Hallucinogen persisting perception disorder (HPPD) is characterized by spontaneous recurrence of visual hallucinations or disturbances after previous consumption of hallucinogens, such as lysergic ...acid diethylamide (LSD). The underlying physiological mechanisms are unknown and there is no standardized treatment strategy available.
A 33-year-old male patient presented with persistent visual distortions (halos around objects, intensified colors, positive after images, and trails following moving objects) that developed after repeated use of hallucinogenic drugs at the age of 18. Symptoms developed gradually and worsened several months later, resulting in various pharmacological and psychosocial treatment attempts that remained unsuccessful, however. At presentation, 32-channel electroencephalography (EEG) showed increased delta activity over the occipital brain regions, reminiscent of occipital intermittent rhythmic delta activity (OIRDA) usually seen in children. Two sessions of cathodal (inhibitory) transcranial direct current stimulation (tDCS) over 30 min attenuated visual hallucinations and occipital delta activity by approximately 60%. The response persisted for over four weeks.
Pathological delta activity over occipital brain regions may play an important role in the development and perpetuation of HPPD and can be attenuated by non-invasive brain stimulation.
Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing ...impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer’s disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.
Abstract Background The rise of a new generation of intelligent neuroprostheses, brain-computer interfaces (BCI) and adaptive closed-loop brain stimulation devices hastens the clinical deployment of ...neurotechnologies to treat neurological and neuropsychiatric disorders. However, it remains unclear how these nascent technologies may impact the subjective experience of their users. To inform this debate, it is crucial to have a solid understanding how more established current technologies already affect their users. In recent years, researchers have used qualitative research methods to explore the subjective experience of individuals who become users of clinical neurotechnology. Yet, a synthesis of these more recent findings focusing on qualitative methods is still lacking. Methods To address this gap in the literature, we systematically searched five databases for original research articles that investigated subjective experiences of persons using or receiving neuroprosthetics, BCIs or neuromodulation with qualitative interviews and raised normative questions. Results 36 research articles were included and analysed using qualitative content analysis. Our findings synthesise the current scientific literature and reveal a pronounced focus on usability and other technical aspects of user experience. In parallel, they highlight a relative neglect of considerations regarding agency, self-perception, personal identity and subjective experience. Conclusions Our synthesis of the existing qualitative literature on clinical neurotechnology highlights the need to expand the current methodological focus as to investigate also non-technical aspects of user experience. Given the critical role considerations of agency, self-perception and personal identity play in assessing the ethical and legal significance of these technologies, our findings reveal a critical gap in the existing literature. This review provides a comprehensive synthesis of the current qualitative research landscape on neurotechnology and the limitations thereof. These findings can inform researchers on how to study the subjective experience of neurotechnology users more holistically and build patient-centred neurotechnology.
To study the prevalence of autoantibodies to glial and neuronal antigens with a focus on glial acidic fibrillary protein (GFAP) in patients with dementia.
Sera of 127 patients with different forms of ...dementia and sera of 82 age-matched patients with various neurological diseases except for dementia, as well as sera from 15 age-matched healthy controls were analyzed for anti-glial or anti-neuronal IgG using 1) primary murine embryonic hippocampus cell cultures, 2) murine brain sections, 3) immunoblotting on mouse brain homogenates and 4) astrocyte cultures. Sera reacting with astrocytes in hippocampus cell cultures were further analyzed using HEK293 cells transfected with human GFAP.
IgG in serum from 45 of 127 (35.5%) patients with dementia but only 8 of 97 (8.2%, p ≤ 0.001) controls bound to either glial or neuronal structures in cultured murine hippocampus cells. In these cultures antibodies to astrocytes were detected in 35 of 127 (27.5%) of the dementia patients, whereas in controls antibodies to astrocytes were detected in 4 sera only (4.1%, p ≤ 0.001). Among the sera exhibiting reactivity to astrocytes, 14 of 35 (40%) showed immunoreaction to HEK293 cells transfected with GFAP in dementia patients, representing 11% of all sera. Within the 4 immunoreactive control sera reacting with astrocytes one reacted with GFAP (1.0% of total immunoreactivity, p = 0.003).
Autoantibodies to glial epitopes in general and to GFAP in particular are more frequent in patients with dementia than in age-matched controls without dementia, thus indicating the need for further investigations regarding the potential pathophysiological relevance of these antibodies.
•Autoantibodies to astrocytes occur with higher frequencies in dementia patients than in control patients without dementia.•GFAP was identified as target protein in 50% of the sera from dementia patients targeting exclusively astrocytes.•Seropositivity to GFAP might represent a subgroup of autoimmune dementia.
Objective
Investigating retinal thickness may complement existing biological markers for dementia and other neurodegenerative diseases. Although retinal thinning is predictive for cognitive decline, ...it remains to be investigated if and how this feature aligns with neurodegeneration elsewhere in the brain, specifically in early disease stages.
Methods
Using optical coherence tomography and magnetic resonance imaging, we examined retinal thickness as well as hippocampal structure in patients with amnestic mild cognitive impairment and healthy controls.
Results
The groups did not differ in hippocampal and retinal thickness measures. However, we detected a correlation of peripapillary retinal nerve fiber layer thickness and hippocampal thickness in healthy people but not in cognitively impaired patients. The ratio of hippocampus to retina thickness was significantly smaller in patients with mild cognitive impairment and correlated positively with cognitive performance.
Conclusions
Different temporal trajectories of neurodegeneration may disrupt transregional brain structure associations in patients with amnestic mild cognitive impairment.
