Willful Modulation Of Brain Activity Research Articles

Mapping preserved real-world cognition in severely brain-injured patients.

Decoding the contents of consciousness from brain activity is one of most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command. Recent work has used a different approach, where the similarity of any given patient's brain activity to that of healthy controls during naturalistic paradigms can help detect high-level cognition and consciousness. This approach is easy to administer, brief, and does not require compliance with arbitrary task instructions. Therefore, it is suited to probing consciousness and revealing residual cognition in highly impaired comatose patients, thus helping to improve diagnosis and prognostication for this vulnerable patient group.

Isolation Syndrome after Cardiac Arrest and Therapeutic Hypothermia

Here, we present the first description of an isolation syndrome in a patient who suffered prolonged cardiac arrest and underwent a standard therapeutic hypothermia protocol. Two years after the arrest, the patient demonstrated no motor responses to commands, communication capabilities, or visual tracking at the bedside. However, resting neuronal metabolism and electrical activity across the entire anterior forebrain was found to be normal despite severe structural injuries to primary motor, parietal, and occipital cortices. In addition, using quantitative electroencephalography, the patient showed evidence for willful modulation of brain activity in response to auditory commands revealing covert conscious awareness. A possible explanation for this striking dissociation in this patient is that altered neuronal recovery patterns following therapeutic hypothermia may lead to a disproportionate preservation of anterior forebrain cortico-thalamic circuits even in the setting of severe hypoxic injury to other brain areas. Compared to recent reports of other severely brain-injured subjects with such dissociation of clinically observable (overt) and covert behaviors, we propose that this case represents a potentially generalizable mechanism producing an isolation syndrome of blindness, motor paralysis, and retained cognition as a sequela of cardiac arrest and therapeutic hypothermia. Our findings further support that highly-preserved anterior cortico-thalamic integrity is associated with the presence of conscious awareness independent from the degree of injury to other brain areas.

Detecting and interpreting conscious experiences in behaviorally non-responsive patients

Decoding the contents of consciousness from brain activity is one of the most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. The lack of consistent behavioral responsivity engenders unique challenges to decoding any conscious experiences these patients may have solely based on their brain activity. For this reason, paradigms that have been successful in healthy individuals cannot serve to interpret conscious mental states in this patient group. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command, in order to decode the presence of willful brain-based responses in this patient group. In recent work, we have used naturalistic paradigms, such as watching a movie or listening to an audio-story, to demonstrate that a common neural code supports conscious experiences in different individuals. Moreover, we have demonstrated that this code can be used to interpret the conscious experiences of a patient who had remained non-responsive for several years. This approach is easy to administer, brief, and does not require compliance with task instructions. Rather, it engages attention naturally through meaningful stimuli that are similar to the real-world sensory information in a patient's environment. Therefore, it may be particularly suited to probing consciousness and revealing residual brain function in highly impaired, acute, patients in a comatose state, thus helping to improve diagnostication and prognostication for this vulnerable patient group from the critical early stages of severe brain-injury.

Implementing novel imaging methods for improved diagnosis of disorder of consciousness patients

The clinical evaluation of consciousness in disorder of consciousness (DOC) patients based on their exhibited behavior is difficult and remains erroneous in many cases. Recent studies demonstrated different levels of stimulus processing as well as evidence of some level of awareness in sub-groups of these patients. The aim of the current study was to examine the plausibility and challenges of implementing a clinical service for evaluation of consciousness level in DOC patients.Eleven Patients (ages 11–67) diagnosed as being in vegetative or minimal conscious states were included. Functional MRI evaluations included auditory, language, voice familiarity, imagery, and visual tests.In 9 patients auditory-related activation was found, however only in 5 of the subjects was differential activation found for language. Six patients exhibited differential response to their own name. In three patients a response to visual stimuli was identified. In one patient the auditory and linguistic systems were clearly activated in a hierarchical pattern, and moreover willful modulation of brain activity was identified in the imagery test.We discuss the importance of using a wide battery of tests, the difference between our clinical cohort and previous publications, as well as the challenges of clinically implementing this method. Translating novel imaging methods into the clinical evaluation of DOC patients is essential for better diagnosis and may encourage treatment development.

