Case report: Concurrent low-volume subdural hematoma and ipsilateral ischemic stroke presenting as capsular warning syndrome: a complex case with anticoagulation dilemma and dual pathology.

Background: The simultaneous emergence of low-volume subdural hematoma and ipsilateral ischemic stroke in an atrial fibrillation patient who is under anticoagulation therapy is a rare and intricate clinical case. This report accentuates the diagnostic and treatment complexities associated with these consecutive neurological conditions. Case presentation: An 83 years-old male patient initially presented with acute dyspnea, raising the suspicion of pulmonary embolism. After exclusion of pulmonary embolism through CT angiography, the patient experienced a sudden onset of left-sided hemiparesis without prior history of head trauma but with chronic intake of apixaban due to atrial fibrillation. Subsequent cranial CT tomography revealed a small right parietal subdural hematoma. After reversal of the anticoagulation therapy, surgical evacuation of the subdural hematoma was successfully performed. However, in the postoperative period, the patient developed new neurological symptoms that could not be explained by the reduced size of the subdural hematoma on a follow-up CT scan. Cranial MRI revealed the coexistence of acute ischemic stroke in the right corona radiata. The recent surgical procedure precluded guideline-recommended stroke treatment. Discussion: This case underscores the complexities of diagnosing and treating concomitant small volume subdural hematoma and ischemic stroke, especially if the latter occurs in the corona radiata resulting in fluctuating symptoms known as "capsular warning syndrome." Reversal and secondary discontinuation of anticoagulant therapy for surgical intervention highlight the inherent risk of thrombotic events in anticoagulated patients. The development of tailored treatment strategies requires a multidisciplinary approach, and further research and guidelines are required in similar complex scenarios. Conclusion: The presence of both a small subdural hematoma and an ipsilateral ischemic stroke presenting as capsular warning syndrome in an anticoagulated patient highlights the intricacy of their care. This case calls for a comprehensive and collaborative strategy to address complicated clinical scenarios.

Control of sustained attention and impulsivity by Gq-protein signalling in parvalbumin interneurons of the anterior cingulate cortex.

The anterior cingulate cortex (ACC) has been implicated in attention deficit hyperactivity disorder (ADHD). More specifically, an appropriate balance of excitatory and inhibitory activity in the ACC may be critical for the control of impulsivity, hyperactivity, and sustained attention which are centrally affected in ADHD. Hence, pharmacological augmentation of parvalbumin- (PV) or somatostatin-positive (Sst) inhibitory ACC interneurons could be a potential treatment strategy. We, therefore, tested whether stimulation of Gq-protein-coupled receptors (GqPCRs) in these interneurons could improve attention or impulsivity assessed with the 5-choice-serial reaction-time task in male mice. When challenging impulse control behaviourally or pharmacologically, activation of the chemogenetic GqPCR hM3Dq in ACC PV-cells caused a selective decrease of active erroneous-i.e. incorrect and premature-responses, indicating improved attentional and impulse control. When challenging attention, in contrast, omissions were increased, albeit without extension of reward latencies or decreases of attentional accuracy. These effects largely resembled those of the ADHD medication atomoxetine. Additionally, they were mostly independent of each other within individual animals. GqPCR activation in ACC PV-cells also reduced hyperactivity. In contrast, if hM3Dq was activated in Sst-interneurons, no improvement of impulse control was observed, and a reduction of incorrect responses was only induced at high agonist levels and accompanied by reduced motivational drive. These results suggest that the activation of GqPCRs expressed specifically in PV-cells of the ACC may be a viable strategy to improve certain aspects of sustained attention, impulsivity and hyperactivity in ADHD.

Distinct contributions of GluA1-containing AMPA receptors of different hippocampal subfields to salience processing, memory and impulse control.

