scholarly journals Autoantibodies against NMDA receptor 1 modify rather than cause encephalitis

2021 ◽  
Author(s):  
Justus B. H. Wilke ◽  
Martin Hindermann ◽  
Stefan A. Berghoff ◽  
Svenja Zihsler ◽  
Sahab Arinrad ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Immune Cell ◽  
Brain Inflammation ◽  
Receptor Internalization ◽  
Prefrontal Cortical ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis ◽  
Cortical Regions ◽  
Firm Evidence

AbstractThe etiology and pathogenesis of “anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis” and the role of autoantibodies (AB) in this condition are still obscure. While NMDAR1-AB exert NMDAR-antagonistic properties by receptor internalization, no firm evidence exists to date that NMDAR1-AB by themselves induce brain inflammation/encephalitis. NMDAR1-AB of all immunoglobulin classes are highly frequent across mammals with multiple possible inducers and boosters. We hypothesized that “NMDAR encephalitis” results from any primary brain inflammation coinciding with the presence of NMDAR1-AB, which may shape the encephalitis phenotype. Thus, we tested whether following immunization with a “cocktail” of 4 NMDAR1 peptides, induction of a spatially and temporally defined sterile encephalitis by diphtheria toxin-mediated ablation of pyramidal neurons (“DTA” mice) would modify/aggravate the ensuing phenotype. In addition, we tried to replicate a recent report claiming that immunizing just against the NMDAR1-N368/G369 region induced brain inflammation. Mice after DTA induction revealed a syndrome comprising hyperactivity, hippocampal learning/memory deficits, prefrontal cortical network dysfunction, lasting blood brain-barrier impairment, brain inflammation, mainly in hippocampal and cortical regions with pyramidal neuronal death, microgliosis, astrogliosis, modest immune cell infiltration, regional atrophy, and relative increases in parvalbumin-positive interneurons. The presence of NMDAR1-AB enhanced the hyperactivity (psychosis-like) phenotype, whereas all other readouts were identical to control-immunized DTA mice. Non-DTA mice with or without NMDAR1-AB were free of any encephalitic signs. Replication of the reported NMDAR1-N368/G369-immunizing protocol in two large independent cohorts of wild-type mice completely failed. To conclude, while NMDAR1-AB can contribute to the behavioral phenotype of an underlying encephalitis, induction of an encephalitis by NMDAR1-AB themselves remains to be proven.

Dopamine Increases the Gain of the Input-Output Response of Rat Prefrontal Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 2985-2997 ◽  
Author(s):  
Kay Thurley ◽  
Walter Senn ◽  
Hans-Rudolf Lüscher
Keyword(s):  
Working Memory ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
D1 Receptors ◽  
Input Output ◽  
Prefrontal Cortical ◽  
Noisy Input ◽  
Relationship Of

Dopaminergic modulation of prefrontal cortical activity is known to affect cognitive functions like working memory. Little consensus on the role of dopamine modulation has been achieved, however, in part because quantities directly relating to the neuronal substrate of working memory are difficult to measure. Here we show that dopamine increases the gain of the frequency-current relationship of layer 5 pyramidal neurons in vitro in response to noisy input currents. The gain increase could be attributed to a reduction of the slow afterhyperpolarization by dopamine. Dopamine also increases neuronal excitability by shifting the input-output functions to lower inputs. The modulation of these response properties is mainly mediated by D1 receptors. Integrate-and-fire neurons were fitted to the experimentally recorded input-output functions and recurrently connected in a model network. The gain increase induced by dopamine application facilitated and stabilized persistent activity in this network. The results support the hypothesis that catecholamines increase the neuronal gain and suggest that dopamine improves working memory via gain modulation.

scholarly journals 'To do or not to do'? The neurobiology of decision-making in daily life: I. Getting the basics

