Slowed peak resting frequency and MEG overactivation in survivors of severe sepsis and septic shock

Götz, Theresa; Baumbach, Philipp; Huonker, Ralph; Kranczioch, Cornelia; Witte, Otto W.; Debener, Stefan; Klingner, Carsten M.; Brunkhorst, Frank M.; Günther, Albrecht

doi:10.1016/j.clinph.2015.07.021

Cited by 9 publications

(14 citation statements)

References 52 publications

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“…While this change initially affects thalamic function locally, once it reaches the dynamical attractor state of TCD, pathological oscillations will persistently propagate through circuits of the neocortex, affecting increasingly more distal areas. Consistent with this notion is a recent link between TCD and severe sepsis and septic shock [ 39 ]. Sepsis is a severe inflammatory response to an infection, leading to sepsis-associated encephalopathy due to brain-cell damage, impaired neurotransmission, and neurodegeneration [ 40 – 42 ].…”

Section: Discussionsupporting

confidence: 54%

“…As a result, patients often suffer from a rapid decline in cognitive function, including impaired memory, attention, and visual-spatial processing. It has been proposed that the neuropathological processes following sepsis additionally lead to the development of TCD, as the patients' EEG display the distinctive slowing of the dominant α-peak into high-θ range [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

et al. 2016

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The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamo-cortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through divergent intrathalamic circuits, and entrains thalamo-cortical pathways by means of propagating low-frequency oscillations beyond the restricted region of the lesion. Hence, pathological stroke-induced thalamo-cortical dynamics can be the source of diaschisis, and account for the dissociation between lesion location and non-specific symptoms of stroke such as neuropathic pain and hemispatial neglect.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

et al. 2016

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“…Of the 18 retained articles [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], 61% of them included a neuropsychologist as a co-author. 66.7% of studies used longitudinal designs, while 33.3% used cross-sectional designs.…”

Section: Resultsmentioning

confidence: 99%

Sepsis and Cognitive Assessment

Jones

Dion

Efron

et al. 2021

JCM

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Sepsis disproportionally affects people over the age of 65, and with an exponentially increasing older population, sepsis poses additional risks for cognitive decline. This review summarizes published literature for (1) authorship qualification; (2) the type of cognitive domains most often assessed; (3) timelines for cognitive assessment; (4) the control group and analysis approach, and (5) sociodemographic reporting. Using key terms, a PubMed database review from January 2000 to January 2021 identified 3050 articles, and 234 qualified as full text reviews with 18 ultimately retained as summaries. More than half (61%) included an author with an expert in cognitive assessment. Seven (39%) relied on cognitive screening tools for assessment with the remaining using a combination of standard neuropsychological measures. Cognitive domains typically assessed were declarative memory, attention and working memory, processing speed, and executive function. Analytically, 35% reported on education, and 17% included baseline (pre-sepsis) data. Eight (44%) included a non-sepsis peer group. No study considered sex or race/diversity in the statistical model, and only five studies reported on race/ethnicity, with Caucasians making up the majority (74%). Of the articles with neuropsychological measures, researchers report acute with cognitive improvement over time for sepsis survivors. The findings suggest avenues for future study designs.

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“…Increased delta and theta power, with high inter-individual variability, as well as a general slowing of oscillatory activity in the REM-like state under urethane is in line with slowing of EEG activity during awake, or wake-like states, described in sepsis patients. Relative increases in delta and theta power and reduced spectral peak frequencies were found in septic patients [51][52][53][54]. Increased slowing was associated with poor outcomes, including delirium [54] and death [55].…”

Section: Discussionmentioning

confidence: 97%

Sepsis-Induced Brain State Instability

Kala

Leemburg

Ježek

2022

Preprint

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Background Sepsis-associated brain dysfunction (SABD) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome. It is associated with high mortality and a majority of survivors suffer long-term neurological consequences. Sleep is commonly affected in sepsis and there is a strong correlation between its impairment and development of other complications or increased mortality in sepsis patients. Here, we investigate the effects of sepsis on brain activity patterns in order to better understand possible sources of sleep-wake disturbances associated with severe systemic inflammation. Methods We studied the effects of high LPS doses (10mg/kg) on oscillatory brain states in an acute rat model of sepsis under urethane anaesthesia, which maintains REM- and NREM sleep-like states. Twelve Long-Evans rats (6 LPS, 6 controls) were implanted with eight independently movable tetrodes in the dorsal hippocampus. Baseline LFP activity was recorded for 3 hours after saline injection, followed by another 3 hours after LPS or saline injection. REM and NREM were automatically classified based on LFP activity and quantified. Within- and between-state dynamics were analysed using a 2-D state space approach based on spectral power ratios. Aperiodic and periodic components of the power spectrum were quantified for each state. Blood serum samples and brains were collected for IL-1β quantification and histological verification of electrode placement. Results Soon after LPS injection we observed a robust fragmentation of both oscillatory states resulting in a three-fold increase in the number of state transitions that lasted for several hours, although the overall time spent in either state did not change. Analysis of power spectra showed opposing shifts in low frequency oscillations (1–9 Hz) in REM and NREM that resulted in increased similarity between both states in 2-D state space. Conclusions The observed increased spectral similarity between REM and NREM and increased instability within the states may point to a mechanism underlying the severe sleep fragmentation described both in sepsis patients and in SABD animal models.

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Slowed peak resting frequency and MEG overactivation in survivors of severe sepsis and septic shock

Cited by 9 publications

References 52 publications

The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

Sepsis and Cognitive Assessment

Sepsis-Induced Brain State Instability

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