Effect of Exoskeleton-Assisted Rehabilitation Over Prefrontal Cortex in Multiple Sclerosis Patients: A Neuroimaging Pilot Study.

Application of a passive and fully articulated exoskeleton, called Human Body Posturizer (HBP), has been demonstrated to improve mobility, response accuracy and ambulation in multiple sclerosis (MS) patients. By using functional magnetic imaging (fMRI) during a visuomotor discrimination task, we performed a pilot study to evaluate the effect of HBP over the neural correlates of motor and cognitive functions which are typically impaired in MS patients. Specifically, we tested the effect of a 6-week multidisciplinary rehabilitation intervention on two groups of MS patients: a control group who followed a standard physiotherapeutic rehabilitation protocol, and an experimental group who used the HBP during physical exercises in addition to the standard protocol. We found that, after treatment, the experimental group exhibited a significant lower activity (as compared to the control group) in the inferior frontal gyrus. This post-treatment activity reduction can be explained as a retour to a normal range, being the amount of iFg activity observed in the experimental patients very similar to that observed in healthy subjects. These findings indicate that the use of HBP during rehabilitation intervention normalizes the prefrontal activity, mitigating the cortical hyperactivity associated to MS.

Effect of task complexity on motor and cognitive preparatory brain activities.

In the present study, we investigated scalp-recorded activities of motor and cognitive preparation preceding stimulus presentation in relatively simple and complex visual motor discriminative response tasks (DRTs). Targets and non-targets were presented (with equal probability) in both tasks, and the complexity of the task depended on the discrimination and categorization processing load, which was based on the number of stimuli used (two stimuli in the simple- and four in the complex-DRT, respectively). We recorded event-related potentials (ERPs) in 16 participants in simple-DRT and 16 participants in complex-DRT. At the behavioral level, the performance was faster and more accurate in simple-DRT. Two pre-stimulus ERPs were considered: the central Bereitschaftspotential (BP) and the prefrontal negativity (pN). Both components showed earlier onset and larger amplitude in the complex-DRT. Overall, the simple-DRT required less motor and cognitive preparation in premotor and prefrontal areas compared to the complex-DRT. Present findings also suggest that the pN component was not reported in previous studies, likely because most ERP literature focusing on pre-stimulus ERP used simple-DRTs, and with such a task the pN amplitude is small and can easily go undetected.

Females are more proactive, males are more reactive: neural basis of the gender-related speed/accuracy trade-off in visuo-motor tasks.

In the present study, we investigated neural correlates associated with gender differences in a simple response task (SRT) and in a discriminative response task (DRT) by means of event-related potential (ERP) technique. 120 adults participated in the study, and, based on their sex, were divided into two groups matched for age and education level. Behavioral performance was assessed with computing response speed, accuracy rates and response consistency. Pre- and post-stimulus ERPs were analyzed and compared between groups. Results indicated that males were faster than females in all tasks, while females were more accurate and consistent than males in the more complex tasks. This different behavioral performance was associated with distinctive ERP features. In the preparation phase, males showed smaller prefrontal negativity (pN) and visual negativity (vN), interpreted as reduced cognitive preparation to stimulus occurrence and reduced reliance on sensory proactive readiness, respectively. In the post-stimulus phase, gender differences were present over occipital (P1, N1, P2 components) and prefrontal (pN1, pP1, pP2 components) areas, suggesting allocation of attentional resources at distinct stages of information processing in the two groups. Overall, the present data provide evidence in favor of a more proactive and cautious cognitive processing in females and a more reactive and fast cognitive processing in males. In addition, we confirm that (1) gender is an important variable to be considered in ERP studies on perceptual processing and decision making, and (2) the pre-stimulus component analysis can provide useful information concerning neural correlates of upcoming performance.

Modality-specific sensory readiness for upcoming events revealed by slow cortical potentials.

