Injury patterns associated with cognitive motor dissociation.

In unconscious appearing patients with acute brain injury, wilful brain activation to motor commands without behavioural signs of command following, known as cognitive motor dissociation (CMD), is associated with functional recovery. CMD can be detected by applying machine learning to EEG recorded during motor command presentation in behaviourally unresponsive patients. Identifying patients with CMD carries clinical implications for patient interactions, communication with families, and guidance of therapeutic decisions but underlying mechanisms of CMD remain unknown. By analysing structural lesion patterns and network level dysfunction we tested the hypothesis that, in cases with preserved arousal and command comprehension, a failure to integrate comprehended motor commands with motor outputs underlies CMD. Manual segmentation of T2-fluid attenuated inversion recovery and diffusion weighted imaging sequences quantifying structural injury was performed in consecutive unresponsive patients with acute brain injury (n = 107) who underwent EEG-based CMD assessments and MRI. Lesion pattern analysis was applied to identify lesion patterns common among patients with (n = 21) and without CMD (n = 86). Thalamocortical and cortico-cortical network connectivity were assessed applying ABCD classification of power spectral density plots and weighted pairwise phase consistency (WPPC) to resting EEG, respectively. Two distinct structural lesion patterns were identified on MRI for CMD and three for non-CMD patients. In non-CMD patients, injury to brainstem arousal pathways including the midbrain were seen, while no CMD patients had midbrain lesions. A group of non-CMD patients was identified with injury to the left thalamus, implicating possible language comprehension difficulties. Shared lesion patterns of globus pallidus and putamen were seen for a group of CMD patients, which have been implicated as part of the anterior forebrain mesocircuit in patients with reversible disorders of consciousness. Thalamocortical network dysfunction was less common in CMD patients [ABCD-index 2.3 (interquartile range, IQR 2.1-3.0) versus 1.4 (IQR 1.0-2.0), P < 0.0001; presence of D 36% versus 3%, P = 0.0006], but WPPC was not different. Bilateral cortical lesions were seen in patients with and without CMD. Thalamocortical disruption did not differ for those with CMD, but long-range WPPC was decreased in 1-4 Hz [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.7-0.9] and increased in 14-30 Hz frequency ranges (OR 1.2; 95% CI 1.0-1.5). These structural and functional data implicate a failure of motor command integration at the anterior forebrain mesocircuit level with preserved thalamocortical network function for CMD patients with subcortical lesions. Amongst patients with bilateral cortical lesions preserved cortico-cortical network function is associated with CMD detection. These data may allow screening for CMD based on widely available structural MRI and resting EEG.

Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.

BACKGROUND: Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing. METHODS: We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4). RESULTS: Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01). CONCLUSIONS: Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.

Stable, chronic in-vivo recordings from a fully wireless subdural-contained 65,536-electrode brain-computer interface device.

Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-µm-thick, mechanically flexible micro-electrocorticography (µECoG) BCI, integrating 256×256 electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording and 16,384 stimulation channels, from which we can simultaneously record up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.

Measuring the Burden of Infodemics: Summary of the Methods and Results of the Fifth WHO Infodemic Management Conference.

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

Cognitive-motor dissociation and time to functional recovery in patients with acute brain injury in the USA: a prospective observational cohort study.

