Activation Of Different Regions Research Articles

Neural Correlates of Symptom Remission Among Adults Receiving EMDR Therapy for PTSD: A Systematic Review and Meta-Analysis of 20 Years of Research

The present systematic review and meta-analysis provide an updated assessment of how eye movement desensitization and reprocessing (EMDR) therapy affects the human brain during treatment for posttraumatic stress disorder (PTSD). Brain region activity was assessed using resting-state functional magnetic resonance imaging, and trauma symptom severity was measured using the PTSD Checklist for the DSM-5 (PCL-5). We used PubMed, EMBASE, and ScienceDirect as our primary databases. Selected articles were subjected to seven eligibility criteria, and 22 articles remained for statistical analysis. Article quality was measured using the QUADAS-2 instrument, which showed that our review sample comprised high-quality articles. Statistical analyses implicated a forest plot meta-analysis of PCL-5 scores pretreatment and posttreatment, an activation likelihood estimation (ALE) meta-analysis of brain region activation after treatment, and a linear regression analysis that served as our method of statistical synthesis between forest plot and ALE results. Our forest plot showed that EMDR had a robust effect on decreasing PCL-5 scores during treatment (g= −2.92). Our ALE meta-analysis indicated the activation of different regions in the default mode and salience, limbic, and ventral attention networks. Statistical synthesis showed a robust correlation between PCL-5 score decrease and increased brain function (β = −.94). We also measured publication bias in our review sample with a funnel plot and Egger’s test of random effects (p= .280).

Anodal Transcranial Direct Current Stimulation of Anterior Cingulate Cortex Modulates Subcortical Brain Regions Resulting in Cognitive Enhancement.

Transcranial direct current stimulation (tDCS) has been widely utilized in research settings and modulates brain activity. The application of anodal tDCS on the prefrontal cortex has indicated improvement in cognitive functioning. The cingulate cortex, situated in the medial aspect of the prefrontal cortex, has been identified as a core region performing cognitive functions. Most of the previous studies investigating the impact of stimulation on the prefrontal cortex stimulated the dorsolateral prefrontal cortex (DLPFC), however, the impact of stimulation on cingulate has not been explored. The current study investigates the effect of stimulation on the resting-state functional connectivity of the anterior cingulate cortex with other regions of the brain and changes in behavioral results in a color-word Stroop task, which has repeatedly elicited activation in different regions of the cingulate. Twenty subjects were randomly assigned to the experimental and sham group, and their medial prefrontal area was stimulated using MRI compatible tDCS. Resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive Stroop task were monitored before, during, and after the stimulation. Neuroimaging results indicated a significant decrease in resting-state functional connectivity in the experimental group during and after stimulation as compared to before stimulation in two clusters including right insular cortex, right central operculum cortex, right frontal operculum cortex and right planum polare with the left anterior cingulate cortex (L-ACC) selected as the seed. The behavioral results indicated a significant decrease in reaction time (RT) following stimulation in the experimental group compared to the sham group. Moreover, the change in functional connectivity in subcortical regions with L-ACC as the seed and change in RT was positively correlated. The results demonstrated that ACC has a close functional relationship with the subcortical regions, and stimulation of ACC can modulate these connections, which subsequently improves behavioral performance, thus, providing another potential target of stimulation for cognitive enhancement.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04318522.

Canonical correlation analysis of brain prefrontal activity measured by functional near infra-red spectroscopy (fNIRS) during a moral judgment task

