Biology subjects

Storm, J. F.

Publications and source records attributed to Storm, J. F..

7 recordsLinked to original sources

bioRxiv2024

Effects of ketamine and propofol on muscarinic plateau potentials in rat neocortical pyramidal cells

Propofol and ketamine are widely used general anaesthetics, but have different effects on consciousness: propofol gives a deeply unconscious state, with little or no dream reports, whereas vivid dreams are often reported after ketamine anaesthesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, while propofol is a {gamma}-aminobutyric-acid (GABAA) agonist, but these mechanisms do not fully explain how these drugs alter consciousness. Most previous in vitro studies of cellular mechanisms of anaesthetics have used brain slices or neurons in a nearly "comatose" state, because no "arousing" neuromodulators were added. Here we tested mechanisms of anaesthetics in slices after adding the cholinergic agonist muscarine to partly mimic an "awake-like" state. Using whole-cell patch-clamp recordings from layer 2/3 pyramidal cells (L2/3PCs) in rat medial prefrontal cortex (mPFC) slices, we saw that muscarine induced long-lasting depolarizing plateau potentials (PPs) and spiking following brief depolarizing current injections. According to leading theories of consciousness and working memory, L2/3PCs and PPs are particularly important for these cognitive functions. After 2 hours of pre-incubation with ketamine or propofol, the muscarine-induced PPs were altered in different ways: 3 {micro}M propofol reduced the PPs and (significantly) spiking, whereas 20 {micro}M ketamine seemed to enhance PPs and spiking (non-significantly). Brief wash-in of these drug concentrations failed to induce such effects, probably due to insufficient equilibration by diffusion in the slices. In contrast, pre-incubation with 100 {micro}M ketamine suppressed the PPs and spiking. The different effects on PPs may be related to contrasting clinical effects: ketamine causing atypical anaesthesia with vivid, "psychedelic" dreaming while propofol causes less dreaming. However, high ketamine or propofol concentrations both suppressed PPs, suggesting possible connections between PPs, desynchronized activity, and consciousness. More experiments are needed to test these tentative conclusions.

neuroscience↗

bioRxiv2023

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex

The prefrontal cortex (PFC) is important for executive functions, including attention, planning, decision-making, and memory, and is proposed by some leading theories to be crucial for consciousness. In particular, the global neuronal workspace theory proposes that PFC layer 2/3 pyramidal cells (L2/3PCs) contribute crucially to the global workspace, and hence to consciousness, due to their long-range connections to other cortical areas. Plateau potentials, periods of depolarisation with action potential firing outlasting the stimuli that induced them, have been suggested to help maintain working memory and to contribute to executive functions and consciousness. We therefore investigated plateau potentials and their mechanisms in PFC layer 2/3 pyramidal neurons. Using whole-cell somatic recordings from L2/3PCs in rat PFC brain slices, we found that the metabotropic cholinergic agonist muscarine reliably induced long-lasting plateau potentials with spiking following a train of evoked action potentials. Similar plateaus were induced by a metabotropic glutamate receptor (mGluR) agonist. Pharmacological tests suggested that these plateaus were dependent on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and required the presence of external calcium (Ca2+) and internal Ca2+ stores, but not voltage-gated Ca2+ channels. Using local Ca2+ applications, we found that the responsible Ca2+ influx is most likely distributed on the somatic and/or basal dendritic compartments rather than on the (distal) apical dendrite. We used knife cuts to disconnect apical dendrites, sometimes less than 50 {micro}m from the soma, and found that the plateaus did not depend on the distal apical dendrite, since truncated cells generated plateaus with as many spikes as control cells. These results indicate that layer 2/3PCs can generate plateau potentials with sustained spiking independently of distal apical dendrites.

neuroscience↗

bioRxiv2022

The activity of deep cortical layers characterizes thecomplexity of brain responses during wakefulnessfollowing electrical stimulation

It has been suggested that the complexity of the brain is closely related to its state of consciousness. The perturbational complexity index (PCI) has been used in humans and rodents to distinguish conscious from unconscious states based on the global cortical responses (recorded by electroencephalography; EEG) to local cortical stimulation (CS). However, it has been unclear how different cortical layers respond to CS and contribute to the resulting intra- and inter-areal cortical communication and PCI. A detailed investigation of these local dynamics is needed to understand the basis for PCI. We hypothesized that the complexity level of global cortical responses (PCI) corresponds to variations in layer-specific activity and connectivity patterns. We investigated global cortical dynamics and layer specific activity in mice, combining cortical electrical stimulation, global EEG, and local multi-electrode, laminar recordings from layers 1-6 in somatosensory cortex, during wakefulness and general anesthesia (sevoflurane). We found that transition from wake to sevoflurane anesthesia correlated with a drop in global and local PCI values (complexity). This was accompanied by a local decrease in neural firing rate, spike-field coherence, and long-range functional connectivity specific to deep layers (L5, L6). Our results suggest that deep cortical layers are mechanistically important for changes in PCI, and thereby for variations in the states of consciousness. HighlightsO_LIAnesthesia caused a reduction in the perturbational complexity index (PCIST) at both global (inter-areal) and local (intra-areal, across layers) cortical scales. C_LIO_LIDeep cortical layers (L6 and L5), exhibited strong connectivity with remote cortical areas during wakefulness but not during anesthesia. C_LIO_LILayer 6 showed the strongest modulation of spike firing and spike field coherence compared to more superficial layers during wakefulness. C_LI

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bioRxiv2021

Does the posteromedial cortex play a primary role for the capacity for consciousness in rats?

