent (BOLD) contamination are two important issues for experimental design and CBV quantification. Both BOLD and CBV‐weighted fMRI are based upon the susceptibility effect, to which spin‐echo and gradient‐echo sequences have different sensitivities. In the present study, CBV‐weighted fMRI was conducted using spin‐echo and gradient‐echo sequences at 9.4T by systematically changing the doses of contrast agent. Results suggest that BOLD contamination is a significant component in CBV‐weighted fMRI at high field, particularly when relatively low dose of contrast agent is administered. A mathematical model was developed to quantify the extravascular (EV) BOLD effect. With a TE of 35 ms, the EV BOLD effect was estimated to account for 76 ± 12% of the observed spin‐echo fMRI signal at 9.4T. These data suggest that correcting BOLD effect may be necessary for accurately quantifying activation‐induced CBV changes at high field. Magn Reson Med 58:616–621, 2007.

Registering and Analyzing Rat fMRI Data in the Stereotaxic Framework by Exploiting Intrinsic Anatomical Features

The value of analyzing neuroimaging data on a group level has been well established in human studies. However, there is no standard procedure for registering and analyzing functional magnetic resonance imaging (fMRI) data into common space in rodent fMRI studies. An approach for performing rat imaging data analysis in the stereotaxic framework is presented. This method is rooted in the biological observation that the skull shape and size of rat brain are essentially the same as long as their weights are within certain range. Registration is performed using rigid-body transformations without scaling or shearing, preserving the unique properties of the stable shape and size inherent in rat brain structure. Also, it does not require brain tissue masking and is not biased towards surface coil sensitivity profile. A standard rat brain atlas is used to facilitate the identification of activated areas in common space, allowing accurate region of interest analysis. This technique is evaluated from a group of rats (n=11) undergoing routine MRI scans; the registration accuracy is estimated to be within 400 microm. The analysis of fMRI data acquired with an electrical forepaw stimulation model demonstrates the utility of this technique. The method is implemented within the Analysis of Functional NeuroImages (AFNI) framework and can be readily extended to other studies.

Neurotransmission-Related Genetic Polymorphisms, Negative Affectivity Traits, and Gender Predict Tobacco Abstinence Symptoms across 44 Days with and without Nicotine Patch

Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with 1 or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes.

Effects of nicotine on brain responses to emotional pictures

Given that nicotine reduces negative affect, one would expect nicotine to have different effects on brain responses to emotionally negative stimuli than it does on responses to emotionally neutral or positive stimuli. However, no studies have assessed this possibility. The present study assessed the effects of nicotine patch versus placebo patch on brain event-related potential (ERP) responses to emotion-inducing negative, positive, and neutral color pictures in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included four experimental sessions. After overnight smoking deprivation (12 hr or more), active nicotine patches were applied to participants during one of the first two sessions and during one of the last two sessions. Placebo patches were applied during the other two sessions. Nicotine reduced frontal ERP processing voltage negativity (from 144-488 ms poststimulus onset) evoked by viewing emotionally negative pictures to a greater extent than it did when emotionally neutral pictures were viewed, whereas it had no effect on processing negativity evoked by positive pictures. Nicotine also enhanced P390 amplitudes evoked by emotionally negative pictures more than it did when emotionally neutral and positive pictures were viewed. Across picture types, nicotine (relative to placebo) reduced N300 amplitude (more at anterior and dorsal sites) and increased P390 amplitude. Overall, nicotine influenced ERPs to emotionally neutral and positive pictures less than it did to negative pictures.

Platelet monoamine oxidase B activity changes across 31 days of smoking abstinence

Although recent studies demonstrate that tobacco cigarette smoke substantially inhibits both central nervous system and blood platelet monoamine oxidase (MAO) activity, little is known about the time course of MAO increases after smoking cessation. Therefore, changes in platelet MAO-B activity and mood were assessed before and at multiple times after quitting smoking. Quitting smoking was associated with a significant (22%) increase in MAO activity by day 3 and with a maximum increase (about 50%) by day 10 that was maintained through day 31 of abstinence. However, abstinence-related increases in depressive mood peaked at day 2 of abstinence, a week more rapidly than the peak increase in MAO-B activity. Neither mood nor MAO-B activity returned to baseline or smoking control levels across the 31-day abstinence period. The asynchrony of increased negative affect and MAO-B activity during the first few days of abstinence may reflect any of several possibilities. First, the duration of the platelet life cycle may not reflect central MAO-B or MAO-A activity. Second, MAO-B may not contribute to or index mood changes during the first days of abstinence though it may contribute to protracted abstinence-induced negative affect. These findings are discussed in terms of the hypothesis that platelet MAO activity reflects central nervous system MAO changes that promote increased depressive affect resulting from smoking abstinence.

Low- but Not High-Frequency LFP Correlates with Spontaneous BOLD Fluctuations in Rat Whisker Barrel Cortex

Resting-state magnetic resonance imaging (rsMRI) is thought to reflect ongoing spontaneous brain activity. However, the precise neurophysiological basis of rsMRI signal remains elusive. Converging evidence supports the notion that local field potential (LFP) signal in the high-frequency range correlates with fMRI response evoked by a task (e.g., visual stimulation). It remains uncertain whether this relationship extends to rsMRI. In this study, we systematically modulated LFP signal in the whisker barrel cortex (WBC) by unilateral deflection of rat whiskers. Results show that functional connectivity between bilateral WBC was significantly modulated at the 2 Hz, but not at the 4 or 6 Hz, stimulus condition. Electrophysiologically, only in the low-frequency range (<5 Hz) was the LFP power synchrony in bilateral WBC significantly modulated at 2 Hz, but not at 4- or 6-Hz whisker stimulation, thus distinguishing these 2 experimental conditions, and paralleling the findings in rsMRI. LFP power synchrony in other frequency ranges was modulated in a way that was neither unique to the specific stimulus conditions nor parallel to the fMRI results. Our results support the hypothesis that emphasizes the role of low-frequency LFP signal underlying rsMRI.