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Gamma-aminobutyric acid (GABA) and glutamate are implicated in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), though findings from magnetic resonance spectroscopy (MRS) are inconsistent. Furthermore, the relationship between GABAA-receptor availability and rTMS outcomes remains largely unexplored. In this study, GABA and glutamate levels in the dorsal anterior cingulate cortex (dACC) were measured using a 1H-MRS MEGA-PRESS sequence in 42 patients with bipolar or unipolar depression, both before and after a sham-controlled, double-blind clinical trial involving intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex. A subset of 28 patients also underwent [11C]flumazenil positron emission tomography (PET) to measure whole-brain GABAA-receptor availability and mean receptor availability in the nucleus accumbens and dACC. Depressive symptoms were assessed using the self-rated Montgomery Åsberg Depression Rating Scale (MADRS-S). The results indicated no significant changes in neurotransmitter levels or GABAA-receptor availability post-iTBS in either the active or sham conditions. However, changes in MADRS-S scores after active iTBS were positively correlated with changes in GABA levels in the dACC (r(13) = 0.54, p = 0.04) and baseline GABAA-receptor availability in the nucleus accumbens (r(11) = 0.66, p = 0.02). These correlations were absent in the sham group. The findings suggest that a reduction in GABA within targeted frontostriatal circuits can be part of the antidepressant mechanism of iTBS, challenging previous research. Additionally, they indicate a potential predictive role for frontostriatal GABAA-receptor availability in the treatment of depression using dorsomedial prefrontal iTBS.

Background: Depression is characterized by disturbed emotion processing, with aberrant neural and physiological responses to emotional stimuli. Here, we applied an emotion anticipation and processing paradigm to investigate brain neural and electrodermal reactivities in patients with depression compared with healthy controls.

Methods: The study included 42 patients (27 females) and 44 healthy controls (21 females). Subjects underwent functional magnetic resonance imaging with simultaneous measurement of electrodermal activity. During scanning, red or green color cues were presented, followed by pictures of negative or positive valence, respectively. Behavioral valence and arousal ratings of the picture stimuli were conducted after scanning. Anhedonia was assessed through a semi-structured interview in both subject groups.

Results: Patients perceived positive pictures as less positive than controls did. Positive anticipation (i.e., green color cues) elicited stronger activations in the anterior cingulate cortex and the right insula in patients than in healthy controls, indicating salience network disturbances. An exploratory analysis of all regions in the Automated Anatomical Labeling Atlas 2 found significant differences in activity to positive anticipation between groups in several brain regions involved in cognition and emotion processing. Positive and negative anticipation elicited stronger electrodermal responses in healthy controls. However, electrodermal reactivity to negative pictures was higher in patients than in controls.

Conclusions: Ongoing depression affects emotion anticipation and processing at the behavioral, neural, and physiological levels. These findings contribute to increased understanding of the disorder.

Past results suggest that fear extinction and the return of extinguished fear are compromised in adolescents. However, findings have been inconclusive as there is a lack of fear extinction and extinction retention studies including children, adolescents and adults. In the present study, 36 children (6-9 years), 40 adolescents (13-17 years) and 44 adults (30-40 years), underwent a two-day fear conditioning task. Habituation, acquisition, and extinction were performed on the first day and an extinction retention test > 24 h later. Skin conductance responses were recorded during all phases of fear conditioning and functional magnetic resonance imaging (fMRI) was conducted during the fear retention test. All groups acquired and extinguished fear as measured with SCR, with no group differences in SCR during extinction retention. The groups had largely similar neural fear responses during the retention test, apart from adolescents displaying stronger amygdala fear response than children, with no differences between adolescents and adults. The findings do not support an adolescent extinction dip, and there was only marginal evidence of progressive changes in fear conditioning across development. In contrast to findings in rodents, fear conditioning in humans may elicit similar physiological responses and recruit similar neural networks from childhood to adulthood.

PURPOSE: Autoimmune encephalitis (AIE) is a group of conditions that are insufficiently understood and difficult to diagnose. Several publications indicate that FDG PET has superior sensitivity compared with MRI. This study aimed to perform a systematic review of publications to assess the characteristics and frequency of brain FDG PET compared with MRI findings at the individual level in AIE, including case reports and case series. The resulting meta-analysis is complementary to previous publications with large or medium-sized cohorts.

