A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations

Abstract

Background:The 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. Objective:We aim to address these limitations by introducing PCI ST , a fast method for estimating perturbational complexity of any given brain response signal.Methods: PCI ST 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). Results:When calculated on TMS/hd-EEG potentials, PCI ST 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.Conclusions: PCI ST 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.

Local sleep-like cortical reactivity in the awake brain after focal injury

“…Thus, for each patient we estimated the maximum PCI st calculated on all the sixty channels following the stimulation of the contralesional site. Results at the group level were in line with previous observation (30) in conscious brain-injured individuals and showed that, for all three groups, average maximum PCI st values (mean ± SE: 41.1 ± 2.4, 28.5 ± 3.1 and 42.5 ± 2, for the MCA ischemia, the severe multifocal and the subcortical lesion groups, respectively; Table S2) were above the empirical threshold (PCI st threshold value: 23.02; (27)) for consciousness obtained from a benchmark population (382 TMS/hd-EEG sessions performed on 108 healthy subjects). However, a ONE-way ANOVA (GROUP effect F(2, 27)=9.3, p=0.00082) showed a significantly lower maximum PCI st value for the severe multifocal lesions group compared to the other two groups (all p-values <0.004, Bonferroni corrected), confirming the role of multifocal brain lesions in partially affecting overall signal complexity (PCI st was found lower than the benchmark empirical threshold in patients n.17 and 18, gray text in Table S2).…”

“…a significant suppression of high frequency (>20 Hz) EEG power compared to baseline (19,20,26) confined to the perilesional stimulated site ( Figure 1B,C and D). Furthermore, we aimed at assessing the effects of local cortical OFF-periods on local signal complexity as measured by the adaptation of a recently proposed index of perturbational complexity (PCI st ; (27)) TMS reveals local, sleep-like cortical OFF-periods over the affected hemisphere only in patients with corticosubcortical lesions irrespective of the etiology In the MCA ischemia group, TMS-evoked EEG potentials (TEPs) obtained from the stimulation of the contralesional site were low-amplitude, fast-frequency recurrent scalp waves similar to those previously observed in healthy awake individuals (Figure1B and Figure 2A, red trace; (25,28)). When TMS was applied using the same stimulation parameters over the perilesional site, TEPs were characterized by a local slow EEG potential ( Figure 1B, C and 2A, blue traces) associated with an initial broad-band activation followed by a significant suppression of high frequency EEG power starting roughly at 150 ms after TMS (mean±SEM: 167±14 ms) over the four channels closest to the stimulation site ( Figure 1B and C).…”

“…Further we assessed the impact of focal brain injuries on the global spatiotemporal dynamics of TEPs, which reflect the overall capacity of thalamocortical circuits to engage in complex patterns of causal interactions, typically present in conscious awake individuals (27,29). Thus, for each patient we estimated the maximum PCI st calculated on all the sixty channels following the stimulation of the contralesional site.…”

“…For each EEG derivation, power spectral density (PSD) estimates were computed using the Welch's method with 2-s Hanning windows and 50% overlap (applying the pwelch function in the MATLAB signal processing toolbox). For each patient, average PSD was calculated over the same four channels used for TMS/EEG analysis (contralesional, perilesional): average PSD across segments was computed for each frequency bin and then further averaged across bins pertaining to the classical frequency ranges: delta (0.5-4.5Hz), theta (4.5-8 Hz), alpha (8)(9)(10)(11)(12), beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and gamma (30-40 Hz) ( Figure S1A). In parallel to the PSD analysis, filtered continuous EEG data were re-referenced according to a longitudinal bipolar montage based on the 10-20 system (78) including the following EEG derivations: 'Fp1_F5', 'F7_T3', 'T3_T5', 'T5_O1' 'Fp1_F3', 'F3_C3', 'C3_P3', 'P3_O1', 'Fz_Cz', 'Cz_Pz' ,'Fp2_F6', 'F6_T4', 'T4_T6', 'T6_O2', 'Fp2_F4', 'F4_C4', 'C4_P4', and 'P4_O2'.…”

Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome

“…The association between neural chanting and loss of consciousness is consistent with the integrated information theory of consciousness (IIT) 26,27 , which asserts that spatially extended, low-frequency (i.e., delta) rhythms lead to a loss of information differentiation 28 and a breakdown of effective connectivity within the thalamocortical system 29 , as neural signaling pauses diffusely at the troughs of delta oscillations 30,31 and loss of consciousness results. In translational work, consciousness is also linked to neural complexity by the perturbational complexity index, a successful method of inferring consciousness based on the brain's electrophysiological "echo" following a magnetic pulse 9,32 .…”