Human brain activity allows to anticipate future events and to prepare the next action accordingly; consistently, event-related potential (ERP) studies found action preparatory brain activities in the premotor and prefrontal cortex. In the present study, we investigated the preparatory activity in the sensory cortical regions. Slow cortical potentials were recorded during passive tasks, i.e., subjects expected for a sensory stimulus and no motor or cognitive response were required. In particular, we tested the hypothesis that perceptual anticipatory cortical mechanisms were modality specific. Three groups of 21 young adults underwent passive perceptual tasks in different sensory modalities (visual, auditory, or somatosensory). We confirmed the presence of a visual negativity (vN) component for the visual modality starting about 800 ms before stimulus with source in extrastriate areas and we found novel modality-specific sensory readiness components for the auditory and somatosensory modalities. The auditory positivity (aP) started about 800 ms before stimulus with source in bilateral auditory cortices and the somatosensory negativity (sN) started about 500 ms before stimulus with source in the somatosensory secondary cortex, contralateral to the stimulated hand. The scalp topography and intracranial sources of these three slow preparatory activities were mirrored with inverted polarity at early post-stimulus stage evoking the well-known visual P1, auditory N1, and somatosensory P100 components. Present findings contribute to widening the family of slow wave preparatory components, providing evidence about the relationship between top-down and bottom-up processing in sensory perception.

Weak proactive cognitive/motor brain control accounts for poor children's behavioral performance in speeded discrimination tasks.

BACKGROUND: Motor and inhibitory control rely on frontal cortex activity, which is known to reach full maturation only in late adolescence. The development of inhibitory control has been studied using event-related potentials (ERP), focusing on reactive processing (i.e. the N2 and the P3 components). Scarce information exists concerning pre-stimulus activity as that represented by the Bereinshafstpotential (BP) and by the prefrontal negativity (pN). Further, no literature exists concerning the post-stimulus components originating within the anterior insula (pN1, pP1, pP2). This study aims at associating children performance with these motor-cognitive processing in frontal brain areas. METHODS: High-resolution EEG recordings were employed to measure ERPs from 18 children (12 years old) and 18 adults (28 years old) during a visuo-motor discriminative response task. Response time (RT), commission (CE) and omission errors, and RT variability were compared between groups. At brain level, two pre-stimulus (BP and pN) and seven post-stimulus (P1; pN1; N1; pP1; N2; pP2; P3) ERP components were compared between groups. RESULTS: Children showed slower and more variable RTs and poorer inhibition (higher CEs) than adults. At electrophysiological level, children presented smaller BP and pN. After stimulus onset, children showed lower amplitude of N1, pP1, P3, and pP2 components. The P1, pP1, N2 and P3 were delayed compared to adults. CONCLUSIONS: Our results demonstrate that children are characterized by less intense task-related proactive activities in frontal cortex, which may account for subsequent poor and delayed reactive processing and, thus, for inaccurate and slow performance.

Exercise-related cognitive effects on sensory-motor control in athletes and drummers compared to non-athletes and other musicians.

Both playing a musical instrument and playing sport produce brain adaptations that might affect sensory-motor functions. While the benefits of sport practice have traditionally been attributed to aerobic fitness, it is still unknown whether playing an instrument might induce similar brain adaptations, or if a specific musical instrument like drums might be associated to specific benefits because of its high energy expenditure. Since the aerobic costs of playing drums was estimated to be comparable to those of average sport activities, we hypothesized that these two groups might show both behavioral and neurocognitive similarities. To test this hypothesis, we recruited 48 young adults and divided them into four age-matched groups: 12 drummers, 12 athletes, 12 no-drummer musicians and 12 non-athletes. Participants performed a visuo-motor discriminative response task, namely the Go/No-go, and their cortical activity was recorded by means of a 64-channel electroencephalography (EEG). Behavioral performance showed that athletes and drummers were faster than the other groups. Electrophysiological results showed that the pre-stimulus motor preparation (i.e. the Bereitschaftspotential or BP) and attentional control (i.e., the prefrontal negativity or pN), and specific post-stimulus components like the P3 and the pP2 (reflecting the stimulus categorization process) were enhanced in the athletes and drummers' groups. Overall, these results suggest that playing sport and drums led to similar benefits at behavioral and cognitive level as detectable in a cognitive task. Explanations of these findings, such as on the difference between drummers and other musicians, are provided in terms of long-term neural adaptation mechanisms and increased visuo-spatial abilities.

The proactive self-control of actions: Time-course of underlying brain activities.

