Marika Berchicci

Benefits of Physical Exercise on the Aging Brain: The Role of the Prefrontal Cortex

Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15–86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35–40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

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.

The neurophysiology of central and peripheral fatigue during sub-maximal lower limb isometric contractions

Fatigue has been defined as an exercise-induced decline in force generation capacity because of changes at both the peripheral and central levels. Movement is preceded and accompanied by brain activities related to the preparation and execution of movement (movement related cortical potentials, MRCP), which have been correlated with the perception of effort (RPE). We combined force measurements, surface electromyography (sEMG), peripheral electrical stimulation (maximal twitch, MT) and MRCP analysis to further our understanding of the neural correlates of peripheral and central changes during a fatiguing task involving the lower limbs. Eighteen healthy volunteers performed 4 blocks of isometric knee extensions at 40% of the maximal voluntary contraction (MVC) for a total of 240 2-s contractions. At the baseline and after each block, we measured RPE, MT and MVC. We simultaneously recorded the force of the knee extensor muscles, root mean square (RMS) of the sEMG of the vastus lateralis muscle, and electroencephalography (EEG) from 64 channels. The MRCPs were extracted from the EEG recordings and averaged in the early (Block 1–2) and late (Block 3–4) blocks. Two cohorts were obtained by cluster analysis based on the RPE (i.e., perception of effort) and MT (i.e., peripheral fatigue). We observed a significant decline in both the MVC (−13%) and RMS (−25%) of the sEMG signal over the course of the task; thus, muscle fatigue had occurred in all of the participants regardless of the cohort. The MRCP amplitude was larger in the fatigued than the non-fatigued MT cohort in the supplementary and premotor areas, whereas the MRCP amplitude was larger in the fatigued than the non-fatigued RPE cohort in the aforementioned areas, and also in the primary motor and prefrontal cortices (PFC). The increase in the positive activity of the PFC, along with the perception of effort, represents a novel result, suggesting that it is modulated more by the perception of effort than peripheral fatigue.

The effects of aging on conflict detection.

Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The ‘aging switch effect’ on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.

Individual differences in response speed and accuracy are associated to specific brain activities of two interacting systems

The study investigates the neurocognitive stages involved in the speed-accuracy trade-off (SAT). Contrary to previous approach, we did not manipulate speed and accuracy instructions: participants were required to be fast and accurate in a go/no-go task, and we selected post-hoc the groups based on the subjects’ spontaneous behavioral tendency. Based on the reaction times, we selected the fast and slow groups (Speed-groups), and based on the percentage of false alarms, we selected the accurate and inaccurate groups (Accuracy-groups). The two Speed-groups were accuracy-matched, and the two Accuracy-groups were speed-matched. High density electroencephalographic (EEG) and stimulus-locked analyses allowed us to observe group differences both before and after the stimulus onset. Long before the stimulus appearance, the two Speed-groups showed different amplitude of the Bereitschaftspotential (BP), reflecting the activity of the supplementary motor area (SMA); by contrast, the two Accuracy-groups showed different amplitude of the prefrontal negativity (pN), reflecting the activity of the right prefrontal cortex (rPFC). In addition, the post-stimulus event-related potential (ERP) components showed differences between groups: the P1 component was larger in accurate than inaccurate group; the N1 and N2 components were larger in the fast than slow group; the P3 component started earlier and was larger in the fast than slow group. The go minus no-go subtractive wave enhancing go-related processing revealed a differential prefrontal positivity (dpP) that peaked at about 330 ms; the latency and the amplitude of this peak were associated with the speed of the decision process and the efficiency of the stimulus-response mapping, respectively. Overall, data are consistent with the view that speed and accuracy are processed by two interacting but separate neurocognitive systems, with different features in both the anticipation and the response execution phases.

