Disentangling Cerebellar and Parietal Contributions to Gait and Body Schema: A Repetitive Transcranial Magnetic Stimulation Study.

The overlap between motor and cognitive signs resulting from posterior parietal cortex (PPC) and cerebellar lesions can mask their relative contribution in the sensorimotor integration process. This study aimed to identify distinguishing motor and cognitive features to disentangle PPC and cerebellar involvement in two sensorimotor-related functions: gait and body schema representation. Thirty healthy volunteers were enrolled and randomly assigned to PPC or cerebellar stimulation. Sham stimulation and 1 Hz-repetitive-Transcranial-Magnetic-Stimulation were delivered over P3 or cerebellum before a balance and a walking distance estimation task. Each trial was repeated with eyes open (EO) and closed (EC). Eight inertial measurement units recorded spatiotemporal and kinematic variables of gait. Instability increased in both groups after real stimulation: PPC inhibition resulted in increased instability in EC conditions, as evidenced by increased ellipse area and range of movement in medio-lateral and anterior-posterior (ROMap) directions. Cerebellar inhibition affected both EC (increased ROMap) and EO stability (greater displacement of the center of mass). Inhibitory stimulation (EC vs. EO) affected also gait spatiotemporal variability, with a high variability of ankle and knee angles plus different patterns in the two groups (cerebellar vs parietal). Lastly, PPC group overestimates distances after real stimulation (EC condition) compared to the cerebellar group. Stability, gait variability, and distance estimation parameters may be useful clinical parameters to disentangle cerebellar and PPC sensorimotor integration deficits. Clinical differential diagnosis efficiency can benefit from this methodological approach.

Disrupted relationship between intrinsic neural timescales and alpha peak frequency during unconscious states - A high-density EEG study.

Our brain processes the different timescales of our environment's temporal input stochastics. Is such a temporal input processing mechanism key for consciousness? To address this research question, we calculated measures of input processing on shorter (alpha peak frequency, APF) and longer (autocorrelation window, ACW) timescales on resting-state high-density EEG (256 channels) recordings and compared them across different consciousness levels (awake/conscious, ketamine and sevoflurane anaesthesia, unresponsive wakefulness, minimally conscious state). We replicate and extend previous findings of: (i) significantly longer ACW values, consistently over all states of unconsciousness, as measured with ACW-0 (an unprecedented longer version of the well-know ACW-50); (ii) significantly slower APF values, as measured with frequency sliding, in all four unconscious states. Most importantly, we report a highly significant correlation of ACW-0 and APF in the conscious state, while their relationship is disrupted in the unconscious states. In sum, we demonstrate the relevance of the brain's capacity for input processing on shorter (APF) and longer (ACW) timescales - including their relationship - for consciousness. Albeit indirectly, e.g., through the analysis of electrophysiological activity at rest, this supports the mechanism of temporo-spatial alignment to the environment's temporal input stochastics, through relating different neural timescales, as one key predisposing factor of consciousness.

Clinical, cognitive, and morphometric profiles of progressive supranuclear palsy phenotypes.

