Characteristics of the performance of a dual task, voluntary postural control, and calculation by patients with consequences of traumatic brain injury

Comprehensive clinical (MMSE, FIM and MPAI-3 and Berg scales) and stabilographic evaluation was carried out in 14 patients (with a mean age of 25.7 ± 4.7 years) with consequences of traumatic brain injury (TBI) in comparison with the data on 40 healthy subjects (with a mean age of 29.8 ± 2.5 years) performing separate and dual tasks, including voluntary postural control and calculation. According to the clinical evaluation, all the patients were divided into two groups: group 1 with a moderate deficit (eight patients) and group 2 with a marked functional deficit (six patents). The parameters of the quality of motor and, especially, cognitive subtask performance in both separate and dual tasks were lower than the normative values in all the patients, especially in group 2 patients. Types of dual tasks where the quality of the motor subtask performance was higher than in separate tasks were revealed in healthy subjects and some group 1 patients. The stabilographic parameters characterizing the quality of subtask performance by TBI patients were revealed. Dual tasks could be used for diagnostic purposes such as an additional method for evaluating the adaptive capacity of TBI patients, and certain types of dual tasks could become a promising approach for the recovery of TBI patients at the late stages of rehabilitation.     

fMRI-EEG assessment of cerebral reactivity to motor tasks in patients with brain tumor

A comprehensive study with the assessment of reactive responses to motor tasks was performed in nine patients with a tumor localized in the frontal divisions of the brain using two methodological approaches: functional magnetic resonance imaging (fMRI) and EEG. The data obtained were compared to the results of a similar study on 12 healthy subjects. It was established that cerebral pathology was associated with disorders of functional specialization and an increase in the diffuse component of reactivity. The fMRI responses were characterized by greater intactness compared to the EEG parameters of reactive changes. These features are especially marked when an afferent stimulus is sent to the damaged hemisphere. The characteristics of the involvement of individual EEG bands in the formation of motor responses and changes in the fMRI response topography are determined by the degree of cerebral dysfunction reflected by the pattern of baseline EEG reorganization and the severity of the motor defect. The predominant increase in the coherence of slow rhythms in the damaged hemisphere irrespective of the target of the afferent stimulus in patients with severe cerebral dysfunction reflects the dominant formation of a pathological focus and is indicative of a greater, compared to healthy subjects, involvement of deep brain structures in the reactive process, which is confirmed by the fMRI data.     

Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague–Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option.     

EEG θ rhythm in preterm and full-term infants at the age of five months in endogenous attention

EEG indicators of endogenous attention (EnA) were studied in healthy infants carried to term and extremely preterm infants at a corrected age of five months. The cortical topography of the spectral amplitudes of the EEG θ rhythm was studied during long-term attention of the children to a new visual stimulus (exogenous attention, ExA) and during the retention of anticipatory attention under the conditions of constant appearance and disappearance of a stimulus in the paradigm of visual expectation (EnA). The relationship between reactive changes in the EEG θ rhythm during the retention of EnA and the behavioral parameters of the infant’s ability to retain this type of attention was also assessed. In five-month-old infants, the retention of EnA, in contrast to simpler types of attention to an exogenous stimulus, was accompanied by the appearance of a highly synchronized EEG θ rhythm (3.6–5.2 Hz) with a topical amplitude maximum in the lower temporal associative areas of the cortex. The ability to maintain EnA in children of this age is directly related to the reactive increase in the θ rhythm in the lower temporal areas of the cortex during the retention of EnA as compared to ExA. The deficit of EnA control in healthy extremely preterm (HEP) infants was associated with a relative deficit of the functional synchronization of the θ rhythm in the lower temporal areas of the cortex during the retention of EnA compared to full-term infants. In HEP infants, a decreased synchronization of the θ rhythm was equally typical of EnA and ExA. However, its cortical location depended on the type of attention. The functional nature of the θ rhythm inhibition in HEP infants suggests that this abnormality was related to alterations in the neurotransmitter interactions between the limbic and cortical structures, rather than to structural defects. These alterations could be one of the causes of the partial deficit of EnA in HEP infants.     

EEG and clinical psychophysiological study of functional changes in the chronically ischemic brain upon an increase in cholinergic activity

Electrophysiological and neuropsychological parameters of improvement of the functional state of the brain were studied in patients with mild vascular dementia upon an increase in the activity of cholinergic systems (as a result of treatment with Reminyl). The functional state of the brain was significantly improved as evidenced by a decrease in the EEG spectral power in slow-wave bands and its increase in the band of the γ rhythm, which is involved in cognitive processes in humans. Psychometric tests indicated a significant improvement in cognitive functions.     