Benefits of Physical Exercise on Basic Visuo-Motor Functions Across Age

Motor performance deficits of older adults are due to dysfunction at multiple levels. Age-related differences have been documented on executive functions; motor control becomes more reliant on cognitive control mechanisms, including the engagement of the prefrontal cortex (PFC), possibly compensating for age-related sensorimotor declines. Since at functional level the PFC showed the largest age-related differences during discriminative response task, we wonder whether those effects are mainly due to the cognitive difficulty in stimulus discrimination or they could be also detected in a much easier task. In the present study, we measured the association of physical exercise with the PFC activation and response times (RTs) using a simple response task (SRT), in which the participants were asked to respond as quickly as possible by manual key-press to visual stimuli. Simultaneous behavioral (RTs) and electroencephalographic (EEG) recordings were performed on 84 healthy participants aged 19–86 years. The whole sample was divided into three cohorts (young, middle-aged, and older); each cohort was further divided into two equal sub-cohorts (exercise and not-exercise) based on a self-report questionnaire measuring physical exercise. The EEG signal was segmented in epochs starting 1100 prior to stimulus onset and lasting 2 s. Behavioral results showed age effects, indicating a slowing of RTs with increasing age. The EEG results showed a significant interaction between age and exercise on the activities recorded on the PFC. The results indicates that: (a) the brain of older adults needs the PFC engagement also to perform elementary task, such as the SRT, while this activity is not necessary in younger adults, (b) physical exercise could reduce this age-related reliance on extra cognitive control also during the performance of a SRT, and (c) the activity of the PFC is a sensitive index of the benefits of physical exercise on sensorimotor decline.

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.

Spatiotemporal brain mapping during preparation, perception, and action

Deciding whether to act or not to act is a fundamental cognitive function. To avoid incorrect responses, both reactive and proactive modes of control have been postulated. Little is known, however, regarding the brain implementation of proactive mechanisms, which are deployed prior to an actual need to inhibit a response. Via a combination of electrophysiological and neuroimaging measures (recorded in 21 and 16 participants, respectively), we describe the brain localization and timing of neural activity that underlies the anticipatory proactive mechanism. From these results, we conclude that proactive control originates in the inferior Frontal gyrus, is established well before stimulus perception, and is released concomitantly with stimulus appearance. Stimulus perception triggers early activity in the anterior insula and intraparietal cortex contralateral to the responding hand; these areas likely mediate the transition from perception to action. The neural activities leading to the decision to act or not to act are described in the framework of a three-stage model that includes perception, action, and anticipatory functions taking place well before stimulus onset.

A Passive Exoskeleton Can Push Your Life Up: Application on Multiple Sclerosis Patients

In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the “Human Body Posturizer”, designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

Why do we make mistakes? Neurocognitive processes during the preparation–perception–action cycle and error-detection

The event-related potential (ERP) literature described two error-related brain activities: the error-related negativity (Ne/ERN) and the error positivity (Pe), peaking immediately after the erroneous response. ERP studies on error processing adopted a response-locked approach, thus, the question about the activities preceding the error is still open. In the present study, we tested the hypothesis that the activities preceding the false alarms (FA) are different from those occurring in the correct (responded or inhibited) trials. To this aim, we studied a sample of 36 Go/No-go performers, adopting a stimulus-locked segmentation also including the pre-motor brain activities. Present results showed that neither pre-stimulus nor perceptual activities explain why we commit FA. In contrast, we observed condition-related differences in two pre-response components: the fronto-central N2 and the prefrontal positivity (pP), respectively peaking at 250 ms and 310 ms after the stimulus onset. The N2 amplitude of FA was identical to that recorded in No-go trials, and larger than Hits. Because the new findings challenge the previous interpretations on the N2, a new perspective is discussed. On the other hand, the pP in the FA trials was larger than No-go and smaller than Go, suggesting an erroneous processing at the stimulus-response mapping level: because this stage triggers the response execution, we concluded that the neural processes underlying the pP were mainly responsible for the subsequent error commission. Finally, sLORETA source analyses of the post-error potentials extended previous findings indicating, for the first time in the ERP literature, the right anterior insula as Pe generator.