The alterations of degree centrality in the frontal lobe of patients with panic disorder.

Objective: The brain network in panic disorder (PD) is still an intriguing issue for research. In this study, we hoped to investigate the role of DC (degree centrality) for the pathophysiology of PD, especially for the fear network. Methods: We enrolled 60 patients with PD and 60 controls in the current study. The gender and age were matched for two groups. All participants received the resting-state functional magnetic resonance imaging to survey the baseline brain activity. Then the DC values of all participants were using REST toolbox. We also compared the DC values between PD and controls. The statistical threshold was set as FDR (false discovery rate) < 0.05. Results: The DC values were significantly lower in the right superior frontal gyrus of PD patients compared to controls (FDR < 0.05). In addition, a negative correlation between the DC values and panic severity was observed in the right superior frontal gyrus and left inferior frontal gyrus. However, there was no significant association between the DC values and illness duration. Conclusion: The DC seemed significantly altered in the frontal lobe of PD patients. The role of the frontal lobe might be more emphasized in the pathophysiology research for PD.

Task MRI-Based Functional Brain Network of Major Depression.

This chapter will focus on task magnetic resonance imaging (MRI) to understand the biological mechanisms and pathophysiology of brain in major depressive disorder (MDD), which would have minor alterations in the brain function. Therefore, the functional study, such as task MRI functional connectivity, would play a crucial role to explore the brain function in MDD. Different kinds of tasks would determine the alterations in functional connectivity in task MRI studies of MDD. The emotion-related tasks are linked with alterations in anterior cingulate cortex, insula, and default mode network. The emotional memory task is linked with amygdala-hippocampus alterations. The reward-related task would be related to the reward circuit alterations, such as fronto-straital. The cognitive-related tasks would be associated with frontal-related functional connectivity alterations, such as the dorsolateral prefrontal cortex, anterior cingulate cortex, and other frontal regions. The visuo-sensory characteristics of tasks might be associated with the parieto-occipital alterations. The frontolimbic regions might be major components of task MRI-based functional connectivity in MDD. However, different scenarios and tasks would influence the representations of results.

Fronto-limbic neuroimaging biomarkers for diagnosis and prediction of treatment responses in major depressive disorder.

The neuroimaging is an important tool for understanding the biomarkers and predicting treatment responses in major depressive disorder (MDD). The potential biomarkers and prediction of treatment response in MDD will be addressed in the review article. The brain regions of cognitive control and emotion regulation, such as the frontal and limbic regions, might represent the potential targets for MDD biomarkers. The potential targets of frontal lobes might include anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). For the limbic system, hippocampus and amygdala might be the potentially promising targets for MDD. The potential targets of fronto-limbic regions have been found in the studies of several major neuroimaging modalities, such as the magnetic resonance imaging, near-infrared spectroscopy, electroencephalography, positron emission tomography, and single-photon emission computed tomography. Additional regions, such as brainstem and midbrain, might also play a part in the MDD biomarkers. For the prediction of treatment response, the gray matter volumes, white matter tracts, functional representations and receptor bindings of ACC, DLPFC, OFC, amygdala, and hippocampus might play a role in the prediction of antidepressant responses in MDD. For the response prediction of psychotherapies, the fronto-limbic, reward regions, and insula will be the potential targets. For the repetitive transcranial magnetic stimulation, the DLPFC, ACC, limbic, and visuospatial regions might represent the predictive targets for treatment. The neuroimaging targets of MDD might be focused in the fronto-limbic regions. However, the neuroimaging targets for the prediction of treatment responses might be inconclusive and beyond the fronto-limbic regions.

Task MRI-Based Functional Brain Network of Anxiety.

