Exercise training in ad libitum and food-restricted old rats: effects on metabolic and physiological parameters.

Aging is accompanied by a decline in the healthy function of multiple organs, leading to increased incidence and mortality from diseases such as cancer and inflammatory, cardiovascular and neurodegenerative diseases. Dietary restriction is the most effective experimental intervention known to consistently slow the aging process and with positive effects on health span in different organisms, from invertebrates to mammals. Age is also associated with progressive decline in physical activity levels in a wide range of animal species: therefore, regular physical exercise could represent a safe intervention to antagonize aging. In this research we explore the effects of exercise training initiated in late middle aged rats fed with different lifelong dietary regimens: one group was fed ad libitum and the second group was subjected to every-other-day fasting. These two groups might represent examples of "normal" aging and "successful" aging. The study shows the effects of exercise and food restriction and their interaction on plasma levels of total antioxidant capacity, lactate, amino acids, and on products of protein oxidation in soleus and tibialis anterior muscles. In addition, we evaluated body composition measurement by bioelectrical impedance analysis and muscle strength by grasping test. Results show that late-onset exercise training has the potential to improve some metabolic and physiological parameters in rats with the same "chronological age" but different "biological age", without negative effects, and highlight the relevance of a personalised and selected exercise protocol, since the responsiveness to exercise may depend on the individual's "biological age".

Percutaneous Venous Angioplasty in Patients with Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency: A Randomized Wait List Control Study.

BACKGROUND: Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. The aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. METHODS: 66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated into vPTA-yes group (n = 31) or vPTA-not group (n = 35, control group). vPTA was performed immediately 15 days after randomization in the PTA-yes group and 6 months later in the control group. Evoked potentials (EPs), clinical-functional measures (CFMs), and upper limb kinematic measures (ULKMs) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in the vPTA-not group (T1). RESULTS: Comparing the vPTA-yes and vPTA-not group, the CFM-derived composite functional outcome showed 11 (37%) versus 7 (20%) improved, 1 (3%) versus 3 (8%) stable, 0 versus 7 (20%) worsened, and 19 (61%) versus 18 (51%) mixed patients (χ2 = 8.71, df = 3, P = 0.03). Unadjusted and adjusted (for baseline confounding variables) odds ratio at 95% confidence interval were, respectively, 1.93 (1.3-2.8), P value 0.0007, and 1.85 (1.2-1.7), P value 0.002. EP- and ULKM-derived composite functional outcome showed no significant difference between the two groups. CONCLUSIONS: Venous angioplasty can positively impact a few CFMs especially for the quality of life but achieving disability improvement is unlikely.

Caregiver burden and family functioning in different neurological diseases.

Aim of this study is to examine caregiver burden and family functioning in different neurological conditions. Forty-two primary caregivers of patients with Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease and other dementia (AD), Parkinson's Disease (PD), Acquired Brain Injuries (ABI) and Multiple Sclerosis (MS) were administered scales for the evaluation of caregiver burden (CBI) and family functioning (FACES IV). Caregiver burden was overall high, with caregivers of patients with ALS and ABI having exceeded the CBI cut-off score for possible burn-out. The average scores of caregivers of patients with AD or other dementia and PD were close to the cut-off score, whereas those of caregivers of patients with MS were significantly lower than the others. Family cohesion, family satisfaction and the quality of family communication were associated with reduced levels of caregiver burden, whereas disengagement was associated with a higher burden. The data from the present study confirm that caregiver burden is a relevant issue in the context of neurological diseases, especially for those causing higher degrees of impairment. Significant correlations with family functioning emerged as well, highlighting the importance of studying and treating caregiver burden within the context of family relations.

Whole body vibration and treadmill training in Parkinson's disease rehabilitation: effects on energy cost and recovery phases.