Increasing Awareness in Unawareness

Our understanding of the pathophysiology of chronic disorders of consciousness continues to be illuminated by creative functional neuroimaging studies, yet the diagnosis and classification of these disorders remain based on clinical examination findings.1Naci andOwen2 supplement thegrowingevidence that functionalmagnetic resonance imaging (fMRI) can uncover cognitive functioning that cannot be elicited by neurological examination. They show that selective auditory attention and the capacity to follow commands and communicate canbedetected ina fewpatients in aminimally conscious state (MCS) or a vegetative state (VS) who are otherwise utterly unresponsive. Their convincingdata raise themore general question that I consider here of how these findings impact the nosology and diagnostic criteria of chronic disorders of consciousness. In their classic text The Diagnosis of Stupor and Coma3 in 1966, Plum and Posner explained that consciousness can be assessed in its 2 clinical dimensions: wakefulness and awareness. Healthy people have both and comatose patients have neither. They also defined locked-in syndrome (LIS) as a state of profound paralysis (de-efferentation) with intact cognition that may be mistaken for unconsciousness by an unwary examiner who is misled by the patient’s markedlydiminishedvoluntarymotor repertoire. In 1972, Jennett and Plum4 defined the persistent VS (PVS) as the ironic and tragic dissociation of the 2 components of consciousness: wakefulness remained preserved despite abolished awareness. In 1994, theMulti-Society Task Force on PVS provided clinical criteria for PVS that have been accepted for the past 2 decades,which at aminimumrequire the complete absence of any evidence of awareness of self or environment by a careful neurological examination.5,6 The task force offered the caveats that any determination of the quality of a person’s awareness was entirely inferential based on a reasoned interpretationof theperson’s responses to stimuli and that the absence of clinical evidence of awareness did not necessarily constitute proof of unawareness, a point made more forcefully by critics.7 The task force’s clinical criteria for the VS were delineated almost entirely as negatives—stipulating what behaviors patients inVS lacked the capacity todo—all ofwhichmust be absent.5,6 The task force’s choice of negative criteria for the syndromewas accurate clinically but invited false-positivediagnosticerrorsbecause the fact thataparticularbehaviorcould notbeobservedoreliciteddidnotnecessarilyprove that itwas fully absent. The failure to elicit a behavior could result from factors other than the direct effects of the primary brain injury, such as from inadequacies of the neurological examination, samplingerror, the failureof thepatient to respond to the voice of a physician to the same extent as to a beloved family member, concomitantmetabolic or toxic encephalopathies, or adverse effects of medication. The situation became better defined in 2002 when a new diagnostic entity, the MCS, was delineated to classify profoundly unresponsive patients who demonstrated behaviors that requiredat leastperiodicor fragmentaryawareness.8 Like theVS, theMCS is a heterogeneous clinical syndromeencompassing diverse pathologies but sharing certain clinical findings. When the diagnostic criteria were scrupulously followed, it became clear thatmanypatients initially believed to be inVSwereactually inMCS,which is farmorecommon.1Naci and Owen cited studies showing that false-positive diagnostic error for VS remains disturbingly high. It also seems likely that the task force’s high estimate of VS prevalence resulted frommisclassification of some patients inMCS as being in VS because MCS was not a recognized diagnosis in the brain injury databases studied by the task force. In2006, theassumptionthatVScanbediagnosedwithperfect accuracybyaneurological examinationwas shakenby the brief reportofOwenetal9of ayoungwoman inVS for 5months following a traumatic brain injury whose fMRI measurements duringmental imagery tasks shewas asked to perform disclosedthatshewasaware.Theneurologyandcognitiveneuroscience communities initially were skeptical and questioned whether the elicited findings were artifact or, if they were valid, what quality of conscious cognitive life they indicated. Since then, Owen et al and other investigators have reported similar findings of “willful modulation of brain activity”10measured in fMRIparadigms in a fewpatients inVS and MCS who were clinically unresponsive, as in their current report. Notably, the number of these cases remains small andmost patients had traumatic brain injury, particularly diffuse axonal injury, and not hypoxic-ischemic neuronal injury. Many of the patients in VS showing this capacity subsequently improved to clinically demonstrable awareness, suggesting that the finding of willful modulation of brain activity also may be a predictive marker for clinical improvement in those patients for whom VS or severe MCS represented a transient state of unresponsiveness on a path to spontaneous improvement after traumatic brain injury. The findingof fMRIevidenceofawarenessdespitenoclinical evidence of awareness suggests that, at times, even anoptimal neurological examinationmay not be sensitive enough todetect awareness.Most studies haveused theComaRecovery Scale–Revisedor a similar specializedneurological examiEditorial page 1229

“Complete Motor Locked-In” and Consequences for the Concept of Minimally Conscious State

The demonstration by Monti et al. (2010) of willful modulation of brain activity in persistent vegetative state implies the exceptional condition of a "complete motor locked-in syndrome." As a consequence, the contradictory character of the diagnosis minimally conscious state should be recognized because behaviorally observed minimal cognitive responsiveness does not exclude a higher level of well-differentiated self-consciousness. Introduction of the descriptive entities "complete motor locked-in syndrome" and "minimal cognitive responsiveness" is therefore advocated in the service of diagnostic precision.

Willful Modulation of Brain Activity in Disorders of Consciousness

Willful Modulation of Brain Activity in Disorders of Consciousness

Willful Modulation of Brain Activity in Disorders of Consciousness

Willful Modulation of Brain Activity in Disorders of Consciousness

Willful Modulation of Brain Activity in Disorders of Consciousness

The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient's capacity to show behavioral signs of awareness is diminished. At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient's ability to generate willful, neuroanatomically specific, blood-oxygenation-level-dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions. Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside. These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive.