Search

Objective Electroconvulsive therapy ( ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. Cognitive side-effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. Methods Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual ( TAU) in an in-patient setting. Matched healthy participants served as controls ( HC). Verbal memory was tested with the California Verbal Learning Test ( CVLT) before the specific treatment started ( ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. Results Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short- and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT-treated patients, but not in the other groups. No differences between the groups were found at follow-up. Conclusion Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients. [ABSTRACT FROM AUTHOR]

MRI and MRS in small rodents demand very high sensitivity. Cryogenic transmit/receive radiofrequency probes (CryoProbes) designed for 1H MRI of mouse brain provide an attractive option for increasing the performance of small-animal MR systems. As the Larmor frequency of 13C nuclei is four times lower than that for 1H nuclei, an even larger sensitivity improvement is expected for 13C applications. The aim of this work was to evaluate the performance of a prototype 13C CryoProbe™ for mouse brain MRS. To investigate the possible gain of the 13C CryoProbe™, we acquired localized single-voxel 13C spectra and chemical shift images of a dimethyl sulfoxide phantom with the CryoProbe™, as well as with two room temperature resonators. The cryogenically cooled resonator achieved approximately four-fold higher signal-to-noise ratio in phantom tests when compared with the best-performing room temperature coil. In addition, we present localized 13C spectra of mouse brain obtained with the CryoProbe™, as well as with one of the room temperature coils, demonstrating the performance in vivo. In summary, the cryogenic cooling technique significantly enhances the 13C signal sensitivity at 9.4 T and enables the investigation of metabolism within mouse brain. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Despite MEGA-PRESS being a robust method for editing the GABA resonance, there are macromolecule resonances at the same chemical shift that are coedited with this sequence. Although this is a known problem, it is still often overlooked. We aimed to evaluate the amount of macromolecule signal coedited, as well as the gender and age dependencies for the GABA resonance at 3.01 ppm using MEGA-PRESS with two different editing pulse frequencies. Forty-five healthy subjects (21-52 years) were included in an in vivo single voxel MEGA-PRESS study at 3.0 T. Phantom measurements were conducted to measure the signal loss when switching the editing pulse between 1.5 and 1.9 ppm instead of the mostly used switching between 1.9 and 7.5 ppm. The in vivo GABA signal detected by switching the editing pulse frequencies between 1.5 and 1.9 ppm was only 50% of the mean GABA detected by switching the editing pulse frequencies between 1.9 and 7.5 ppm. No gender differences were detected. A small age dependency was observed for GABA plus macromolecules, but not for GABA, suggesting an age-dependent macromolecule increase. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Echo-planar spectroscopic imaging (EPSI) is one of the fastest spectroscopic imaging (SI) methods. It has been applied to 1H MR spectroscopy (MRS) studies of the human brain in vivo. However, to our knowledge, EPSI with detection of the 31P nucleus to monitor phosphorus-containing neurometabolites has not yet been considered. In this work, eight different 31P-{1H} EPSI sequence versions with spectral widths ranging from 313 Hz to 2.27 kHz were implemented on a clinical 1.5T whole-body MR tomograph. The sequence versions utilized the heteronuclear nuclear Overhauser effect (NOE) for 31P signal enhancement. The sensitivity observed in experiments with model solutions was in good agreement with theoretical predictions. In vivo measurements performed on healthy volunteers ( N = 16) demonstrated the feasibility of performing two-dimensional (2D) 31P-{1H} EPSI in the human brain, and the technique enabled fast acquisition of well-resolved localized spectra. Magn Reson Med 57:784-790, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of alcohol induced neurotoxicity, and neuroprogenetor cell expansion during recovery from alcohol dependence. [ABSTRACT FROM AUTHOR]