We investigated in patients with mild cognitive impairment, if and how retinal thinning aligns with neurodegeneration elsewhere in the brain. We detected a correlation of peripapillary retinal nerve fiber layer thickness and hippocampal thickness in healthy control participants but not in the cognitively impaired individuals. Different temporal trajectories of neurodegeneration may disrupt transregional brain structure associations in early neurodegeneration.
Pathophysiological hallmarks of Alzheimer's disease (AD) include extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies also demonstrated a role of neuroinflammation ...in the progression of the disease. Clinical trials and animal studies using low-dose radiation therapy (LDRT) have shown therapeutic potential for AD. This systematic review summarizes the current evidence on the use of LDRT for the treatment of AD, outlines potential mechanisms of action, and discusses current challenges in the planning of future trials.
A systematic review of human and animal studies as well as registered clinical trials describing outcomes for RT in the treatment of AD was conducted. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published until July 1, 2023, were included.
The initial search yielded 993 articles. After the removal of duplicates and ineligible publications, a total of 16 (12 animal, 4 human) studies were included. Various dose regimens were utilized in both animal and human trials. The results revealed that LDRT reduced the number of amyloid plaques and neurofibrillary tangles, and it has a role in the regulation of genes and protein expression involved in the pathological progression of AD. LDRT has demonstrated reduced astro- and microgliosis, anti-inflammatory and neuroprotective effects, and an alleviation of symptoms of cognitive deficits in animal models. Most studies in humans suggested improvements in cognition and behavior. None of the trials or studies described significant (>grade 2) toxicity.
Preclinical studies, animal studies, and early clinical trials in humans have shown a promising role for LDRT in the treatment of AD pathologies, although the underlying mechanisms are yet to be fully explored. Phase I/II/III trials are needed to assess the long-term safety, efficacy, and optimal treatment parameters of LDRT in AD treatment.
•Cognitive deficits are a core symptom of major depressive disorder.•Dementia risk does not predict cognitive deficits in young depressed adults.•Recurrent depression contributes to cognitive ...impairment in young people.
: Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated with reduced cognitive performance in older people. Although cognitive impairment is also frequent during and after depressive episodes, it may occur irrespective of age, which makes it difficult to determine, whether this symptom indicates a risk for or shared mechanisms with neurodegeneration. We therefore investigated the influence of genetic and brain imaging risk factors for dementia on cognitive impairment in young people with major depressive disorder.
We used magnetic resonance imaging, APOE genotyping and neurocognitive assessments to examine young adults (mean age: 29.1 ± 6.3 years) with major depressive disorder and a current depressive episode, presenting with or without cognitive deficits.
Neither hippocampal thickness nor APOE genotype predicted cognitive impairment. Patients with objective cognitive deficits reported a greater number of previous depressive episodes.
Our results have to be interpreted with caution. The small sample size could have prevented the detection of effects. Complementing research methods and investigations across the life span would be necessary to reveal possible interactions between risk factors for dementia, neurodegeneration, depression, and age.
In young adults, recurrent depressive episodes may increase the likelihood for cognitive deficits, while common risk factors for dementia do not.
•Radiotherapy of brain tumors may cause dose-dependent side-effects.•HipPro Pilot study using structural MRI and comprehensive neurocognitive evaluation.•Hippocampal thickness or objective memory ...performance did not change.•Subjective memory impairment was associated with symptoms of depression.•Future studies of memory impairment should assess depressive symptoms.
Radiotherapy in patients with primary brain tumors may affect hippocampal structure and cause dyscognitive side-effects.
Using structural MRI and comprehensive neurocognitive evaluation, we investigated associations between hippocampal structure and memory deficits in 15 patients with WHO grade 3 and grade 4 gliomas receiving standard radio(chemo)therapy.
We did not find changes in hippocampal thickness or cognitive abilities three months after completing radiotherapy. However, subjective memory impairment was associated with symptoms of depression, but not with objective memory performance, cortical thickness of the hippocampus or radiation dose.
Irrespective of whether there is a bidirectional relationship between affective changes and subjective cognitive dysfunction in these patients, depressive symptoms remain a target for intervention to improve their quality of life. The results of our pilot study highlight that future assessment of side effects of radiotherapy concerning memory should include assessments of depressive symptoms.
•Cognitive deficits are common in patients with a depressive episode.•Extrahippocampal thinning is associated with cognitive deficits in depression.•A neurodegenerative origin of cognitive impairment ...in depression is unlikely.
Cognitive deficits are common in patients with a depressive episode although the predictors for their development and severity remain elusive. We investigated whether subjective and objective cognitive impairment in young depressed adults would be associated with cortical thinning in medial temporal subregions.
High-resolution magnetic resonance imaging, cortical unfolding data analysis, and comprehensive assessments of subjective and objective cognitive abilities were performed on 27 young patients with a depressive episode (mean age: 29.0 ± 5.8 years) and 23 older participants without a history of a depressive disorder but amnestic mild cognitive impairment (68.5 ± 6.6 years) or normal cognition (65.2 ± 8.7 years).
Thickness reductions in parahippocampal, perirhinal and fusiform cortices were associated with subjective memory deficits only among young patients with a depressive episode and a measurable cognitive impairment.
Long-term longitudinal data would be desirable to determine the trajectories of cognitive impairment associated with depression in patients with or without cortical structure changes.
The presence of clinically significant cognitive deficits in young people with a depressive episode may identify a patient population with extrahippocampal cortical thinning.
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