BACKGROUND: Although physical treatment is recognized as being beneficial for patients with Parkinson's disease (PD), there is scant literature on the type of rehabilitation program most useful for patients with PD. The aim of the present study was to investigate the effects of two different training protocols (aerobic treadmill training, AER and whole body vibration training, WBVT) on energy cost and adaptations after exercise and recovery phases, by means of the oxygen consumption measurement and the assay of metabolic biochemical substrates. METHODS: Twenty male patients with idiopathic Parkinson's disease, aged 51-66 years, were enrolled. Patients were randomly assigned to the training groups. The total work time was 20 min per group for 4 weeks, four times a week. In both groups, training intensity was monitored by the ratings of perceived exertion (RPE). Workload was gradually increased until patients worked up to the exertion level of 13 to 15 on the 20-point Borg scale RPE. The outcome measures were oxygen consumption, free fatty acid (FFA), and amino acid (AA) levels. RESULTS: The oxygen consumption during exercises does not show significant differences between the two training groups. Instead, only in the AER group, excess post-exercise oxygen consumption measurements increased significantly (p < 0.01) as well as FFA availability (p < 0.01). CONCLUSION: The WBVT does not appear to require a long time of recovery and leads to less feeling of fatigue, whereas AER needs an appropriate recovery time after the training session.

Effects of a Home-Based Family-Centred Early Habilitation Program on Neurobehavioural Outcomes of Very Preterm Born Infants: A Retrospective Cohort Study.

Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years' corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months' corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant's developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps.

Family functioning in severe brain injuries: correlations with caregivers' burden, perceived social support and quality of life.

Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

N400-like responses to three-chord harmonic sequences with unexpected out of key endings: scalp topography, cortical sources, and perspectives for a clinical use.

A series of ERP components, each provided with both a precise timing with respect to stimulation and a specific cortical localization, reflects the temporal succession of processing stages of music information. This makes the musical stimulus potentially usable to probe residual brain functions in non-communicating patients with disorders of consciousness. In an attempt to find a simple stimulation protocol that was suitable for use in a clinical setting, the purpose of this study was to verify whether a minimum-length musical stimulus, provided with a definite music-syntactic connotation, was still able to elicit musical ERPs in a group of eight healthy subjects. The stimulus was composed of the minimum number of chords necessary and sufficient to enable the subject to predict a plausible closure of the sequence (priming) and, at the same time, to provide him/her with the closing chord of the sequence (target), either congruous (probable closing) or not (improbable closing) to the tonal context. The subject's task was to discriminate and recognize the irregular targets. The components that were expected to be elicited, in this experimental situation, were ERAN, N5, P600/LPC. Conversely, in addition to these former components, we unexpectedly observed a N400-like component. To determine whether this component was a real N400, we submitted our data to a sLORETA analysis in order to identify its cortical generators. Irregular chords showed higher current densities with respect to regular ones on the right-sided medial and superior temporal gyri, superior and inferior parietal lobules, fusiform and parahippocampal gyri, and on the bilateral posterior cingulate cortex. In particular, the N400-like wave seems to share with the word-primed music-elicited N400 certain generators that are located in cortical areas BA 21/37 and BA 22. This suggests that even chord-primed chord targets can convey extra-musical meanings and that, consequently, they might be useful in assessing residual higher-order information-processing capabilities in non-communicating patients with disorders of consciousness.

Evolution of Severe Closed Head Injury: Assessing Ventricular Volume and Behavioral Measures at 30 and 90 Days Post-Injury.

Background: Assessing functional outcomes in Severe Closed Head Injury (SCHI) is complex due to brain parenchymal changes. This study examines the Ventricles to Intracranial Volume Ratio (VBR) as a metric for these changes and its correlation with behavioral scales. Methods: Thirty-one SCHI patients were included. VBR was derived from CT scans at 3, 30, and 90 days post-injury and compared with Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) assessments at 30 and 90 days. Results: Ten patients were excluded post-decompressive craniectomy or ventriculoperitoneal shunt. Findings indicated a VBR decrease at 3 days, suggesting acute phase compression, followed by an increase from 30 to 90 days, indicative of post-acute brain atrophy. VBR correlated positively with the Marshall score in the initial 72 h, positioning it as an early indicator of subsequent brain atrophy. Nevertheless, in contrast to the Marshall score, VBR had stronger associations with DRS and ERBI at 90 days. Conclusions: VBR, alongside behavioral assessments, presents a robust framework for evaluating SCHI progression. It supports early functional outcome correlations informing therapeutic approaches. VBR's reliability underscores its utility in neurorehabilitation for ongoing SCHI assessment and aiding clinical decisions.