The morphological changes in thin-layer tissues of Nicotiana tabacum L. cv. Samsun, cultured on Murashige and Skoog medium with 1 μM each of naphthalene acetic acid (NAA) and benzyladenine (BA), were studied during the first 8 days of culture with light and scanning electron microscopy. The first three days of culture are characterized by enlargement of all cells and cell divisions starting in the cortical parenchyma cells adjacent to the medium. Between days 3 and 6. epidermal and/or subepidermal cells start to divide, resulting in division centers, which lead to flower bud formation. The hormones NAA and BA in different concentrations affect the formation and distribution of flower buds, bud morphology and callus formation. BA influences particularly bud formation and bud morphology, while NAA affects callus formation in particular. In addition, polarity may occur in the formation of both callus and flower buds, the degree of which depends upon the hormone concentrations. [ABSTRACT FROM AUTHOR]

The in vitro development of flower buds was studied on tissue explants of epidermis and subepidermal cortex from the flower stalks of Nicotiana tabacum L. cv. Samsun. The number of flower buds formed depended mainly on cytokinin concentration. Auxin acted as a modifier in a complex way. In early development, NAA at 1 μM decreased the number of buds initiated and delayed bud emergence. At a later stage, auxin promoted bud outgrowth at the same concentration. Optimal results were obtained when explants were first incubated at low auxin concentration for 3-5 days and subsequently transferred to an elevated auxin level. Physiological processes that lead to flower bud initiation start very soon after the onset of incubation. This was inferred from experiments whereby explants were first cultured at an inductive cytokinin concentration and then transferred to a non-inductive hormone level. [ABSTRACT FROM AUTHOR]

Alcohol Use Disorder has been associated with impairments of functional connectivity between neural networks underlying reward processing and cognitive control. Evidence for aberrant functional connectivity between the striatum, insula, and frontal cortex in alcohol users exists at rest, but not during cue-exposure. In this study, we investigated functional connectivity changes during a cue-reactivity task across different subgroups of alcohol consumers. Ninety-six participants (ranging from light social to heavy social drinkers and nonabstinent dependent to abstinent dependent drinkers) were examined. A functional magnetic resonance imaging cue-reactivity paradigm was administered, during which alcohol-related and neutral stimuli were presented. Applying psychophysiological interaction analyses, we found: (a) Abstinent alcohol-dependent patients compared with non-abstinent dependent drinkers showed a greater increase of functional connectivity of the ventral striatum and anterior insula with the anterior cingulate cortex and dorsolateral prefrontal cortex during the presentation of alcohol cues compared with neutral cues. (b) Subjective craving correlated positively with functional connectivity change between the posterior insula and the medial orbitofrontal cortex and negatively with functional connectivity change between the ventral striatum and the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex. (c) Compulsivity of alcohol use correlated positively with functional connectivity change between the dorsolateral prefrontal cortex and the ventral striatum, anterior insula, and posterior insula. Results suggest increased cognitive control over cue-processing in abstinent alcohol-dependent patients, compensating high levels of cue-provoked craving and compulsive use. Clinical trial registration details: ClinicalTrials.gov ID: NCT00926900., (© 2020 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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., (Copyright © 2017 by the Research Society on Alcoholism.)

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., (Copyright © 2013 by the Research Society on Alcoholism.)

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., (Copyright © 2012 by the Research Society on Alcoholism.)

Pre-clinical research indicates that opioids reduce extracellular glutamate in acute opioid treatment, whereas during withdrawal, glutamatergic neurotransmission is increased and withdrawal symptoms can be blocked by glutamate receptor antagonists. The glutamate hypothesis of addiction suggests that withdrawal-associated hyperglutamatergic states destabilize the glutamatergic system chronically and contribute to relapse. magnetic resonance spectroscopy at three tesla optimized for glutamate assessment (TE 80 ms) was performed in the anterior cingulate gyrus (ACC) and frontal white matter (fWM) of 17 opiate-dependent patients during opiate maintenance therapy and 20 healthy controls. Controlling for age and gray matter content, glutamate in the ACC was positively associated with the number of previous withdrawals. For glutamate + glutamine (Glx), a significant group-age interaction was found. Whereas Glx declines with age in healthy controls, Glx increases with age in opiate-dependent patients. The number of previous withdrawals did not correlate with age. In fWM spectra, increased Cho concentrations were observed in opiate-dependent patients. Both new findings, the positive correlation of glutamate and previous withdrawals and increasing Glx with age in contrast to an age-dependent Glx decrease in controls indicate a destabilization of the glutamate system in opiate-dependent patients and support the glutamate hypothesis of addiction. Increased Cho concentrations in fWM corroborate findings of WM abnormalities in opioid-dependent subjects., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)

