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A 15-year-old patient with sickle cell disease with recessive homozygous haemoglobin S/HbSS suffered several crises developmentally after the last of which the patient fell into coma. CT scan then revealed a large infarct of the right cerebral hemisphere. Three weeks after the event, the patient began to demonstrate spontaneous eye opening and spastic quadriparesis with no evidence of command-following, gestural or verbal communication, visual pursuit or purposeful motor behaviour. Our case was in an 'unresponsive wakefulness syndrome' with atrophy of lateral and frontal regions of both hemispheres, demonstrated by MRI and preservation of circulation in the posterior arterial system, documented by MR angiography. Currently observed are spontaneous eye opening, preserved visual and auditory startle reflexes, normal brainstem reflexes, and grasp, palmomental and sucking reflexes. Our case demonstrates partial recovery of awareness with significant brain lesions, reflecting preserved brain activity as an indication of the modular nature of functional networks.

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PRIMARY OBJECTIVE: The objective of this study is to assess the functional state of the autonomic nervous system in healthy individuals and in individuals in coma using measures of heart rate variability (HRV) and to evaluate its efficiency in predicting mortality. DESIGN AND METHODS: Retrospective group comparison study of patients in coma classified into two subgroups, according to their Glasgow coma score, with a healthy control group. HRV indices were calculated from 7 min of artefact-free electrocardiograms using the Hilbert-Huang method in the spectral range 0.02-0.6 Hz. A special procedure was applied to avoid confounding factors. Stepwise multiple regression logistic analysis (SMLRA) and ROC analysis evaluated predictions. RESULTS: Progressive reduction of HRV was confirmed and was associated with deepening of coma and a mortality score model that included three spectral HRV indices of absolute power values of very low, low and very high frequency bands (0.4-0.6 Hz). The SMLRA model showed sensitivity of 95.65%, specificity of 95.83%, positive predictive value of 95.65%, and overall efficiency of 95.74%. CONCLUSIONS: HRV is a reliable method to assess the integrity of the neural control of the caudal brainstem centres on the hearts of patients in coma and to predict patient mortality.

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Key autonomic functions are in continuous development during adolescence which can be assessed using the heart rate variability (HRV). However, the influence of different demographic and physiological factors on HRV indices has not been fully explored in adolescents. In this study we aimed to assess the effect of age, gender, and heart rate on HRV indices in two age groups of healthy adolescents (age ranges, 13-16 and 17-20 years) and two groups of healthy young adults (21-24 and 25-30 years). We addressed the issue using 5-min ECG recordings performed in the sitting position in 255 male and female participants. Time, frequency, and informational domains of HRV were calculated. Changes in HRV indices were assessed using a multiple linear regression model to adjust for the effects of heart rate, age, and gender. We found that heart rate produced more significant effects on HRV indices than age or gender. There was a progressive reduction in HRV with increasing age. Sympathetic influence increased with age and parasympathetic influence progressively decreased with age. The influence of gender was manifest only in younger adolescents and young adults. In conclusion, age, gender, and particularly heart rate have a substantial influence on HRV indices, which ought to be considered to avoid biases in the study of the autonomic nervous system development. The lack of the gender-related effects on HRV indices in late adolescence could be related to non-completely achieved maturity of the autonomic mechanisms, which deserves further exploration.

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Literature reports on the very high frequency (VHF) range of 0.4-0.9 Hz in heart rate variability (HRV) are scanty. The VHF presence in cardiac transplant patients and other conditions associated with reduced vagal influence on the heart encouraged us to explore this spectral band in healthy subjects and in patients diagnosed with cardiac autonomic neuropathy (CAN), and to assess the potential clinical value of some VHF indices. The study included 80 healthy controls and 48 patients with spinocerebellar ataxia type 2 (SCA2) with CAN. The electrocardiographic recordings of short 5-min duration were submitted to three different spectral analysis methods, including the most generally accepted procedure, and the two novel methods using the Hilbert-Huang transform. We demonstrated the presence of VHF activity in both groups of subjects. However, VHF power spectral density, expressed in relative normalized units, was significantly greater in the SCA2 patients than that in healthy subjects, amounting to 36.1 ± 17.4% vs. 22.9 ± 14.1%, respectively, as also was the instantaneous VHF spectral frequency, 0.58 ± 0.05 vs. 0.64 ± 0.07 Hz, respectively. These findings were related to the severity of CAN. We conclude that VHF activity of HRV is integral to the cardiovascular autonomic control.

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In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other.

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A group of 21 autistic children were studied for determining the relationship between the anatomic (AC) versus functional (FC) connectivity, considering short-range and long-range brain networks. AC was assessed by the DW-MRI technique and FC by EEG coherence calculation, in three experimental conditions: basal, watching a popular cartoon with audio (V-A), and with muted audio track (VwA). For short-range connections, basal records, statistical significant correlations were found for all EEG bands in the left hemisphere, but no significant correlations were found for fast EEG frequencies in the right hemisphere. For the V-A condition, significant correlations were mainly diminished for the left hemisphere; for the right hemisphere, no significant correlations were found for the fast EEG frequency bands. For the VwA condition, significant correlations for the rapid EEG frequencies mainly disappeared for the right hemisphere. For long-range connections, basal records showed similar correlations for both hemispheres. For the right hemisphere, significant correlations incremented to all EEG bands for the V-A condition, but these significant correlations disappeared for the fast EEG frequencies in the VwA condition. It appears that in a resting-state condition, AC is better associated with functional connectivity for short-range connections in the left hemisphere. The V-A experimental condition enriches the AC and FC association for long-range connections in the right hemisphere. This might be related to an effective connectivity improvement due to full video stimulation (visual and auditory). An impaired audiovisual interaction in the right hemisphere might explain why significant correlations disappeared for the fast EEG frequencies in the VwA experimental condition.

