Behavioural improvements with thalamic stimulation after severe traumatic brain injury

Schiff, Nicholas D.; Giacino, Joseph T.; Kalmar, Kathleen; Victor, Jonathan D.; Baker, Kenneth B.; Gerber, M.; Fritz, Brandon M.; Eisenberg, Bob; O'Connor, Jane M.; Kobylarz, Erik; Farris, Sierra; Machado, André G.; McCagg, C.; Plum, Fred; Fins, Joseph J.; Rezai, Ali R.

doi:10.1038/nature06041

Cited by 887 publications

(714 citation statements)

References 20 publications

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“…In this process, longitudinal TMS/EEG measurements also offer the fundamental readout to direct and titrate intervention toward the desired endpoint of PCI max > PCI*. Finally, unresponsive patients in whom TMS/EEG already documents a core of high complexity should be selected for intensive interventions aimed at restoring responsiveness to the external environment, such as by increasing behavioral output through thalamic stimulation50 or by establishing communication through active paradigms or brain–machine interface 51, 52…”

Section: Discussionmentioning

confidence: 99%

Stratification of unresponsive patients by an independently validated index of brain complexity

Casarotto

Comanducci

Rosanova

et al. 2016

Annals of Neurology

342

430

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ObjectiveValidating objective, brain‐based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness—the Perturbational Complexity Index (PCI)—in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs).MethodsThe benchmark population encompassed 150 healthy controls and communicative brain‐injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]).ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition.InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high‐PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718–729

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Section: Discussionmentioning

confidence: 99%

Stratification of unresponsive patients by an independently validated index of brain complexity

Casarotto

Comanducci

Rosanova

et al. 2016

Annals of Neurology

342

430

View full text Add to dashboard Cite

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“…Indeed, these areas are the most metabolically active cortical regions in normal conscious waking, are mostly impaired in patients in coma or VS/UWS whereas they are minimally active in MCS patients. Its critical role in consciousness was confirmed by a much mediatized case of 'miracle recovery from coma' named Terry Wallis [30]. Nineteen years after his traumatic brain injury this patient was still considered 'vegetative' and started to speak.…”

Section: Tracking the Recovery Of Consciousness Networkmentioning

confidence: 98%

“…These early functional connectivity studies highlight the importance of connectivity measurements in the emergence of human conscious awareness. In particular, global yet specific cerebral functional identification of thalamo-cortical connectivity has lead to the development of thalamic deep brain stimulation paradigms for the treatment of post-traumatic MCS patients [30]. …”

mentioning

confidence: 99%

Consciousness supporting networks

Demertzi¹,

Soddu²,

Laureys³

2013

Current Opinion in Neurobiology

161

106

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Author's personal copy In most cases authors Consciousness supporting networksAthena Demertzi, Andrea Soddu and Steven LaureysFunctional neuroimaging shows that patients with disorders of consciousness exhibit disrupted system-level functional connectivity. Unresponsive/''vegetative state'' patients preserve wakefulness networks of brainstem and basal forebrain but the cerebral networks accounting for external perceptual awareness and internal self-related mentation are disrupted. Specifically, the 'external awareness' network encompassing lateral fronto-temporo-parietal cortices bilaterally, and the 'internal awareness' network including midline anterior cingulate/mesiofrontal and posterior cingulate/ precuneal cortices, are functionally disconnected. By contrast, patients in minimally conscious state 'minus', who show nonreflex behaviors, are characterized by right-lateralized recovery of the external awareness network. Similarly, patients who evolve to minimally conscious state 'plus' and respond to commands recover the dominant left-lateralized language network. Now, the use of active experimental paradigms targeting at detecting motor-independent signs of awareness or even establishing communication with these patients, challenge these two clinical boundaries. Such advances are naturally accompanied by legitimate neuroscientific and ethical queries demanding our attention on the medical implementations of this new knowledge. What is 'minimally conscious'?At present there is no generally accepted definition of consciousness [1]. As clinicians, we will reduce the complexity of this term and define consciousness operationally, separating two main components: wakefulness and awareness [2]. Wakefulness has been shown to critically depend upon the functional integrity of subcortical arousal systems over 50 years ago [(e.g., see 3)]. The level of wakefulness can be estimated by simple behavioral criteria based on eye opening ranging from absent, over stimulus-induced to spontaneous sustained eye opening.For instance, every night when falling asleep, we experience a decrease of the level of wakefulness up to the point we lose awareness of our environment. Awareness is more difficult to define and more challenging to assess behaviorally [4]. We have recently proposed to reduce the phenomenological complexity of awareness into two further components: external awareness, namely everything we perceive through our senses (what we see, hear, feel, smell and taste), and internal awareness or stimulusindependent thoughts. Interestingly, the switch between the external and internal milieu was found not only to characterize overt...

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“…An interesting field of experimental clinical research relates to targeting a frontocortical-striatopallidal-thalamocortical mesocircuit that activates the frontal cortex, with the aim of improving consciousness, awareness or cognitive skills. HFS of the central thalamus [135] or LFS (activation) of the brainstem reticular formation in the pedunculopontine area [66] or the nucleus basalis Meynert [67] improved alertness and higher cognitive functions in single patients in blinded conditions. Aggressive behaviour related to schizophrenia or to mental retardation has been a classical indication for psychosurgery.…”

Section: Reviewmentioning

confidence: 99%