Cortical source of blink-related delta oscillations and their correlation with levels of consciousness.

Recently, blink-related delta oscillations (delta BROs) have been observed in healthy subjects during spontaneous blinking at rest. Delta BROs have been linked with continuous gathering of information from the surrounding environment, which is classically attributed to the precuneus. Furthermore, fMRI studies have shown that precuneal activity is reduced or missing when consciousness is low or absent. We therefore hypothesized that the source of delta BROs in healthy subjects could be located in the precuneus and that delta BROs could be absent or reduced in patients with disorders of consciousness (DOC). To test these hypotheses, electroencephalographic (EEG) activity at rest was recorded in 12 healthy controls and nine patients with DOC (four vegetative states, and five minimally conscious states). Three-second-lasting EEG epochs centred on each blink instance were analyzed in both time- (BROs) and frequency domains (event-related spectral perturbation or ERSP and intertrial coherence or ITC). Cortical sources of the maximum blink-related delta power, corresponding to the positive peak of the delta BROs, were estimated by standardized Low Resolution Electromagnetic Tomography. In control subjects, as expected, the source of delta BROs was located in the precuneus, whereas in DOC patients, delta BROs were not recognizable and no precuneal localization was possible. Furthermore, we observed a direct relationship between spectral indexes and levels of cognitive functioning in all subjects participating in the study. This reinforces the hypothesis that delta BROs reflect neural processes linked with awareness of the self and of the environment.

Pointing in cervical dystonia patients.

Introduction: The normal hemispheric balance can be altered by the asymmetric sensorimotor signal elicited by Cervical Dystonia (CD), leading to motor and cognitive deficits. Methods: Directional errors, peak velocities, movement and reaction times of pointing towards out-of-reach targets in the horizontal plane were analysed in 18 CD patients and in 11 aged-matched healthy controls. Results: CD patients displayed a larger scatter of individual trials around the average pointing direction (variable error) than normal subjects, whatever the arm used, and the target pointed. When pointing in the left hemispace, all subjects showed a left deviation (constant error) with respect to the target position, which was significantly larger in CD patients than controls, whatever the direction of the abnormal neck torsion could be. Reaction times were larger and peak velocities lower in CD patients than controls. Discussion: Deficits in the pointing precision of CD patients may arise from a disruption of motor commands related to the sensorimotor imbalance, from a subtle increase in shoulder rigidity or from a reduced agonists activation. Their larger left bias in pointing to left targets could be due to an increased right parietal dominance, independently upon the direction of head roll/jaw rotation which expands the left space representation and/or increases left spatial attention. These deficits may potentially extend to tracking and gazing objects in the left hemispace, leading to reduced skills in spatial-dependent motor and cognitive performance.

Positive effects of robotic exoskeleton training of upper limb reaching movements after stroke.

This study, conducted in a group of nine chronic patients with right-side hemiparesis after stroke, investigated the effects of a robotic-assisted rehabilitation training with an upper limb robotic exoskeleton for the restoration of motor function in spatial reaching movements. The robotic assisted rehabilitation training was administered for a period of 6 weeks including reaching and spatial antigravity movements. To assess the carry-over of the observed improvements in movement during training into improved function, a kinesiologic assessment of the effects of the training was performed by means of motion and dynamic electromyographic analysis of reaching movements performed before and after training. The same kinesiologic measurements were performed in a healthy control group of seven volunteers, to determine a benchmark for the experimental observations in the patients' group. Moreover degree of functional impairment at the enrolment and discharge was measured by clinical evaluation with upper limb Fugl-Meyer Assessment scale (FMA, 0-66 points), Modified Ashworth scale (MA, 0-60 pts) and active ranges of motion. The robot aided training induced, independently by time of stroke, statistical significant improvements of kinesiologic (movement time, smoothness of motion) and clinical (4.6 ± 4.2 increase in FMA, 3.2 ± 2.1 decrease in MA) parameters, as a result of the increased active ranges of motion and improved co-contraction index for shoulder extension/flexion. Kinesiologic parameters correlated significantly with clinical assessment values, and their changes after the training were affected by the direction of motion (inward vs. outward movement) and position of target to be reached (ipsilateral, central and contralateral peripersonal space). These changes can be explained as a result of the motor recovery induced by the robotic training, in terms of regained ability to execute single joint movements and of improved interjoint coordination of elbow and shoulder joints.

