Meccanismi neurofisiologici dei disturbi Meccanismi neurofisiologici dei disturbi degli stati di coscienzadegli stati di coscienza

Paolo M. RossiniPaolo M. Rossini

Clinica Neurologica, Università Cattolica, Policlinico . Gemelli, Roma

• Neural correlates of consciousness can be separated into – structure necessary for control of the quantitative (level) features of conscious state;– structure involved in generating the qualitative (content) features of conscious experiences.

• The transition between different levels of consciousness can be modulated pharmacologically as in drug-induced anesthesia.

• The content of subjective experience constitutes the sensations, emotions, memories, intentions and feelings that are familiar to us and that color our inner world.

Consciousness: a simplified neurological vision

The level of consciusness is the degree of wafefulness or arousal, wich ranges from alertness through drowsiness to coma. It depends on the integrity of ascending ponto-mesodiencephalic reticular pathways and widespread thalamocortical projections and can be quantified through assessment of an individual’s motor and verbal responses to external stimuli (GCS).

- Bjorn Ibsen in the 1950s in Copenhagen invention of the positive pressure mechanical ventilator

- Fred Plum and Jerome Posner 1960s ‘locked-in syndrome’: comatose patients recovering consciousness but remaining unable to move or speak, classically communicating only via eye movements

- Bryan Jennett from Glasgow and Fred Plum in 1972 vegetative state: patients awaken from their coma (i.e. they open their eyes) but remain unaware (i.e. they exhibit solely reflex behaviour)

- The Aspen Neurobehavioral Conference Workgroup in 2002 some patients showed signs of voluntary behaviour (and hence could not be considered vegetative) but remained unable to communicate functionally. The minimally conscious state (MCS) diagnostic criteria were reported

Consciousness: some breakpoints

Coherence analysis of the EEG-MEG signals have been used to estimate the degree of functional connectivity among cortical areas. It represents the covariance of the EEG spectral activity at two recording sites and can be considered as a measure of temporal synchronization of signals recorded at pairs of sites. Ideally, coherence estimates temporal synchronization or functional coupling of the two cortical populations generating signals collected at the two scalp sites. Decreased coherence reflects reduced functional connection. This analysis only measure the linear component of the functional coupling of the brain oscillations when compared to modern nonlinear approaches.

Cortico-cortical connectivity Cortico-cortical connectivity

- STRUCTURALSTRUCTURAL

- FUNCTIONALFUNCTIONAL

- EFFECTIVE (& dynamic !)- EFFECTIVE (& dynamic !)

Disorders of consciousness

The assessment of persons with disorders of consciousness is fraught with difficulties and challenges.

Disorders of consciousness are not distinguished by a particular pathology or quantifiable marker. Instead, the diagnostic decision-making process is informed by the clinical team’s interpretation of the behaviours exhibited by a patient over a period of observation.

The interpretation of exhibited behaviours is complicated by the fact that we currently have an incomplete knowledge of consciousness and there remains debate as to whether behaviours should be classified as conscious.

In a review of 40 patients referred to a specialist rehabilitation unit, Andrews and colleagues considered 17 (43%) of the patients as having been misdiagnosed.

Is neurophysiology able to evaluate perception and consciousness? Some recent examples…

Volume 8, Number 10, October 2005

Electroencephalography and Clinical NeurophysiologyVolume 1, Issues 1-4, 1949, Pages 455-473

Neurophysiology and consciousness: not only diagnosis Therapeutic aspects: from 1949…cat’s brain…

John Hughlings Jackson’s “Highest Centers”:

he proposed that consciousness was impaired when higher cortical function became disorganized and lacked integrative ability

Consciousness: what can we learn from neurophysiology and epilepsy

Penfield and Jasper’s Centrencephalic Theory:

From the 1930s to the 1950 they posited that a system existed within the brain that could be responsible for integrating the actions of the two hemispheres of the brain.

They saw that epileptic patients who had had large portions of cerebral cortex or corpus callosum removed suffered little to no impairment of consciousness, while pressure applied to the brainstem resulted in immediate and reversible loss of consciousness

Penfield

Jasper

• Epilepsy can lead to transient impairment of consciousness, providing a window into the mechanisms necessary for normal consciousness

• Complete loss of consciousness occurs when epileptic activity involves both cortical and subcortical structures, as in tonic-clonic seizures and absence seizures.

• Electrical stimulation of temporal lobe structures has been shown to evoke similar subjective experiences

Neurophysiology and consciousness: epilepsy contribution

Englot et al.

Complex partial seizure

Simple partial seizure

(Impaired consciousness)

(Unimpaired consciousness)

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Profound alteration of consciousness

Preserved consciousness

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The Network Inhibition Hypothesis

Following Moruzzi & Magoun 1949

Laureys et al.

SEPs- median nerve stimulation

PSV patient with preserved peripheral and primary cortical responses

ERPPrimary cortical components N1–P2—however, without any differentiation between frequent and rare stimuli, in a male patient, 51, anoxic brain injury

Apart of the primary complex, a delayed P3 to rarestimuli in a female, 29, subarachnoidal hemorrhage

A long-latency, significant positive deflection (‘P600’) to the counted word category (animals) in the semantic oddball, a female, 19, PVS after a postoperative intraventricular hemorrhage.

An N400 in the Word pair experiment to semantically unrelated words, in contrast to a positivity to related words, in a male, 42, head injury.

An N400 to incongruent end words in the Sentence experiment, in a male, 61, MCS following bilateralinfarcts in basal ganglia. Only one lead (Cz) is presented

Luauté et al.,

Wijnen et al.

A woman, unconscious for 20 years, spontaneously produces infrequent, isolated words unrelated to any environmental context

T1 horizontal MRI image FDG-PET

isolated regions in the left hemisphere expressing

higher levels of metabolism

T1 MRI image of sagittal sections through the brainstem from right

hemisphere revealing total destruction of the

thalamus

fMRI…and EEG??

50 PSV patients and 30 cognitively normal subjects

Eye closed EEG- LORETA analysis;

Rec group: recovery group (3 months); Non Rec: non recovery group (3 months)

Prognosis in patients in a persistent vegetative state (VS) consciousness may be regarded as complex systems whose outputs show a degree of unpredictability experimentallyquantifiable by means of nonlinear parameters such as approximate entropy (ApEn).

- 38 Vegetative patients and 40 controls

- Nonlinear dynamics applied to EEG

DYNAMIC CORRELATES OF NEURAL REDISUAL COMPLEXITY MIGHT HELP IN PREDICTING OUTCOMES IN VS

Controls

VS

To 2007…human brain…

…or lost in connection?GRAZIE PER L’ATTENZIONE