Search

Background: The association of impaired dopaminergic neurotransmission with the development and maintenance of alcohol use disorder is well known. More specifically, reduced dopamine D2/3 receptors in the striatum of subjects with alcohol dependence (AD) compared to healthy controls have been found in previous studies. Furthermore, alterations of gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the anterior cingulate cortex (ACC) of AD subjects have been documented in several studies. However, the interaction between cortical Glu levels and striatal dopamine D2/3 receptors has not been investigated in AD thus far., Methods: This study investigated dopamine D2/3 receptor availability via 18F-fallypride positron emission tomography (PET) and GABA as well as Glu levels via magnetic resonance spectroscopy (MRS) in 19 detoxified AD subjects, 18 healthy controls (low risk, LR) controls and 19 individuals at high risk (HR) for developing AD, carefully matched for sex, age and smoking status., Results: We found a significant negative correlation between GABA levels in the ACC and dopamine D2/3 receptor availability in the associative striatum of LR but not in AD or HR individuals. Contrary to our expectations, we did not observe a correlation between Glu concentrations in the ACC and striatal D2/3 receptor availability., Conclusions: The results may reflect potential regulatory cortical mechanisms on mesolimbic dopamine receptors and their disruption in AD and individuals at high risk, mirroring complex neurotransmitter interactions associated with the pathogenesis of addiction. This is the first study combining 18F-fallypride PET and MRS in AD subjects and individuals at high risk., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Introduction: The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer's disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population., Methods: Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education., Results: Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13]., Conclusion: Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala's value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A variety of information sources are used in the best-evidence diagnostic procedure in child and adolescent mental healthcare, including evaluation by referrers and structured assessment questionnaires for parents. However, the incremental value of these information sources is still poorly examined., Aims: To quantify the added and unique predictive value of referral letters, screening, multi-informant assessment and clinicians' remote evaluations in predicting mental health disorders., Method: Routine medical record data on 1259 referred children and adolescents were retrospectively extracted. Their referral letters, responses to the Strengths and Difficulties Questionnaire (SDQ), results on closed-ended questions from the Development and Well-Being Assessment (DAWBA) and its clinician-rated version were linked to classifications made after face-to-face intake in psychiatry. Following multiple imputations of missing data, logistic regression analyses were performed with the above four nodes of assessment as predictors and the five childhood disorders common in mental healthcare (anxiety, depression, autism spectrum disorders, attention-deficit hyperactivity disorder, behavioural disorders) as outcomes. Likelihood ratio tests and diagnostic odds ratios were computed., Results: Each assessment tool significantly predicted the classified outcome. Successive addition of the assessment instruments improved the prediction models, with the exception of behavioural disorder prediction by the clinician-rated DAWBA. With the exception of the SDQ for depressive and behavioural disorders, all instruments showed unique predictive value., Conclusions: Structured acquisition and integrated use of diverse sources of information supports evidence-based diagnosis in clinical practice. The clinical value of structured assessment at the primary-secondary care interface should now be quantified in prospective studies.

Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18 F-fallypride positron emission tomography ( 18 F-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future., (© 2020 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Objective: To quantify general practitioners' (GPs) sensitivity to anxiety disorders (ADs) when confronted with the range of symptoms common to children with ADs. Also, to explore GPs' conscious preferences and implicit tendencies for referral of children with ADs to mental healthcare., Design and Setting: In a cross-sectional vignette-based survey, all attendees of a Dutch continuing medical education conference for primary care physicians were presented with subtitled audio fragments of five vignettes that we constructed to mimic symptom presentation of children with ADs in general practice. We asked attendees to select per vignette the most plausible diagnoses and most adequate referral option, and for their general referral preferences when they suspect each of the most common mental health problems., Participants: A sample of 229 GPs, resulting in a total of 1128 vignette evaluations., Main Outcome Measure: GPs' selection rate of ADs in the five vignettes compared with a benchmark provided by mental health professionals (MHPs)., Results: Overall, recognition of ADs was less likely in GPs compared with MHPs (OR=0.26, 95% CI 0.15 to 0.46). GPs varied in their recognition of anxiety, with 44.1% not once selecting anxiety as the probable presenting problem. When asked explicitly, 63.9% of the GPs reported that they would refer a child to mental healthcare when they suspect probable ADs. By contrast, only 12.0% of the GPs who recognised anxiety in the vignettes actually selected that referral option., Conclusion: A significant fraction of GPs did not notice the depicted symptoms as anxiety. Despite the widespread prevalence of ADs, GPs seem to overlook anxiety already in their early diagnostic opinion. Improving GPs' familiarity with initial symptom presentation, ADs' base-rate, relevance and impact yields potential for timely recognition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent research on neural and behavioral consequences of transcranial direct current stimulation (tDCS) has highlighted the impact of individual factors, such as brain anatomy which determines current field distribution and may thus significantly impact stimulation effects. Computational modeling approaches may significantly advance our understanding of such factors, but the association of simulation-based tDCS-induced fields and neurophysiological outcomes has not been investigated., Objectives: To provide empirical evidence for the relationship between tDCS-induced neurophysiological outcomes and individually induced electric fields., Methods: We applied tDCS during eyes-closed resting-state functional resonance imaging (rsfMRI) and assessed pre-post magnetic resonance spectroscopy (MRS) in 24 participants. We aimed to quantify effects of 15-min tDCS using the "classical" left SM1-right supraorbital area montage on sensorimotor network (SMN) strength and gamma-aminobutyric acid (GABA) and glutamate concentrations, implementing a cross-over counterbalanced design with three stimulation conditions. Additional structural anatomical MRI sequences and recordings of individual electrode configurations allowed individual electric field simulations based on realistic head models of all participants for both conditions., Results: On a neurophysiological level, we observed the expected reduction of GABA concentrations and increase in SMN strength, both during anodal and cathodal compared to sham tDCS, replicating previous results. The magnitudes of neurophysiological modulations induced by tDCS were significantly associated with simulation-based electric field strengths within the targeted left precentral gyrus., Conclusion: Our findings corroborate previous reports on tDCS-induced neurophysiological modulations and further advance the understanding of underlying mechanisms by providing first empirical evidence for the association of the injected electric field and neuromodulatory effects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Transcranial direct current stimulation (tDCS) modulates human behavior, neuronal patterns, and metabolite concentrations, with exciting potential for neurorehabilitation. However, the understanding of tDCS-induced alterations on the neuronal level is incomplete, and conclusions from young adults, in whom the majority of studies have been conducted, cannot be easily transferred to older populations. Here, we investigated tDCS-induced effects in older adults ( N = 48; age range, 50-79 years) using magnetic resonance spectroscopy to quantify GABA levels as well as resting-state functional magnetic resonance imaging to assess sensorimotor network strength and interhemispheric connectivity. In a randomized, counterbalanced, crossover design, we applied anodal tDCS (atDCS), cathodal tDCS (ctDCS), and sham tDCS (stDCS) over the left sensorimotor region. We observed a significant reduction of GABA levels after atDCS compared with stDCS, reflecting the preserved neuromodulatory effect of atDCS in older adults. Moreover, resting-state functional coupling was decreased during atDCS compared with stDCS, most likely indicating augmented efficiency in brain network functioning. Increased levels of interhemispheric connectivity with age were diminished by atDCS, suggesting stimulation-induced functional decoupling. Further, the magnitude of atDCS-induced local plasticity was related to baseline functional network strength. Our findings provide novel insight into the neuronal correlates underlying tDCS-induced neuronal plasticity in older adults and thus might help to develop tDCS interventions tailored to the aging brain. SIGNIFICANCE STATEMENT Transcranial direct current stimulation (tDCS) modulates human behavior, neuronal patterns, and metabolite concentrations, with exciting potential for neurorehabilitation. However, the understanding of tDCS-induced alterations on the neuronal level is incomplete, and conclusions from young adults cannot be easily transferred to older populations. We used a systematic multimodal imaging approach to investigate the neurophysiological effects of tDCS in older adults and found stimulation-induced effects on GABA levels, reflecting augmented local plasticity and functional connectivity, suggesting modulation of network efficiency. Our findings may help to reconcile some of the recent reports on the variability of tDCS-induced effects, not only implicating age as a crucial modulating factor, but detailing its specific impact on the functionality of neural networks., (Copyright © 2017 the authors 0270-6474/17/374065-09$15.00/0.)

The two-fold benefit of 1 H magnetic resonance spectroscopy (MRS) at high B 0 fields - enhanced sensitivity and increased spectral dispersion - has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ-aminobutyric acid (GABA), it may be advantageous to analyze steady-state, rather than dynamic, conditions. Thus, the aim of this study was to use short-TE 1 H MRS methodology at 7 T to detect differences in steady-state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin-echo full-intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady-state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced 1 H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition., (Copyright © 2016 John Wiley & Sons, Ltd.)

In everyday life we are confronted with inputs of multisensory stimuli that need to be integrated across our senses. Individuals vary considerably in how they integrate multisensory information, yet the neurochemical foundations underlying this variability are not well understood. Neural oscillations, especially in the gamma band (>30Hz) play an important role in multisensory processing. Furthermore, gamma-aminobutyric acid (GABA) neurotransmission contributes to the generation of gamma band oscillations (GBO), which can be sustained by activation of metabotropic glutamate receptors. Hence, differences in the GABA and glutamate systems might contribute to individual differences in multisensory processing. In this combined magnetic resonance spectroscopy and electroencephalography study, we examined the relationships between GABA and glutamate concentrations in the superior temporal sulcus (STS), source localized GBO, and illusion rate in the sound-induced flash illusion (SIFI). In 39 human volunteers we found robust relationships between GABA concentration, GBO power, and the SIFI perception rate (r-values=0.44 to 0.53). The correlation between GBO power and SIFI perception rate was about twofold higher when the modulating influence of the GABA level was included in the analysis as compared to when it was excluded. No significant effects were obtained for glutamate concentration. Our study suggests that the GABA level shapes individual differences in audiovisual perception through its modulating influence on GBO. GABA neurotransmission could be a promising target for treatment interventions of multisensory processing deficits in clinical populations, such as schizophrenia or autism., (Copyright © 2015 Elsevier Inc. All rights reserved.)