2007 ◽  
Vol 1 (1) ◽  
pp. 10-17 ◽  
Author(s):  
André Palmini ◽  
Victor Geraldi Haase
Keyword(s):  
Decision Making ◽  
Everyday Life ◽  
Theory And Practice ◽  
Moral Issues ◽  
Temporal Perspective ◽  
Prefrontal Cortical ◽  
Cortical Regions

Abstract The constant conflict between decisions leading to immediate pleasurable consequences versus behaviors aiming at long-term social advantages is reviewed here in the framework of the evolutionary systems regulating behavior. The inescapable temporal perspective in decision-making in everyday life is highlighted and integrated with the role of the executive functions in the modulation of subcortical systems. In particular, the representations of the 'non-existent' future in the prefrontal cortical regions and how these representations can bridge theory and practice in everyday life are addressed. Relevant discussions regarding the battle between emotions and reasons in the determination of more complex decisions in the realm of neuroeconomics and in moral issues have been reserved for a second essay.

The role of the amygdala in bipolar disorder development

2008 ◽  
Vol 20 (4) ◽  
pp. 1285-1296 ◽  
Author(s):  
Amy Garrett ◽  
Kiki Chang
Keyword(s):  
Bipolar Disorder ◽  
Structure And Function ◽  
Prefrontal Cortical ◽  
Amygdala Activity ◽  
Psychiatric Conditions ◽  
Cortical Regions ◽  
And Function ◽  
Experienced Emotion

AbstractThe amygdala has received great interest as a possible neurophysiological substrate of bipolar disorder (BD). This review summarizes information about the structure and function of the amygdala with attention to its role in experienced emotion and mood. We review the evidence for amygdala pathology in psychiatric conditions and discuss the role of the amygdala in BD during development. There appear to be consistent findings in the neuroimaging literature that suggest an etiological model for BD that involves abnormalities in the structure and function of the amygdala, but also depends on the failure of prefrontal cortical regions to modulate amygdala activity. In addition, evidence is accumulating to suggest that this model has flexible outcomes, depending on factors intrinsic and extrinsic to BD, and may follow several possible paths across the course of maturational development.

scholarly journals Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons

2021 ◽  
Author(s):  
Marta Krzyżanowska ◽  
Krzysztof Rębała ◽  
Johann Steiner ◽  
Michał Kaliszan ◽  
Dorota Pieśniak ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Ribosomal Dna ◽  
Pyramidal Neurons ◽  
Quantitative Polymerase Chain Reaction ◽  
Anterior Cingulate ◽  
Rdna Transcription ◽  
Relative Level ◽  
Prefrontal Cortical ◽  
Dorsolateral Cortex ◽  
Cortical Regions

AbstractPrefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

scholarly journals Emerging role of free triiodothyronine in patients with anti-N-methyl-D-aspartate receptor encephalitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tuo Ji ◽  
Zhi Huang ◽  
Yajun Lian ◽  
Chengze Wang ◽  
Qiaoman Zhang
Keyword(s):  
Clinical Decision Making ◽  
Clinical Decision ◽  
Nonparametric Tests ◽  
Clinical Prediction ◽  
Free Triiodothyronine ◽  
Icu Admission ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis

AbstractWe aimed to investigate the role of free triiodothyronine (FT3) in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. 137 consecutive inpatients (2016–2019) were registered prospectively and followed up for 12 months. 96 eligible patients were included in the study. The modified Rankin scale (mRS) score was collected, and the score of 3–6 was defined as a poor outcome. The patients were equally classified into 3 subgroups based on their FT3 levels obtained within 24 h of admission, and the subgroup differences were analyzed by parametric or nonparametric tests as appropriate. Logistic regression analysis was performed. We found that there was no difference in the mRS scores upon admission among 3 subgroups, however, patients in the low-FT3 subgroup tended to have higher disease severity during hospitalization and worse outcome in follow-up visits, represented by higher chances of intense care unit (ICU) admission (P < 0.001), longer hospital stay (P < 0.001), greater maximum mRS scores during hospitalization (P = 0.011), lower rates of getting clinical improvement within 4 weeks of starting treatment (P = 0.006), and higher percentages of poor 1-year outcome (P = 0.002). The level of FT3 was an independent factor correlated with ICU admission (P = 0.002) and might be a potential predictor for 1-year outcome. Our preliminary results suggest that the FT3 may be a risk factor involved in the evolution and progression of anti-NMDAR encephalitis, whereas the underline mechanisms remain to be explored. Attention should be paid to these patients with relatively low FT3 upon admission, which might possibly aid clinical prediction and guide clinical decision-making.

