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.

Normative event-related potentials from sensory and cognitive tasks reveal occipital and frontal activities prior and following visual events.

In the present study, we report the results from a large sample of participants (N = 136), selected based on their EEG quality, to obtain event-related potential (ERP) normative data. All participants were tested in Simple Response Task (SRT) and Discriminative Response Task (DRT). A subset of 36 participants was tested also in Passive Vision task. Both pre- and post-stimulus ERPs were analyzed and compared among different tasks. Spatiotemporal patterns of all the observed components were analyzed using source analysis. Beside the well-known ERP components, we also described recently identified prefrontal components: the pre-stimulus prefrontal negativity (pN) associated to proactive cognitive (mainly inhibitory) control within the inferior frontal gyrus (iFg); the post-stimulus prefrontal N1, P1 and P2 (pN1, pP1 and pP2) involved in perceptual and visual-motor awareness (pN1 and pP1), and in stimulus-response mapping and decision-making (pP2) localized within the insular cortex. The large sample of high-quality EEG datasets allowed to identify four additional components: the pre-stimulus visual negativity (vN) originating in extrastriate visual areas and interpreted as a visual readiness activity; the post-stimulus prefrontal N2 and N3 (pN2 and pN3) components interpreted as feedback reactivation of the anterior insular cortex; and the post-stimulus prefrontal P3 (pP3), interpreted as persisting inhibitory activity of the iFg for inhibited trials.

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.

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.

Sight and sound of actions share a common neural network.

The mirror-neuron system (MNS) connects sensory information that describes an action with a motor plan for performing that action. Recently, studies using the repetition-suppression paradigm have shown that strong activation occurs in the left premotor and superior temporal areas in response to action-related, but not non-action-related, stimuli. However, few studies have investigated the mirror system by using event-related potentials (ERPs) and employing more than one sensory modality in the same sample. In the present study, we compared ERPs that occurred in response to visual and auditory action/non-action-related stimuli to search for evidence of overlapping activations for the two modalities. The results confirmed previous studies that investigated auditory MNS and extended these studies by showing that similar activity existed for the visual modality. Furthermore, we confirmed that the responses to action- and non-action-related stimuli were distinct by demonstrating that, in the case of action-related stimuli, activity was restricted mainly to the left hemisphere, whereas for non-action-related stimuli, activity tended to be more bilateral. The time course of ERP brain sources showed a clear sequence of events that subtended the processing of action-related stimuli. This activity seemed to occur in the left temporal lobe and, in agreement with findings from previous studies of the mirror-neuron network, the information involved appeared to be conveyed subsequently to the premotor area. The left temporo-parietal activity observed following a delay might reflect processing associated with stimulus-related motor preparation.

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.

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.

Abnormal motor preparation in severe traumatic brain injury with good recovery.

Movement-related cortical potentials (MRCPs) were examined in seven patients with severe traumatic brain injury (TBI) and 12 matched control subjects. All patients had clinically established good recovery by the time of testing. Flexion movements of the index finger of the left or right hand were recorded in two (alternating and repetitive) self-paced conditions and in one externally triggered condition. In control subjects, the bereitschaftspotential (BP) component of MRCP was detected approximately 2000 msec prior to movement onset in the self-paced conditions and was larger and earlier in the alternating compared to the repetitive condition. The BP component was absent in the externally triggered condition. In TBI patients, the BP was greatly reduced and no difference between the alternating-repetitive conditions was detected; in contrast, only small differences were present in the controls for the negative slope (NS) and MP components and no difference for the reafferent positivity (RAP) component. A dipole analysis indicated the supplementary motor area and the premotor area as the likely generators of BP and NS' components, respectively. Gradientrecalled echo magnetic resonance imaging allowed the detection of a number of small hypointense lesions primarily located in the frontal lobes, as in diffuse axonal injury. This pattern of results indicates a selective deficit in motor preparation and a relatively spared pattern of activation during and following movement in these patients. Imaging data appear generally consistent with the pattern of MRCPs observed in the patient group. Implications of these results for the problem of slowness in TBI patients are discussed.

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.

An analysis of audio-visual crossmodal integration by means of event-related potential (ERP) recordings.

Crossmodal integration was studied in humans by presenting random sequences of auditory (brief noise bursts), visual (flashes), and audiovisual (simultaneous noise bursts and flashes) stimuli from a central location at irregular intervals between 600 and 800 ms. The subjects' task was to press a button to infrequent and unpredictable (P=0.15) target stimuli that could be either a more intense noise burst, a brighter flash, or a combination of the two. In accordance with previous studies, behavioral data showed that bimodal target stimuli were responded to much faster and were identified more accurately than the unimodal target stimuli. The neural basis of this crossmodal interaction was investigated by subtracting the ERPs to the auditory (A) and the visual (V) stimuli alone from the ERP to the combined audiovisual (AV) stimuli (i.e. interaction=AV-(A+V)). Using this approach, we replicated previous reports of both early (at around 40 ms) and late (after 100 ms) ERP interaction effects. However, it appears that the very early interaction effects can be largely accounted for by an anticipatory ERP that precedes both the unimodal and bimodal stimuli. In calculating the ERP interaction this slow shift is subtracted twice, resulting in an apparent shift of the opposite polarity that may be confounded with actual crossmodal interactions.