The International Parkinson's and Movement Disorder Society (MDS) criteria for progressive supranuclear palsy (PSP) have broadened the clinical spectrum of the disease and established phenotypic characterization according to the predominant manifestation at onset. The objective of this study is to describe clinical/cognitive and imaging features of a monocentric cohort of PSP patients, highlighting different patterns of functional disability according to the assigned phenotype. We retrospectively reviewed clinical/imaging data of 53 PSP patients diagnosed with probable PSP according to the MDS criteria and 40 age/sex-matched healthy controls (HCs). Neurological/neuropsychological assessments were performed using standardized scales, as well as comprehensive magnetic resonance imaging (MRI) morphometric measurements. In our cohort, there were 24/53 PSP-RS (Richardson's syndrome), 13/53 PSP-P (Parkinsonism), 7/53 PSP-PGF (Progressive gait freezing), and 9/53 PSP-Cog (Cognitive impairment). PSP-Cog presented the worst motor profiles, the highest percentages of dementia and impaired functional autonomy; 4/9 PSP-Cog and 2/7 PSP-PGF died. PSP-P had the lowest motor/cognitive burden. All MRI parameters had good discriminative efficacy vs. HCs, with P/M 2.0 discriminating PSP-PGF from PSP-RS and PSP-Cog. We highlighted discrete clinical and imaging patterns that best characterize different PSP phenotypes. PSP-Cog and PSP-PGF/RS manifest greater incidence of dementia and motor disability, respectively, while PSP-P has a more benign course. The identification of different phenotypes may be the expression of different progression patterns requiring tailored approaches in terms of follow-up and treatment. These findings support the concept of discrete patterns of Tau pathology within the PSP spectrum and encourage research for phenotype-specific outcome measures.

Prospective assessment of early developmental markers and their association with neuropsychological impairment.

Children who experience adversities in the pre-perinatal period are at increased risk of developing impairment later in life, despite the absence of overt brain and neurological abnormalities. However, many of these children exhibit sequelae several years after a period of normal appearance. As a result, the need for reliable developmental assessments for the early detection of infants at high risk of adverse neurodevelopmental outcomes has emerged. The Griffiths Mental Developmental Scales have a promising but poorly explored prognostic ability. This longitudinal study evaluated the predictive power of the Griffiths Mental Developmental Scales at 12 and 24 months on the cognitive and neuropsychological profile at 6 years of age in a sample of 70 children with a history of prematurity or perinatal asphyxia but without brain and neurological abnormalities. We found that the Griffiths Mental Developmental Scales at 24 months had good predictive ability on the intelligence quotient at 6 years and the capacity to predict some neuropsychological performances. On the other hand, the Griffiths Mental Developmental Scale at 12 months was not associated with the performance at 6 years or 24 months.   Conclusion: Data on brain development converge to indicate that the first two years of age represent a critical stage of development, particularly for children experiencing mild pre-perinatal adversities who are thought to exhibit white matter dysmaturity. For this reason, this age is crucial for identifying which children are at major risk, leaving enough time to intervene before overt deficits become apparent. Brain development in the first 2 years could explain the limited reliability of early neurodevelopmental testing. What is Known: • Pre-perinatal adversities increase the risk of developing neurodevelopmental disorders. • The predictive ability of the Griffith scale is poorly explored in low-grade conditions. What is New: • The predictive ability of the Griffith scale has been investigated in low-risk children. • A complete neuropsychological profile could offer a more accurate prediction than the intellectual quotient.

Probing Intrinsic Neural Timescales in EEG with an Information-Theory Inspired Approach: Permutation Entropy Time Delay Estimation (PE-TD).

Time delays are a signature of many physical systems, including the brain, and considerably shape their dynamics; moreover, they play a key role in consciousness, as postulated by the temporo-spatial theory of consciousness (TTC). However, they are often not known a priori and need to be estimated from time series. In this study, we propose the use of permutation entropy (PE) to estimate time delays from neural time series as a more robust alternative to the widely used autocorrelation window (ACW). In the first part, we demonstrate the validity of this approach on synthetic neural data, and we show its resistance to regimes of nonstationarity in time series. Mirroring yet another example of comparable behavior between different nonlinear systems, permutation entropy-time delay estimation (PE-TD) is also able to measure intrinsic neural timescales (INTs) (temporal windows of neural activity at rest) from hd-EEG human data; additionally, this replication extends to the abnormal prolongation of INT values in disorders of consciousness (DoCs). Surprisingly, the correlation between ACW-0 and PE-TD decreases in a state-dependent manner when consciousness is lost, hinting at potential different regimes of nonstationarity and nonlinearity in conscious/unconscious states, consistent with many current theoretical frameworks on consciousness. In summary, we demonstrate the validity of PE-TD as a tool to extract relevant time scales from neural data; furthermore, given the divergence between ACW and PE-TD specific to DoC subjects, we hint at its potential use for the characterization of conscious states.