Magnetic resonance imaging (MRI) is a good tool for researchers to understand the biological mechanisms and pathophysiology of the brain due to the translational characteristics of MRI methods. For the psychiatric illness, this kind of mental disorders usually have minor alterations when compared to traditional neurological disorders. Therefore the functional study, such as functional connectivity, would play a significant role for understanding the pathophysiology of mental disorders. This chapter would focus on the discussion of task MRI-based functional network studies in anxiety. For social anxiety disorder, the limbic system, such as the temporal lobe, amygdala, and hippocampus, would show alterations in the functional connectivity with frontal regions, such as anterior cingulate, prefrontal, and orbitofrontal cortices. PD has anterior cingulate cortex-amygdala alterations in fear conditioning, frontoparietal alterations in attention network task, and limbic-prefrontal alterations in emotional task. A similar amygdala-based aberrant functional connectivity in specific phobia is observed. The mesocorticolimbic and limbic-prefrontal functional alterations are found in generalized anxiety disorder. The major components of task MRI-based functional connectivity in anxiety include limbic and frontal regions which might play a vital role for the origination of anxiety under different scenarios and tasks.

Promising Neuroimaging Biomarkers in Depression.

The neuroimaging has been applied in the study of pathophysiology in major depressive disorder (MDD). In this review article, several kinds of methodologies of neuroimaging would be discussed to summarize the promising biomarkers in MDD. For the magnetic resonance imaging (MRI) and magnetoencephalography field, the literature review showed the potentially promising roles of frontal lobes, such as anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). In addition, the limbic regions, such as hippocampus and amygdala, might be the potentially promising biomarkers for MDD. The structures and functions of ACC, DLPFC, OFC, amygdala and hippocampus might be confirmed as the biomarkers for the prediction of antidepressant treatment responses and for the pathophysiology of MDD. The functions of cognitive control and emotion regulation of these regions might be crucial for the establishment of biomarkers. The near-infrared spectroscopy studies demonstrated that blood flow in the frontal lobe, such as the DLPFC and OFC, might be the biomarkers for the field of near-infrared spectroscopy. The electroencephalography also supported the promising role of frontal regions, such as the ACC, DLPFC and OFC in the biomarker exploration, especially for the sleep electroencephalogram to detect biomarkers in MDD. The positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in MDD demonstrated the promising biomarkers for the frontal and limbic regions, such as ACC, DLPFC and amygdala. However, additional findings in brainstem and midbrain were also found in PET and SPECT. The promising neuroimaging biomarkers of MDD seemed focused in the fronto-limbic regions.

The neural markers of MRI to differentiate depression and panic disorder.

Depression and panic disorder (PD) share the common pathophysiology from the perspectives of neurotransmitters. The relatively high comorbidity between depression and PD contributes to the substantial obstacles to differentiate from depression and PD, especially for the brain pathophysiology. There are significant differences in the diagnostic criteria between depression and PD. However, the paradox of similar pathophysiology and different diagnostic criteria in these two disorders were still the issues needing to be addressed. Therefore the clarification of potential difference in the field of neuroscience and pathophysiology between depression and PD can help the clinicians and scientists to understand more comprehensively about significant differences between depression and PD. The researchers should be curious about the underlying difference of pathophysiology beneath the significant distinction of clinical symptoms. In this review article, I tried to find some evidences for the differences between depression and PD, especially for neural markers revealed by magnetic resonance imaging (MRI). The distinctions of structural and functional alterations in depression and PD are reviewed. From the structural perspectives, PD seems to have less severe gray matter alterations in frontal and temporal lobes than depression. The study of white matter microintegrity reveals more widespread alterations in fronto-limbic circuit of depression patients than PD patients, such as the uncinate fasciculus and anterior thalamic radiation. PD might have a more restrictive pattern of structural alterations when compared to depression. For the functional perspectives, the core site of depression pathophysiology is the anterior subnetwork of resting-state network, such as anterior cingulate cortex, which is not significantly altered in PD. A possibly emerging pattern of fronto-limbic distinction between depression and PD has been revealed by these explorative reports. The future trend for machine learning and pattern recognition might confirm the differentiation pattern between depression and PD based on the explorative results.

Fear Network Model in Panic Disorder: The Past and the Future.

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.

The regional homogeneity of cingulate-precuneus regions: The putative biomarker for depression and anxiety.