PATIENTS AND METHODS: The review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and aimed to identify all studies with at least 1 case of AIE in which brain FDG PET was performed. Results from MRI and FDG PET were extracted on a patient-by-patient basis.

RESULTS: The literature search yielded 1303 results, of which 234 studies were included, containing 498 cases. Abnormal FDG PET findings are reported in 93% compared with 55% with MRI. The affected brain regions, rates of unilateral versus bilateral findings, and hypermetabolism versus hypometabolism are descriptively presented in tables categorized according to the associated antibody.

CONCLUSIONS: FDG PET detected abnormalities more frequently than MRI, particularly in cases with anti-NMDAR and anti-GABA-B antibodies. Findings include a high prevalence of hypermetabolism in the medial temporal lobes, but also a high prevalence of parietal and occipital hypometabolism. Results differed depending on the associated antibody. Overall, the findings strengthen the importance of FDG PET in patients with suspected AIE, and the antibody-related patterns of regional metabolic abnormalities indicate a high potential for further development as a diagnostic and prognostic tool.

There is growing evidence suggesting that immunological mechanisms play a significant role in the development of psychiatric symptoms in certain patient subgroups. However, the relationship between clinical red flags for suspected autoimmune psychiatric disease and signs of central nervous system (CNS) pathology (e.g., routine cerebrospinal fluid (CSF) alterations, CNS damage markers, neurophysiological or neuroimaging findings) has received limited attention. Here, we aimed to describe the prevalence and distribution of potential CNS pathologies in psychiatric patients in relation to clinical red flags for autoimmune psychiatric disease and psychiatric symptoms. CSF routine findings and CNS damage markers; neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP) and total Tau (t-Tau), in CSF from 127 patients with psychiatric disease preselected for suspected immunological involvement were related to recently proposed clinical red flags, psychiatric features, and MRI and EEG findings. Twenty-one percent had abnormal routine CSF findings and 27% had elevated levels of CNS damage markers. Six percent had anti-neuronal antibodies in serum and 2% had these antibodies in the CSF. Sixty-six percent of patients examined with MRI (n = 88) had alterations, mostly atrophy or nonspecific white matter lesions. Twenty-seven percent of patients with EEG recordings (n = 70) had abnormal findings. Elevated NfL levels were associated with comorbid autoimmunity and affective dysregulation symptoms. Elevated t-Tau was associated with catatonia and higher ratings of agitation/hyperactivity. Elevated GFAP was associated with acute onset, atypical presentation, infectious prodrome, tics, depressive/anxiety symptom ratings and overall greater psychiatric symptom burden. In conclusion, preselection based on suspected autoimmune psychiatric disease identifies a population with a high prevalence of CSF alterations suggesting CNS pathology. Future studies should examine the value of these markers in predicting treatment responses.

This study aimed to evaluate the predictive value and clinical impact of a clinically implemented artificial neural network software model. The software detects intracranial hemorrhage (ICH) from head computed tomography (CT) scans and artificial intelligence (AI)-identified positive cases are then annotated in the work list for early radiologist evaluation. The index test was AI detection by the program Zebra Medical Vision-HealthICH+. Radiologist-confirmed ICH was the reference standard. The study compared whether time benefits from using the AI model led to faster escalation of patient care or surgery within the first 24 h. A total of 2,306 patients were evaluated by the software, and 288 AI-positive cases were included. The AI tool had a positive predictive value of 0.823. There was, however, no significant time reduction when comparing the patients who required escalation of care and those who did not. There was also no significant time reduction in those who required acute surgery compared with those who did not. Among the individual patients with reduced time delay, no cases with evident clinical benefit were identified. Although the clinically implemented AI-based decision support system showed adequate predictive value in identifying ICH, there was no significant clinical benefit for the patients in our setting. While AI-assisted detection of ICH shows great promise from a technical perspective, there remains a need to evaluate the clinical impact and perform external validation across different settings.

Background: Impaired cognitive ability is one of the most frequently reported neuropsychiatric symptoms in the post-COVID phase among patients. It is unclear whether this condition is related to structural or functional brain changes.