Natural oscillation frequencies in the two lateral prefrontal cortices induced by Transcranial Magnetic Stimulation.

Different cortical regions respond with distinct rhythmic patterns of neural oscillations to Transcranial Magnetic Stimulation (TMS). We investigated natural frequencies induced by TMS in left and right homologous dorsolateral prefrontal cortices (DLPFC) and related hemispheric differences. In 12 healthy young adults, single-pulse TMS was delivered in different blocks close to F3 and F4 channels to target left and right DLPFC. An occipital site near PO3 was stimulated as control. TMS-related spectral perturbation analyses were performed on recorded EEG data. A widespread unspecific increase in theta power was observed for all stimulation sites. However, occipital TMS induced greater alpha activity and a 10.58 Hz natural frequency, while TMS over the left and right DLPFC resulted in similar beta band modulations and a natural frequency of 18.77 and 18.5 Hz, respectively. In particular, TMS-related specific increase in beta activity was stronger for the right than the left DLPFC. The right DLPFC is more specifically tuned to its natural beta frequency when it is directly stimulated by TMS than with TMS over the left counterpart (or a posterior region), while the left DLPFC increases its beta activity more similarly irrespective of whether it is directly stimulated or through right homologous stimulation. These results yield important implications for both basic neuroscience research on inter-hemispheric prefrontal interactions and clinical applications.

Asymmetric Dopamine Transporter Loss Affects Cognitive and Motor Progression in Parkinson's Disease.

BACKGROUND: Asymmetric hemispheric loss of dopaminergic neurons is one of the characteristic features of Parkinson's disease (PD). However, it is still debated if right or left asymmetry differently affects cognitive and motor progression. OBJECTIVES: The objective of this study was to investigate, for the first time, the relevance of dopamine transporter (DAT) asymmetry on cognitive and motor manifestations at onset and at 4-year progression in drug-naïve PD. METHODS: From the Parkinson's Progression Markers Initiative multicenter cohort, we identified 249 right-handed patients with PD with baseline asymmetry greater than 20% in putamen DAT binding at single-photon emission computed tomography. A predominant putamen asymmetry was found on the left in 143 patients (PD-left), and on the right side in 106 patients (PD-right); we compared them with 196 healthy controls. Patients were followed longitudinally (2-year and 4-year visits), examining their clinical, cognitive, and imaging data. RESULTS: At baseline, the PD-left group showed worse performance on the Symbol Digit Modality Test, an attention and processing-speed test, and lower cerebrospinal fluid ß-amyloid levels than the PD-right group. These differences were maintained at follow-up, declining over time in both groups. By contrast, the PD-right group showed greater motor impairment at baseline, which increased over 4 years. Striatal DAT binding decreased over time in both groups, but the PD-right group showed a steeper decline, particularly during the first 2-year follow-up. Putaminal asymmetry assessed at baseline was maintained over time. CONCLUSIONS: These findings suggest that hemispheric asymmetric dopaminergic denervation influences PD cognitive and motor performance as well as progression. Predominant right hemisphere nigrostriatal dopaminergic loss is associated with greater motor severity, whereas more pronounced left hemisphere denervation affects cognitive manifestations at onset and their progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deconstructing Dravet syndrome neurocognitive development: A scoping review.