Visual evoked potentials are affected by trunk rotation in neglect patients.

Steady-state visual evoked potentials (VEPs) were recorded in four patients with unilateral visuo-spatial neglect, stimulating either the left or the right hemifield. In the standard condition (head and body oriented straight ahead towards the stimulus) the left hemifield VEP was delayed. When the body was turned to the left, however, the two hemifield latencies were comparable. These results were confirmed with the transient VEP technique. No effect of trunk rotation was observed in a group of patients with left brain damage and without neglect. The results imply that the sensory afferents from neck muscles might restore the altered occipital activity and suggest that the same conditions which modulate neglect modulate VEPs latencies.

Spatial attention has different effects on the magno- and parvocellular pathways.

Attention was directed to the left or to the right of the fixation point by the lateral presentation of a target on which the subject had to perform an attention demanding task. A (task-irrelevant) grating displayed in the left visual field was the visual evoked potential (VEP) stimulus. Gratings modulated either in luminance or colour contrast at various temporal frequencies were used in order to maximise the activation of magno- or parvocellular pathways. VEPs recorded in attended and unattended conditions were compared. For luminance stimuli, both latency and amplitude of VEPs were modified by attention. For chromatic stimuli, attention affected the amplitude but not the latency of VEPs. Spatial attention uses different mechanisms when magno- or parvocellular systems are involved.

Abnormal visual event-related potentials in obsessive-compulsive disorder without panic disorder or depression comorbidity.

Visual event-related potentials and spline map topography during a discriminative response task (DRT) were studied in 8 obsessive-compulsive disorder (OCD) patients without comorbidity for panic disorder or depression and in 12 age-matched controls. In the DRT task (like in a go/no-go task) the subject had to press a button when the target stimuli appeared and had to retain the response when the non-target stimulus appeared (vertical bars were intermixed with an equal probability of horizontals). OC patients had greater N1 latency than controls and their N1 and P3 amplitude was larger for the target stimuli, but not for non-target stimuli. In the normals, non-target stimuli (no-go task) produced a larger activation than target stimuli (go task). In the OCD patients the target stimuli produced the same large activation as the non-target. These findings are consistent with theories that consider OCD to be an attentional disorder deriving from a misallocating of cognitive resources. Moreover, spline map topography confirmed that P3 hyperactivation is localised principally on the frontal lobes.

Effects of sustained, voluntary attention on amplitude and latency of steady-state visual evoked potential: a costs and benefits analysis.

OBJECTIVE: Steady-state visual evoked potentials (VEPs) were recorded to study the mechanisms that underlie visual attention. METHODS: VEPs were recorded from 1 cycle/degree sinusoidal grating contrast reversed at various temporal frequencies (6-10 Hz). This was displayed in one hemifield. A letter search display was flashed at a random rate in the other hemifield. The subject performed a demanding task on the recording stimulus (attended condition) or on the opposite side stimulus (unattended condition). Alternatively, he/she passively fixated on the fixation point (passive condition). RESULTS: Relative to the passive condition, attended stimuli elicited enhanced-amplitude and shortened-latency VEP (benefits). Costs (i.e. responses to passive vs. unattended stimuli) were more marked for latency. CONCLUSIONS: VEP latency may be the key of a priority-based attention mechanism acting at an early level.

Electrophysiological analysis of cortical mechanisms of selective attention to high and low spatial frequencies.

OBJECTIVES: This study investigated whether short-latency (<100ms) event-related potential (ERP) components were modulated during attention to spatial frequency (SF) cues. METHODS: Sinusoidally modulated checkerboard stimuli having high (5 cycles per degree (cpd)) or low (0.8cpd) SF content were presented in random order at intervals of 400-650ms. Subjects attended to either the high or low SF stimuli, with the task of detecting targets of slightly higher or lower SF, respectively, than the above standards. ERPs were recorded from 42 scalp sites during task performance and spatio-temporal analyses were carried out on sensory-evoked and attention-related components. RESULTS: Attended high SF stimuli elicited an early negative difference potential (ND120) starting at about 100ms, whereas attended low SF stimuli elicited a positivity (PD130) in the same latency range. The neural sources of both effects were estimated with dipole modeling to lie in dorsal, extrastriate occipital areas. Earlier evoked components evoked at 60-100ms that were modeled with striate and extrastriate cortical sources were not affected by attention to SF. Starting at 150ms, attended stimuli of both SFs elicited a broad selection negativity (SN) that was localized to ventral extrastriate visual cortex. The SN was larger over the left/right cerebral hemisphere for attended stimuli of high/low SF. CONCLUSIONS: These results support the view that attention to SF does not involve a mechanism of amplitude modulation of early-evoked components prior to 100ms. Attention to high and low SF information involves qualitatively different and hemispherically specialized neural processing operations.