OBJECTIVES: In addition to clinical interview, the modern putative biomarker to differentiate depression and anxiety would be warranted. The translational medicine characteristics of neuroimaging, such as the regional homogeneity (ReHo), is an option for depression and anxiety. Therefore we designed this study trying to identify the biomarker pattern for depression and anxiety. METHODS: Resting-state functional magnetic resonance imaging was acquired for 53 patients with first-episode medicine-naïve major depressive disorder (MDD), 53 first-episode medicine-naïve patients with panic disorder (PD) and 54 controls. The calculation of ReHo was performed. The ANOVA repeated measures were applied for the 3 groups to investigate the putative differences between MDD and PD (FDR corrected p < 0.05). RESULTS: After multiple comparisons, the major findings of ReHo were found in the bilateral anterior cingulate cortex and bilateral precuneus. MDD group had lower ReHo values than PD group in the left anterior cingulate cortex. MDD group had significant alterations of ReHo in the left anterior cingulate cortex and bilateral precuneus when compared to controls. PD group had alterations in the bilateral precuneus when compared to controls. CONCLUSION: The specific cingulate alterations might be a putative ReHo biomarker to differentiate MDD from PD in cingulate-precuneus background for ReHo alterations.

Functional network-based statistics in depression: Theory of mind subnetwork and importance of parietal region.

OBJECTIVE: The functional network analysis of whole brain is an emerging field for research in depression. We initiated this study to investigate which subnetwork is significantly altered within the functional connectome in major depressive disorder (MDD). METHODS: The study enrolled 52 first-episode medication-naïve patients with MDD and 40 controls for functional network analysis. All participants received the resting-state functional imaging using a 3-Tesla magnetic resonance scanner. After preprocessing, we calculated the connectivity matrix of functional connectivity in whole brain for each subject. The network-based statistics of connectome was used to perform group comparisons between patients and controls. The correlations between functional connectivity and clinical parameters were also performed. RESULTS: MDD patients had significant alterations in the network involving "theory of mind" regions, such as the left precentral gyrus, left angular gyrus, bilateral rolandic operculums and left inferior frontal gyrus. The center node of significant network was the left angular gyrus. No significant correlations of functional connectivity within the subnetwork and clinical parameters were noted. CONCLUSION: Functional connectivity of "theory of mind" subnetwork may be the core issue for pathophysiology in MDD. In addition, the center role of parietal region should be emphasized in future study.

The Relief Effects of Ramelteon on Refractory Chronic Migraine: A Case Report.

The selective melatonin receptor agonism effect of ramelteon is useful for insomnia. Here we wanted to present a refractory chronic migraine case, who had significant improvements in migraine after using ramelteon. The possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects.

Gray matter increases in fronto-parietal regions of depression patients with aripiprazole monotherapy: An exploratory study.

We investigated the treatment effects of aripiprazole monotherapy in first-episode medication-naïve patients with major depressive disorder (MDD). The accompanying changes in the gray matter volume (GMV) were also explored.Fifteen patients completed the trial and received structural scans by 3-Tesla magnetic resonance imaging at baseline and partially responding state (sixth week). To account for the test-retest bias, 27 healthy controls were scanned twice within 6 weeks. We utilized optimized voxel-based morphometry with different comparisons between groups.The partially responding patients with MDD had greater GMV in left middle frontal gyrus and left superior parietal gyrus when compared with baseline. However, they had decreases in the GMV of right orbitofrontal gyrus and right inferior temporal gyrus after response. The partially responding patients with MDD still had residual GMV deficits in right superior frontal gyrus when compared with controls. However, the lack of second patient group without aripiprazole intervention would be a significant limitation to interpret the aripiprazole-specific effects on GMV.The changes in the GMV of fronto-parieto-temporal regions and residual GMV deficits in the superior frontal gyrus might represent "state-dependent brain changes" and "residual-deficit brain regions," respectively, for aripiprzole monotherapy in MDD.

Gray matter alterations and correlation of nutritional intake with the gray matter volume in prediabetes.

