Intervention-Induced Changes in Balance and Task-Dependent Neural Activity in Adults with Acquired Brain Injury: A Pilot Randomized Control Trial.

Advances in neuroimaging technology, like functional near-infrared spectroscopy (fNIRS), support the evaluation of task-dependent brain activity during functional tasks, like balance, in healthy and clinical populations. To date, there have been no studies examining how interventions, like yoga, impact task-dependent brain activity in adults with chronic acquired brain injury (ABI). This pilot study compared eight weeks of group yoga (active) to group exercise (control) on balance and task-dependent neural activity outcomes. Twenty-three participants were randomized to yoga (n = 13) or exercise groups (n = 10). Neuroimaging and balance performance data were collected simultaneously using a force plate and mobile fNIRS device before and after interventions. Linear mixed-effects models were used to evaluate the effect of time, time x group interactions, and simple (i.e., within-group) effects. Regardless of group, all participants had significant balance improvements after the interventions. Additionally, regardless of group, there were significant changes in task-dependent neural activity, as well as distinct changes in neural activity within each group. In summary, using advances in sensor technology, we were able to demonstrate preliminary evidence of intervention-induced changes in balance and neural activity in adults with ABI. These preliminary results may provide an important foundation for future neurorehabilitation studies that leverage neuroimaging methods, like fNIRS.

Sensing, feeling and regulating: investigating the association of focal brain damage with voluntary respiratory and motor control.

Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal or limbic regions on the sensation and regulation of breathing patterns. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire, and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia and left medial temporal lobe showed reduced performance relative to individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60 bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnoea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol.

INTRODUCTION: Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. METHODS AND ANALYSES: The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current's frequency targets alpha brain oscillations (8-13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8-13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers' burden. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l'Île-de-Montréal (Project ID 2021-2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial's results will be published on a public trial registry database (ClinicalTrials.gov). TRIAL REGISTRATION NUMBER: NCT05833568.

The Left-Right Side-Specific Neuroendocrine Signaling from Injured Brain: An Organizational Principle.

A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene-gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.

The diverse role of corticotropin-releasing factor (CRF) and its CRF1 and CRF2 receptors under pathophysiological conditions: Insights into stress/anxiety, depression, and brain injury processes.

Corticotropin-releasing factor (CRF, corticoliberin) is a neuromodulatory peptide activating the hypothalamic-pituitary-adrenal (HPA) axis, widely distributed in the central nervous system (CNS) in mammals. In addition to its neuroendocrine effects, CRF is essential in regulating many functions under physiological and pathophysiological conditions through CRF1 and CRF2 receptors (CRF1R, CRF2R). This review aims to present selected examples of the diverse and sometimes opposite effects of CRF and its receptor ligands in various pathophysiological states, including stress/anxiety, depression, and processes associated with brain injury. It seems interesting to draw particular attention to the fact that CRF and its receptor ligands exert different effects depending on the brain structures or subregions, likely stemming from the varied distribution of CRFRs in these regions and interactions with other neurotransmitters. CRFR-mediated region-specific effects might also be related to brain site-specific ligand binding and the associated activated signaling pathways. Intriguingly, different types of CRF molecules can also influence the diverse actions of CRF in the CNS.

The disengagement deficit after right-hemisphere damage: Distinct roles of lateral frontal and parietal damage.

An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.

Effect of blast orientation, multi-point blasts, and repetitive blasts on brain injury.

Explosions in the battlefield can result in brain damage. Research on the effects of shock waves on brain tissue mainly focuses on the effects of single-orientation blast waves, while there have been few studies on the dynamic response of the human brain to directional explosions in different planes, multi-point explosions and repetitive explosions. Therefore, the brain tissue response and the intracranial pressure (ICP) caused by different blast loadings were numerically simulated using the CONWEP method. In the study of the blast in different directions, the lateral explosion blast wave was found to cause greater ICP than did blasts from other directions. When multi-point explosions occurred in the sagittal plane simultaneously, the ICP in the temporal lobe increased by 37.8 % and the ICP in the parietal lobe decreased by 17.6 %. When multi-point explosions occurred in the horizontal plane, the ICP in the frontal lobe increased by 61.8 % and the ICP in the temporal lobe increased by 12.2 %. In a study of repetitive explosions, the maximum ICP of the second blast increased by 40.6 % over that of the first blast, and that of the third blast increased by 61.2 % over that of the second blast. The ICP on the brain tissue from repetitive blasts can exceed 200 % of that of a single explosion blast wave.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome.

OBJECTIVE: To characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. METHODS: 109 preterm infants (23-28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. RESULTS: Thirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6-40.0 µV and 222.7-257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). CONCLUSIONS: NCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SIGNIFICANCE: The NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

The neural correlates of limb apraxia: An anatomical likelihood estimation meta-analysis of lesion-symptom mapping studies in brain-damaged patients.