Purpose: In this study, we present a multimodal magnetic resonance imaging study of 36 post-COVID patients and 36 individually matched controls who had a mild form of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection from March 2020 to February 2022. This study aimed to investigate structural and functional brain alterations and their correlation with post-COVID symptoms and neurocognitive functions.

Materials and methods: The study protocol comprised an assessment of physical fatigue [Fatigue Severity Scale (FSS)], mental fatigue (Mental Fatigue Scale (MFS)], depression [Montgomery Asberg Depression Rating Scale (MADRS)], anxiety [Hospital Anxiety and Depression Scale (HAD)], post-COVID Symptoms Severity Score, and neurocognitive status [Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)]. The magnetic resonance imaging protocol included morphological sequences, arterial spin labeling (ASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (fMRI) sequences. Using these protocols, the assessments of macrostructural abnormalities, perfusion, gray matter density, white matter integrity, and brain connectivity were performed.

Results: Post-COVID patients had higher levels of physical fatigue, mental fatigue, depression, and anxiety than controls and showed cognitive impairment in all the RBANS domains except in Visuospatial/Construction. The subjective mental fatigue correlated with objective impaired cognitive ability in the RBANS test, particularly in the Attention domain. There were no differences between patients and controls regarding macrostructural abnormalities, regional volumes, regional perfusion metrics, gray matter density, or DTI parameters. We observed a significant positive correlation between RBANS Total Scale Index score and gray matter volume in the right superior/middle-temporal gyrus (p < 0.05) and a significant negative correlation between the white matter integrity and post-COVID symptoms (p < 0.05) in the same area. The connectivity differences were observed between patients and controls in a few regions, including the right middle frontal gyrus, an important area of convergence of the dorsal and ventral attention networks. We also noted a positive correlation between post-COVID symptoms and increased connectivity in the right temporoparietal junction, which is part of the ventral attention system.

Conclusion: In non-hospitalized subjects with post-COVID, we did not find any structural brain changes or changes in perfusion, compared to controls. However, we noted differences in connectivity within an important area for attention processes, which may be associated with post-COVID brain fog.

INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.

METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.

RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.

CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Approximately 100,000 persons live with Alzheimer's disease in Sweden. As the population ages, the need for diagnostics and disease-modifying treatment grows. Previously available treatments provide moderate symptom relief but do not affect disease progression. New antibody treatments show promising results and are typically well tolerated. However, adverse events include brain edema and hemorrhages, which can be detected early by MRI. These treatments require substantial resources, including increased use of MRI and radiological expertise. The introduction of new therapies will lead to higher regional healthcare costs and demands for specialized diagnostics. Implementing these therapies therefore necessitates national preparation and planning for coordinated and efficient management, addressing the significant societal and economic challenges posed by Alzheimer's disease.

I Sverige lever ca 100 000 personer med Alzheimers sjukdom.

Behovet av diagnos och effektiv behandling ökar med en åldrande befolkning.

Antikroppsbehandling riktad mot amyloid-beta har nyligen erhållit begränsat godkännande i EU och Storbritannien och har tidigare godkänts i bland annat USA, Kina och Japan.

De nya läkemedlen har visat lovande resultat, men kan orsaka ödem och blödningar i hjärnan. MR kan tidigt upptäcka biverkningarna, kallade ARIA, och är vägledande för om behandling ska fortgå, avbrytas eller avslutas helt.

Ett införande av de nya läkemedlen i Sverige skulle kräva stora kringresurser och prioriteringar, vilket manar till nationell förberedelse och samordning med god representation från berörda specialiteter.

I Sverige lever ca 100 000 personer med Alzheimers sjukdom.

Behovet av diagnos och effektiv behandling ökar med en åldrande befolkning.

Antikroppsbehandling riktad mot amyloid-beta har nyligen erhållit begränsat godkännande i EU och Storbritannien och har tidigare godkänts i bland annat USA, Kina och Japan.

De nya läkemedlen har visat lovande resultat, men kan orsaka ödem och blödningar i hjärnan. MR kan tidigt upptäcka biverkningarna, kallade ARIA, och är vägledande för om behandling ska fortgå, avbrytas eller avslutas helt.

Ett införande av de nya läkemedlen i Sverige skulle kräva stora kringresurser och prioriteringar, vilket manar till nationell förberedelse och samordning med god representation från berörda specialiteter.