Proactive brain control optimizes upcoming actions and inhibits unwanted responses. In the present event-related potential (ERP) study, participants freely decided in advance whether to respond or not to an upcoming stimulus, then prepared or not the action according to their decision; finally, a stimulus was delivered, and subjects had to respond (or not). During the decision-making stage, a prefrontal negativity raised bilaterally in case no-response was decided, reflecting the first brain signal of proactive inhibition. Simultaneously, slow activity raised over premotor cortices independently from the decision taken, and then raised during the preparation phase only in the case of response decision (as a sort of accelerator). When the decision was not to respond, the prefrontal activity remained sustained (as a sort of brake) and showed a right-lateralized distribution during the preparation phase. Overall, we described the time-course of a proactive accelerating-braking system regulating self-control of actions.

Beyond the "Bereitschaftspotential": Action preparation behind cognitive functions.

Research on preparatory brain processes taking place before acting shows unexpected connections with cognitive processing. From 50 years, we know that motor-related brain activity can be measured by electrocortical recordings 1-3s before voluntary actions. This readiness potential has been associated with increasing excitably of premotor and motor areas and directly linked to the kinematic of the upcoming action. Now we know that the mere motor preparation is only one function of a more complex preparatory activity. Recent research shows that before any action many cognitive processes may occur depending on various aspects of the action, such as complexity, meaning, emotional valence, fatigue and consequences of the action itself. In addition to studies on self-paced action, the review considers also studies on externally-triggered paradigms showing differences in preparation processes related to age, physical exercise, and task instructions. Evidences from electrophysiological and neuroimaging recording indicate that in addition to the motor areas, the prefrontal, parietal and sensory cortices may be active during action preparation to anticipate future events and calibrate responses.

New insights into old waves. Matching stimulus- and response-locked ERPs on the same time-window.

We compared the effect of locking the event-related potentials (ERPs) on the stimulus vs. the response in a simple (SRT) and in a discriminative (DRT, equally probable Go/No-go) visuo-motor task. The accurate alignment of stimulus- and response-locked ERPs on the same time scale was obtained selecting a group of 27 participants with low inter-individual response time (RT) variation in the two tasks to reduce the jitter of RTs. Two-second epochs were defined for the analyses based on averaged RTs in the two tasks. Results show that the preparatory pre-stimulus activities (i.e., the pN and the BP components) were not affected by the different locking in both SRT and DRT. As expected, the exogenous post-stimulus P1 and N1 components (and the P2, present only in SRT) were larger in stimulus- than response-locked averaging; the same trend was observed for the less-known prefrontal N1 and P1 components (pN1 and pP1) that were larger in stimulus-locked averaging (the effect was not significant in SRT). The prefrontal pP2 component was only present in DRT peaking around 370 ms, and did not show an effect of locking. The frontal-central N2 component was enhanced by response-locked averaging in SRT, while it did not show effects of locking in DRT. The P3 component peaked at about 350ms over central sites in SRT, and at about 500ms over parietal sites in DRT; in both cases its amplitude was larger in response- than in stimulus-locked averaging. Overall, the amplitude of the preparatory components was independent from locking, the exogenous components were enhanced by stimulus locking, and the late components were more related to the response than to the stimulus. Concluding, to investigate action preparation, perception, and perceptual-decisional activity ERP studies should adopt stimulus-locked averaging with an appropriate baseline and longer pre-stimulus interval, or use both types of locking.

Effect of target probability on pre-stimulus brain activity.

Studies on perceptual decision-making showed that manipulating the proportion of target and non-target stimuli affects the behavioral performance. Tasks with high frequency of targets are associated to faster response times (RTs) conjunctively to higher number of errors (reflecting a response bias characterized by speed/accuracy trade-off) when compared to conditions with low frequency of targets. Electroencephalographic studies well described modulations of post-stimulus event-related potentials as effect of the stimulus probability; in contrast, in the present study we focused on the pre-stimulus preparatory activities subtending the response bias. Two versions of a Go/No-go task characterized by different proportion of Go stimuli (88% vs. 12%) were adopted. In the task with frequent go trials, we observed a strong enhancement in the motor preparation as indexed by the Bereitschaftspotential (BP, previously associated with activity within the supplementary motor area), faster RTs, and larger commission error rate than in the task with rare go trials. Contemporarily with the BP, a right lateralized prefrontal negativity (lateral pN, previously associated with activity within the dorsolateral prefrontal cortex) was larger in the task with rare go trial. In the post-stimulus processing stage, we confirmed that the N2 and the P3 components were larger for rare trials, irrespective of the Go/No-go stimulus category. The increase of activities recorded in the preparatory phase related to frequency of targets is consistent with the view proposed in accumulation models of perceptual decision for which target frequency affects the subjective baseline, reducing the distance between the starting-point and the response boundary, which determines the response speed.

