Hemodialysis shake-up on the front lines of the Covid-19 pandemic: the Treviglio Hospital experience.

The new coronavirus disease (Covid-19) pandemic in Italy formally started on 21st February 2020, when a 38-years old man was established as the first Italian citizen with Covid-19 in Codogno, Lombardy region. In a few days, the deadly coronavirus swept beyond expectations across the city of Bergamo and its province, claiming thousands of lives and putting the hospital in Treviglio under considerable strain. Since designated Covid-dialysis hospitals to centrally manage infected hemodialysis patients were not set up in the epidemic areas, we arranged to treat all our patients. We describe the multiple strategies we had to implement fast to prevent/control Covid-19 infection and spread resources in our Dialysis Unit during the first surge of the pandemic in one of the worst-hit areas in Italy. The recommendations provided by existing guidelines and colleagues with significant experience in dealing with Covid-19 were combined with the practical judgement of our dialysis clinicians, nurses and nurse's aides.

Clustering the Brain With "CluB": A New Toolbox for Quantitative Meta-Analysis of Neuroimaging Data.

In this paper we describe and validate a new coordinate-based method for meta-analysis of neuroimaging data based on an optimized hierarchical clustering algorithm: CluB (Clustering the Brain). The CluB toolbox permits both to extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and to explore each single cluster of activation for its composition according to the cognitive dimensions of interest. This last step, called "cluster composition analysis," permits to explore neurocognitive effects by adopting a factorial-design logic and by testing the working hypotheses using either asymptotic tests, or exact tests either in a classic inference, or in a Bayesian-like context. To perform our validation study, we selected the fMRI data from 24 normal controls involved in a reading task. We run a standard random-effects second level group analysis to obtain a "Gold Standard" of reference. In a second step, the subject-specific reading effects (i.e., the linear t-contrast "reading > baseline") were extracted to obtain a coordinates-based database that was used to run a meta-analysis using both CluB and the popular Activation Likelihood Estimation method implemented in the software GingerALE. The results of the two meta-analyses were compared against the "Gold Standard" to compute performance measures, i.e., sensitivity, specificity, and accuracy. The GingerALE method obtained a high level of accuracy (0.967) associated with a high sensitivity (0.728) and specificity (0.971). The CluB method obtained a similar level of accuracy (0.956) and specificity (0.969), notwithstanding a lower level of sensitivity (0.14) due to the lack of prior Gaussian transformation of the data. Finally, the two methods obtained a good-level of concordance (AC1 = 0.93). These results suggested that methods based on hierarchical clustering (and post-hoc statistics) and methods requiring prior Gaussian transformation of the data can be used as complementary tools, with the GingerALE method being optimal for neurofunctional mapping of pooled data according to simpler designs, and the CluB method being preferable to test more specific, and localized, neurocognitive hypotheses according to factorial designs.

Music Education at School: Too Little and Too Late? Evidence From a Longitudinal Study on Music Training in Preadolescents.

It is widely believed that intensive music training can boost cognitive and visuo-motor skills. However, this evidence is primarily based on retrospective studies; this makes it difficult to determine whether a cognitive advantage is caused by the intensive music training, or it is instead a factor influencing the choice of starting a music curriculum. To address these issues in a highly ecological setting, we tested longitudinally 128 students of a Middle School in Milan, at the beginning of the first class and, 1 year later, at the beginning of the second class. 72 students belonged to a Music curriculum (30 with previous music experience and 42 without) and 56 belonged to a Standard curriculum (44 with prior music experience and 12 without). Using a Principal Component Analysis, all the cognitive measures were grouped in four high-order factors, reflecting (a) General Cognitive Abilities, (b) Speed of Linguistic Elaboration, (c) Accuracy in Reading and Memory tests, and (d) Visuospatial and numerical skills. The longitudinal comparison of the four groups of students revealed that students from the Music curriculum had better performance in tests tackling General Cognitive Abilities, Visuospatial skills, and Accuracy in Reading and Memory tests. However, there were no significant curriculum-by-time interactions. Finally, the decision to have a musical experience before entering middle school was more likely to occur when the cultural background of the families was a high one. We conclude that a combination of family-related variables, early music experience, and pre-existent cognitive make-up is a likely explanation for the decision to enter a music curriculum at middle school.

As Time Goes by: A rTMS Study on Age-Related Changes in Sentence Comprehension.