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Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition.

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ADD/ADHD is the most common and most studied neurodevelopmental problem. Recent statistics from the U.S. Center for Disease Control state that 11% or approximately one out of every nine children in the US and one in five high school boys are diagnosed with ADD/ADHD. This number is thought to be increasing at around 15-20% per year. The US National Institute of Mental Health's Multi-modal Treatment Study has shown that medication has no long-term benefit for those with ADHD. To effectively address ADD/ADHD from within the framework of child public health, an interdisciplinary strategy is necessary that is based on a neuroeducational model that can be readily implemented on a large-scale within the educational system. This study is based on previous findings that ADD/ADHD children possess underactivity between sub-cortical and cortical regions. An imbalance of activity or arousal in one area can result in functional disconnections similar to that seen in split-brain patients. Since ADD/ADHD children exhibit deficient performance on tests developed to measure perceptual laterality, evidence of weak laterality or failure to develop laterality has been found across various modalities (auditory, visual, tactile). This has reportedly resulted in abnormal cerebral organization and ineffective cortical specialization necessary for the development of language and non-language function. This pilot study examines groups of ADD/ADHD and control elementary school children all of whom were administered all of the subtests of the Wechsler Individual Achievement Tests, the Brown Parent Questionnaire, and given objective performance measures on tests of motor and sensory coordinative abilities. Results measured after a 12-week remediation program aimed at increasing the activity of the hypothesized underactive right hemisphere function, yielded significant improvement of greater than 2 years in grade level in all domains except in mathematical reasoning. The treated group also displayed a significant improvement in behavior with a reduction in Brown scale behavioral scores. Non-treated control participants did not exhibit significant differences during the same 12 week period in academic measurements. Controls were significantly different from treatment participants in all domains after a 12-week period. The non-treatment group also demonstrated an increase in behavioral scores and increased symptoms of ADD/ADHD over the same time period when compared to the treated group. Results are discussed in the context of the concept of functional disconnectivity in ADD/ADHD children.

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OBJECTIVE: To assess the autonomic nervous system (ANS) in coma by heart rate variability (HRV). METHODS: Sixteen comatose patients and 22 normal subjects with comparable ages and genders were studied. Patients were classified in two subgroups according to the Glasgow Coma Scale (GCS). Time, frequency, and informational HRV domain indices were calculated. RESULTS: A notable reduction of HRV was found in patients. Regarding the time domain indices, the triangular index, and the Delta_RRs, were significantly reduced in the subgroup with GCS=3. Absolute power for the whole frequency spectrum decreased whenever GCS scores were lower. A significant decrement was found for absolute power of the VLF and LF bands in the subgroup of GCS=3, and although it was lower for the HF band in these patients, those changes were not statistically significantly different. The LF/HF ratio and the Shannon´s entropy indices were significantly reduced in the subgroup with GCS=3. Our results are discussed regarding the progressive dysfunction the ANS networks when coma deepens. CONCLUSIONS: The HRV procedure is a powerful tool to assess the ANS in comatose patients. SIGNIFICANCE: HRV is a minimally invasive, low-cost methodology, suitable for assessing the ANS in coma.

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There exists much controversy in providing an effective definition of human death, largely due to the lack of a rigorous separation and ordered formulation of three distinct elements: a universally accepted definition of death, the medical criterion (anatomical substrata) for determining that death has occurred, and the tests to prove that the criterion has been satisfied. The papers herein review medical standards, philosophical arguments, neurophysiological knowledge, behavioural and cognitive theory and the legal ramifications of the brain-oriented standards of death (whole brain, brainstem and higher brain). The papers examine the notion of connectivities and networks of conscious experience in order to formulate an effective definition of death, based on the basic physiopathological mechanisms of consciousness. We cannot simply differentiate and locate arousal as a function of the ascending reticular activating system, and awareness as a function of the cerebral cortex. Substantial interconnections among the brainstem, subcortical structures, and the neocortex are essential integrating components of human consciousness. This paper attempts to reconcile the brain-oriented standards that are currently inconsistent. The thread of the arguments is the basis for a standard of human death that includes consciousness as the most important function of the body, because it provides the capacity for integrating the functions of the body. The notion of consciousness as the ultimate integrative function is more consistent with the biologically-based systems than the more philosophically-based notions of personhood. Both sides of the argument are presented herein.

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BACKGROUND: We report a 15 year-old girl with sickle cell disease, who developed important cognitive impairment due to multiple strokes, and who had been diagnosed with PVS. Nonetheless, when she was later admitted to our Institute, according to the presence of inconsistent but clearly demonstrable behavioral evidence of consciousness awareness, we changed our diagnosis to MCS. METHODS: This patient was studied by T1 MRI images, co-registration of fractional anisotropy (FA), and SPECT with MRI. RESULTS: Brain structures were mainly preserved in posterior areas of both cerebral hemispheres, although small tissue islands were present in both frontal lobes, mainly preserved in the right one. SPECT showed CBF preservation in posterior brain regions and in the cerebellum, and in those frontal small islands of tissue lateralized to the right frontal lobe; meanwhile FA showed preservation of anatomical connectivity among posterior and frontal brain regions. These remaining cortical regions are also connected with the thalami. CONCLUSION: These results showing connectivity among posterior and frontal cortical and probably with other subcortical regions, and CBF preservation in these areas, might explain the recovery of minimum awareness despite huge anatomical brain lesions.

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