Relationship of white matter lesion severity with early and late outcomes after mechanical thrombectomy for large vessel stroke.

BACKGROUND: White matter lesions (WML) are associated with poor outcome after mechanical thrombectomy (MT) for large vessel stroke; the reasons are uncertain. To elucidate this issue we sought to determine the association of WML with multiple early and late outcome measures after MT. METHODS: We retrospectively analyzed 181 MT patients prospectively included in our local stroke registry (January 2012 to November 2016). Using multiple regression modeling, we assessed whether WML was independently associated with early outcomes (successful recanalization, degree of National Institutes of Health Stroke Scale (NIHSS) improvement, hemorrhagic transformation, duration of hospitalization) as well as an unfavorable 90-day modified Rankin Scale score (mRS) (≥3) and 90-day survival. Explorative analyses examined the association with the 90-day home-time and 90-day risk for hospital readmission. RESULTS: WML were not significantly associated with early outcome measure (P>0.05, each). Patients with moderate-to-severe WML more often had an unfavorable mRS (OR 2.93, 95% CI 1.04 to 8.33) and risk of death (HR 1.98, 95% CI 1.03 to 3.84) after adjustment for pertinent confounders. Patients with moderate-to-severe WML had a significantly shorter home-time (19±32 vs 47±38 days, P<0.001) and Kaplan-Meier analyses indicated a significantly greater risk for hospital readmission within 90 days (log rank P=0.045), with the most frequent reasons being recurrent stroke and transient ischemic attack. CONCLUSION: Our analyses suggest that poor outcomes among patients with moderate-to-severe WML were related to factors unrelated to procedural success and risk. WML should not be used to render treatment decisions in otherwise eligible patients. Aggressive monitoring of medical complications after MT could represent a viable strategy to improve outcome in affected patients.

Engram Excitement.

Engram cells can encode and switch between multiple mnemonic functions, but how they intrinsically do so is unknown. Pignatelli, Ryan, and colleagues show that upon memory recall, the engram's excitability is transiently elevated, allowing its bearer to adapt to changing environments.

The mysteries of remote memory.

Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process-the standard theory of memory consolidation-would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might already ab ovo be encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

Discharge properties of neurons of the median raphe nucleus during hippocampal theta rhythm in the rat.

The serotonin (5-HT)-containing median raphe nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the median raphe nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. These cells were subdivided into theta-on (68%) and theta-off (32%) based on increased or decreased rates of activity with theta, respectively. They were further classified as slow-firing (~1 Hz), moderate-firing (5-11 Hz), or fast-firing (>12 Hz) theta-on or theta-off cells. The slow-firing cells as well as a subset of moderate-firing theta-off cells displayed characteristics of "classic" serotonin-containing raphe neurons. All fast-firing neurons were theta-on cells and showed either tonic or phasic (rhythmical) increases in activity with theta. We propose that: (1) the slow-firing cells (on and off) as well as a subset of moderate-firing theta-off cells are serotonergic neurons; (2) the phasic and tonic fast-firing theta-on cells are GABAergic cells; and (3) these populations of cells mutually interact in the modulation of the hippocampal EEG. An activation of local serotonergic and GABAergic theta-on cells would inhibit 5-HT slow- or moderate-firing theta-off projection cells to release or generate theta, whereas the suppression of serotonergic- or GABAergic theta-on cells would disinhibit 5-HT theta-off cells, resulting in a blockade of theta or a desynchronization of the hippocampal EEG. A role for the median raphe nucleus in memory-associated functions of the hippocampus is discussed.

Is partial coherence a viable technique for identifying generators of neural oscillations?

Partial coherence measures the linear relationship between two signals after the influence of a third signal has been removed. Gersch proposed in 1970 that partial coherence could be used to identify sources of driving for multivariate time series. This idea, referred to in this paper as Gersch Causality, has received wide acceptance and has been applied extensively to a variety of fields in the signal processing community. Neurobiological data from a given sensor include both the signals of interest and other unrelated processes collectively referred to as measurement noise. We show that partial-coherence-based Gersch Causality is extremely sensitive to signal-to-noise ratio; that is, for a group of three or more simultaneously recorded time series, the time series with the highest signal-to-noise ratio (i.e., relatively noise free) is often identified as the "driver" of the group, irrespective of the true underlying patterns of connectivity. This hypothesis is tested both theoretically and on experimental time series acquired from limbic brain structures during the theta rhythm.