FMRI-EEG estimation of cerebral reactivity to motor tasks in patients with brain tumors

fMRI (1.5 or 3 T) and EEG studies with estimation of reactive responses on motor task (by right or left hand) were performed in 9 patients with tumors localized in frontal lobe of the brain. Results of this investigation were compared with results of the similar study in 12 healthy persons. It was shown that in cases of the brain pathology disorders of functional specialization and increase of diffuse component of reactivity was observed, fMRI-responses had been characterized the more intact reactions than reactive changes of EEG parameters. This specificity was described in cases of afferent loads in damaged hemisphere. Peculiarity of including different spectral bands in forming of EEG responses on motor tasks and changes of fMRI-answer depend on degree of cerebral decompensation, reflected in the of baseline EEG reorganization and degree of motor defect. Predominantly an increase of EEG coherence in delta-band with the predominance of reaction in the damaged hemisphere in cases of addressing any afferent load was observed in patients with severe cerebral decompensation and reflect dominant character of pathological focus forming. This data indicate on the more including of the deep brain structures in process of reactivity in patients compared with healthy persons and confirmed by fMRI-data.     

Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.     

The Molecular Mechanisms Affecting N-Acetylaspartate Homeostasis Following Experimental Graded Traumatic Brain Injury

To characterize the molecular mechanisms of N-acetylaspartate (NAA) metabolism following traumatic brain injury (TBI), we measured the NAA, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentrations and calculated the ATP/ADP ratio at different times from impact, concomitantly evaluating the gene and protein expressions controlling NAA homeostasis (the NAA synthesizing and degrading enzymes N-acetyltransferase 8-like and aspartoacylase, respectively) in rats receiving either mild or severe TBI. The reversible changes in NAA induced by mild TBI were due to a combination of transient mitochondrial malfunctioning with energy crisis (decrease in ATP and in the ATP/ADP ratio) and modulation in the gene and protein levels of N-acetyltransferase 8-like and increase of aspartoacylase levels. The irreversible decrease in NAA following severe TBI, was instead characterized by profound mitochondrial malfunctioning (constant 65% decrease of the ATP/ADP indicating permanent impairment of the mitochondrial phosphorylating capacity), dramatic repression of the N-acetyltransferase 8-like gene and concomitant remarkable increase in the aspartoacylase gene and protein levels. The mechanisms underlying changes in NAA homeostasis following graded TBI might be of note for possible new therapeutic approaches and will help in understanding the effects of repeat concussions occurring during particular periods of the complex NAA recovery process, coincident with the so called window of brain vulnerability.     

The circadian intracranial pressure would be a prognostic factor in traumatic brain injury?

Traumatic brain injury (TBI) generally influences circadian rhythms and has been implicated changes in circadian rhythm. Whether TBI-induced changes in circadian rhythm may affect the prognosis or recovery from TBI remains to be investigated. Sixty-two patients with TBI were continuously monitored for intracranial pressure (ICP) during the first 24 hours after the implantation of ICP monitor. The data from each patient were analyzed using the least squares fit of a 24-h cosine function by single cosinor method. Parameters of circadian A (Amplitude)/M (MESOR) were used to evaluate the circadian rhythm of the patients. Student’s t-test and Pearson’s chi-squared test were utilized to analyze the differences between good prognosis group and poor prognosis. A linear regression analysis was then applied to calculate the correlation between circadian A/M of ICP and Glasgow Coma Scale (GCS) before discharge, the Extended Glasgow Outcome Scale (GOS-E), the dosage of mannitol, and time spent in the intensive care unit (ICU), respectively. The results demonstrated that circadian A/M of patients’ ICP exhibited a positive correlation with GCS scores taken before discharge, GOS-E scores, and was negatively correlated with the amount of mannitol, and time spent in the ICU. We conclude that changes in the ICP circadian rhythm in TBI patients could reflect an internal signal of brain damage and, therefore, may be useful to predict a patient’s prognosis and recovery from TBI.     

