Vincenza Tarantino

Neuropsychological Performance 10 Years After Immunization in Infancy With Thimerosal-Containing Vaccines

OBJECTIVE. Thimerosal, a mercury compound used as a preservative in vaccines administered during infancy, has been suspected to affect neuropsychological development. We compared the neuropsychological performance, 10 years after vaccination, of 2 groups of children exposed randomly to different amounts of thimerosal through immunization. METHODS. Children who were enrolled in an efficacy trial of pertussis vaccines in 1992–1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 μg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect. RESULTS. Nearly 70% of the invited subjects participated in the neuropsychological assessment (N = 1403). Among the 24 neuropsychological outcomes that were evaluated, only 2 were significantly associated with thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test. CONCLUSIONS. Given the large number of statistical comparisons performed, the few associations found between thimerosal exposure and neuropsychological development might be attributable to chance. The associations found, although statistically significant, were based on small differences in mean test scores, and their clinical relevance remains to be determined.

Automatic Temporal Expectancy: A High-Density Event-Related Potential Study

How we compute time is not fully understood. Questions include whether an automatic brain mechanism is engaged in temporally regular environmental structure in order to anticipate events, and whether this can be dissociated from task-related processes, including response preparation, selection and execution. To investigate these issues, a passive temporal oddball task requiring neither time-based motor response nor explicit decision was specifically designed and delivered to participants during high-density, event-related potentials recording. Participants were presented with pairs of audiovisual stimuli (S1 and S2) interspersed with an Inter-Stimulus Interval (ISI) that was manipulated according to an oddball probabilistic distribution. In the standard condition (70% of trials), the ISI lasted 1,500 ms, while in the two alternative, deviant conditions (15% each), it lasted 2,500 and 3,000 ms. The passive over-exposition to the standard ISI drove participants to automatically and progressively create an implicit temporal expectation of S2 onset, reflected by the time course of the Contingent Negative Variation response, which always peaked in correspondence to the point of S2 maximum expectation and afterwards inverted in polarity towards the baseline. Brain source analysis of S1- and ISI-related ERP activity revealed activation of sensorial cortical areas and the supplementary motor area (SMA), respectively. In particular, since the SMA time course synchronised with standard ISI, we suggest that this area is the major cortical generator of the temporal CNV reflecting an automatic, action-independent mechanism underlying temporal expectancy.

Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials

The neuromodulatory effects of repetitive transcranial magnetic stimulation (rTMS) have been mostly investigated by peripheral motor-evoked potentials (MEPs). New TMS-compatible EEG systems allow a direct investigation of the stimulation effects through the analysis of TMS-evoked potentials (TEPs). We investigated the effects of 1-Hz rTMS over the primary motor cortex (M1) of 15 healthy volunteers on TEP evoked by single pulse TMS over the same area. A second experiment in which rTMS was delivered over the primary visual cortex (V1) of 15 healthy volunteers was conducted to examine the spatial specificity of the effects. Single-pulse TMS evoked four main components: P30, N45, P60 and N100. M1-rTMS resulted in a significant decrease of MEP amplitude and in a significant increase of P60 and N100 amplitude. There was no effect after V1-rTMS. 1-Hz rTMS appears to increase the amount of inhibition following a TMS pulse, as demonstrated by the higher N100 and P60, which are thought to originate from GABAb-mediated inhibitory post-synaptic potentials. Our results confirm the reliability of the TMS-evoked N100 as a marker of cortical inhibition and provide insight into the neuromodulatory effects of 1-Hz rTMS. The present finding could be of relevance for therapeutic and diagnostic purposes.

The time course of temporal discrimination: An ERP study

OBJECTIVE The question of how temporal information is processed by the brain is still a matter of debate. This study aimed to elucidate the brain electrical activity associated with a visual temporal discrimination task. METHODS For this purpose, 44 participants were required to compare pairs of sequentially presented time intervals: a fixed standard interval (1000ms), and an equal-to-standard, longer (1200ms) or shorter (800ms) comparison interval. Behavioural data and event-related potentials (ERPs) were analyzed. RESULTS Long intervals were more rapidly identified than short intervals. The amplitude of the contingent negative variation (CNV) found at frontocentral sites before the end of the comparison interval was significantly affected by the difference between its duration and the standard one. The amplitude and the scalp distribution of ERPs registered after the offset of the comparison interval were linearly modulated by its absolute duration. CONCLUSIONS ERP components associated with the offset of the comparison intervals clarified the involvement of working memory processes and different brain structures in temporal discrimination. SIGNIFICANCE This study further improves our understanding of the cognitive processes and neural substrates underlying temporal discrimination in healthy subjects and lays the ground for the investigation of clinical samples with time processing deficits.

Electrophysiological Correlates of Strategic Monitoring in Event-Based and Time-Based Prospective Memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks. The addition of an event-based or a time-based PM task to an ongoing activity led to a similar sustained positive modulation of the ERPs in the ongoing trials, mainly expressed over prefrontal and frontal regions. This modulation might index the retrieval mode mechanism, similarly engaged in the two PM tasks. On the other hand, two further ERP modulations were shown specifically in an event-based PM task. An increased positivity was shown at 400–600 ms post-stimulus over occipital and parietal regions, and might be related to target checking. Moreover, an early modulation at 130–180 ms post-stimulus seems to reflect the recruitment of attentional resources for being ready to respond to the event-based PM cue. This latter modulation suggests the existence of a third mechanism specific for the event-based PM; that is, the “readiness mode”.

Aging and prospective memory: the role of working memory and monitoring processes

Background and aims: Remembering to execute an earlier planned action is essential in everyday life, and is a prerequisite for independent living in old age. The purpose of the present study was to determine the influence of age in performing a prospective memory (PM) task and to analyze the differential contribution of working memory and attentional monitoring demands. Methods: In Experiment 1, a group of young and two groups of old adults were assigned to one of two low-demanding conditions: a picture-naming task (only-Naming) and a picture-naming plus a PM task (Naming+PM). In Experiment 2, a group of young and two groups of old adults performed one of two high-demanding conditions, in which working memory and attentional monitoring processes were examined, using a listening span-like task and a 1-back task within the PM paradigm of Experiment 1. Results: Prospective memory performance declined with age even in the low-demanding condition (Experiment 1). Young participants showed PM failures only when the 1-back task was added to the low-demanding condition. Older participants exhibited a marked decline, particularly in the working memory load condition. Conclusions: These results suggest that even low-demanding prospective memory tasks are resource-consuming in old age, and that working memory efficiency, affected by the aging process, plays a crucial role in the successful accomplishment of PM actions.

The neuropsychological profile of infantile Duchenne muscular dystrophy.

It has been shown that children with Duchenne muscular dystrophy (DMD) exhibit specific cognitive deficits. However, the neuropsychological profile has not yet been fully characterized. In order to control for the contribution of motor impairments as a confounding variable that is usually present when assessing children with muscular pathologies, we compared children with DMD to a group of children with an autoimmune pathology that does not entail either brain or cognitive dysfunction but does imply motor impairment: juvenile rheumatoid arthritis (JRA). An extensive neuropsychological evaluation was administered, including intelligence, perception, language, memory and learning, attention, executive function, praxis and reasoning. As the main result, in children with DMD we found significantly lower performances in verbal IQ, verbal short-term memory and phonological abilities, as well as in praxis and executive functioning domains. A wide range of cognitive domains, including verbal abilities, executive functioning, and praxis, must be taken into account when assessing neuropsychological functioning in children with DMD. In particular, subtle executive function impairment could be considered as a subclinical marker of cognitive impairment in developmental disorders.

Spatiotemporal neurodynamics underlying internally and externally driven temporal prediction: A high spatial resolution erp study

Temporal prediction (TP) is a flexible and dynamic cognitive ability. Depending on the internal or external nature of information exploited to generate TP, distinct cognitive and brain mechanisms are engaged with the same final goal of reducing uncertainty about the future. In this study, we investigated the specific brain mechanisms involved in internally and externally driven TP. To this end, we employed an experimental paradigm purposely designed to elicit and compare externally and internally driven TP and a combined approach based on the application of a distributed source reconstruction modeling on a high spatial resolution electrophysiological data array. Specific spatiotemporal ERP signatures were identified, with significant modulation of contingent negative variation and frontal late sustained positivity in external and internal TP contexts, respectively. These different electrophysiological patterns were supported by the engagement of distinct neural networks, including a left sensorimotor and a prefrontal circuit for externally and internally driven TP, respectively.

An investigation of the neural circuits underlying reaching and reach-to-grasp movements: from planning to execution

Experimental evidence suggests the existence of a sophisticated brain circuit specifically dedicated to reach-to-grasp planning and execution, both in human and non-human primates (Castiello, 2005). Studies accomplished by means of neuroimaging techniques suggest the hypothesis of a dichotomy between a “reach-to-grasp” circuit, involving the anterior intraparietal area, the dorsal and ventral premotor cortices (PMd and PMv – Castiello and Begliomini, 2008; Filimon, 2010) and a “reaching” circuit involving the medial intraparietal area and the superior parieto-occipital cortex (Culham et al., 2006). However, the time course characterizing the involvement of these regions during the planning and execution of these two types of movements has yet to be delineated. A functional magnetic resonance imaging study has been conducted, including reach-to-grasp and reaching only movements, performed toward either a small or a large stimulus, and Finite Impulse Response model (Henson, 2003) was adopted to monitor activation patterns from stimulus onset for a time window of 10 s duration. Data analysis focused on brain regions belonging either to the reaching or to the grasping network, as suggested by Castiello and Begliomini (2008). Results suggest that reaching and grasping movements planning and execution might share a common brain network, providing further confirmation to the idea that the neural underpinnings of reaching and grasping may overlap in both spatial and temporal terms (Verhagen et al., 2013). But, although responsive for both actions, they show a significant predominance for either one of the two actions and such a preference is evident on a temporal scale.

Effect of duration of breastfeeding on neuropsychological development at 10 to 12 years of age in a cohort of healthy children

Aim  The aim of this article was to explore the effect of duration of breastfeeding on neurocognitive development.