scholarly journals A critical reflection on our first patient presenting with Anti-Nmethyl- D-aspartate receptor encephalitis

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Susanne Buechner ◽  
Igor Florio ◽  
Gabriele J. Sixt ◽  
Francesco Teatini
Keyword(s):  
Treatment Guidelines ◽  
Autoimmune Encephalitis ◽  
Complete Recovery ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis ◽  
One Year

One of the best characterized autoimmune encephalitis is the Anti-Nmethyl-D-aspartate receptor (NMDAR) encephalitis, which may occur in the presence of cancer. First- and second-line immunotherapy and oncological investigations are suggested. We present here a case of an 18-year-old female who was our first patient suffering from Anti-NMDAR encephalitis more than 9 years ago. She was satisfactorily treated with intravenous immunoglobulins and high dose steroid therapy. After more than one year the patient had a relapse. First-line immunotherapy was repeated; however, a complete recovery was achieved only after plasmapheresis. Afterwards, she continued maintenance immunotherapy with steroids for two years and with Azathioprine for about five years associated to regular oncological assessment. In the last years our therapeutical approach of Anti-NMDARencephalitis has significantly changed. Nevertheless, established treatment guidelines are still missing and the role of long-term maintenance immunotherapy is largely unexplored. In addition, oncological revaluation might be indicated in selected patients.

scholarly journals Prefrontal cortex and cognitive control: new insights from human electrophysiology

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1696 ◽  
Author(s):  
Alik S. Widge ◽  
Sarah R. Heilbronner ◽  
Benjamin Y. Hayden
Keyword(s):  
Cognitive Control ◽  
Large Scale ◽  
Field Potential ◽  
Neural Basis ◽  
Prefrontal Cortical ◽  
Open Questions ◽  
Multiple Regions ◽  
Human Electrophysiology ◽  
Cortical Regions

Cognitive control, the ability to regulate one’s cognition and actions on the basis of over-riding goals, is impaired in many psychiatric conditions. Although control requires the coordinated function of several prefrontal cortical regions, it has been challenging to determine how they work together, in part because doing so requires simultaneous recordings from multiple regions. Here, we provide a précis of cognitive control and describe the beneficial consequences of recent advances in neurosurgical practice that make large-scale prefrontal cortical network recordings possible in humans. Such recordings implicate inter-regional theta (5–8 Hz) local field potential (LFP) synchrony as a key element in cognitive control. Major open questions include how theta might influence other oscillations within these networks, the precise timing of information flow between these regions, and how perturbations such as brain stimulation might demonstrate the causal role of LFP phenomena. We propose that an increased focus on human electrophysiology is essential for an understanding of the neural basis of cognitive control.

scholarly journals CA2 Neuronal Activity Controls Hippocampal Oscillations and Social Behavior

2017 ◽  
Author(s):  
Georgia M. Alexander ◽  
Logan Y. Brown ◽  
Shannon Farris ◽  
Daniel Lustberg ◽  
Caroline Pantazis ◽  
...  
Keyword(s):  
Social Behavior ◽  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Cell Activity ◽  
Experimental System ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Prefrontal Cortical ◽  
Relative Contribution