Individuals differ in the extent to which they make decisions in different moral dilemmas. In this study, we investigated the relationship between functional brain activities during moral decision making and psychopathic personality traits in a healthy population. We measured the hemodynamic activities of the brain by functional near-infrared spectroscopy (fNIRS). FNIRS is an evolving non-invasive neuroimaging modality which is relatively inexpensive, patient friendly and robust to subject movement. Psychopathic traits were evaluated through a self-report questionnaire called the Psychopathic Personality Inventory Revised (PPI-R). We recorded functional brain activities of 30 healthy subjects while they performed a moral judgment (MJ) task. Regularized canonical correlation analysis (R-CCA) was applied to find the relationships between activation in different regions of prefrontal cortex (PFC) and the core psychopathic traits. Our results showed a significant canonical correlation between PFC activation and PPI-R content scale (PPI-R-CS). Specifically, coldheartedness and carefree non-planfulness were the only PPI-R-CS factors that were highly correlated with PFC activation during personal (emotionally salient) MJ, while Machiavellian egocentricity, rebellious nonconformity, coldheartedness, and carefree non-planfulness were the core traits that exhibited the same dynamics as PFC activation during impersonal (more logical) MJ. Furthermore, ventromedial prefrontal cortex (vmPFC) and left lateral PFC were the most positively correlated regions with PPI-R-CS traits during personal MJ, and the right vmPFC and right lateral PFC in impersonal MJ.

MicroPET-CT study of the association between odor stimulation and olfactory related brain activation in rats

Objective: Using (18)F-fluorodeoxyglucose ((18)F-FDG) and microPET-CT to test the feasibility of (18)F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of (18)F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of (18)F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat's brain after PEA stimulation included bed nucleus and insula. Activation regions of rat's brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions: Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat's brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.

Visualization of Brain Connectivity during Emotion induction

Visualization of Brain Connectivity during Emotion induction

Asymmetric Weighting to Optimize Regional Sensitivity in Combined fMRI-MEG Maps

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are neuroimaging techniques that measure inherently different physiological processes, resulting in complementary estimates of brain activity in different regions. Combining the maps generated by each technique could thus provide a richer understanding of brain activation. However, present approaches to integration rely on a priori assumptions, such as expected patterns of brain activation in a task, or use fMRI to bias localization of MEG sources, diminishing fMRI-invisible sources. We aimed to optimize sensitivity to neural activity by developing a novel method of integrating data from the two imaging techniques. We present a data-driven method of integration that weights fMRI and MEG imaging data by estimates of data quality for each technique and region. This method was applied to a verbal object recognition task. As predicted, the two imaging techniques demonstrated sensitivity to activation in different regions. Activity was seen using fMRI, but not MEG, throughout the medial temporal lobes. Conversely, activation was seen using MEG, but not fMRI, in more lateral and anterior temporal lobe regions. Both imaging techniques were sensitive to activation in the inferior frontal gyrus. Importantly, integration maps retained activation from individual activation maps, and showed an increase in the extent of activation, owing to greater sensitivity of the integration map than either fMRI or MEG alone.

Status Epilepticus-Related Hippocampal Injury in the Immature Rat Brain

Status epilepticus (SE)-related neuronal degeneration and glial activation in different regions of the developing rat hippocampus were investigated in an age- and time-dependent manner. Wistar rat pups of postnatal day (P) 7, 15, and 21 were injected i.p. with lithium+pilocarpine to induce SE or saline to make controls. Rats were sacrificed at 2, 12, 24 h, 3 days and 7 days after SE induction. Neurodegeneration in the hippocampus was assessed by Fluoro-Jade B staining. The expressions of the astrocyte marker (GFAP) and microglia marker (Iba-1) were evaluated by immunohistochemistry. In P7 rats, there was no neuronal damage at any time points in SE. Two hours after SE induction, the number of degenerating neurons in the hippocampus significantly increased in the CA1 region of P15 rats and in both CA1 and CA3 regions of P21 rats. Degenerating neurons in the dentate gyrus appeared at 24 h after SE in P15 and P21 rats. In P7 rats, there was no up-regulation of GFAP- or Iba-1-positive cells in SE. The expression of GFAP was dramatically elevated at 12 h in the CA1 and CA3 regions of P15 rats. The number of GFAP-positive cells did not increase in the dentate gyrus until 24 h after SE induction in P15 rats. In P21 SE rats, the mentioned index increased in the CA1, CA3, and dentate gyrus at 2 h. The number of Iba-1-positive cells increased significantly in the CA1, CA3, and dentate gyrus at 12 h in P15 rats and as early as at 2 h in P21 rats. These findings suggest that SE-related neuronal damage and glial activation in the immature brain are, in general, less intense than in the adult one, and the development of these processes in different structures of the hippocampus demonstrates significant temporal and spatial specificity.