BACKGROUND: Recovery trajectories of clinically unresponsive patients with acute brain injury are largely uncertain. Brain activation in the absence of a behavioural response to spoken motor commands can be detected by EEG, also known as cognitive-motor dissociation. We aimed to explore the role of cognitive-motor dissociation in predicting time to recovery in patients with acute brain injury. METHODS: In this observational cohort study, we prospectively studied two independent cohorts of clinically unresponsive patients (aged ≥18 years) with acute brain injury. Machine learning was applied to EEG recordings to diagnose cognitive-motor dissociation by detecting brain activation in response to verbal commands. Survival statistics and shift analyses were applied to the data to identify an association between cognitive-motor dissociation and time to and magnitude of recovery. The prediction accuracy of the model that was built using the derivation cohort was assessed using the validation cohort. Functional outcomes of all patients were assessed with the Glasgow Outcome Scale-Extended (GOS-E) at hospital discharge and at 3, 6, and 12 months after injury. Patients who underwent withdrawal of life-sustaining therapies were censored, and death was treated as a competing risk. FINDINGS: Between July 1, 2014, and Sept 30, 2021, we screened 598 patients with acute brain injury and included 193 (32%) patients, of whom 100 were in the derivation cohort and 93 were in the validation cohort. At 12 months, 28 (15%) of 193 unresponsive patients had a GOS-E score of 4 or above. Cognitive-motor dissociation was seen in 27 (14%) patients and was an independent predictor of shorter time to good recovery (hazard ratio 5·6 [95% CI 2·5-12·5]), as was underlying traumatic brain injury or subdural haematoma (4·4 [1·4-14·0]), a Glasgow Coma Scale score on admission of greater than or equal to 8 (2·2 [1·0-4·7]), and younger age (1·0 [1·0-1·1]). Among patients discharged home or to a rehabilitation setting, those diagnosed with cognitive-motor dissociation consistently had higher scores on GOS-E indicating better functional recovery compared with those without cognitive-motor dissociation, which was seen as early as 3 months after the injury (odds ratio 4·5 [95% CI 2·0-33·6]). INTERPRETATION: Recovery trajectories of clinically unresponsive patients diagnosed with cognitive-motor dissociation early after brain injury are distinctly different from those without cognitive-motor dissociation. A diagnosis of cognitive-motor dissociation could inform the counselling of families of clinically unresponsive patients, and it could help clinicians to identify patients who will benefit from rehabilitation. FUNDING: US National Institutes of Health.

Development of a brain-computer interface for patients in the critical care setting.

OBJECTIVE: Behaviorally unresponsive patients in intensive care units (ICU) are unable to consistently and effectively communicate their most fundamental physical needs. Brain-Computer Interface (BCI) technology has been established in the clinical context, but faces challenges in the critical care environment. Contrary to cue-based BCIs, which allow activation only during pre-determined periods of time, self-paced BCI systems empower patients to interact with others at any time. The study aims to develop a self-paced BCI for patients in the intensive care unit. METHODS: BCI experiments were conducted in 18 ICU patients and 5 healthy volunteers. The proposed self-paced BCI system analyzes EEG activity from patients while these are asked to control a beeping tone by performing a motor task (i.e., opening and closing a hand). Signal decoding is performed in real time and auditory feedback given via headphones. Performance of the BCI system was judged based on correlation between the optimal and the observed performance. RESULTS: All 5 healthy volunteers were able to successfully perform the BCI task, compared to chance alone (p<0.001). 5 of 14 (36%) conscious ICU patients were able to perform the BCI task. One of these 5 patients was quadriplegic and controlled the BCI system without any hand movements. None of the 4 unconscious patients were able to perform the BCI task. CONCLUSIONS: More than one third of conscious ICU patients and all healthy volunteers were able to gain control over the self-paced BCI system. The initial 4 unconscious patients were not. Future studies will focus on studying the ability of behaviorally unresponsive patients with cognitive motor dissociation to control the self-paced BCI system.

Intrathecal baclofen toxicity in a patient with acute kidney injury.

A 9-year old male patient with a past medical history of congenital cytomegalovirus (CMV) infection and spastic quadriplegic cerebral palsy with an intrathecal baclofen pump was admitted to a tertiary care hospital with respiratory depression and unresponsiveness for approximately two days. He had a recent two-week hospital stay for respiratory failure due to pneumonia. After being prescribed antibiotics and being sent home, he had developed copious diarrhea. On readmission, he was found to be dehydrated and in acute renal failure. A physical exam revealed hypotonia throughout, in a patient who typically had spasticity with contractures. The Pediatric Rehabilitation Medicine service was consulted for possible baclofen toxicity. Some signs and symptoms of baclofen toxicity include respiratory depression, seizures, CNS depression, hypotonia, hypotension, absent deep tendon reflexes, lethargy, ataxia, and cardiac arrhythmias. His intrathecal baclofen (ITB) dose was reduced, and signs/symptoms of ITB overdose began to resolve. As renal function improved, spasticity returned, necessitating increase in ITB dosing toward the premorbid dose.