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., (2011 by the Research Society on Alcoholism.)

Aims: During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence., Design, Setting and Participants: Non-abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol-dependent according to DSM-IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined., Measurements: We used a cue-reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented., Findings: In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue-induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive-compulsive craving, and furthermore we found a positive association between cue-induced activation in the dorsal striatum and obsessive-compulsive craving in all participants., Conclusions: In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

Alcohol drinking is highly prevalent in many cultures and contributes to the global burden of disease. In fact, it was shown that alcohol constitutes 3.2% of all worldwide deaths in the year 2006 and is linked to more than 60 diseases, including cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders, injuries and foetal alcohol syndrome. Alcoholism, which has been proven to have a high genetic load, is one potentially fatal consequence of chronic heavy alcohol consumption, and may be regarded as one of the most prevalent neuropsychiatric diseases afflicting our society today. The aim of the integrated genome research network 'Genetics of Alcohol Addiction'--which is a German inter-/trans-disciplinary life science consortium consisting of molecular biologists, behavioural pharmacologists, system biologists with mathematicians, human geneticists and clinicians--is to better understand the genetics of alcohol addiction by identifying and validating candidate genes and molecular networks involved in the aetiology of this pathology. For comparison, addictive behaviour to other drugs of abuse (e.g. cocaine) is studied as well. Here, we present an overview of our research consortium, the current state of the art on genetic research in the alcohol field, and list finally several of our recently published research highlights. As a result of our scientific efforts, better insights into the molecular and physiological processes underlying addictive behaviour will be obtained, new targets and target networks in the addicted brain will be defined, and subsequently, novel and individualized treatment strategies for our patients will be delivered., (© 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.)

Background: Activation of the anterior cingulate cortex (ACC) in a spatial working memory task has been associated with risk factors for alcohol use disorders such as low alcohol effects and positive alcohol expectations in adolescents. To transfer these results into adults, we used the same task in adults., Methods: During functional magnetic resonance imaging, 12 light social, 7 heavy social, and 11 non-abstinent-dependent alcohol drinkers performed a spatial working memory task and completed measures of automatic alcohol-related thoughts and behavior (Obsessive-Compulsive Drinking Scale-OCDS), alcohol use of the last 90 days, and general intelligence., Results: Behavioral performance in the spatial working memory task was not significantly different in all 3 groups. Controlling for differences in general intelligence alcohol-dependent participants showed a higher task-related activation of the dorsal ACC (dACC) in comparison with light and heavy social drinkers. Measures of the OCDS were positively correlated with the activation in the left hippocampus and right thalamus in all participants., Conclusions: Our results support the findings of increased dACC activation during a spatial working memory task as a risk factor for alcohol dependence. Increased task-related activation in the dACC was only observed in alcohol-dependent participants and not in heavy social drinkers with comparable alcohol consumption. Furthermore, the absence of behavioral performance differences between groups as well as an association between dACC activation and working memory performance indicates subtle working memory deficits. Low capacity of working memory has been linked to more automatic and less self-regulated behavior in studies on natural reward processing. Therefore, additional neural activation during performance of the non-alcohol-related working memory task in participants with higher OCDS values in the left hippocampus and the right thalamus may be a consequence of decreased neural capacity because of distracting alcohol-related thoughts.