Limb apraxia is a motor disorder frequently observed following a stroke. Apraxic deficits are classically assessed with four tasks: tool use, pantomime of tool use, imitation, and gesture understanding. These tasks are supported by several cognitive processes represented in a left-lateralized brain network including inferior frontal gyrus, inferior parietal lobe (IPL), and lateral occipito-temporal cortex (LOTC). For the past twenty years, voxel-wise lesion symptom mapping (VLSM) studies have been used to unravel the neural correlates associated with apraxia, but none of them has proposed a comprehensive view of the topic. In the present work, we proposed to fill this gap by performing a systematic Anatomic Likelihood Estimation meta-analysis of VLSM studies which included tasks traditionally used to assess apraxia. We found that the IPL was crucial for all the tasks. Moreover, lesions within the LOTC were more associated with imitation deficits than tool use or pantomime, confirming its important role in higher visual processing. Our results questioned traditional neurocognitive models on apraxia and may have important clinical implications.

Deciphering seizure semiology in corpus callosum injuries: A comprehensive systematic review with machine learning insights.

INTRODUCTION: Seizure disorders have often been found to be associated with corpus callosum injuries, but in most cases, they remain undiagnosed. Understanding the clinical, electrographic, and neuroradiological alternations can be crucial in delineating this entity. OBJECTIVE: This systematic review aims to analyze the effects of corpus callosum injuries on seizure semiology, providing insights into the neuroscientific and clinical implications of such injuries. METHODS: Adhering to the PRISMA guidelines, a comprehensive search across multiple databases, including PubMed/Medline, NIH, Embase, Cochrane Library, and Cross-ref, was conducted until September 25, 2023. Studies on seizures associated with corpus callosum injuries, excluding other cortical or sub-cortical involvements, were included. Machine learning (Random Forest) and deep learning (1D-CNN) algorithms were employed for data classification. RESULTS: Initially, 1250 articles were identified from the mentioned databases, and additional 350 were found through other relevant sources. Out of all these articles, 41 studies met the inclusion criteria, collectively encompassing 56 patients The most frequent clinical manifestations included generalized tonic-clonic seizures, complex partial seizures, and focal seizures. The most common callosal injuries were related to reversible splenial lesion syndrome and cytotoxic lesions. Machine learning and deep learning analyses revealed significant correlations between seizure types, semiological parameters, and callosal injury locations. Complete recovery was reported in the majority of patients post-treatment. CONCLUSION: Corpus callosum injuries have diverse impacts on seizure semiology. This review highlights the importance of understanding the role of the corpus callosum in seizure propagation and manifestation. The findings emphasize the need for targeted diagnostic and therapeutic strategies in managing seizures associated with callosal injuries. Future research should focus on expanding the data pool and exploring the underlying mechanisms in greater detail.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Effect of Combining Intrauterine Cerebral Blood Flow Changes with Electrical Activity on Prognostic Evaluation of Brain Injury.

OBJECTIVES: We sought to investigate the value of combining intrauterine cerebral blood flow changes with brain electrical activity examination in evaluating the prognosis of brain injury. METHODS: A total of 90 preterm infants were enrolled and divided into 2 groups: the brain damaged preterm infants group (n = 55) and the nonbrain damaged preterm infants group (n = 35). The diagnostic efficacy of combining intrauterine cerebral blood flow changes with electroencephalogram (EEG) activity examination in predicting the prognosis of preterm infants with brain injury was evaluated using T-test. Pearson linear correlation was applied to analyze the relationship between fetal intrauterine cerebral blood flow changes combined with electrical activity examination and the prognosis of brain injury. RESULTS: Significant differences were seen in pulse index, the ratio of peak systolic velocity to end diastolic velocity ratio, and other indexes between the 2 groups (P < 0.05). The combined approach of intrauterine cerebral blood flow changes with EEG activity examination demonstrated significantly higher values for area under the curve, sensitivity and negative predictive value compared to using intrauterine cerebral blood flow changes or EEG activity examination alone (P < 0.05). A positive correlation was found between fetal intrauterine cerebral blood flow and electrical activity examination (P < 0.05). CONCLUSIONS: Combining the assessment of intrauterine cerebral blood flow changes with cerebral electrical activity examination proved beneficial in diagnosing the prognosis of brain injury and provided an important reference for early clinical intervention.

Temperature Control in Acute Brain Injury: An Update.

