Giorgio Arcara

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.

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”.

The communicative impairment as a core feature of schizophrenia: Frequency of pragmatic deficit, cognitive substrates, and relation with quality of life

BACKGROUND Impairments in specific aspects of pragmatic competence, supporting the use of language in context, are largely documented in schizophrenia and might represent an indicator of poor outcome. Yet pragmatics is rarely included in clinical settings. This paper aims to promote a clinical consideration of pragmatics as a target of assessment and intervention. We investigated the frequency of the pragmatic deficit, its cognitive substrates, and the relation with quality of life. METHODS Pragmatic abilities were compared in a sample of patients with schizophrenia and healthy controls based on a comprehensive pragmatic test (APACS). We assessed also for psychopathology, cognition, social cognition, and quality of life. We explored the co-occurrence of deficits in different domains, and we used multiple regressions to investigate the effect of cognition and social cognition on pragmatics, and of pragmatics on quality of life. RESULTS Pragmatic abilities, especially comprehending discourse and non-literal meanings, were compromised in schizophrenia, with 77% of patients falling below cutoff. Pragmatic deficit co-occurred with cognitive or socio-cognitive deficits in approximately 30% of cases. Multiple regression analysis confirmed the interplay of cognition and social cognition in pragmatic behavior. Quality of life was predicted by symptoms and by pragmatic abilities. CONCLUSIONS The high frequency of impairment suggests that the pragmatic deficit is a core feature of schizophrenia, associated with quality of life. Cognitive and socio-cognitive abilities might represent necessary though not sufficient building blocks for the acquisition of pragmatic abilities throughout development. Therefore, a more precise incorporation of pragmatics in the description of the pathology is of high clinical and translational relevance.

Communication and pragmatic breakdowns in amyotrophic lateral sclerosis patients.

While there is increasing attention toward cognitive changes in amyotrophic lateral sclerosis (ALS), the domain of pragmatics, defined as the ability to integrate language and context to engage in successful communication, remains unexplored. Here we tested pragmatic abilities in 33 non-demented ALS patients and 33 healthy controls matched for age and education through 6 different tasks, ranging from discourse organization to the comprehension of figurative language, further grouped in three composite measures for pragmatic production, pragmatic comprehension and global pragmatic abilities. For a subgroup of patients, assessment included executive functions and social cognition skills. ALS patients were impaired on all pragmatic tasks relative to controls, with 45% of the patients performing below cut-off in at least one pragmatic task, and 36% impaired on the global pragmatic score. Pragmatic breakdowns were more common than executive deficit as defined by the consensus criteria, and approximately as prevalent as deficits in social cognition. Multiple regression analyses support the idea of an interplay of executive and social cognition abilities in determining the pragmatic performance, although all these domains show some degree of independence. These findings shed light on pragmatic impairment as a relevant dimension of ALS, which deserves further consideration in defining the cognitive profile of the disease, given its vital role for communication and social interaction in daily life.

Is “Hit and Run” a Single Word? The Processing of Irreversible Binomials in Neglect Dyslexia

The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials (IBs), i.e., word pairs linked by a conjunction (e.g., “hit and run,” “dead or alive”). In order to test their lexical status, the phenomenon of neglect dyslexia is explored. People with left-sided neglect dyslexia show a clear lexical effect: they can read IBs better (i.e., by dropping the leftmost words less frequently) when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that IBs tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process.

Does executive control really play a crucial role in explaining age-related cognitive and neural differences?

OBJECTIVE The present study investigated the role of executive control in accounting for the cognitive and electrophysiological alterations occurring in healthy aging. METHOD Younger and older adults performed the inhibitory control task (ICT), a task composed of 3 types of trials that vary in the degree and kind of executive control subprocesses required. We analyzed event-related potentials (ERPs) elicited by these ICT trials and focused on the ERP components related to executive control subprocesses: P3b (updating), no-go P3 (inhibition), and reorienting negativity (RON; shifting). RESULTS Compared with younger adults, older adults exhibited worse performance on the ICT and a delay in the latency of all the ERPs investigated. These age-related differences occurred regardless of the amount of executive control required because they were not influenced by the type of trial. The RON amplitude, an index of shifting, was found markedly attenuated in older adults relative to younger adults. CONCLUSIONS Executive control, as a unitary function, cannot explain the age-related differences observed, which are more likely to reflect a general slowing of processes with aging. However, when we take into account the specific subprocesses of executive control, the one that seems to be particularly affected by aging is shifting, as revealed by the age-related alterations in the RON parameters.