Neurophysiological indices of CNS plasticity in the course of treatment of head trauma in adolescents

Using the methods of quantitative EEG analysis and cognitive evoked potentials, we investigated delayed consequences of head trauma (HT) after nootropic therapy with cerebrolysin. The study was performed in 30 12-to 19-year-old adolescents who had had severe HT with brain contusion one to five years prior to the study and manifested asthenic symptoms. During the study, they underwent treatment with 30 daily intramuscular injections of cerebrolysin at a dose of 0.1 ml/kg body weight. A positive effect on the functional state of the brain was found in 77% of patients. It was expressed as the appearance of the occipital α rhythm in the EEGs, an increase in the EEG spectral power, normalization of frequency parameters of the α rhythm, a decrease in the power spectrum of the low-frequency θ and δ EEG activity, and shortening of the P300 peak latency. These changes were associated with an improvement of the general clinical state and the psychometric indices of attention and memory in the patients.     

The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury

Traumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up-regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well-known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.     

EEG markers of upright posture in healthy individuals

The EEG spectral-coherence parameters were analyzed in 10 healthy individuals (mean age, 22 ± 0.67 years) at different steps of verticalization, from the lying position to the sitting and standing positions. The maximal changes in all EEG parameters were revealed when the upright posture was maintained in the absence of visual control. Under these conditions, a power increase for the fast EEG components (the ??- and ??-bands) was observed, as was an additional increase when the conditions of maintaining the upright posture were complicated. According to the results of the EEG??s coherent analysis, human verticalization revealed a specific increase for most of the EEG rhythm ranges in the right hemisphere, especially in the frontocentral and occipitoparietal regions, as well as for the interhemispheric coherences for these leads reflecting the involvement of both cortical and subcortical structures in these processes. When the posture maintenance conditions were complicated, an additional coherence increase in the fast EEG bands (the ??-rhythm) was observed in the frontal cortical regions, which was evidence of the increase in the executive functions under these conditions.     

Comparison of methods for clustering independent EEG components in healthy subjects and patients with postconcussion syndrome after traumatic brain injury

The efficiencies of three clustering methods for independent components of 19-channel baseline EEG in location of pathological cerebral activity sources were compared. The samples comprised 518 healthy subjects and 87 patients with postconcussion syndrome after traumatic brain injury (TBI). Clustering of independent component topographies, the spatial coordinates of equivalent dipole sources corresponding to independent component topographies, and locations of the maximums of the equivalent source current density calculated by standardized low resolution electromagnetic tomography (sLORETA) were compared. A comparison of the power spectra of independent components showed a significant increase in the EEG power in the Δ, θ, and α bands for sources located in the frontal and temporal lobes of TBI patients compared to healthy subjects. The method of clustering of independent component topographies proved to be the most sensitive of the methods compared.     

Assessment of the Course of Rehabilitation of Patients with Craniocerebral Injury According to Posturographic, Encephalographic, and Clinical Indices

Electroencephalographic and posturographic characteristics were studied in 26 patients with severe craniocerebral injury (CCI) in the course of rehabilitation. Comparison of electroencephalographic and clinical data with posturographic indices revealed the informative value of the latter for the assessment of the recovery of postural control in patients with consequences of CCI during their rehabilitation. The posturographic indices of patients differed from the relative normal values of these characteristics; their specific changes were also observed during recovery of vertical posture maintenance with and without visual control at different rehabilitation stages. It was shown that visual afferent inflow is more important for the recovery of postural control in early periods after CCI, whereas the role of proprioceptive inflow increases at later stages of rehabilitation. Coordination of changes in the EEG and postural characteristics in the course of patient rehabilitation was demonstrated. These findings suggest that the proposed approach can be useful in dynamic assessment of the state of patients with consequences of CCI.     

Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide,cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

Background aimsAn intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated.MethodsThe authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563).ResultsAt 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86).ConclusionsThis study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.     

Brain Mechanisms of Voluntary Regulation of Activity during Acquisition of the Skill of Writing in Seven- to Eight-Year-Old Children

With the aim of studying the formation of brain mechanisms of voluntary activity regulation in junior schoolchildren and the role of these mechanisms in the acquisition of the skill of writing, a complex neuropsychological investigation was carried out. In the EEG of children with learning problems and a deficit of voluntary activity regulation (VAR), signs of the functional immaturity of the fronto–thalamic regulatory system (FTS) were found. Comparative neuropsychological analysis revealed a specific impairment of the VAR in these children in the form of pronounced impulsiveness, instability of a program, problems in switching over from one program to another, and self-control difficulties. It is concluded that the functional maturation of the FTS is a mechanism of VAR development. It is shown that the VAR deficiency in children with FTS immaturity is combined with a delay in the development of semantic and mediating speech functions. It was found that the features of the development of the higher mental functions in seven- to eight-year-old children with FTS immaturity specifically affect both the semantic and graphic aspects of writing acquisition.     