From cognitive motor preparation to visual processing: The benefits of childhood fitness to brain health.

The association between a fit body and a fit brain in children has led to a rise of behavioral and neuroscientific research. Yet, the relation of cardiorespiratory fitness on premotor neurocognitive preparation with early visual processing has received little attention. Here, 41 healthy, lower and higher fit preadolescent children were administered a modified version of the Eriksen flanker task while electroencephalography (EEG) and behavioral measures were recorded. Event-related potentials (ERPs) locked to the stimulus onset with an earlier than usual baseline (-900/-800 ms) allowed investigation of both the usual post-stimulus (i.e., the P1, N1 and P2) as well as the pre-stimulus ERP components, such as the Bereitschaftspotential (BP) and the prefrontal negativity (pN component). At the behavioral level, aerobic fitness was associated response accuracy, with higher fit children being more accurate than lower fit children. Fitness-related differences selectively emerged at prefrontal brain regions during response preparation, with larger pN amplitude for higher than lower fit children, and at early perceptual stages after stimulus onset, with larger P1 and N1 amplitudes in higher relative to lower fit children. Collectively, the results suggest that the benefits of being aerobically fit appear at the stage of cognitive preparation prior to stimulus presentation and the behavioral response during the performance of a task that challenges cognitive control. Further, it is likely that enhanced activity in prefrontal brain areas may improve cognitive control of visuo-motor tasks, allowing for stronger proactive inhibition and larger early allocation of selective attention resources on relevant external stimuli.

Development of mu rhythm in infants and preschool children.

Mu rhythm is an idling rhythm that originates in the sensorimotor cortex during rest. The frequency of mu rhythm, which is well established in adults, is 8-12 Hz, whereas the limited results available from children suggest a frequency as low as 5.4 Hz at 6 months of age, which gradually increases to the adult value. Understanding the normal development of mu rhythm has important theoretical and clinical implications since we still know very little about this signal in infants and how it develops with age. We measured mu rhythm over the left hemisphere using a pediatric magnetoencephalography (MEG) system in 25 infants (11-47 weeks), 18 preschool children (2-5 years) and 6 adults (20-39 years) for two 5-min sessions during two intermixed conditions: a rest condition in which the hands were at rest, and a prehension condition in which the subject squeezed a pipette with his/her right hand. In all participants, mu rhythm was present over the frontoparietal area during the rest condition, but was clearly suppressed during the prehension condition. Mu rhythm peak frequency, determined from the amplitude spectra, increased rapidly as a function of age from 2.75 Hz at 11 weeks to 8.25 Hz at 47 weeks (r2 = 0.83). It increased very slowly during the preschool period (3.1 ± 0.9 years; 8.5 ± 0.54 Hz). The frequency in these children was, however, lower than in adults (10.3 ± 1.2 Hz). Our results show a rapid maturation in spontaneous mu rhythm during the first year of life.

[Determinants of short-term memory: is there a difference between young adults and postmenopausal women?]. / Fattori determinanti la memoria a breve termine: esiste una differenza tra giovani donne e donne in postmenopausa?

AIM: The literature indicates that several variables are influencing cognitive health. The aim of the study was to investigate the main determinants of the short-term memory among anthropometric, dietary and performance variables in a sample of healthy women. The role played by the age was also investigated. METHODS: Forty-five healthy overweight women were recruited through general physicians: 23 were young adults (24.63±4.17 years) and 22 were postmenopausal (53.30±2.95 years). Overweight condition was assessed according to the age-adjusted reference values. Participants were analyzed for Digit Span, blood pressure, body composition, aerobic fitness and dietary habits. RESULTS: Young adults and postmenopausal women did not differ either in Digit Span or in dietary habits. In postmenopausal women Digit Span was positively correlated with body weight, body mass index, body fat, waist circumference and daily intake of vitamin D. Linear regression model indicated vitamin D as the only significant predictor variable of Digit Span. In young adults Digit Span had no correlations with the others investigated variables. CONCLUSION: In postmenopause, vitamin D daily intake is important not only for skeletal, but also for cognitive health. Even though young adults and post-menopausal women did not differ for health status, short-term memory in young adulthood seems to be differently linked with the investigated variables than during post-menopause.