Schizophrenia is associated with a broad range of severe and currently pharmacoresistant cognitive deficits. Prior evidence suggests that hypofunction of AMPA-type glutamate receptors (AMPARs) containing the subunit GLUA1, encoded by GRIA1, might be causally related to impairments of selective attention and memory in this disorder, at least in some patients. In order to clarify the roles of GluA1 in distinct cell populations, we investigated behavioural consequences of selective Gria1-knockout in excitatory neurons of subdivisions of the prefrontal cortex and the hippocampus, assessing sustained attention, impulsivity, cognitive flexibility, anxiety, sociability, hyperactivity, and various forms of short-term memory in mice. We found that virally induced reduction of GluA1 across multiple hippocampal subfields impaired spatial working memory. Transgene-mediated ablation of GluA1 from excitatory cells of CA2 impaired short-term memory for conspecifics and objects. Gria1 knockout in CA3 pyramidal cells caused mild impairments of object-related and spatial short-term memory, but appeared to partially increase social interaction and sustained attention and to reduce motor impulsivity. Our data suggest that reduced hippocampal GluA1 expression-as seen in some patients with schizophrenia-may be a central cause particularly for several short-term memory deficits. However, as impulse control and sustained attention actually appeared to improve with GluA1 ablation in CA3, strategies of enhancement of AMPAR signalling likely require a fine balance to be therapeutically effective across the broad symptom spectrum of schizophrenia.

A low-cost open-source 5-choice operant box system optimized for electrophysiology and optophysiology in mice.

Operant boxes enable the application of complex behavioural paradigms to support circuit neuroscience and drug discovery research. However, commercial operant box systems are expensive and often not optimised for combining behaviour with neurophysiology. Here we introduce a fully open-source Python-based operant-box system in a 5-choice design (pyOS-5) that enables assessment of multiple cognitive and affective functions. It is optimized for fast turn-over between animals, and for testing of tethered mice for simultaneous physiological recordings or optogenetic manipulation. For reward delivery, we developed peristaltic and syringe pumps based on a stepper motor and 3D-printed parts. Tasks are specified using a Python-based syntax implemented on custom-designed printed circuit boards that are commercially available at low cost. We developed an open-source graphical user interface (GUI) and task definition scripts to conduct assays assessing operant learning, attention, impulsivity, working memory, or cognitive flexibility, alleviating the need for programming skills of the end user. All behavioural events are recorded with millisecond resolution, and TTL-outputs and -inputs allow straightforward integration with physiological recordings and closed-loop manipulations. This combination of features realizes a cost-effective, nose-poke-based operant box system that allows reliable circuit-neuroscience experiments investigating correlates of cognition and emotion in large cohorts of subjects.

Lack of redundancy between electrophysiological measures of long-range neuronal communication.

BACKGROUND: Communication between brain areas has been implicated in a wide range of cognitive and emotive functions and is impaired in numerous mental disorders. In rodent models, various metrics have been used to quantify inter-regional neuronal communication. However, in individual studies, typically, only very few measures of coupling are reported and, hence, redundancy across such indicators is implicitly assumed. RESULTS: In order to test this assumption, we here comparatively assessed a broad range of directional and non-directional metrics like coherence, Weighted Phase Lag Index (wPLI), phase-locking value (PLV), pairwise phase consistency (PPC), parametric and non-parametric Granger causality (GC), partial directed coherence (PDC), directed transfer function (DTF), spike-phase coupling (SPC), cross-regional phase-amplitude coupling, amplitude cross-correlations and others. We applied these analyses to simultaneous field recordings from the prefrontal cortex and the ventral and dorsal hippocampus in the schizophrenia-related Gria1-knockout mouse model which displays a robust novelty-induced hyperconnectivity phenotype. Using the detectability of coupling deficits in Gria1-/- mice and bivariate correlations within animals as criteria, we found that across such measures, there is a considerable lack of functional redundancy. Except for three pairwise correlations-PLV with PPC, PDC with DTF and parametric with non-parametric Granger causality-almost none of the analysed metrics consistently co-varied with any of the other measures across the three connections and two genotypes analysed. Notable exceptions to this were the correlation of coherence with PPC and PLV that was found in most cases, and partial correspondence between these three measures and Granger causality. Perhaps most surprisingly, partial directed coherence and Granger causality-sometimes regarded as equivalent measures of directed influence-diverged profoundly. Also, amplitude cross-correlation, spike-phase coupling and theta-gamma phase-amplitude coupling each yielded distinct results compared to all other metrics. CONCLUSIONS: Our analysis highlights the difficulty of quantifying real correlates of inter-regional information transfer, underscores the need to assess multiple coupling measures and provides some guidelines which metrics to choose for a comprehensive, yet non-redundant characterization of functional connectivity.