Abstract The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on ...diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.
Improved understanding of the neurobiological correlates of resilience would be an important step toward recognizing individuals at risk of developing post-traumatic stress disorder (PTSD) or other ...trauma-related diseases, enabling both preventative measures and individually tailored therapeutic approaches. Studies on vulnerability factors allow drawing conclusions on resilience. Structural changes of cortical and subcortical structures, as well as alterations in functional connectivity and functional activity, have been demonstrated to occur in individuals with PTSD symptoms. Relevant areas of interest are hippocampus, amygdala, insula, anterior cingulate cortex, and prefrontal cortex, as well as related brain networks, such as the default-mode, salience, and central executive network. This review summarizes the existing literature and integrates findings from cross-sectional study designs with two-group designs (trauma exposed individuals with and without PTSD), three-group designs (with an additional group of unexposed, healthy controls), twin-studies and longitudinal studies. In terms of structural findings, decreased hippocampal volume in PTSD individuals might be either a vulnerability factor or a result of trauma exposure, or both. Reduced anterior cingulate cortex and prefrontal cortex volumes seem to be predisposing factors for increased vulnerability. Regarding functional connectivity, increased amygdala connectivity has been demonstrated selectively in PTSD individuals, as well as increased default-mode-network and salience network connectivity. In terms of functional activity, increased amygdala and anterior cingulate cortex activities, and decreased prefrontal cortex activity as a response to external stimuli have been associated with higher vulnerability. Increased prefrontal cortex activity seemed to be a protective factor. Selecting adequate study designs, optimizing the diagnostic criteria, as well as differentiating between types of trauma and accounting for other factors, such as gender-specific differences, would be well-served in future research. Conclusions on potential preventative measures, as well as clinical applications, can be drawn from the present literature, but more studies are needed.
Altered cerebral connectivity is one of the core pathophysiological mechanism underlying the development and progression of information-processing deficits in schizophrenia. To date, most diffusion ...tensor imaging (DTI) studies used fractional anisotropy (FA) to investigate disrupted white matter connections. However, a quantitative interpretation of FA changes is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of white matter alterations could be achieved by measuring fiber density (FD) - a novel non-tensor-derived diffusion marker. This study investigates, for the first time, FD alterations in schizophrenia patients. FD and FA maps were derived from diffusion data of 25 healthy controls (HC) and 21 patients with schizophrenia (SZ). Using tract-based spatial statistics (TBSS), group differences in FD and FA were investigated across the entire white matter. Furthermore, we performed a region of interest (ROI) analysis of frontal fasciculi to detect potential correlations between FD and positive symptoms. As a result, whole brain TBSS analysis revealed reduced FD in SZ patients compared to HC in several white matter tracts including the left and right thalamic radiation (TR), superior longitudinal fasciculus (SLF), corpus callosum (CC), and corticospinal tract (CST). In contrast, there were no significant FA differences between groups. Further, FD values in the TR were negatively correlated with the severity of positive symptoms and medication dose in SZ patients. In summary, a novel diffusion-weighted data analysis approach enabled us to identify widespread FD changes in SZ patients with most prominent white matter alterations in the frontal and subcortical regions. Our findings suggest that the new FD measure may be more sensitive to subtle changes in the white matter microstructure compared to FA, particularly in the given population. Therefore, investigating FD may be a promising approach to detect subtle changes in the white matter microstructure of altered connectivity in schizophrenia.
Negative symptoms are a core feature of schizophrenia and also found in healthy individuals in subclinical forms. According to the current literature the two negative symptom domains, apathy and ...diminished expression may have different underlying neural mechanisms. Previous observations suggest that striatal dysfunction is associated with apathy in schizophrenia. However, it is unclear whether apathy is specifically related to ventral or dorsal striatal alterations. Here, we investigated striatal dysfunction during reward anticipation in patients with schizophrenia and a non-clinical population, to determine whether it is associated with apathy.
Chronic schizophrenia patients (n = 16) and healthy controls (n = 23) underwent an event- related functional MRI, while performing a variant of the Monetary Incentive Delay Task. The two negative symptom domains were assessed in both groups using the Brief Negative Symptoms Scale.
In schizophrenia patients, we saw a strong negative correlation between apathy and ventral and dorsal striatal activation during reward anticipation. In contrast, there was no correlation with diminished expression. In healthy controls, apathy was not correlated with ventral or dorsal striatal activation during reward anticipation.
This study replicates our previous findings of a correlation between ventral striatal activity and apathy but not diminished expression in chronic schizophrenia patients. The association between apathy and reduced dorsal striatal activity during reward anticipation suggests that impaired action-outcome selection is involved in the pathophysiology of motivational deficits in schizophrenia.
Striatal dysfunction is thought to be a fundamental element in schizophrenia. Striatal dopamine dysfunction impacts on reward processing and learning and is present even at rest. Here, we addressed ...the question whether and how spontaneous neuronal activity in the striatum is altered in schizophrenia. We therefore assessed intrinsic striatal activity and its relation with disorder states and symptom dimensions in patients with schizophrenia. We performed resting-state functional (rs-fMRI) and structural magnetic resonance imaging as well as psychometric assessment in 21 schizophrenic patients during psychosis. On average 9 months later, we acquired follow-up data during psychotic remission and with comparable levels of antipsychotic medication. Twenty-one age- and sex-matched healthy controls were included in the study. Independent component analysis of fMRI data yielded spatial maps and time-courses of coherent ongoing blood-oxygen-level-dependent signal fluctuations, which were used for group comparisons and correlation analyses with scores of the positive and negative syndrome scale. During psychosis, coherent intrinsic activity of the striatum was increased in the dorsal part and correlated with positive symptoms such as delusion and hallucination. In psychotic remission of the same patients, activity of the ventral striatum was increased and correlated with negative symptoms such as emotional withdrawal and blunted affect. Results were controlled for volumetric and medication effects. These data provide first evidence that in schizophrenia intrinsic activity is changed in the striatum and corresponds to disorder states and symptom dimensions.