Dravet syndrome (DS) is a rare severe epilepsy syndrome associated with slowed psychomotor development and behavioral disorders from the second year onward in a previously seemingly normal child. Among cognitive impairments, visuospatial, sensorimotor integration, and expressive language deficits are consistently reported. There have been independent hypotheses to deconstruct the typical cognitive development in DS (dorsal stream vulnerability, cerebellar-like pattern, sensorimotor integration deficit), but an encompassing framework is still lacking. We performed a scoping review of existing evidence to map the current understanding of DS cognitive and behavioral developmental profiles and to summarize the evidence on suggested frameworks. We searched PubMed, Scopus, PsycInfo, and MEDLINE to identify reports focusing on cognitive deficits and/or behavioral abnormalities in DS published between 1978 and March 15, 2020. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Twenty-one reports were selected and tabulated by three independent reviewers based on predefined data extraction and eligibility forms. Eighteen reports provided assessments of global intelligence quotients with variable degrees of cognitive impairment. Eleven reports analyzed single subitems contribution to global cognitive scores: these reports showed consistently larger impairment in performance scales compared to verbal ones. Studies assessing specific cognitive functions demonstrated deterioration of early visual processing, fine and gross motor abilities, visuomotor and auditory-motor integration, spatial processing, visuo-attentive abilities, executive functions, and expressive language. Behavioral abnormalities, reported from 14 studies, highlighted autistic-like traits and attention and hyperactivity disorders, slightly improving with age. The cognitive profile in DS and some behavioral and motor abnormalities may be enclosed within a unified theoretical framework of the three main hypotheses advanced: a pervasive sensorimotor integration deficit, encompassing an occipito-parietofrontal circuit (dorsal stream) dysfunction and a coexistent cerebellar deficit.

Romantic love affects emotional processing of love-unrelated stimuli: An EEG/ERP study using a love induction task.

The aim of the present study was to investigate (a) the neural correlates of a love induction task (LIT) including listening to love-related songs and thinking about the romantic relationship, and (b) the effects of romantic love on the emotional processing of love-unrelated stimuli during a passive viewing task. The EEG was recorded in two groups of university students: people in love (Love Group, LG, N = 22, 19 F) and people not in love (Control Group, CG, N = 20, 15 F). The LIT induced higher pleasantness and arousal in the LG than in the CG, as well as higher alpha activity in occipital-right electrodes, suggesting active mental imagery and internal focused attention. During the picture viewing task, the LG displayed larger N1 amplitudes than the CG in response to unpleasant pictures, and lower amplitudes of the late positive potential to both pleasant and unpleasant pictures at frontal sites. Overall, these results suggest an early attentional modulation of the neural responses to unpleasant, mood-incongruent cues, followed by an implicit emotional down-regulation of arousing stimuli, which might have important implications for everyday attitudes and behaviors.

Neonatal spectral EEG is prognostic of cognitive abilities at school age in premature infants without overt brain damage.

Prematurity is a prototype of biological risk that could affect the late neurocognitive outcome; however, the condition itself remains a non-specific marker. This longitudinal 6-year study aimed to evaluate the prognostic role of neonatal spectral EEG in premature infants without neurological complications. The study cohort was 26 children born 23-34 gestational ages; all neonates underwent multichannel EEG recordings at 35 weeks post-conception. EEG data were transformed into the frequency domain and divided into delta (0.5-4 Hz), theta (5-7 Hz), alpha (8-13 Hz), and beta (14-20 Hz) frequency bands. At 6 years, a neuropsychological and behavioral evaluation was performed. Correlations between spectral bands and neuropsychological assessments were performed with a conservative and robust Bayesian correlation model using weakly informative priors. The correlation of neuropsychological tasks to spectral frequency bands highlighted a significant association with visual and auditory attention tests. The performance on the same tests appears to be mainly impaired.Conclusions: We found that spectral EEG frequencies are independent predictors of performance in attention tasks. We hypothesized that spectral EEG might reflect early circuitries' imbalance in the reticular ascending system and cumulative effect on ongoing development, pointing to the importance of early prognostic instruments. What is Known: • Prematurity is a non-specific marker of late neurocognitive risk. • Precise prognostic instruments are lacking, mostly in patients with low-grade conditions. What is New: • Longitudinal long-term studies are scarce but crucial for the inferential attributive process. • Spectral EEG frequencies are independent predictors of performance in attention tasks.

