Altered spontaneous activity of posterior cingulate cortex and superior temporal gyrus are associated with a smoking cessation treatment outcome using varenicline revealed by regional homogeneity

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain function. However, little is known about the associations between the local spontaneous brain activity and smoking cessation treatment outcomes. In the present analysis, we aimed to evaluate whether the local features of spontaneous brain activity prior to the target quit date was associated with the smoking cessation outcomes. All the participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 23 smokers succeeded in quitting smoking and 32 failed. Smokers underwent functional magnetic resonance imaging (fMRI) scanning prior to an open label smoking cessation treatment trial. Regional homogeneity (ReHo) was used to measure spontaneous brain activity, and whole-brain voxel-wise comparisons of ReHo were performed to detect brain regions with altered spontaneous brain activity between relapser and quitter groups. After controlling for potentially confounding factors including years of education, years smoked, cigarettes smoked per day and FTND score as covariates, compared to quitters, relapsers displayed significantly decreased ReHo in bilateral posterior cingulate cortex (PCC), as well as increased ReHo in left superior temporal gyrus (STG). These preliminary results suggest that regional brain function variables may be promising predictors of smoking relapse. This study provided novel insights into the neurobiological mechanisms underlying smoking relapse. A deeper understanding of the neurobiological mechanisms associated with relapse may result in novel pharmacological and behavioral interventions.     

Altered regional spontaneous neuronal activity in blepharospasm: a resting state fMRI study

The resting state amplitude of low-frequency fluctuations (ALFF) in functional magnetic resonance imaging (fMRI) is believed to reflect spontaneous cerebral neural activity. The pathophysiology of blepharospasm (BSP), which is characterized by motor symptoms and also sensory symptoms, remains unclear. The present study aims to localize possible cerebral functional abnormalities in BSP patients using resting state fMRI, and explore their possible associations with clinical variables. Voxel-based analysis was used to characterize the difference of ALFF between eighteen BSP patients and eighteen matched healthy controls. Separate correlation analyses were conducted to explore the possible association between ALFF values of significantly different areas and clinical measures including onset age, disease duration, symptom severity evaluated by Jankovic rating scale (JRS), and presence of geste antagoniste. The whole-brain analysis indicated that the BSP group had significantly decreased ALFF in the left thalamus while increased ALFF in the left orbitofrontal areas extending from middle frontal gyrus to inferior frontal gyrus. The mean ALFF in the left thalamus was negatively correlated with the subscore of JRS-frequency (r = ?0.484, p = 0.042) and JRS total score (r = ?0.477, p = 0.045). A borderline positive correlation was detected between the mean ALFF in the left orbitofrontal area and disease duration(r = 0.485, p = 0.049). Our findings suggest sensorimotor integration is abnormal in BSP, and dysfunctional activity of thalamus may be used to measuring symptom severity in BSP patients.     

Platelet monoamine oxidase: low activity in cigarette smokers

Platelet monoamine oxidase (MAO) activity and plasma thiocyanate concentration (an index of smoking behavior) were measured in 109 normal male and female volunteers. MAO activity was significantly lower and plasma thiocyanate concentration significantly higher in smoking volunteers than in nonsmoking volunteers. A significant negative correlation between MAO activity and thiocyanate concentration was observed in female smokers (rs = 0.43, n = 36) but not for male smokers (rs = 0.02, n = 31). In nine smokers who gave up smoking, mean (+/- SD) platelet MAO activity increased significantly (17.5 +/- 4.1 nmole/mg/hour to 24.6 +/- 4.2 nmole/mg/hour). At the same time, mean (+/- SD) plasma thiocyanate concentrations decreased significantly (144 +/- 41 microM to 50 +/- 12 microM). These data suggest that smoking directly or indirectly reduced platelet MAO activity.     

Abnormal regional spontaneous neural activity in treatment‐refractory depression revealed by resting‐state fMRI

Treatment‐refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting‐state functional MRI (rs‐fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment‐refractory (NDD) as comparison groups. Results were analyzed using a data‐driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo‐limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

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 (0.01-0.08Hz) 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.     