AbstractHippocampal oscillations arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions and behaviors. Although much progress has been made toward identifying the relative contribution of specific neuronal populations in hippocampal oscillations, far less is known about the role of hippocampal area CA2, which is thought to support social aspects of episodic memory. Furthermore, the little existing evidence on the role of CA2 in oscillations has led to conflicting conclusions. Therefore, we sought to identify the specific contribution of CA2 pyramidal neurons to brain oscillations using a controlled experimental system. We used excitatory and inhibitory DREADDs in transgenic mice to acutely and reversibly manipulate CA2 pyramidal cell activity. Here, we report on the role of CA2 in hippocampal-prefrontal cortical network oscillations and social behavior. We found that excitation or inhibition of CA2 pyramidal cells bidirectionally regulated hippocampal and prefrontal cortical low gamma oscillations and inversely modulated hippocampal ripple oscillations. Further, CA2 inhibition impaired social approach behavior. These findings support a role for CA2 in low gamma generation and ripple modulation within the hippocampus and underscore the importance of CA2 neuronal activity in extrahippocampal oscillations and social behavior.

scholarly journals Managing severe behavioral symptoms of a patient with anti-NMDAR encephalitis: case report and findings in current literature

2015 ◽  
Vol 37 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Vanina Lima Monteiro ◽  
Felipe José Nascimento Barreto ◽  
Paulo Marcos Brasil Rocha ◽  
Paulo Henrique Teixeira do Prado ◽  
Frederico Duarte Garcia ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Behavioral Symptoms ◽  
Healthcare Team ◽  
Liaison Psychiatry ◽  
Neuropsychiatric Complications ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis ◽  
Consultation Liaison Psychiatry ◽  
High Doses

Objective: Psychiatric symptoms emerge in the early stages of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, and patients often seek treatment in psychiatric departments before visiting any other general medical services. Numerous articles about anti-NMDAR encephalitis have been published in the scientific community worldwide, but few emphasize the role of psychiatry in symptom management.Case description: We describe the case of a patient with anti- -NMDAR encephalitis seen in our service and discuss the management of behavioral symptoms based on current scientific literature. High doses of atypical antipsychotics and benzodiazepines were used to control agitation, and trazodone was administered to treat insomnia.Comments: Consultation-liaison psychiatry may help the healthcare team adjust the management of neuropsychiatric complications that might affect inpatients with anti-NMDAR encephalitis.

Item-specific Training Reduces Prefrontal Cortical Involvement in Perceptual Awareness

2008 ◽  
Vol 20 (10) ◽  
pp. 1777-1787 ◽  
Author(s):  
Johan Eriksson ◽  
Anne Larsson ◽  
Lars Nyberg
Keyword(s):  
Brain Activity ◽  
Perceptual Awareness ◽  
Top Down ◽  
Bottom Up ◽  
Prefrontal Cortical ◽  
Marked Decline ◽  
Cortical Regions ◽  
Cortical Involvement ◽  
Reduced Activity

Previous studies on the neural correlates of perceptual awareness implicate sensory-specific regions and higher cortical regions such as the prefrontal cortex (PFC) in this process. The specific role of PFC regions is, however, unknown. PFC activity could be bottom-up driven, integrating signals from sensory regions. Alternatively, PFC regions could serve more active top-down processes that help to define the content of consciousness. To compare these alternative views of PFC function, we used functional magnetic resonance imaging and measured brain activity specifically related to conscious perception of items that varied in ease of identification (by being presented 0, 12, or 60 times previously). A bottom-up account predicts that PFC activity would be largely insensitive to stimulus difficulty, whereas a top-down account predicts reduced PFC activity as identification becomes easier. The results supported the latter prediction by showing reduced activity for previously presented compared to novel items in the PFC and several other regions. This was further confirmed by a functional connectivity analysis showing that the interaction between frontal and visual sensory regions declined as a function of ease of identification. Given the attribution of top-down processing to PFC regions in combination with the marked decline in PFC activity for easy items, these findings challenge the prevailing notion that the PFC is necessary for consciousness.

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