Effect of the Trigeminal Nerve Stimulation on Auditory Event-Related Potentials.

Trigeminal sensorimotor activity stimulates arousal and cognitive performance, likely through activation of the locus coeruleus (LC). In this study we investigated, in normal subjects, the effects of bilateral trigeminal nerve stimulation (TNS) on the LC-dependent P300 wave, elicited by an acoustic oddball paradigm. Pupil size, a proxy of LC activity, and electroencephalographic power changes were also investigated. Before TNS/sham-TNS, pupil size did not correlate with P300 amplitude across subjects. After TNS but not sham-TNS, a positive correlation emerged between P300 amplitude and pupil size within frontal and median cortical regions. TNS also reduced P300 amplitude in several cortical areas. In both groups, before and after TNS/sham-TNS, subjects correctly indicated all the target stimuli. We propose that TNS activates LC, increasing the cortical norepinephrine release and the dependence of the P300 upon basal LC activity. Enhancing the signal-to-noise ratio of cortical neurons, norepinephrine may improve the sensory processing, allowing the subject to reach the best discriminative performance with a lower level of neural activation (i.e., a lower P300 amplitude). The study suggests that TNS could be used for improving cognitive performance in patients affected by cognitive disorders or arousal dysfunctions.

Blink-related delta oscillations in the resting-state EEG: a wavelet analysis.

Over the past decades, many studies have linked the variations in frequency of spontaneous blinking with certain aspects of information processing and in particular with attention and working memory functions. On the other hand, according to the theory postulated by Crick and Koch, the actual function of primary consciousness is based on the reciprocal interaction between attention and working memory in the automatic and serial mode. The purpose of this study was to investigate for electrophysiological correlates compatible with the cognitive nature of spontaneous blinking, by using the EEG recordings obtained in a group of seven healthy volunteers while they rested quietly though awake, with their eyes open, but not actively engaged in attention-demanding goal-directed behaviours. The global wavelet analysis - at total of 189 three-second EEG epochs time-locked to the blink - revealed an increase in the delta band signal corresponding to the blink. In particular, a reconstruction of the EEG signal by means of inverse-wavelet transform (IWT) showed a blink-related P300-like wave at mid-parietal site. We assumed this phenomenon to represent an electrophysiological sign of the automatic processing of contextual environmental information. This might play a role in maintaining perceptive awareness of the environment at a low level of processing, while the subject is not engaged in attention-demanding tasks but rather introspectively oriented mental activities or free association(s).

Higher level gait disorders in subcortical chronic vascular encephalopathy: a single photon emission computed tomography study.

BACKGROUND: the so-called higher level gait disorders include several types of gait disorders in which there are no major modifications in strength, tone, sensitivity, coordination and balance. Brain activation sites related to walking have been investigated using SPECT in humans. The aim of the study was to investigate brain activation during walking in subjects with high-level gait disorders due to chronic subcortical vascular encephalopathy. SUBJECTS: twelve patients with a chronic vascular encephalopathy were enrolled in the study. Seven subjects had apraxic gait while in the other five the gait was normal. All patients had undergone a recent cerebral magnetic resonance that revealed diffused chronic ischemic lesions within the white matter. METHODS: all 12 patients underwent a regional cerebral blood flow (rCBF) brain SPECT study with (99m)Tc-Bicisate on two separate days and under two different conditions: at rest (baseline) and while walking (functional). RESULTS: the rCBF increase induced by the treadmill test (functional-baseline), bilaterally in the medial frontal gyrus and in the anterior lobes of the cerebellum, resulted significantly (P < 0.001) lower in patients with gait apraxia versus those without it. CONCLUSIONS: this study of the brain with SPECT records the areas of perfusion deficit that appear in apraxic subjects when they walk, compared with the recordings obtained with the same investigation performed at rest.

A Case of Carbon Monoxide-Induced Delayed Neurological Sequelae Successfully Treated with Hyperbaric Oxygen Therapy, N-Acetylcysteine, and Glucocorticoids: Clinical and Neuroimaging Follow-Up.