Is two better than one? Limb activation treatment combined with contralesional arm vibration to ameliorate signs of left neglect.

In the present study, we evaluated the effects of the Limb Activation Treatment (LAT) alone and in combination with the Contralateral Arm Vibration (CAV) on left neglect (LN) rehabilitation. We conceived them as techniques that both prompt the activation of the lesioned right hemisphere because of the activation (with the LAT as an active technique) and the stimulation (with the CAV as a passive technique) of the left hemibody. To test the effect of the simultaneous use of these two techniques (i.e., LAT and CAV) on visuo-spatial aspects of LN, we described the case of an LN patient (GR), who showed high intra-individual variability (IIV) in performance. Given the high IIV of GR, we used an ABAB repeated-measures design to better define the effectiveness of the combined application of LAT and CAV, as a function of time. The results showed an improvement of GR’s performance on the Bells test following the combined application of LAT and CAV, with respect to the application of LAT alone. We did not find, however, significant effects of treatment on two other LN tests (i.e., Line bisection and Picture scanning). We propose that the combined application of LAT and CAV can be beneficial for some aspects of LN.

A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living.

The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities.

Communication in Multiple Sclerosis: Pragmatic Deficit and its Relation with Cognition and Social Cognition

Objective Cognitive functions have been largely investigated in multiple sclerosis. Less attention has been paid to social communication abilities, despite their presumptive affect on quality of life. We run the first comprehensive assessment of pragmatic skills in multiple sclerosis, evaluating also the relationship between pragmatics and other cognitive domains. Methods Forty-two multiple sclerosis patients and 42 controls were tested for pragmatic abilities, neuro-cognition, social cognition, depression, and fatigue. Results Patients performed poorly in most pragmatic tasks compared to controls. Globally, 55% of patients performed below the 5th percentile in the total pragmatic score. Notably, pragmatic skills did not differ between cognitively impaired and unimpaired patients. However, an association was found between pragmatics and verbal fluency, as measured in the Word List Generation. Finally, we observed an association of pragmatic abilities with social cognition, and a trend with psychosocial functioning. Conclusion Overall, the study shows a diffuse pragmatic impairment in multiple sclerosis, not associated with the patients global neuropsychological profile. By contrast, our findings suggest a close relation between pragmatics and specific cognitive aspects such as executive functions, and between pragmatics and social cognition. This study underlines the need of looking beyond classical cognitive performance, to consider underestimated communicative disturbances of high clinical relevance.

Does predictability matter? Effects of cue predictability on neurocognitive mechanisms underlying prospective memory

Prospective memory (PM) represents the ability to successfully realize intentions when the appropriate moment or cue occurs. In this study, we used event-related potentials (ERPs) to explore the impact of cue predictability on the cognitive and neural mechanisms supporting PM. Participants performed an ongoing task and, simultaneously, had to remember to execute a pre-specified action when they encountered the PM cues. The occurrence of the PM cues was predictable (being signaled by a warning cue) for some participants and was completely unpredictable for others. In the predictable cue condition, the behavioral and ERP correlates of strategic monitoring were observed mainly in the ongoing trials wherein the PM cue was expected. In the unpredictable cue condition they were instead shown throughout the whole PM block. This pattern of results suggests that, in the predictable cue condition, participants engaged monitoring only when subjected to a context wherein the PM cue was expected, and disengaged monitoring when the PM cue was not expected. Conversely, participants in the unpredictable cue condition distributed their resources for strategic monitoring in more continuous manner. The findings of this study support the most recent views—the “Dynamic Multiprocess Framework” and the “Attention to Delayed Intention” (AtoDI) model—confirming that strategic monitoring is a flexible mechanism that is recruited mainly when a PM cue is expected and that may interact with bottom-up spontaneous processes.