Theta and alpha oscillations as signatures of internal and external attention to delayed intentions: A magnetoencephalography (MEG) study.

BACKGROUND: Remembering to execute delayed intentions (i.e., prospective memory, PM) entails the allocation of internal and external attention. These processes are crucial for rehearsing PM intentions in memory and for monitoring the presence of the PM cue in the environment, respectively. AIM: The study took advantage of the excellent spatial and temporal resolution of magnetoencephalography (MEG) to delineate the neural mechanisms of the memory and monitoring processes underlying PM. METHOD: The spatio-temporal dynamic of theta and alpha oscillations were explored in 21 participants in two PM tasks compared to a baseline condition (i.e., a lexical decision task with no PM instruction). The PM tasks varied for the load of internally-directed attention (Retrospective-load task) vs externally-directed attention (Monitoring-load task). RESULTS: Increase in theta activity was observed in the Retrospective-load task, and was particularly expressed in the regions of the Default Mode Network, such as in medial temporal regions, precuneus, posterior cingulate cortex and medial prefrontal cortex. Alpha decrease was the most relevant feature of the Monitoring-load task, and it was expressed over bilateral occipital, occipito-parietal and fronto-temporal regions, as well as over left dorsal fronto-parietal regions. CONCLUSIONS: Theta and alpha oscillations are strictly associated with the direction of attention during the PM tasks. In particular, theta increase is linked to internal attention necessary for maintaining the intention active in working memory, whereas alpha decrease supports the external attention for detecting the PM cue in the environment.

Electroencephalographic functional connectivity in extreme prematurity: a pilot study based on graph theory.

BACKGROUND: Connectivity studies based on functional magnetic resonance imaging (MRI) provided new insights in neonatal brain development but cannot be performed at bedside in the clinical setting. The electroencephalogram (EEG) connectivity has been less studied, particularly using the new approach based on graph theory. This study aimed to explore the functional EEG connectivity using graph theory analysis at an early post-conception age in extremely premature and late-preterm babies free of medical complications and overt brain damage. METHODS: Sixteen neonates (8 extremely low gestational age (ELGA) and 8 late-preterm infants), both groups having performed multichannel EEG recordings at 35 weeks' post-conception, were recruited in a single tertiary-level neonatal intensive care unit and well-baby nursery, respectively. Global (i.e., small-worldness) and local (i.e., clustering and strength) connectivity measures were calculated on a single-subject connectivity matrix of EEG data. RESULTS: Both ELGA and late-preterm infants showed small-worldness organization at 35 weeks' post-conception. The ELGA group had the strength parameter of the theta frequency band lower in the right than in the left hemisphere. This asymmetry did not emerge in the late-preterm group. Moreover, the mean strength parameter was significantly greater in the right hemisphere in the late preterms than in the ELGA group. CONCLUSION: EEG connectivity measures could represent an index of left-to-right maturation and developmental disadvantage in extremely preterm infants.

Time perception in childhood absence epilepsy: Findings from a pilot study.

OBJECTIVES: With this explorative study, we aimed to examine time perception in children with childhood absence epilepsy (CAE) and to compare those children with a matched control group. The study also investigated the association between the neuropsychological performance of the group with CAE and time judgment. We hypothesize that children with CAE could fail in time perception and that this may be because of a common underlying substrate with executive impairments. METHODS: Thirteen children with CAE, aged 6-13 years, and 17 healthy children were recruited. All children performed the time bisection task; the children with CAE also performed a cognitive and neuropsychological assessment. We performed a univariate analysis using each parameter of the bisection task (bisection point [BP]) and Weber ratio (WR) as dependent variables, the group (patients vs. controls) as fixed factors and age at evaluation and vocabulary scores as covariates. In the subgroup of patients, we correlated bisection task parameters with neuropsychological tests using a nonparametric partial correlation; the analysis has corrected for age at evaluation. RESULTS: The BP and WR measures differed between controls and patients with CAE. In the subgroup of patients also performing a neuropsychological assessment, we found a correlation between the WR measure and performance on the inhibition test (r = -0.641, p = .025), coding test (r = -0.815, p = .014), and Trail Making Test B (TMT B) (r = 0.72, p = .042). CONCLUSIONS: We found an altered time perception in a pilot study of a small group of children with CAE. A neurophysiological mechanism underlying CAE seems to influence cognitive and behavioral deficits and time sensibility.