It remains unclear how specific cortical regions contribute to the brains overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brains overall capacity for consciousness. We recorded electroencephalographic (EEG) responses to cortical electrical stimulation in 6 rats, and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power (HF/LF) from spontaneous EEG activity at each electrode. We repeated these measurements during wakefulness, and under the influence of ketamine anaesthesia at two doses: the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly down with deeper anaesthesia. The high-dose effect was selectively associated with reduced HF/LF ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia, was associated with similar spectral changes in frontal, but not posterior cortical regions. These findings seem to support the claim that the posteromedial cortex may play a primary role for the capacity for consciousness. Such region-specific associations between cortical activation and the overall capacity for consciousness must be accounted for by theories of consciousness.

neuroscience↗

bioRxiv2020

General anaesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats

The capacity of the human brain to sustain complex dynamics consistently drops when consciousness fades. Several recent studies in humans found a remarkable reduction of the complexity of cortical responses to local stimulation during dreamless sleep, general anaesthesia, and coma. So far, this perturbational complexity has never been estimated in non-human animals in vivo. Here, we quantify the complexity of electroencephalographic responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anaesthesia. We confirm the changes previously observed in humans: from highly complex evoked activity during wakefulness, to simpler responses, suppression of high frequencies, and reduced phase-locking with propofol and sevoflurane. We then deepen our mechanistic understanding by analyzing functional connectivity, and by showing how these parameters dissociate with ketamine, and depend on intensity and site of stimulation. This approach opens the way for further direct investigations of the mechanisms underlying brain complexity and consciousness.

neuroscience↗

bioRxiv2019

Measures of states of consciousness during attentional and cognitive load

BackgroundDeveloping and testing methods for reliably assessing states of consciousness in humans is important for both basic research and clinical purposes. Several potential measures, partly grounded in theoretical developments, have been proposed, and some of them seem to reliably distinguish between conscious and unconscious brain states. However, the degrees to which these measures may also be affected by changes in brain activity or conditions that can occur within conscious brain states have rarely been tested. In this study we test whether several of these measures are modulated by attentional load and related use of cognitive resources.\n\nMethodsWe recorded EEG from 12 participants while they passively received three types of stimuli: (1) transcranial magnetic stimulation (TMS) pulses (for measuring perturbational complexity), (2) auditory stimuli (for detection of auditory pattern deviants), or (3) audible clicks from a clock (spontaneous EEG, for measures of signal diversity and functional connectivity). We investigated whether the measures significantly differed between the passive condition and a attentional and cognitively demanding working memory task.\n\nResultsOur results showed that in the attention-based auditory P3b ERP measure (global auditory pattern deviant) was significantly affected by increased attentional and cognitive load, while the various measures based on spontaneous and perturbed EEG were not affected.\n\nConclusionMeasures of conscious state based on complexity, diversity, and effective connectivity, are not affected by attentional and cognitive load, suggesting that these measures can be used to test both for the presence and absence of consciousness.

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bioRxiv2019

Increased signal diversity/complexity of spontaneous EEG in humans given sub-anaesthetic doses of ketamine

ObjectiveHow and to what extent electrical brain activity is affected in pharmacologically altered states of consciousness, where it is mainly the phenomenological content rather than the level of consciousness that is altered, is not well understood. An example is the moderately psychedelic state caused by low doses of ketamine. Therefore, we investigated whether and how measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective assessments of consciousness.\n\nMethodsHigh-density electroencephalography (EEG, 62 channels) was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and after administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from the global EEG responses to local TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE).\n\nResultsAlthough no significant difference was found in the index of TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all the three measures of spontaneous EEG signal diversity showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity also correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine doses.\n\nConclusionThe results suggest that PCI and spontaneous signal diversity may be complementary and potentially measure different aspects of consciousness. Thus, our results seem compatible with PCI being indicative of the brains ability to sustain consciousness, as indicated by previous research, while it is possible that spontaneous EEG signal diversity may be indicative of the complexity of conscious content. The observed sensitivity of the latter measures to visual input seems to support such an interpretation. Thus, sub-anaesthetic ketamine may increase the complexity of both the conscious content (experience) and the brain activity underlying it, while the level, degree, or general capacity of consciousness remains largely unaffected.

neuroscience↗