The neurophysiology of prediabetes plays an important role in preventive medicine. The dysregulation of glucose metabolism is likely linked to changes in neuron-related gray matter. Therefore, we designed this study to investigate gray matter alterations in medication-naive prediabetic patients. We expected to find alterations in the gray matter of prediabetic patients.A total of 64 prediabetic patients and 54 controls were enrolled. All subjects received T1 scans using a 3-T magnetic resonance imaging machine. Subjects also completed nutritional intake records at the 24-hour and 3-day time points to determine their carbohydrate, protein, fat, and total calorie intake. We utilized optimized voxel-based morphometry to estimate the gray matter differences between the patients and controls. In addition, the preprandial serum glucose level and the carbohydrate, protein, fat, and total calorie intake levels were tested to determine whether these parameters were correlated with the gray matter volume.Prediabetic patients had lower gray matter volumes than controls in the right anterior cingulate gyrus, right posterior cingulate gyrus, left insula, left super temporal gyrus, and left middle temporal gyrus (corrected P < 0.05; voxel threshold: 33). Gray matter volume in the right anterior cingulate was also negatively correlated with the preprandial serum glucose level gyrus in a voxel-dependent manner (r = -0.501; 2-tailed P = 0.001).The cingulo-temporal and insula gray matter alterations may be associated with the glucose dysregulation in prediabetic patients.

The Explorative Analysis to Revise Fear Network Model for Panic Disorder: Functional Connectome Statistics.

Functional connectome analysis in panic disorder (PDO) is a relatively new field for research. We tried to investigate the functional connectome alterations in PDO to re-examine the precision and role of fear network model for the pathophysiology of PDO.We enrolled 53 PDO patients and 54 controls with imaging data in this study. After preprocessing, we calculated the connectivity matrix of functional connectivity in whole brain for each subject. Then network-based statistics (The University of Melbourne and Melbourne Health, Australia) of connectome was used to perform group comparisons between patients and controls. The correlation between network measures of significant subnetwork and illness duration or severity of PDO was also performed.Within the 6 network models, only 1 network survived after multiple corrections. We found decreased functional connectivity in the edges between the following nodes: the left parahippocampal gyrus, bilateral precentral gyri, bilateral middle cingulate gyri, bilateral supramarginal gyri, bilateral calcarine fissures, and right lingual gyrus. The central hubs were the left parahippocampal gyrus and left precentral gyrus. The importance of limbic areas and connection with sensory and motor regions might shed light on the revision of fear network model for the pathophysiology of PDO.

The White Matter Microintegrity Alterations of Neocortical and Limbic Association Fibers in Major Depressive Disorder and Panic Disorder: The Comparison.

The studies regarding to the comparisons between major depressive disorder (MDD) and panic disorder (PD) in the microintegrity of white matter (WM) are uncommon. Therefore, we tried to a way to classify the MDD and PD. Fifty-three patients with 1st-episode medication-naive PD, 54 healthy controls, and 53 patients with 1st-episode medication-naive MDD were enrolled in this study. The controls and patients were matched for age, gender, education, and handedness. The diffusion tensor imaging scanning was also performed. The WM microintegrity was analyzed and compared between 3 groups of participants (ANOVA analysis) with age and gender as covariates. The MDD group had lower WM microintegrity than the PD group in the left anterior thalamic radiation, left uncinate fasciculus, left inferior fronto-occipital fasciculus, and bilateral corpus callosum. The MDD group had reductions in the microintegrity when compared to controls in the bilateral superior longitudinal fasciculi, inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, and corpus callosum. The PD group had lower microintegrity in bilateral superior longitudinal fasciculi and left inferior fronto-occipital fasciculus when compared to controls. The widespread pattern of microintegrity alterations in fronto-limbic WM circuit for MDD was different from restrictive pattern of alterations for PD.

Alterations of neocortico-limbic association fibers and correlation with diet in prediabetes diagnosed by impaired fasting glucose.