Altered regional homogeneity in post-traumatic stress disorder: a restingstate functional magnetic resonance imaging study

Objective Little is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder (PTSD). Comparison of the resting-state patterns of intrinsic functional synchronization, as measured by functional magnetic resonance imaging (fMRI), between groups with and without PTSD following a traumatic event can help identify the neural mechanisms of the disorder and targets for intervention. Methods Fifty-four PTSD patients and 72 matched traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with blood oxygen level-dependent (BOLD) fMRI and analyzed using the measure of regional homogeneity (ReHo) during the resting state. Results PTSD patients presented enhanced ReHo in the left inferior parietal lobule and right superior frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual gyrus, relative to traumatized individuals without PTSD. Conclusion Our findings showed that abnormal brain activity exists under resting conditions in PTSD patients who had been exposed to a major earthquake. Alterations in the local functional connectivity of cortical regions are likely to contribute to the neural mechanisms underlying PTSD.     

High levels of dopamine activity in the basal ganglia of cigarette smokers

OBJECTIVE: The authors' goal was to study presynaptic dopamine activity in smoking and nonsmoking human subjects in vivo. METHOD: [(18)F]Fluorodopa ([(18)F]DOPA) uptake K(i) values in the basal ganglia of nine smoking and 10 nonsmoking healthy men were measured with positron emission tomography. RESULTS: Significantly higher [(18)F]DOPA uptake was observed in both the putamen (average 17.3% higher) and the caudate (average 30.4% higher) of smokers than in those of nonsmokers. CONCLUSIONS: Smoking is related to greater dopamine activity in the human basal ganglia. Nicotine-induced dopamine activity may be a relevant mechanism in dependence on cigarette smoking.     

Altered brain activity processing in high-anxiety rodents revealed by challenge paradigms and functional mapping

Pathological anxiety involves aberrant processing of emotional information that is hypothesized to reflect perturbations in fear/anxiety pathways. The affected neurobiological substrates in patients with different anxiety disorders are just beginning to be revealed. Important leads for this research can be derived from findings obtained in psychopathologically relevant rodent models of enhanced anxiety, by revealing where in the brain neuronal processing in response to diverse challenges is different to that in animals with lower anxiety levels. Different functional mapping methods in various rodent models, including psychogenetically selected lines or genetically modified animals, have been used for this purpose. These studies show that the divergent anxiety-related behavioral response of high-anxiety- vs. normal and/or low-anxiety rodents to emotional challenges is associated with differential neuronal activation in restricted parts of proposed fear/anxiety circuitries including brain areas thought to be important in stress, emotion and memory. The identification of neuronal populations showing differential activation depends in part on the applied emotional challenge, indicating that specific facets of elicited fear or anxiety preferentially engage particular parts of the fear/anxiety circuitry. Hence, only the use of an array of different challenges will reveal most affected brain areas. A number of the neuronal substrates identified are suggested as candidate mediators of dysfunctional brain activation in pathological anxiety. Indeed, key findings revealed in these rodent models show parallels to observations in human symptom provocation studies comparing anxiety disorder patients with healthy volunteers. Work to investigate exactly which of the changed neuronal activation patterns in high-anxiety rodents has to be modulated by therapeutic drugs to achieve effective anxiolysis and via which neurochemical pathways this can be accomplished is at its early stages but has identified a small number of promising candidates. Extending these approaches should help to provide further insight into these mechanisms, revealing new leads for therapeutic targets and strategies.     

Enhanced corticobulbar excitability in chronic smokers during visual exposure to cigarette smoking cues

Background

Neuroimaging studies of chronic smokers report altered activity of several neural regions involved in the processing of rewarding outcomes. Neuroanatomical evidence suggests that these regions are directly connected to the tongue muscle through the corticobulbar pathways. Accordingly, we examined whether corticobulbar excitability might be considered a somatic marker for nicotine craving.

Methods

We compared motor-evoked potential (MEP) amplitudes recorded from the tongue and the extensor carpi radialis (control muscle) of chronic smokers under drug withdrawal and intake conditions as well as a nonsmoker group. All participants were tested during passive exposure to pictures showing a smoking cue or a meaningless stimulus. In the intake condition, chronic smokers were asked to smoke a real cigarette (CSn: group 1) or a placebo (CSp: group 2).