Integrating role of voluntary postural control recovery during rehabilitation of patients with traumatic brain injury

Results of complex clinical, stabilographic and electroencephalographic (EEG) examination of 20 patients (28 +/- 6.9 years) suffered a severe traumatic brain injury (STBI) are presented. The examination was carried out in early terms after the STBI before and after a course of stabilographic training (ST) with a visual feedback as compared to a group of 18 healthy volunteers (26 +/- 5.8 years). The 4- to 6-week course of ST consisted of 8-15 sessions. Before the course, the patients experienced problems in different kinds of activity, maximum in the motor sphere. The EEG study revealed a decrease in the power and coherence of the alpha rhythm and an increase in the power of the slow spectral bands (delta). The ST restored not only the postural control of patients, but also reduced the defects in other spheres. The EEG study showed an increase in the alpha-rhythm power maximum in the occipital-parietal areas and a tendency to normalization of its regional specificity. In all examined patients, the interhemispheric coherence increased for different EEG-rhythms, especially of the alpha-band, in the central and parietal brain areas. The described EEG changes can be a marker of the integrating role of postural control and an important stage in restoration of integrative brain activity in early terms after the STBI accompanied by improvement of damaged functions.     

Electrographic Correlates of Brain Reactions to Afferent Stimuli in Postcomatose Unconscious States after Severe Brain Injury

Analysis of the character and systemic organization of cerebral reactions to external effects aids in adequate evaluation of functional and adaptive human capabilities in norm and pathology. Changes in the spatiotemporal organization of the EEG (according to visual and spectral coherence analyses, as well as localization of equivalent dipole sources of pathological EEG phenomena) and the electrooculogram in response to afferent stimuli at different stages of postcomatose recovery of mental activity were studied in 84 patients with severe brain injury in a prolonged postcomatose unconscious state. Both standard indifferent (a rhythmically flashing light and an acoustic tone) and functionally significant (a moving contrasting black-and-white strip, a red spot, the mother’s voice, music, etc.) afferent stimuli were used. Functionally different reactive changes in the EEG were detected even in deep inhibition of consciousness (a vegetative state). EEG reactions including a strengthening of pathological foci in the CNS with dominant features suggested a poor prognosis. In the absence of such foci, a positive activating effect on mental recovery was found for afferent stimulation, in particular, functionally significant stimulation. Selective sensitivity of the CNS to certain external stimuli was observed for certain unconscious states.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 5–15.Original Russian Text Copyright © 2005 by Sharova.     

Interhemispheric EEG Coherence during Rehabilitation of Patients after Severe Craniocerebral Injury

Dynamic clinical and EEG examinations (78 observations) were carried out in 17 patients suffering from severe craniocerebral injury during the course of their rehabilitation. Successful recovery of functions to the point of social and family readaptation was reached in 61% of patients (group I), and in 39% of patients the results were poor (group II). The complex of EEG coherence parameters (six rhythmic bands, mean coherence levels for 26 intrahemispheric and 8 interhemispheric derivation pairs, and the asymmetry coefficient of the EEG coherence) was analyzed in patients in comparison with normal values (20 right-handers). The rehabilitation was most efficient in cases when a certain dynamic sequence of patterns of interhemispheric relations of the EEG coherence was observed. First, a stable formation of right-hemispheric dominance was observed (most expressed in the centrofrontal areas in the range). This asymmetry pattern was phenomenologically associated with the recovery of the emotional sphere and positive dynamics in the motor and autonomic spheres. Later on, formation of the left-hemispheric dominance of the EEG coherence was observed (in the frontotemporal areas in the – ranges. This pattern was associated with complication of the cognitive functions. In the most severe forms of brain damage, the rehabilitation process was accompanied by changes in the interhemispheric EEG coherence with the elements of stealing from one of the hemispheres, which was correlated with clinical dynamics. Different types of the dynamics of reactive changes in the EEG coherence were revealed in patients of the two groups: successive formation of a generalized and then local modally specific reaction to afferent stimuli was observed in group I, while the generalized type of reactivity persisted in group II until the end of rehabilitation. It is suggested that the different sequence of formation of the interhemispheric EEG coherence reflects the involvement of different brain regulation systems in different orders into the integrative activity, i.e., some specific features of the rehabilitation process.