[Nimesulide in the treatment of osteoarthrosis and extra-articular rheumatism]. / La nimesulide nel trattamento della osteoartrosi e dei reumatismi extra-articolari.

Nimesulide is a new non-steroidal anti-inflammatory drug which seems to be characterized by a low inhibitory action on prostaglandin synthesis and a high inhibitory action on oxygen free radicals production. The aim of this trial was to determine the effect of Nimesulide on degenerative joint disease and on non-articular rheumatism. One hundred and forty, 64 females and 76 males aged 51.9 +/- 1.2 years, affected with osteoarthritis or non-articular rheumatism (fibromyalgia, periarthritis, tendinitis, tenosynovitis, bursitis and enthesitis) were studied. Nimesulide was administered at a daily dosage of 200 mg. A significative improvement in the clinical parameters studied was observed in all the patients, but a more remarkable progress was noted in the group with non-articular rheumatism. The incidence of adverse reactions was irrelevant: 2 patients complained of epigastralgia that subsided reducing the daily dosage to 100 mg.

Asymptomatic and symptomatic gastroduodenal patients affected by rheumatic disease treated with non-steroidal anti-inflammatory drugs.

It is becoming more apparent that the common gastritis and ulcer complications associated with non steroidal anti-inflammatory drugs (NSAID's) are distinct from classic peptic ulcer disease. To assess the incidence of gastrointestinal lesions and the existence of correlation with gastrointestinal symptoms, patients affected by rheumatic diseases treated with NSAIDs were carefully questioned to evaluate gastrointestinal symptoms and then underwent an esophagogastroduodenoscopic examination. The study demonstrates a relevant absence of gastrointestinal symptoms with an high incidence of gastric mucosal lesions in this patients. Asymptomatic lesions seem to be a characteristic feature of NSAID gastropathy. The blockade of synthesis of prostaglandins, due to the inhibition of cyclooxygenase by NSAIDs, may create an environment conducive to gastritis or ulcer disease and may be responsible of the absence of gastrointestinal symptoms.

Impaired growth hormone response to clonidine in obesity.

Clonidine, an imidazoline derivative, is an antihypertensive agent which reduces sympathetic tone by acting in the central nervous system to stimulate alpha-2 adrenoceptors. There is evidence that dopamine and norepinephrine modulate the secretion of GH. Stimulation of GH release is a well-known effect of clonidine in man. Obesity is characterized by an impairment of GH release in response to various stimuli. The aim of this work is to study GH release in response to alpha-2 adrenoceptors stimulation by clonidine in obesity. 12 volunteer obese subjects were studied. 10 normal weight subjects, sex and age matched, were controls. The GH responsiveness was tested with a single oral dose of clonidine (0.15 mg). Blood was sampled for GH radioimmunoassay at 0', 30', 60', 90', 120', 150', 180'. Serum GH basal levels were not significant different in obese subjects compared to controls. In obese subjects, no significant changes occurred in blood GH concentration after clonidine. In normal weight controls, instead, a significant increase of GH values was reached at 90' (P less than 0.05) and at 120' (P less than 0.05) after clonidine. The impairment of GH release after clonidine in obese subjects might be in a reduced serotonin release or in a failure of the hypothalamic-pituitary system to stimulate plasma GH caused by a diminished GH releasing factor stimulatory effect or by an excessive endorphin or somatostatin secretion in obesity.

Acute rheumatoid factor positive (IgM) polyarthritis associated with a Klebsiella pneumonitis.

The authors report a case of a patient suffering from acute polyarthritis with a high rheumatoid factor titre, associated with a Klebsiella pneumonitis. A polyclonal B lymphocyte activation or a possible cross reaction between rheumatoid factor and an antigen related to Klebsiella may explain the elevated production of rheumatoid factor observed.