3D-printed mechanochromic materials.

We describe the preparation and characterization of photo- and mechanochromic 3D-printed structures using a commercial fused filament fabrication printer. Three spiropyran-containing poly(ε-caprolactone) (PCL) polymers were each filamentized and used to print single- and multicomponent tensile testing specimens that would be difficult, if not impossible, to prepare using traditional manufacturing techniques. It was determined that the filament production and printing process did not degrade the spiropyran units or polymer chains and that the mechanical properties of the specimens prepared with the custom filament were in good agreement with those from commercial PCL filament. In addition to printing photochromic and dual photo- and mechanochromic PCL materials, we also prepare PCL containing a spiropyran unit that is selectively activated by mechanical impetus. Multicomponent specimens containing two different responsive spiropyrans enabled selective activation of different regions within the specimen depending on the stimulus applied to the material. By taking advantage of the unique capabilities of 3D printing, we also demonstrate rapid modification of a prototype force sensor that enables the assessment of peak load by simple visual assessment of mechanochromism.

Neural mechanisms of smooth pursuit eye movements in schizotypy.

Patients with schizophrenia as well as individuals with high levels of schizotypy are known to have deficits in smooth pursuit eye movements (SPEM). Here, we investigated, for the first time, the neural mechanisms underlying SPEM performance in high schizotypy. Thirty-one healthy participants [N = 19 low schizotypes, N = 12 high schizotypes (HS)] underwent functional magnetic resonance imaging at 3T with concurrent oculographic recording while performing a SPEM task with sinusoidal stimuli at two velocities (0.2 and 0.4 Hz). Behaviorally, a significant interaction between schizotypy group and velocity was found for frequency of saccades during SPEM, indicating impairments in HS in the slow but not the fast condition. On the neural level, HS demonstrated lower brain activation in different regions of the occipital lobe known to be associated with early sensory and attentional processing and motion perception (V3A, middle occipital gyrus, and fusiform gyrus). This group difference in neural activation was independent of target velocity. Together, these findings replicate the observation of altered pursuit performance in highly schizotypal individuals and, for the first time, identify brain activation patterns accompanying these performance changes. These posterior activation differences are compatible with evidence of motion processing deficits from the schizophrenia literature and, therefore, suggest overlap between schizotypy and schizophrenia both on cognitive-perceptual and neurophysiological levels. However, deficits in frontal motor areas observed during pursuit in schizophrenia were not seen here, suggesting the operation of additional genetic and/or illness-related influences in the clinical disorder.

Blockage of glucocorticoid receptors during memory acquisition, retrieval and reconsolidation prevents the expression of morphine-induced conditioned place preferences in mice

Association between the reward caused by consuming drugs and the context in which they are consumed is essential in the formation of morphine-induced conditioned place preference (CPP). Glucocorticoid receptor (GRs) activation in different regions of the brain affects reward-based reinforcement and memory processing. A wide array of studies have demonstrated that blockage of GRs in some brain areas can have an effect on reward-related memory; however, to date there have been no systematic studies about the involvement of glucocorticoids (GCs) in morphine-related reward memory. Here, we used the GR antagonist RU38486 to investigate how GRs blockage affects the sensitization and CPP behavior during different phases of reward memory included acquisition, retrieval and reconsolidation. Interestingly, our results showed RU38486 has the ability to impair the acquisition, retrieval and reconsolidation of reward-based memory in CPP and sensitization behavior. But RU38486 by itself cannot induce CPP or conditioned place aversion (CPA) behavior. Our data provide a much more complete picture of the potential effects that glucocorticoids have on the reward memory of different phases and inhibit the sensitization behavior.

Methylphenidate Effects on Prefrontal Functioning During Attentional-Capture and Response Inhibition

Methylphenidate improves motor response inhibition, typically assessed with the stop-signal task. The exact underlying mechanism for this, however, remains unknown. In addition, recent studies highlight that stop signals can have a confounding attentional-capture effect because of their low frequency in the task. In the current study, we assessed the effects of methylphenidate on neural networks of inhibitory control and attentional-capture within the context of two inhibitory control tasks. The effects of methylphenidate (40 mg) were assessed using functional magnetic resonance imaging in 16 healthy volunteers in a within-subject, double-blind, placebo-controlled design. Methylphenidate significantly reduced activation of different regions within the right inferior frontal gyrus/insula to infrequent stimuli associated with successful inhibition, failed inhibition, and attentional capture. These inferior frontal gyrus regions showed different interregional connections with inhibitory and attention networks. For failed inhibitions, methylphenidate increased activation within performance-monitoring regions, including the superior frontal, anterior cingulate, and parietal-occipital cortices, but only after controlling for attentional capture. Our findings suggest that the improvement of response inhibition seen following methylphenidate administration is due to its influence on underlying attentional mechanisms linked to response control requirements.

Brain Regions Engaged by Part- and Whole-task Performance in a Video Game: A Model-based Test of the Decomposition Hypothesis

Part- and whole-task conditions were created by manipulating the presence of certain components of the Space Fortress video game. A cognitive model was created for two-part games that could be combined into a model that performed the whole game. The model generated predictions both for behavioral patterns and activation patterns in various brain regions. The activation predictions concerned both tonic activation that was constant in these regions during performance of the game and phasic activation that occurred when there was resource competition. The model's predictions were confirmed about how tonic and phasic activation in different regions would vary with condition. These results support the Decomposition Hypothesis that the execution of a complex task can be decomposed into a set of information-processing components and that these components combine unchanged in different task conditions. In addition, individual differences in learning gains were predicted by individual differences in phasic activation in those regions that displayed highest tonic activity. This individual difference pattern suggests that the rate of learning of a complex skill is determined by capacity limits.

Functional mapping in the corpus callosum: A 4 T fMRI study of white matter

IntroductionThe idea of fMRI activation in white matter (WM) is controversial. Our recent work has used two different approaches to investigate whether there is evidence for WM fMRI. The first approach used words and faces to elicit interhemispheric transfer activation in the posterior corpus callosum (Sperry task). The second approach used checkerboard stimuli to elicit similar activation in the anterior corpus callosum (Poffenberger task). Using these different tasks, it has been possible to detect WM activation in different regions. In the current study, we report the results of a critical experiment: demonstrating that callosal activation can be experimentally manipulated within the same set of individuals. MethodsAll subjects completed both the Sperry and Poffenberger tasks. Functional MRI data were acquired at 4T, using an asymmetric spin echo spiral sequence. Data were analyzed with FSL using a model-based approach. Analyses focused on group and individual activations in WM. Results and discussionCorpus callosum activation was elicited for both tasks, with activation varying according to task type. A statistical contrast of the two tasks revealed posterior callosal activation for the Sperry task and anterior callosal activation for the Poffenberger task. The Sperry task showed activation in the isthmus and middle body of the corpus callosum at the group level and in 100% of subjects. The Poffenberger task showed activation in the genu and middle body of the corpus callosum at the group level and in 94% of subjects. The WM activation replicated prior results, with the additional strength of functional mapping within the same group of individuals.

Down And Out. The Functional Effects Of Silencing Calsequestrin 1 Or Deleting Both Calsequestrin Genes In Mammalian Muscle

Calsequestrins 1 and 2 are major calcium binding proteins of the SR in skeletal and cardiac muscle. We transiently suppressed synthesis of CSQ1 in fast twitch muscle of live adult mice by transfection with a plasmid coding for siRNA and a marker. Immunoblots showed reduction of CSQ1 by 40 to 100% in the whole treated (FDB) muscle. Ca2+ transients and Ca2+ release flux were measured in fibers selected for their high expression of the marker and patch clamped. Similar studies were done with FDB fibers from a double-null strain created by crossing CSQ1-null (Paolini et al. 2007) with CSQ2-null mice (Knollmann et al. 2006). Total Ca2+ releasable by maximal prolonged depolarization was decreased by up to 30% in silenced and 40% in KO muscles compared with the wild type. The reduction in CSQ had subtle kinetic consequences. The time course of release flux induced by long depolarization lost a “shoulder” (present in the WT; Royer et al. 2008). This shoulder reflects a component of the SR Ca2+ buffering power characterized by its dependence on [Ca2+]SR. Its loss here identifies the shoulder as a kinetic signature of the presence of CSQ. The KO presents additional anomalies, including asynchronous activation of different regions, and, occasionally, abnormally high initial release flux. Both features may be associated with structural changes like those found in the CSQ1 KO (Paolini, 2007). In conclusion, muscle either transiently or permanently devoid of CSQ is still capable of releasing large quantities of Ca2+. Means of Ca2+ storage unrelated to CSQ appear to play a major role in skeletal muscle. Supported by NIAMS/NIH.

Peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, suppresses CD40 expression and attenuates inflammatory responses after lithium pilocarpine-induced status epilepticus in rats

Inflammatory responses in the brain are involved in the etiopathogenesis and sequelae of seizures. Ligation of microglial CD40 plays a role in the development of inflammatory responses in the central nervous system (CNS). Our study showed that there was an increased CD40 expression on activated microglia in the brain injury after lithium pilocarpine-induced status epilepticus (SE) in rats. Since peroxisome proliferator-activated receptor gamma (PPARγ) acts as a regulator of CNS inflammation and a powerful pharmacological target for counteracting CNS diseases, we investigated the role of the PPARγ agonist, rosiglitazone, in the modulation of CD40 expression and in the pathological processes of inflammation after SE. We found that rosiglitazone inhibited the expression of CD40, tumor necrosis factor (TNF-α), and microglial activation in different regions of hippocampus. The results were indicated by immunohistochemistry, Western blot, and ELISA, respectively. Rosiglitazone also prevented neuronal loss in the CA1 area after SE observed by Nissl-staining. These protective effects were significantly reversed by the co-treatment with T0070907, a selective antagonist of the PPARγ, which clearly demonstrated a PPARγ-dependent mechanism. Our data provide evidence that rosiglitazone considerably attenuates inflammatory responses after SE by suppressing CD40 expression and microglial activation. Our data also support the idea that rosiglitazone might be a potential neuroprotective agent in epilepsy.

Refining the sensory and motor ratunculus of the rat upper extremity using fMRI and direct nerve stimulation

It is well understood that the different regions of the body have cortical representations in proportion to the degree of innervation. Our current understanding of the rat upper extremity has been enhanced using functional MRI (fMRI), but these studies are often limited to the rat forepaw. The purpose of this study is to describe a new technique that allows us to refine the sensory and motor representations in the cerebral cortex by surgically implanting electrodes on the major nerves of the rat upper extremity and providing direct electrical nerve stimulation while acquiring fMRI images. This technique was used to stimulate the ulnar, median, radial, and musculocutaneous nerves in the rat upper extremity using four different stimulation sequences that varied in frequency (5 Hz vs. 10 Hz) and current (0.5 mA vs. 1.0 mA). A distinct pattern of cortical activation was found for each nerve. The higher stimulation current resulted in a dramatic increase in the level of cortical activation. The higher stimulation frequency resulted in both increases and attenuation of cortical activation in different regions of the brain, depending on which nerve was stimulated.

Metastability of the UV luminescence in Mg-doped GaN layers grown by MOVPE on quasi-bulk GaN templates

Optical metastability in Mg-doped GaN layers grown by metal–organic vapor phase epitaxy on thick GaN templates grown by halide vapor phase epitaxy has been studied by photoluminescence (PL) and cathodoluminescence (CL). The total Mg concentration varies from 1×10 19 to 1×10 20 cm −3. Both PL and CL spectra change the initial shape within a few minutes exposure to the excitation source. The effect is permanent at low temperatures but the emission spectrum can be recovered to its initial shape after heating to room temperature. The difference in PL and CL spectra is explained by activation of different regions in the sample by laser and electrons, respectively. In CL the increase of the defect-related luminescence seems to be connected with an enhanced structural defect reaction under electron irradiation, which competes with the regular radiative recombination, while in PL the main effect is related to dissociation of Mg–H complexes with consequent passivation of the residual shallow acceptors.