In patients with schizophrenia in a psychotic episode, intra-striatal intrinsic connectivity is increased in the putamen but not ventral striatum. Furthermore, multimodal changes have been observed ...in the anterior insula that interact extensively with the putamen.
We hypothesised that during psychosis, putamen extra-striatal functional connectivity is altered with both the anterior insula and areas normally connected with the ventral striatum (i.e. altered functional connectivity distinctiveness of putamen and ventral striatum).
We acquired resting-state functional magnetic resonance images from 21 patients with schizophrenia in a psychotic episode and 42 controls.
Patients had decreased functional connectivity: the putamen with right anterior insula and dorsal prefrontal cortex, the ventral striatum with left anterior insula. Decreased functional connectivity between putamen and right anterior insula was specifically associated with patients' hallucinations. Functional connectivity distinctiveness was impaired only for the putamen.
Results indicate aberrant extra-striatal connectivity during psychosis and a relationship between reduced putamen-right anterior insula connectivity and hallucinations. Data suggest that altered intrinsic connectivity links striatal and insular pathophysiology in psychosis.
Neuroimaging studies of major depressive disorder (MDD) have consistently observed functional and structural changes of the hippocampus (HP) and amygdale (AY). Thus, these brain regions appear to be ...critical elements of the pathophysiology of MDD. The HP and AY directly interact and show broad and overlapping intrinsic functional connectivity (iFC) to other brain regions. Therefore, we hypothesized the HP and AY would show a corresponding pattern of aberrant intrinsic connectivity in MDD. Resting-state functional MRI was acquired from 21 patients with MDD and 20 healthy controls. ß-Maps of region-of-interest-based FC for bilateral body of the HP and basolateral AY were used as surrogates for iFC of the HP and AY. Analysis of variance was used to compare ß-maps between MDD and healthy control groups, and included covariates for age and gender as well as gray matter volume of the HP and AY. The HP and AY of MDD patient's showed an overlapping pattern of reduced FC to the dorsomedial-prefrontal cortex and fronto-insular operculum. Both of these regions are known to regulate the interactions among intrinsic networks (i.e., default mode, central executive, and salience networks) that are disrupted in MDD. These results provide the first evidence of overlapping aberrant HP and AY intrinsic connectivity in MDD. Our findings suggest that aberrant HP and AY connectivity may interact with dysfunctional intrinsic network activity in MDD.
Purpose: Diffusion tensor imaging (DTI) adds functional information to morphological magnetic resonance neurography (MRN) in the assessment of the brachial nerve plexus. To determine the most ...appropriate pulse sequence in scan times suited for diagnostic imaging in clinical routine, we compared image quality between simultaneous multi-slice readout-segmented (rs-DTI) and conventional single-shot (ss-DTI) echo-planar imaging techniques.Methods: Institutional Review Board (IRB) approved study including 10 healthy volunteers. The supraclavicular brachial plexus, covering the nerve roots and trunks from C5 to C7, was imaged on both sides with rs-DTI and ss-DTI. Both sequences were acquired in scan times <7 min with b-values of 900 s/mm2 and with isotropic spatial resolution.Results: In rs-DTI image, the overall quality was significantly better and distortion artifacts were significantly lower (P = 0.001–0.002 and P = 0.001–0.002, respectively) for both readers. In ss-DTI, a trend toward lower degree of ghosting and motion artifacts was elicited (reader 1, P = 0.121; reader 2, P = 0.264). No significant differences between the two DTI techniques were found for signal-to-noise ratios (SNR), contrast-to-noise ratios (CNR) and fractional anisotropy (FA) (P ≥ 0.475, P ≥ 0.624, and P ≥ 0.169, respectively). Interreader agreement for all examined parameters and all sequences ranged from intraclass correlation coefficient (ICC) 0.064 to 0.905 and Kappa 0.40 to 0.851.Conclusion: Incomparable acquisition times rs-DTI showed higher image quality and less distortion artifacts than ss-DTI. The trend toward a higher degree of ghosting and motion artifacts in rs-DTI did not deteriorate image quality to a significant degree. Thus, rs-DTI should be considered for functional MRN of the brachial plexus.
The aim of this study was to investigate the effect of acute dopamine agonistic and antagonistic manipulation on the visual-cue induced blood oxygen level-dependent signal response in healthy ...volunteers. Seventeen healthy volunteers in a double-blind placebo-controlled cross-over design received either a dopamine antagonist, agonist or placebo and underwent functional magnetic resonance imaging. Using classical inference and Bayesian statistics, we found no effect of dopaminergic modulation on properties of visual-cue induced blood oxygen level-dependent signals in the visual cortex, particularly on distinct properties of the haemodynamic response function (amplitude, time-to-peak and width). Dopamine-related effects modulating the neurovascular coupling in the visual cortex might be negligible when measured via functional magnetic resonance imaging.
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