Impaired working memory performance in opioid-dependent patients is related to reduced insula gray matter volume: a voxel-based morphometric study.

Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.

ACC GABA levels are associated with functional activation and connectivity in the fronto-striatal network during interference inhibition in patients with borderline personality disorder.

Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD.

Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats.

BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. RESULTS: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. CONCLUSIONS: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.

fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (ß=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.

Longitudinal Mapping of Gyral and Sulcal Patterns of Cortical Thickness and Brain Volume Regain during Early Alcohol Abstinence.

We explored brain volume recovery in terms of cortical thickness (CTh; gyral, sulcal pattern) and surface area (SA), as well as subcortical volume recovery in the first 2 weeks of abstinence in 49 alcohol-dependent patients (ADPs). A widespread reduction of CTh in ADPs at day 1 of abstinence compared to healthy controls, with more pronounced differences in sulci relative to gyri was found. After 2 weeks of abstinence, partial recovery to varying degrees of CTh loss in ADPs was observed for several regions. The longitudinal CTh changes were greater in sulci than in gyri of affected regions. No longitudinal change in SAs and subcortical volumes was found. Alterations of CTh contribute to brain volume loss in alcoholism and recovery during early abstinence. Sulci seem to be more vulnerable to excessive alcohol consumption and to drive abstinence-induced volume recovery. During the initial 2 weeks of abstinence no subcortical volume regain was observed. Either the time span was too short or the lower subcortical volume could represent a predisposing trait marker.

The Exercising Brain: Changes in Functional Connectivity Induced by an Integrated Multimodal Cognitive and Whole-Body Coordination Training.

This study investigated the impact of "life kinetik" training on brain plasticity in terms of an increased functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI). The training is an integrated multimodal training that combines motor and cognitive aspects and challenges the brain by introducing new and unfamiliar coordinative tasks. Twenty-one subjects completed at least 11 one-hour-per-week "life kinetik" training sessions in 13 weeks as well as before and after rs-fMRI scans. Additionally, 11 control subjects with 2 rs-fMRI scans were included. The CONN toolbox was used to conduct several seed-to-voxel analyses. We searched for functional connectivity increases between brain regions expected to be involved in the exercises. Connections to brain regions representing parts of the default mode network, such as medial frontal cortex and posterior cingulate cortex, did not change. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected. We can conclude that the constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory demands, seems to induce brain plasticity expressed in enhanced connectivity strength of brain regions due to coactivation.

31P RINEPT MRSI and VBM reveal alterations in brain aging associated with major depression.

PURPOSE: Phosphomono- and diesters, the major components of the choline peak in (1) H magnetic resonance spectroscopy, are associated with membrane anabolic and catabolic mechanisms. With the refocused insensitive nuclei-enhanced polarization transfer technique, these phospholipids are edited and enhanced in the (31) P MR spectrum. In depressed patients, alterations of the choline peak and cerebral volume have been found, indicating a possible relation. Thus, combining MR phosphorous spectroscopy and volumetry in depressed patients seems to be a promising approach to detect underlying pathomechanisms. METHODS: Depressed in-patients were either treated with antidepressive medication or with electroconvulsive therapy and compared to matched healthy controls. (31) P magnetic resonance spectroscopy imaging was conducted before and after the treatment phases. A 3D MRI dataset for volumetry was acquired in a dedicated (1) H head coil. RESULTS: Phosphocholine and phosphoethanolamine were increased in depressed patients. Though patients responded to the treatments, phospholipids were not significantly altered. An increased age-related gray matter loss in fronto-limbic regions along with an altered relation of phosphomonoesters/phosphodiesters with age were found in depressed patients. DISCUSSION: The findings of increased phosphomonoesthers and an age*group interaction for gray matter volumes need further research to define the role of phospholipids in major depression and possible associations to gray matter loss.

Transient and sustained BOLD signal time courses affect the detection of emotion-related brain activation in fMRI.

A tremendous amount of effort has been dedicated to unravel the functional neuroanatomy of the processing and regulation of emotion, resulting in a well-described picture of limbic, para-limbic and prefrontal regions involved. Studies applying functional magnetic resonance imaging (fMRI) often use the block-wise presentation of stimuli with affective content, and conventionally model brain activation as a function of stimulus or task duration. However, there is increasing evidence that regional brain responses may not always translate to task duration and rather show stimulus onset-related transient time courses. We assume that brain regions showing transient responses cannot be detected in block designs using a conventional fMRI analysis approach. At the same time, the probability of detecting these regions with conventional analyses may be increased when shorter stimulus timing or a more intense stimulation during a block is used. In a within-subject fMRI study, we presented aversive pictures to 20 healthy subjects and investigated the effect of experimental design (i.e. event-related and block design) on the detection of brain activation in limbic and para-limbic regions of interest of emotion processing. In addition to conventional modeling of sustained activation during blocks of stimulus presentation, we included a second response function into the general linear model (GLM), suited to detect transient time courses at block onset. In the conventional analysis, several regions like the amygdala, thalamus and periaqueductal gray were activated irrespective of design. However, we found a positive BOLD response in the anterior insula (AI) in event-related but not in block-design analyses. GLM analyses suggest that this difference may result from a transient response pattern which cannot be captured by the conventional fMRI analysis approach. Our results indicate that regions with a transient response profile like the AI can be missed in block designs if analyses do not account for transient responses. This may bias conclusions from empirical reports and meta-analyses towards an underestimation of these regions and their role in emotion and emotion regulation. The cognitive processes underlying differential time courses are discussed.

Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol.

Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects.

New insights into the effects of type and timing of childhood maltreatment on brain morphometry.

Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.

Rapid partial regeneration of brain volume during the first 14 days of abstinence from alcohol.

BACKGROUND: Chronic alcohol abuse leads to severe damage of the nervous system, including a change in cerebral metabolism and brain morphology. Global volume reductions of gray matter (GM) and white matter and an increase in cerebrospinal fluid (CSF) occur after severe alcohol consumption, but abstinent alcoholics also demonstrate a brain volume recovery. The aim of this study was to investigate whether volumetric amelioration takes place already within the first 2 weeks of abstinence. METHODS: All 49 alcohol-dependent patients included in this study were scanned within the first 24 hours of detoxification and after 2 weeks of supervised abstinence. Amelioration of volumetric brain loss in alcohol-dependent patients has been investigated, and brain volumes have been compared with 55 healthy control subjects using whole-brain segmentation and a voxel-based morphometric approach. RESULTS: On the first day of abstinence, the global CSF volume was larger and the GM volume was smaller in alcohol-dependent patients compared with healthy controls. The largest clusters with significant volumetric differences were in the cingulate gyrus, precentral and middle frontal gyrus, cerebellum, and insula. Already after 2 weeks of abstinence, a significant albeit partial recovery of GM volume occurred in several brain regions. CONCLUSIONS: Our results show that recovery of GM volume in alcohol-dependent patients starts within a few days after detoxification but varies between brain regions. This suggests that the general ability to recover and the rate as well as onset of the recovery diverges for different brain regions.

Loss of control of alcohol use and severity of alcohol dependence in non-treatment-seeking heavy drinkers are related to lower glutamate in frontal white matter.

BACKGROUND: The development and maintenance of alcohol use disorders (AUD) have been hypothesized to be associated with an imbalance of glutamate (GLU) homeostasis. White matter (WM) loss, especially in anterior brain regions, has been reported in alcohol dependence, which may involve disturbances in both myelin and axonal integrity. Frontal lobe dysfunction plays an important role in addiction, because it is suggested to be associated with the loss of control over substance use. This study investigated magnetic resonance spectroscopy (MRS)-detectable Glu levels in frontal WM of non-treatment-seeking heavy drinkers and its associations with AUD symptoms. METHODS: Single-voxel MR spectra optimized for Glu assessment (TE 80 ms) were acquired at 3T from a frontal WM voxel in a group of heavy drinking, non-treatment-seeking subjects in comparison with a group of subjects with only light alcohol consumption. RESULTS: The results corroborate previous findings of increased total choline in heavy drinking subjects. A negative association of Glu levels with severity of alcohol dependence and especially loss of control over time and amount of alcohol intake was observed. CONCLUSIONS: In contrast to the rather unspecific rise in choline-containing compounds, low Glu in frontal WM may be specific for the shift from nondependent heavy drinking to dependence and does not reflect a simple effect of the amount of alcohol consumption alone.

Pattern and volume of the anterior cingulate cortex in chronic posttraumatic stress disorder (PTSD).

Evidence suggests that the anterior cingulate cortex (ACC) plays a key role in the development of posttraumatic stress disorder (PTSD). Owing to the region's highly variable patterns, three different studies of PTSD have yielded inconsistent volume reductions. Accordingly, in order to measure the correct borders and volumes, the different patterns of the ACC must be considered separately. We examined 15 victims with chronic symptoms of PTSD, all traumatized at the same accident in 1988, comparing them to 15 matched control subjects. After categorizing the ACC according to single, single segmented, double or double segmented cingulate sulcus (CS), we measured the area with a semi-automated procedure using Brain2 software. Fifty-three percent of our PTSD subjects had single segmented CS compared to 23% in control subjects and 25% in the literature. Furthermore, the four patterns showed differences in mean volume over all subjects of up to 13%. We detected no differences in absolute ACC volumes when differentiating between the patterns or in correlation with brain volumes or clinical parameters. This is the first study to differentiate ACC structure into different patterns in PTSD. We found that one pattern was overrepresented which, in turn, could signal vulnerability to develop PTSD. Because of the remarkable volume differences between patterns, future studies should categorize this highly variable region into different patterns for volumetric measurements. However, future investigations in larger samples should confirm our findings and assess to which extend alterations of ACC patterns may influence the incidence of PTSD.

In vivo voxel based morphometry: detection of increased hippocampal volume and decreased glutamate levels in exercising mice.