The dynamic network subserving the three phases of cognitive procedural learning

Cognitive procedural learning is characterized by three phases (cognitive, associative, and autonomous), each involving distinct processes. We performed a behavioral study and a positron emission tomography (PET) activation study using the Tower of Toronto task. The aim of the behavioral study was to determine cognitive predictors for the length of each of the three learning phases, in order to preselect subjects for the PET study. The objective of the second study was to describe the cerebral substrates subtending these three phases. Contrasted with a reference (motor) task, the cognitive phase activated the prefrontal cortex, cerebellum, and parietal regions, all of which became less active as learning progressed. The associative phase was characterized by the activation of the occipital regions, right thalamus, and caudate nucleus. During the autonomous phase, new regions were involved, including the left thalamus and an anterior part of the cerebellum. These results, by employing a direct comparison between phases, provide the first evidence of the involvement and the time course of activation of different regions in each learning phase, in accordance with current models of cognitive procedural learning. The involvement of a frontoparietal network suggests the use of strategies in problem solving during the cognitive phase. The involvement of the occipital regions during the associative and autonomous phase suggests the intervention of mental imagery. Lastly, the activation of the cerebellum during the autonomous phase is consistent with the fact that performance in this phase is determined by psychomotor abilities.

Involvement of the lateral septum and the ventral Hippocampus in the emotional sequelae induced by social defeat: Role of glucocorticoid receptors

An important area of the brain aversive circuitry is the lateral septum (LS), together with its principal connections to diverse Hippocampal regions. The aim of this work was to evaluate whether the LS-Hippocampus network participates in the increased anxiety-like behavior produced by a previous defeat experience. The neural activation of different regions of the Hippocampus was assessed by the number of Fos positive cells in animals previously defeated. A notable elevation in the expression of this protein was observed in CA1, CA2, CA3, and Dentate Gyrus, for both dorsal and ventral Hippocampus. The local administration of a glucocorticoid receptor (GR or type II) antagonist, but not of a mineralcorticoid receptor (MR or type II) antagonist, into the LS before the stressful stimuli prevented a rise in the number of Fos positive cells, especially in the ventral portion of the Hippocampus. Furthermore, to evaluate the role of these hippocampal portions in the modulation of the emotional sequelae induced by defeat, the dorsal or the ventral Hippocampus were inactivated by lidocaine at different times following the social confrontation, with the anxiety-like behavior being assessed in the elevated plus maze the next day. Only the inactivation of the ventral region attenuated the excessive anxiety exhibited by defeated animals. The infusion of lidocaine, 1 h after the confrontation, did not affect this behavioral response. These data suggest a preferential participation of the LS and its connections to the ventral Hippocampus in the emotional sequelae induced by the social defeat. Moreover, the GR localized within the LS played an essential role in the modulation of this emotional state.

Reentry and atrial fibrillation

The mechanisms of human atrial fibrillation (AF) are poorly understood. Experimental studies have demonstrated that cholinergic AF in the sheep heart is maintained by high-frequency reentrant sources (drivers) that result in a consistent left-to-right frequency gradient. More recently, clinical studies have confirmed the existence of a hierarchical organization in the rate of activation of different regions in the atria of patients with paroxysmal and chronic AF. Although maximal dominant-frequency sites were found to play a crucial role in the maintenance of AF in some patients, whether AF drivers in humans are focal or reentrant and whether changes in driver activity alter spatial frequency gradients are unclear. To test the hypothesis that localized functional reentry maintains AF in humans, we determined the effects of adenosine infusion on local dominant frequency at different sites of both atria. In patients with paroxysmal AF, adenosine infusion increases local dominant frequencies, particularly at the pulmonary vein-left atrial junction region, amplifying a left-to-right frequency gradient. In patients with chronic AF, dominant frequency is significantly higher than in patients with paroxysmal AF in all atrial regions surveyed, with the highest adenosine increase of frequencies outside the pulmonary vein region. Adenosine-induced driver acceleration is strongly suggestive of a reentrant mechanism in both groups of AF patients.