Biology subjects

Casali, A. G.

Publications and source records attributed to Casali, A. G..

3 recordsLinked to original sources

bioRxiv2018

A fast and general method to empirically estimate the complexity of distributed causal interactions in the brain

BackgroundThe Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain injured patients, PCI depends on elaborate experimental setups and offline processing and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings. ObjectiveWe aim to address these limitations by introducing PCIST, a fast method for estimating perturbational complexity of any given brain response signal. MethodsPCIST is based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intra-cerebral single-pulse electrical stimulation (SPES). ResultsWhen calculated on TMS/hd-EEG potentials, PCIST performed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracerebral complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG. ConclusionsPCIST represents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.

neuroscience↗

bioRxiv2018

TMS orientation and pulse waveform manipulation activates different neural populations: direct evidence from TMS-EEG

Monophasic and biphasic TMS pulses and coil orientations produce different responses in terms of motor output and sensory perception. Those differences have been attributed to the activation of specific neural populations. However, up to date, direct evidence supporting this hypothesis is still missing since studies were mostly based on indirect measures of cortical activation, i.e., motor evoked potentials or phosphenes. Here, we investigated for the first time the impact of different coil orientations and waveforms on a non-primary cortical area, namely the premotor cortex, by measuring TMS evoked EEG potentials (TEPs). We aimed at determining whether TEPs produced by differently oriented biphasic and monophasic TMS pulses diverge and whether these differences are underpinned by the activation of specific neural populations. To do so, we applied TMS over the right premotor cortex with monophasic or biphasic waveforms oriented perpendicularly (in the anterior-posterior direction and vice-versa) or parallel (latero-medial or medio-laterally) to the target gyrus. EEG was concurrently recorded from 60 electrodes. We analyzed TEPs at the level of EEG sensors and cortical sources both in time and time-frequency domain. Biphasic pulses evoked larger early TEP components, which reflect cortical excitability properties of the underlying cortex, in both parallel directions when compared to the perpendicular conditions. Conversely, monophasic pulses, when oriented perpendicularly to the stimulated gyrus, elicited a greater N100, which is a reliable TEP component linked to GABAb-mediated inhibitory processes, than when parallel to the gyrus. Our results provide direct evidence supporting the hypothesis that TMS pulse waveform and TMS coil orientations affect which neural population is engaged.

neuroscience↗

bioRxiv2018

Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI). Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input. Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the build-up of global complexity (as measured by PCI) in the brain of UWS patients. Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.

neuroscience↗