Results

Results show that MEP amplitudes recorded from the tongues of participants in the CSn and CSp groups under the withdrawal condition were selectively enhanced during exposure to a smoking cue. However, this effect on tongue MEP amplitudes disappeared in the intake condition for both the CSn and CSp groups.

Limitations

Limitations include the fact that the study was conducted in 2 different laboratories, the small sample size, the absence of data on chronic smoker craving strength and the different tastes of the real and placebo cigarettes.

Conclusion

These results suggest that, in chronic smokers, tongue muscle MEP amplitudes are sensitive to neural processes active under the physiological status of nicotine craving. This finding implicates a possible functional link between neural excitability of the corticobulbar pathway and the reward system in chronic smokers.     

Alterations in regional homogeneity of resting-state brain activity in internet gaming addicts

ABSTRACT: BackgroundsInternet gaming addiction (IGA), as a subtype of internet addiction disorder, is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IGA should be studied to unravel the potential heterogeneity of IGA. This study investigated the brain functions in IGA patients with resting-state fMRI. METHODS: Fifteen IGA subjects and fourteen healthy controls participated in this study. Regional homogeneity (ReHo) measures were used to detect the abnormal functional integrations. RESULTS: Comparing to the healthy controls, IGA subjects show enhanced ReHo in brainstem, inferior parietal lobule, left posterior cerebellum, and left middle frontal gyrus. All of these regions are thought related with sensory-motor coordination. In addition, IGA subjects show decreased ReHo in temporal, occipital and parietal brain regions. These regions are thought responsible for visual and auditory functions. CONCLUSIONS: Our results suggest that long-time online game playing enhanced the brain synchronization in sensory-motor coordination related brain regions and decreased the excitability in visual and auditory related brain regions.     

Altered regional homogeneity in patients with ovarian cancer treated with chemotherapy: a resting state fMRI study

Brain Imaging and Behavior - Many patients treated with chemotherapy for non-central nervous system (CNS) cancers experience cognitive dysfunction. However, few studies have investigated...     

Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: An fMRI study using the model of skilled acupuncturists

Studies on training/expertise‐related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise‐related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level‐dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile‐motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state. Hum Brain Mapp 35:1074–1084, 2014. © 2013 Wiley Periodicals, Inc.     

Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia

Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter‐ and intra‐regional neural synchronization and temporal variance of resting state activity in anesthetic‐induced unconsciousness state. Applying an intra‐subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra‐regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency‐dependent effects of SD in the thalamus, which showed abnormally high SD in Slow‐5 (0.01–0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp 35:5368–5378, 2014. © 2014 Wiley Periodicals, Inc.     

Cognitive status of young and older cigarette smokers: data from the international brain database.

Previous studies that have examined the impact of cigarette smoking on cognition have revealed mixed results; some studies report no impact and others report detrimental effects, especially in older individuals. Few studies, however, have examined the effects of cigarette smoking on both young and old healthy individuals using highly robust and standardized methods of cognitive assessment. This study draws on an international database to contrast cognitive differences between younger and older individuals who regularly smoke cigarettes and non-smokers. Data were sampled from 1000 highly screened healthy individuals free of medical or psychiatric health complications. A cohort of 62 regular smokers (n = 45 < 45 years of age; n = 1745 years) with a Fagerstrom nicotine dependency score of 1 or more were identified and matched to a cohort of 62 healthy nonsmokers (n = 43 < 45 years; n = 1945 years) on demographic variables and estimated intelligence. Performances on cognitive measures of attention, reaction time, cognitive flexibility, psychomotor speed, and memory were considered for analysis. As a group, smokers performed more poorly than nonsmokers on one measure of executive function. A significant age and smoking status interaction was identified with older smokers performing more poorly than older nonsmokers and younger smokers on a measure of long-delayed recall of new information. Cigarette smoking is associated with isolated and subtle cognitive difficulties among very healthy individuals.     

Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence.

BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.     

Altered resting activity patterns and connectivity in individuals with complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper‐limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra‐slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03–0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo‐S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo‐S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.     

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder

ObjectiveRapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD.MethodsWe recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects.ResultsCompared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area.ConclusionThe pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.