It is well established that off-line sentence judgment tasks (oSJTs) typically rely on phonological working memory (WM), beyond specific linguistic processing. Nevertheless, empirical findings suggest that a juvenile level of performance in an oSJT could be associated with the recruitment of age-specific additional supportive neural network in healthy aging. In particular, in one of our previous study, healthy elderlies showed the additional activation of associative visual cortices when compared with young controls. We suggested that age-related hyperactivations, during an auditory sentence judgment task, might represent the neurofunctional correlate of the recruitment of compensatory strategies that are necessary to maintain a juvenile level of performance. To explicitly test this hypothesis we adopted repetitive transcranial magnetic stimulation (rTMS). Twelve healthy elderlies and 12 young participants were engaged in an off-line semantic plausibility judgment task while rTMS was delivered over: (1) the left inferior frontal gyrus (LIFG; i.e., a core region of the WM network); (2) the precuneus; and (3) a Control Site (vertex). Results showed a significant main effect of Stimulation Site and a significant Group-by-Stimulation Site interaction effect. In particular, the rTMS stimulation of the LIFG slowed down reaction times (RTs) both in young and healthy elderly participants, while only healthy elderlies showed an increment of RTs during the stimulation of the precuneus. Taken together our results further support the idea that the maintenance of a juvenile level of performance in graceful aging may be associated with task-specific compensatory processes that would manifest them-selves, from the neurofunctional point of view, by the recruitment of additional neural supportive regions.

What is difficult for you can be easy for me. Effects of increasing individual task demand on prefrontal lateralization: A tDCS study.

Neuroimaging studies suggest that the increment of the cognitive load associated with a specific task may induce the recruitment of a more bilateral brain network. In most studies, however, task demand has been manipulated in a static and pre-specified way, regardless of individual cognitive resources. Here we implemented a new paradigm based on a pre-experimental assessment to set up subject-specific levels of task demand and applied tDCS (transcranial direct current stimulation) to assess each hemisphere involvement in task performance. 24 young participants performed a digit span backward (DSB, complex cognitive function) and a paced finger tapping task (pFT, basic motor function) at 3 levels of subject-specific task demand ("low" 5/5 correct answers, "medium" 3/5, "high" 1/5). Anodal tDCS (20min, 1.5mA) was delivered through a target electrode (5 × 5cm) positioned to stimulate both the inferior frontal gyrus and the primary motor area over left and right hemisphere and in sham condition in three different days. A 3 (left, right, sham) × 3 (low, medium, high) mixed-model with random intercept for subjects was run with R software. As expected, in both tasks accuracy decreased with the increment of subject-specific task demand. Moreover, a significant interaction between type of stimulation and subject-specific task demand was found for the reaction times recorded during the DSB and for the accuracy in the pFT: in the most demanding conditions, right anodal tDCS significantly interfered with behavioural performance. Our results suggest that hemispheric lateralization is modulated by the subject-specific level of task demand and this modulation is not task-specific.

How many deficits in the same dyslexic brains? A behavioural and fMRI assessment of comorbidity in adult dyslexics.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading.

Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits.

Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of functional independence or modularity exists in this distributed anatomical-cognitive system.

Framing effects reveal discrete lexical-semantic and sublexical procedures in reading: an fMRI study.

According to the dual-route model, a printed string of letters can be processed by either a grapheme-to-phoneme conversion (GPC) route or a lexical-semantic route. Although meta-analyses of the imaging literature support the existence of distinct but interacting reading procedures, individual neuroimaging studies that explored neural correlates of reading yielded inconclusive results. We used a list-manipulation paradigm to provide a fresh empirical look at this issue and to isolate specific areas that underlie the two reading procedures. In a lexical condition, we embedded disyllabic Italian words (target stimuli) in lists of either loanwords or trisyllabic Italian words with unpredictable stress position. In a GPC condition, similar target stimuli were included within lists of pseudowords. The procedure was designed to induce participants to emphasize either the lexical-semantic or the GPC reading procedure, while controlling for possible linguistic confounds and keeping the reading task requirements stable across the two conditions. Thirty-three adults participated in the behavioral study, and 20 further adult participants were included in the fMRI study. At the behavioral level, we found sizeable effects of the framing manipulations that included slower voice onset times for stimuli in the pseudoword frames. At the functional anatomical level, the occipital and temporal regions, and the intraparietal sulcus were specifically activated when subjects were reading target words in a lexical frame. The inferior parietal and anterior fusiform cortex were specifically activated in the GPC condition. These patterns of activation represented a valid classifying model of fMRI images associated with target reading in both frames in the multi-voxel pattern analyses. Further activations were shared by the two procedures in the occipital and inferior parietal areas, in the premotor cortex, in the frontal regions and the left supplementary motor area. These regions are most likely involved in either early input or late output processes.

Reading the dyslexic brain: multiple dysfunctional routes revealed by a new meta-analysis of PET and fMRI activation studies.

Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimation methods. The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved spatially significant. Following binomial tests on the clusters, we found left hemispheric network specific for normal controls (i.e., of reduced involvement in dyslexics) including the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform regions: these were preferentially associated with reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task, nor cerebellar clusters showed a reduced association with dyslexics. We conclude that the examined literature demonstrates a specific lack of activation of the left occipito-temporal cortex in dyslexia particularly for reading and reading-like behaviors and for visuo-phonological tasks. Additional deficits of motor and attentional systems relevant for reading may be associated with altered functionality of dorsal left fronto-parietal cortex.

Is a lone right hemisphere enough? Neurolinguistic architecture in a case with a very early left hemispherectomy.

We studied the linguistic profile and neurolinguistic organization of a 14-year-old adolescent (EB) who underwent a left hemispherectomy at the age of 2.5 years. After initial aphasia, his language skills recovered within 2 years, with the exception of some word finding problems. Over the years, the neuropsychological assessments showed that EB's language was near-to-normal, with the exception of lexical competence, which lagged slightly behind for both auditory and written language. Moreover, EB's accuracy and speed in both reading and writing words and non-words were within the normal range, whereas difficulties emerged in reading loan words and in tasks with homophones. EB's functional magnetic resonance imaging (fMRI) patterns for several linguistic and metalinguistic tasks were similar to those observed in the dominant hemisphere of controls, suggesting that his language network conforms to a left-like linguistic neural blueprint. However, a stronger frontal recruitment suggests that linguistic tasks are more demanding for him. Finally, no specific reading activation was found in EB's occipitotemporal region, a finding consistent with the surface dyslexia-like behavioral pattern of the patient. While a lone right hemisphere may not be sufficient to guarantee full blown linguistic competences after early hemispherectomy, EB's behavioral and fMRI patterns suggest that his lone right hemisphere followed a left-like blueprint of the linguistic network.

Neural intersections of the phonological, visual magnocellular and motor/cerebellar systems in normal readers: implications for imaging studies on dyslexia.

We used fMRI to explore the extent of the anatomical overlap of three neural systems that the literature on developmental dyslexia associates with reading: the auditory phonological, the visual magnocellular, and the motor/cerebellar systems. Twenty-eight normal subjects performed four tasks during fMRI scans: word and pseudoword reading, auditory rhyming for letter names, visual motion perception, and a motor sequence learning task. We found that the left occipitotemporal cortex (OTC), which previous studies reported to be dysfunctional in dyslexia, can be fractionated into different functional areas: an anterior and lateral area that was activated by both reading and auditory rhyming tasks; a posterior area that was commonly activated by both the reading and the motion perception task and a medial/intermediate area, including the so-called Visual Word Form Area, which was specifically activated by the reading task. These results show that the left OTC is an area of segregated convergence of different functional systems. We compared our results with the hypoactivation pattern reported for reading in a previous cross-cultural PET study on 36 dyslexic subjects from three countries. The region of decreased activation in dyslexia overlapped with regions that are specific for reading and those activated during both the auditory rhyming task and the single word and pseudoword reading task described in the present fMRI study. No overlap was found with the activation patterns for the visual motion perception task or for the motor sequence learning task. These observations challenge current theories of dyslexia.

Reassessing the HAROLD model: is the hemispheric asymmetry reduction in older adults a special case of compensatory-related utilisation of neural circuits?

The HAROLD (hemispheric asymmetry reduction in older adults) model, proposed by Cabeza in 2002, suggests that age-related neurofunctional changes are characterised by a significant reduction in the functional hemispheric lateralisation in the prefrontal cortex (PFC). The supporting evidence, however, has been derived from qualitative explorations of the data rather than from explicit statistical assessments of functional lateralisation. In contrast, the CRUNCH (compensation-related utilisation of neural circuits hypothesis) model posits that elderly subjects recruit additional brain regions that do not necessarily belong to the contralateral hemisphere as much as they rely on additional strategies to solve cognitive problems. To better assess the validity and generalisability of the HAROLD model, we analysed the fMRI patterns of twenty-four young subjects (age range: 18-30 years) and twenty-four healthy elderly subjects (age range: 50-80 years) collected during the performance of two linguistic/semantic tasks (a picture-naming task and a sentence judgment task) and two episodic long-term memory (eLTM) recognition tasks for the same materials. The functional hemispheric lateralisation in each group and the ensuing between-group differences were quantitatively assessed using statistical lateralisation maps (SLMs). The number of clusters showing a genuine HAROLD effect was proportional to the level of task demand. In addition, when quantitatively significant, these effects were not restricted to the PFC. We conclude that, in its original version, the HAROLD model captures only some of the age-related brain patterns observed in graceful ageing. The results observed in our study are compatible with the more general CRUNCH model, suggesting that the former patterns can be considered a special manifestation of age-related compensatory processes.

GOOD or BAD responder? Behavioural and neuroanatomical markers of clinical response to donepezil in dementia.

We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that the BAD-responders had larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.