Carbon monoxide (CO) poisoning is a leading cause of intentional and unintentional poisoning worldwide, associated with mortality and severe morbidity. Some survivors of CO poisoning develop, after a lucid interval, a potentially permanent encephalopathy in the form of cognitive impairment and movement disorders, such as Parkinsonism. One of the most frequent neuroimaging findings is a cerebral white matter damage, but so far its precise cause and specific therapy are still debated. We here report the case of a 33-year-old woman with severe carbon monoxide poisoning who, after a period of lucid interval, presented symptoms of declining motor and cognitive functions. She was treated with 40 sessions of Hyperbaric Oxygen Therapy (HBOT). The therapeutic use of oxygen at supraphysiological pressures might either increase systemic oxidative stress or cause an overproduction of oxygen free radicals as drawbacks. Concurrent use of antioxidants and anti-inflammatory drugs may prevent the side effects of oxygen therapy at supraphysiological pressure due to oxidative stress. For this reason, the patient was also treated with high-dose N-Acetylcysteine and glucocorticoids. Here, we describe the longitudinal monitoring of patient's cognitive abilities and leukoencephalopathy associated with her positive clinical outcome.

Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs).

Acupuncture therapy has been used to treat several disorders in Asian countries and its use is increasing in Western countries as well. Current literature assessed the safety and efficacy of acupuncture in the acute management and rehabilitation of patients with neurologic disorders. In this paper, the role of acupuncture in the treatment of acute severe acquired brain injuries is described, acting on neuroinflammation, intracranial oedema, oxidative stress, and neuronal regeneration. Moreover, beneficial effects of acupuncture on subacute phase and chronic outcomes have been reported in controlling the imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence of neurovegetative crisis. Moreover, acupuncture may have a positive action on the arousal recovery. Further work is needed to understand the effects of specific acupoints on the brain. Allegedly concurrent neurophysiological measurements (e.g., EEG) may help in studying acupuncture-related changes in central nervous system activity and determining its potential as an add-on rehabilitative treatment for patients with consciousness disorders.

EEG Theta Dynamics within Frontal and Parietal Cortices for Error Processing during Reaching Movements in a Prism Adaptation Study Altering Visuo-Motor Predictive Planning.

Modulation of frontal midline theta (fmθ) is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error), at the time when visual feedback (hand appearance) became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP) time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects) suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi-naturalistic motor behaviours.

Cross-correlation time-frequency analysis for multiple EMG signals in Parkinson's disease: a wavelet approach.

Using a wavelet analysis approach, it is possible to investigate better the transient and intermittent behavior of multiple electromyographic (EMG) signals during ballistic movements in Parkinsonian patients. In particular, a wavelet cross-correlation analysis on surface signals of two different shoulder muscles allows us to evidence the related unsteady and synchronization characteristics. With a suitable global parameter extracted from local wavelet power spectra, it is possible to accurately classify the subjects in terms of a reliable statistic and to study the temporal evolution of the Parkinson's disease level. Moreover, a local intermittency measure appears as a new promising index to distinguish the low-frequency behavior from normal subjects to Parkinsonian patients.

A case of post-traumatic minimally conscious state reversed by midazolam: Clinical aspects and neurophysiological correlates.

PURPOSE: We describe the case of a subject in a post-traumatic Minimally Conscious State (MCS) who retrieved full interaction with the environment after midazolam infusion. We studied EEG correlates of the "awakening reaction" in the different domains of frequency, time and cortical topography, along with the intrinsic connectivity within both the task-positive and the linguistic network. METHODS: EEG recorded before and after midazolam administration has been submitted to spectral power analysis, sLORETA analysis and intrinsic connectivity analysis within both functional networks. RESULTS: A critical change in the power spectrum profile was observed after midazolam: a) the power between 1 and 12 Hz decreased, reaching its maximum difference with respect to pre-infusion at about 7 Hz and b) the power between 12 and 30 Hz increased, with a maximum difference at about 15 Hz. At the same time, midazolam induced significant connectivity changes, especially for these two frequency bands, within both functional networks. CONCLUSIONS: We advance some hypotheses about certain aspects of the recovery from the MCS both in terms of anatomo-functional correlations and functional brain systems and we make inferences about the role that some kind of 'catatonic' symptoms might play in determining and/or maintaining this peculiar clinical state.