Temperature control in severe acute brain injury (SABI) is a key component of acute management. This manuscript delves into the complex role of temperature management in SABI, encompassing conditions like traumatic brain injury (TBI), acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), aneurysmal subarachnoid hemorrhage (aSAH), and hypoxemic/ischemic brain injury following cardiac arrest. Fever is a common complication in SABI and is linked to worse neurological outcomes due to increased inflammatory responses and intracranial pressure (ICP). Temperature management, particularly hypothermic temperature control (HTC), appears to mitigate these adverse effects primarily by reducing cerebral metabolic demand and dampening inflammatory pathways. However, the effectiveness of HTC varies across different SABI conditions. In the context of post-cardiac arrest, the impact of HTC on neurological outcomes has shown inconsistent results. In cases of TBI, HTC seems promising for reducing ICP, but its influence on long-term outcomes remains uncertain. For AIS, clinical trials have yet to conclusively demonstrate the benefits of HTC, despite encouraging preclinical evidence. This variability in efficacy is also observed in ICH, aSAH, bacterial meningitis, and status epilepticus. In pediatric and neonatal populations, while HTC shows significant benefits in hypoxic-ischemic encephalopathy, its effectiveness in other brain injuries is mixed. Although the theoretical basis for employing temperature control, especially HTC, is strong, the clinical outcomes differ among various SABI subtypes. The current consensus indicates that fever prevention is beneficial across the board, but the application and effectiveness of HTC are more nuanced, underscoring the need for further research to establish optimal temperature management strategies. Here we provide an overview of the clinical evidence surrounding the use of temperature control in various types of SABI.

Investigating the Link Between Subjective Depth Perception Deficits and Objective Stereoscopic Vision Deficits in Individuals With Acquired Brain Injury.

Individuals with acquired brain injury have reported subjective complaints of depth perception deficits, but few have undergone objective assessments to confirm these deficits. As a result, the literature currently lacks reports detailing the correlation between subjective depth perception deficits and objective stereoscopic vision deficits in individuals with acquired brain injury, particularly those cases that are characterized by a clearly defined lesion. To investigate this relationship, we recruited three individuals with acquired brain injury who experienced depth perception deficits and related difficulties in their daily lives. We had them take neurologic, ophthalmological, and neuropsychological examinations. We also had them take two types of stereoscopic vision tests: a Howard-Dolman-type stereoscopic vision test and the Topcon New Objective Stereo Test. Then, we compared the results with those of two control groups: a group with damage to the right hemisphere of the brain and a group of healthy controls. Performance on the two stereoscopic vision tests was severely impaired in the three patients. One of the patients also presented with cerebral diplopia. We identified the potential neural basis of these deficits in the cuneus and the posterior section of the superior parietal lobule, which play a role in vergence fusion and are located in the caudal region of the dorso-dorsal visual pathway, which is known to be crucial not only for visual spatial perception, but also for reaching, grasping, and making hand postures in the further course of that pathway.

Long-term pituitary function and functional and patient-reported outcomes in severe acquired brain injury.

OBJECTIVE: Assessment of posttraumatic hypothalamic-pituitary dysfunctions is expected to be the most relevant assessment to offer patients with severe intracranial affection. In this study, we aim to investigate the prevalence of hypopituitarism in patients with severe acquired traumatic brain injury (TBI) compared with nontraumatic brain injury (NTBI) and to relate pituitary insufficiency to functional and patient-reported outcomes. DESIGN: This is a prospective study. METHODS: We included patients admitted for inpatient neurorehabilitation after severe TBI (N = 42) and NTBI (N = 18). The patients underwent a pituitary function assessment at a mean of 2.4 years after the injury. Functional outcome was assessed by using Functional Independence Measure and Glasgow Outcome Scale-Extended (both 1 year after discharge from neurorehabilitation) and patient-reported outcome was assessed by using Multiple Fatigue Inventory-20 and EQ-5D-3L. RESULTS: Hypopituitarism was reported in 10/42 (24%) patients with TBI and 7/18 (39%) patients with NTBI (P = .23). Insufficiencies affected 1 axis in 14/17 (82%) patients (13 hypogonadotropic hypogonadism and 1 growth hormone [GH] deficiency) and 2 axes in 3/17 (18%) patients (1 hypogonadotropic hypogonadism and GH deficiency, and 2 hypogonadotropic hypogonadism and arginin vasopressin deficiency). None had central hypoadrenalism or central hypothyroidism. In patients with both TBI and NTBI, pituitary status was unrelated to functioning and ability scores at 1 year and to patient-reported outcome scores at a mean of 2.4 years after the injury. CONCLUSION: Patients with severe acquired brain injury may develop long-term hypothalamus-pituitary insufficiency, with an equal occurrence in patients with TBI and NTBI. In both types of patients, mainly isolated deficiencies, most commonly affecting the gonadal axis, were seen. Insufficiencies were unrelated to functional outcomes and patient-reported outcomes, probably reflecting the complexity and heterogeneous manifestations in both patient groups.