Subclinical executive function impairment in children with asymptomatic, treated phenylketonuria: A comparison with children with immunodeficiency virus.

In this study we compared the neuropsychological profile of phenylketonuria (PKU) and human immunodeficiency virus (HIV) to examine the specificity of the executive function (EF) impairment reported in these two patologies. A total of 55 age-matched children and adolescents were assessed, including 11 patients with PKU, 16 patients with HIV and 28 healthy controls, underwent a neuropsychological assessment. Although neither the PKU nor the HIV group scored below the normative ranges, both groups showed lower scores in neuropsychological tests engaging EFs than controls. In addition, compared to patients with PKU the HIV group performed significantly worse in the Trail-Making Test A, Corsi Span and Verbal Fluency. These findings suggest that EF impairments in PKU (a) are limited to EFs (i.e., working memory and attentional shifting), (b) are not simply due to generalized processing speed deficits and

Intentional binding as a marker of agency across the lifespan.

The feeling of control over actions and their external effects is known as Sense of Agency (SoAg). People usually have a distinctive SoAg for events caused by their own actions. However, if the agent is a child or an older person, this feeling of being responsible for the consequences of an action may differ from what an adult would feel. The idea would be that children and elderly may have a reduced SoAg since their frontal lobes are developing or have started to loose their efficiency. The aim of this study was to elucidate whether the SoAg changes across lifespan, using the Intentional Binding (i.e., the temporal attraction between a voluntary action and its sensory consequence) as implicit measure. Data show that children and elderly are characterized by a reduced SoAg as compared to adults. These findings provide a fundamental step in the characterization of SoAg dynamics throughout individuals' lifetime.

Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) performance in progressive supranuclear palsy and multiple system atrophy.

To determine if Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting cognitive abnormalities in patients with probable progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) compared with Parkinson's disease (PD). In this multicenter observational study, MMSE and MoCA were administered in a random order to 130 patients: 35 MSA, 30 PSP and 65 age, and education and gender matched-PD. We assessed between-group differences for MMSE, MoCA, and their subitems. Receiver-operating characteristic (ROC) curves were calculated. The mean MMSE was higher than the mean MoCA score in each MSA (27.7 ± 2.4 vs. 22.9 ± 3.0, p < 0.0001), PSP (26.0 ± 2.9 vs. 18.2 ± 3.9, p < 0.0001), and PD (27.3 ± 2.0 vs. 22.3 ± 3.5, p < 0.0001). MoCA total score as well as its letter fluency subitem differentiated PSP from MSA and PD with high specificity and moderate sensitivity. More specifically, a cut-off score of 7 F-words or less per minute would support a diagnosis of PSP (PSP vs. PD: 86 % specificity, 70 % sensitivity; PSP vs. MSA: 71 % specificity, 70 % sensitivity). By contrast, MMSE presented an overall ceiling effect for most subitems, except for the pentagon scores, where PSP did less well than MSA or PD patients. These preliminary results suggest that PSP and MSA, similar to PD patients, may present normal MMSE and reduced MoCA performance. Overall, MoCA is more sensitive than MMSE in detecting cognitive impairment in atypical parkinsonism and together with verbal fluency would be a useful test to support PSP diagnosis.

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.

