A 50-Year-Old Man with Left-Sided Weakness and Difficulty Speaking Clearly.

Morning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 50-year-old man who presented for evaluation of weakness on the left side of his body and difficulty speaking clearly.

Capturing the power of seizures: an empirical mode decomposition analysis of epileptic activity in the mouse hippocampus.

Introduction: Various methods have been used to determine the frequency components of seizures in scalp electroencephalography (EEG) and in intracortical recordings. Most of these methods rely on subjective or trial-and-error criteria for choosing the appropriate bandwidth for filtering the EEG or local field potential (LFP) signals to establish the frequency components that contribute most to the initiation and maintenance of seizure activity. The empirical mode decomposition (EMD) with the Hilbert-Huang transform is an unbiased method to decompose a time and frequency variant signal into its component non-stationary frequencies.

Different characteristics of cortical spreading depression in the sleep and wake states.

Objective: The objective of this study is to characterize the effects of the sleep-wake cycle on neurovascular and behavioral characteristics of cortical spreading depression (CSD).

Background: There is an important bi-directional relationship between migraine and the sleep-wake cycle, but the basic mechanisms of this relationship are poorly understood.

Methods: We have developed a minimally invasive microchip system to continuously monitor cerebral blood volume (CBV) with optical intrinsic signal (OIS), head movement, and multiple other physiological and behavioral parameters in freely behaving mice over weeks.

Continuous long-term recording and triggering of brain neurovascular activity and behaviour in freely moving rodents.

A minimally invasive, microchip-based approach enables continuous long-term recording of brain neurovascular activity, heart rate, and head movement in freely behaving rodents. This approach can also be used for transcranial optical triggering of cortical activity in mice expressing channelrhodopsin. The system uses optical intrinsic signal recording to measure cerebral blood volume, which under baseline conditions is correlated with spontaneous neuronal activity.

Identification of neural oscillations and epileptiform changes in human brain organoids.

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations.

Hand posture as localizing sign in adult focal epileptic seizures.

Objective: The aim of this study was to identify specific ictal hand postures (HPs) as localizing signs of the epileptogenic zone (EZ) in patients with frontal or temporal lobe epilepsy.

Methods: In this study, we retrospectively analyzed ictal semiology of 489 temporal lobe or frontal lobe seizures recorded over a 6-year period at the Seizure Disorder Center at University of California, Los Angeles in the USA (45 patients) or at the C. Munari Epilepsy Surgery Center at Niguarda Hospital in Milan, Italy (34 patients).

Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models.

Variants of TREM2 are associated with Alzheimer's disease (AD). To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, we developed BAC transgenic mice expressing human TREM2 (BAC-TREM2) in microglia. We found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model.

Diminished KCC2 confounds synapse specificity of LTP during senescence.

The synapse specificity of long-term potentiation (LTP) ensures that no interference arises from inputs irrelevant to the memory to be encoded. In hippocampi of aged (21-28 months) mice, LTP was relayed to unstimulated synapses, blemishing its synapse specificity. Diminished levels of the K(+)/Cl(-) cotransporter KCC2 and a depolarizing GABAA receptor-mediated synaptic component following LTP were the most likely causes for the spreading of potentiation, unveiling mechanisms hindering information storage in the aged brain and identifying KCC2 as a potential target for intervention.

Novel insights into the behavioral analysis of mice subjected to the forced-swim test.

The forced-swim test (FST) is one of the most widely used rodent behavioral assays, in which the immobility of animals is used to assess the effectiveness of antidepressant drugs. However, the existing, and mostly arbitrary, criteria used for quantification could lead to biased results. Here we believe we uncovered new confounding factors, revealed new indices to interpret the behavior of mice and propose an unbiased means for quantification of the FST.

In vitro gamma oscillations following partial and complete ablation of δ subunit-containing GABAA receptors from parvalbumin interneurons.

Perisynaptic and extrasynaptic δ subunit-containing GABAA receptors (δ-GABAARs) mediate tonic conductances in many neurons. On principal cells of the neocortex and hippocampus they comprise α4 subunits, whereas they usually contain α1 on various interneurons. Specific characteristics of δ-GABAARs are their pharmacology and high plasticity.

Ovarian cycle-linked plasticity of δ-GABAA receptor subunits in hippocampal interneurons affects γ oscillations in vivo.

GABAA receptors containing δ subunits (δ-GABAARs) are GABA-gated ion channels with extra- and perisynaptic localization, strong sensitivity to neurosteroids (NS), and a high degree of plasticity. In selective brain regions they are expressed on specific principal cells and interneurons (INs), and generate a tonic conductance that controls neuronal excitability and oscillations. Plasticity of δ-GABAARs in principal cells has been described during states of altered NS synthesis including acute stress, puberty, ovarian cycle, pregnancy and the postpartum period, with direct consequences on neuronal excitability and network dynamics.

Interneuronal GABAA receptors inside and outside of synapses.

About 20% of the total number of neurons in the brain are interneurons (INs) that utilize GABA as their neurotransmitter. The receptors for GABA have been well studied in principal cells, but INs also express GABA receptors, in particular the GABAA type (GABAARs), which may also be activated in an autocrine manner by the transmitter released by the INs themselves. As more and more neurological and psychiatric disorders are being discovered to be linked to malfunction or deficits of INs, this review will cover how INs communicate with each other through the activation of synaptic and extrasynaptic GABAARs.

Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABA(A) receptors on parvalbumin interneurons.

Gamma (γ) oscillations (30-120 Hz), an emergent property of neuronal networks, correlate with memory, cognition and encoding. In the hippocampal CA3 region, locally generated γ oscillations emerge through feedback between inhibitory parvalbumin-positive basket cells (PV+BCs) and the principal (pyramidal) cells. PV+BCs express δ-subunit-containing GABA(A)Rs (δ-GABA(A)Rs) and NMDA receptors (NMDA-Rs) that balance the frequency of γ oscillations.

GABAA receptor modulation by neurosteroids in models of temporal lobe epilepsies.

Epilepsies consist of a spectrum of neurologic disorders typically characterized by unpredictable and dysfunctional network behaviors in the central nervous system (CNS), which lead to discrete episodes of large bouts of uncontrolled neuronal synchrony that interfere with the normal functioning of the brain. Temporal lobe epilepsy (TLE) is accompanied by changes in interneuronal innervation and modifications in different γ-aminobutyric acid (GABA)(A) receptor subunits. Hormones play an important role in modulating the overall excitability of neurons, and at the same time hormonal pathways are frequently modified during epilepsy.

Excitability changes related to GABAA receptor plasticity during pregnancy.

Alterations in GABA(A) receptor (GABA(A)R) expression and function, similar to those we described previously during pregnancy in the mouse dentate gyrus, may also occur in other brain regions. Here we show, using immunohistochemical techniques, a decreased delta subunit-containing GABA(A)R (deltaGABA(A)R) expression in the dentate gyrus, hippocampal CA1 region, thalamus, and striatum but not in the cerebral cortex. In the face of the highly elevated neurosteroid levels during pregnancy, which can act on deltaGABA(A)Rs, it may be beneficial to decrease the number of neurosteroid-sensitive receptors to maintain a steady-state level of neuronal excitability throughout pregnancy.