PURPOSE: To assess the existence of alterations in the micro-integrity of the fasciculus in prediabetic subjects. The issue of micro-integrity in white matter tracts has not been adequately addressed in prediabetes. MATERIALS AND METHODS: Sixty-four prediabetic subjects and 54 controls were enrolled. All participants completed 24-hour diet records and 3-day diet records and received diffusion tensor imaging at 3T. The data for white matter micro-integrity were analyzed and compared between prediabetic subjects and controls with age and gender as covariates. In addition, voxel-wise regression between white matter micro-integrity, diet, and preprandial glucose levels were used to explore the relationship between white matter micro-integrity and diet or serum glucose levels. RESULTS: We found that prediabetic subjects had significant reductions in the micro-integrity of bilateral anterior thalamic radiation, left inferior longitudinal fasciculus, and left superior longitudinal fasciculus (corrected P < 0.05). In addition, total carbohydrate intake amount and preprandial serum glucose levels were negatively correlated with the micro-integrity in the left inferior longitudinal fasciculus and left anterior thalamic radiation (r: -0.47, corrected P < 0.05). CONCLUSION: Restrictive alterations in the white matter micro-integrity of the anterior thalamic radiation and inferior and superior longitudinal fasciculi might represent the initial "hot spots" for white matter tract alterations, which might play a role in the development of prediabetes. J. Magn. Reson. Imaging 2016;43:1500-1506.

The changes in the low-frequency fluctuations of cingulate cortex and postcentral gyrus in the treatment of panic disorder: The MRI study.

OBJECTIVES: The default brain activities in the treatment of panic disorder (PD) have not been studied well. Therefore we designed this longitudinal study to survey the accompanying changes in the fractional amplitude of low-frequency fluctuations (fALFF) when panic disorder (PD) patients achieved remission. METHODS: We enrolled 21 medicine-naive patients who finished a 6-week therapy of antidepressant. The trial antidepressant was escitalopram. The acquisitions of fALFF in the patients and controls were assessed at baseline and the sixth week. The treatment-related effects and group-related differences (baseline versus sixth week) were obtained by the comparisons of the fALFF data of each group. RESULTS: The treatment-related effects showed increases in the fALFF values of the right middle cingulate cortex (MCC) and left postcentral gyrus (PCG) after remission in PD patients. The improvements in panic severity and antidepressant dose also correlated positively with the increases in the fALFF values of the right middle cingulate cortex. There were still residual group-related differences of fALFF in the occipital lobe and thalamus after remission. CONCLUSIONS: The results probably revealed the treatment-related effects of fALFF in the MCC-PCG regions and group-related differences of fALFF in the occipito-thalamic regions for the antidepressant treatment and remission in PD.

The alterations in regional homogeneity of parieto-cingulate and temporo-cerebellum regions of first-episode medication-naïve depression patients.

This study surveyed the characteristics of the indicator for the synchrony of brain activities, regional homogeneity (ReHo), in patients who were diagnosed with major depressive disorder (MDD) without co-morbidities. Forty-four patients with MDD and twenty-seven normal controls were enrolled in our study. The ReHo outputs of patients and controls were compared by a nonparametric permutation-based method with global brain volume, age, and gender as covariates. In addition, the correlations between the clinical variables (such as depression severity, anxiety severity, illness duration) and ReHo values were also estimated in each group and across both groups. The patients with MDD had lower ReHo values than the controls for the cognitive division of right anterior cingulate cortex and the left inferior parietal lobule. In contrast, the patients had higher values of ReHo than controls for the right inferior temporal lobe and the right cerebellum. Additionally, the ReHo values were negatively correlated with the depression severity and with illness duration in the right anterior cingulate cortex. MDD patients had significant alterations in the ReHo of the parieto-cingulate and temporo-cerebellum regions with opposite trends.

The Accompanying Changes in Brain Structure of a Remitted Depression Patient with the Bupropion Treatment.

The impacts from the bupropion on the brain structures have seldom been mentioned in the literature. The bupropion is a kind of antidepressant with dual action in the norepinephrine and dopamine receptors. Here we have a case to share about the bupropion-related effects in the brain structure.