Neural underpinnings of the 'agent brain': new evidence from transcranial direct current stimulation.

Intentional binding (IB) refers to the temporal compression between a voluntary action and its sensory effect, and it is considered an implicit measure of sense of agency (SoA), that is, the capacity to control one's own actions. IB has been thoroughly studied from a behavioural point of view but only few studies have investigated its neural underpinnings, always using the same two paradigms. Although providing evidence that the supplementary motor complex is involved, findings are still too scarce to draw definitive conclusions. The aim of the present study was to establish a causal relationship between the pre-supplementary motor area (pre-SMA), known for its key role in action planning and initiation, and IB by means of transcranial direct current stimulation (tDCS). Participants underwent anodal, cathodal and sham control stimulations during three separate sessions (Experiment I). Subsequently, they underwent the same stimulation protocol (Experiment II) using as control a region potentially involved in the processing of the sensory effects of voluntary action (i.e., the right primary auditory cortex for the auditory effects of action). A significant reduction in IB was found only after stimulation of the pre-SMA, which supports the causal contribution of this prefrontal area in the perceived linkage between action and its effects. As SoA could be disrupted in many psychiatric and neurological diseases, these results have direct clinical relevance as tDCS could be successfully used in this domain in virtue of the promising advantages it offers for rehabilitation.

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients.

BACKGROUND: Cognitive impairment, mainly characterised by executive dysfunction, occurs in about half of cases in amyotrophic lateral sclerosis (ALS). There is evidence that gender influences some clinical features of the disease, but its influence on the cognitive spectrum is unknown. Our objective was to investigate the impact of gender on cognitive profiles of patients with ALS. METHODS: A retrospective study based on an exhaustive neuropsychological battery was performed in a group of 165 (70 females, 95 males) sporadic, non-demented patients with ALS compared with 134 healthy control participants. This assessment primarily focused on executive, memory and language functions. RESULTS: 47 (29%) patients revealed impairment in executive function and 30 (18%) patients revealed cognitive non-executive impairment. Independent from mood tone and clinical variables, a significantly greater executive impairment was determined in female patients than in male patients and control participants. The relative risk for ALS females having impairment in executive function compared with male patients was 2.6 (95% CI 1.6 to 4.4; p=0.0003). ALS females scored lower in Phonemic Fluency, Trial Making, and Wisconsin Card Sorting test. CONCLUSIONS: Results highlight a significant vulnerability of ALS female patients to develop cognitive dysfunctions peculiar to the disease, independently of bulbar onset. The explicative hypotheses of the data are focused on two interpretative lines not mutually exclusive: the role of gonadal hormones and gender-related brain asymmetry pre-existing to the disease. These findings, never reported before in the literature, can have important implications for models of ALS pathogenesis and for future clinical trial designs.

The effects of focal and nonfocal cues on the neural correlates of prospective memory: insights from ERPs.

The present study is the first designed to investigate behavioral and event-related potential (ERP) correlates of the processes involved in focal and nonfocal prospective memory (PM) tasks. Focal tasks are those in which the features of the PM cue are easily extracted from the ongoing activity, whereas the process is more indirect in nonfocal tasks. Strategic monitoring was associated with a slowing of reaction times in ongoing trials and with frontal and parietal ERP modulations. These effects were greater in the nonfocal task, whereas they were smaller, or even absent for some individuals, in the focal task. This indicates that strategic monitoring is engaged to a greater extent in nonfocal tasks, whereas it is less extensively recruited, or not recruited at all by some individuals, in focal tasks. Indeed, the recognition of the PM cue might also occur automatically in focal tasks, as suggested by the FN400 increase in focal PM trials. Nonfocal tasks are supported by more controlled resources not only in retrieval, but also in postretrieval monitoring and coordinating processes. This was reflected in the enhancement of the prospective positivity and frontal slow wave observed in nonfocal PM trials. We interpreted these results as supporting the multiprocess view of PM.