Voluntary exercise has tremendous effects on adult hippocampal plasticity and metabolism and thus sculpts the hippocampal structure of mammals. High-field (1)H magnetic resonance (MR) investigations at 9.4 T of metabolic and structural changes can be performed non-invasively in the living rodent brain. Numerous molecular and cellular mechanisms mediating the effects of exercise on brain plasticity and behavior have been detected in vitro. However, in vivo attempts have been rare. In this work a method for voxel based morphometry (VBM) was developed with automatic tissue segmentation in mice using a 9.4 T animal scanner equipped with a (1)H-cryogenic coil. The thus increased signal to noise ratio enabled the acquisition of high resolution T2-weighted images of the mouse brain in vivo and the creation of group specific tissue class maps for the segmentation and normalization with SPM. The method was used together with hippocampal single voxel (1)H MR spectroscopy to assess the structural and metabolic differences in the mouse brain due to voluntary wheel running. A specific increase of hippocampal volume with a concomitant decrease of hippocampal glutamate levels in voluntary running mice was observed. An inverse correlation of hippocampal gray matter volume and glutamate concentration indicates a possible implication of the glutamatergic system for hippocampal volume.

Cerebral processing of sharp mechanical pain measured with arterial spin labeling.

INTRODUCTION: Arterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood-oxygen-level-dependent functional neuroimaging is its applicability for low-frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain. METHODS: As a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade. RESULTS: We found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, inferior parietal cortex, parietal operculum, temporal gyrus, temporo-occipital lobe, putamen, and the cerebellum. Contrary to our hypothesis, we did not find any significant increase within ACC, thalamus, or PFC. Moreover, we were able to detect a significant positive correlation between pain intensity ratings and pain-induced perfusion increase in the posterior insula. CONCLUSION: We demonstrate that ASL is suited to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain-induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well.

Effects of alcoholism and continued abstinence on brain volumes in both genders.

BACKGROUND: Alcohol abuse has detrimental effects on cerebral function, metabolism, and volume. Some of these effects were found to be at least partially reversible with continued abstinence. Furthermore, it has been reported that there are different effects of alcohol on brain volumes for women compared with men, but the results concerning the interaction between alcohol dependence and gender are inconsistent. With this study, we aimed to further investigate this question by examining the global gray matter (GM) and white matter (WM) changes as well as regional and local GM changes detected by voxel-based morphometry (VBM) in male and female alcoholic patients a few weeks after detoxification and the corresponding changes in a subgroup of these patients 3 months later. METHODS: A total of 50 patients, consecutively admitted for alcohol withdrawal treatment, participated in this study and were followed up for at least 3 months into abstinence. High-resolution structural images were processed with SPM8 using an optimized VBM protocol. RESULTS: Global cerebrospinal fluid (CSF) volume was increased and WM and GM volume decreased equally in male and female patients. A gender by diagnosis interaction was found neither for global nor for regional volumes or VBM data. VBM whole brain analysis yielded a significant GM volume loss in the patient group in the cingulate gyrus and the insula in both hemispheres. Region of interest analysis for the initial and 3 months follow-up scans yielded significant gains in regional volumes, particularly the cingulate gyrus and the insula in the group of abstinent patients, whereas no volume change at all is found in the patients who had relapsed. CONCLUSIONS: Our study confirms widespread cerebral volume loss in recently detoxified alcoholics. The effects of alcohol dependence seem to have equally adverse effects on brain morphometry in males and females.

Influence of Severity of Type and Timing of Retrospectively Reported Childhood Maltreatment on Female Amygdala and Hippocampal Volume.

Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect.

Electroconvulsive therapy modulates grey matter increase in a hub of an affect processing network.

A growing number of recent studies has suggested that the neuroplastic effects of electroconvulsive therapy (ECT) might be prominent enough to be detected through changes of regional gray matter volumes (GMV) during the course of the treatment. Given that ECT patients are difficult to recruit for imaging studies, most publications, however, report only on small samples. Addressing this challenge, we here report results of a structural imaging study on ECT patients that pooled patients from five German sites. Whole-brain voxel-based morphometry (VBM) analysis was performed to detect structural differences in 85 patients with unipolar depression before and after ECT, when compared to 86 healthy controls. Both task-independent and task-dependent physiological whole-brain functional connectivity patterns of these regions were modeled using additional data from healthy subjects. All emerging regions were additionally functionally characterized using the BrainMap database. Our VBM analysis detected a significant increase of GMV in the right hippocampus/amygdala region in patients after ECT compared to healthy controls. In healthy subjects this region was found to be enrolled in a network associated with emotional processing and memory. A region in the left fusiform gyrus was additionally found to have higher GMV in controls when compared with patients at baseline. This region showed minor changes after ECT. Our data points to a GMV increase in patients post ECT in regions that seem to constitute a hub of an emotion processing network. This appears as a plausible antidepressant mechanism and could explain the efficacy of ECT not only in the treatment of unipolar depression, but also of affective symptoms across heterogeneous disorders.

Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients.

BACKGROUND: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala. METHODS: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval. RESULTS: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase. CONCLUSION: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain.