Publications by authors named "Massimiliano Oliveri"

86 Publications

A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy.

Int J Mol Sci 2020 Oct 15;21(20). Epub 2020 Oct 15.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy.

Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, ) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, ). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit but with a different phenotype. This yet undescribed disease affects a girl with early onset demyelinating neuropathy and a severe motor disability. By whole exome sequencing (WES), we identified a homozygous c.670C>G p.(Leu224Val) variant in the gene. In silico 3D-structure analysis and bioinformatics indicated that this variant could undergo abnormal conformation and could be pathogenic. We compared the patient's clinical, neurophysiological and laboratory data with those from patients carrying p.(His147Arg) in the equatorial domain. Our patient presented signs and symptoms absent in the p.(His147Arg) cases. Molecular dynamics simulation and modelling showed that the Leu224Val mutation that occurs in the CCT5 intermediate domain near the apical domain induces a conformational change in the latter. Noteworthy is the striking difference between the phenotypes putatively linked to mutations in the same CCT subunit but located in different structural domains, offering a unique opportunity for elucidating their distinctive roles in health and disease.
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http://dx.doi.org/10.3390/ijms21207631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589105PMC
October 2020

Out with the Old and in with the New: the Contribution of Prefrontal and Cerebellar Areas to Backward Inhibition.

Cerebellum 2020 Jun;19(3):426-436

Department of Psychology, University "Sapienza" of Rome, Via dei Marsi, 78, 0018, Rome, Italy.

The inhibitory mechanism named backward inhibition (BI) counteracts interference of previous tasks supporting task switching. For instance, if task set A is inhibited when switching to task B, then it should take longer to immediately return to task set A (as occurring in an ABA sequence), as compared to a task set that has not been just inhibited (as occurring in a CBA sequence), because extra time will be needed to overcome the inhibition of task set A.The evidenced prefrontal and cerebellar role in inhibitory control suggests their involvement even in BI. Here, for the first time, we modulated the excitability of multiple brain sites (right presupplementary motor area (pre-SMA), left and right cerebellar hemispheres) through continuous theta burst stimulation (cTBS) in a valuable sham-controlled order-balanced within-subject experimental design in healthy individuals performing two domain-selective (verbal and spatial) task-switching paradigms. Verbal BI was abolished by prefrontal or cerebellar stimulations through opposite alterations of the basal pattern: cTBS on pre-SMA increased CBA reaction times, disclosing the current prefrontal inhibition of any interfering old task. Conversely, cerebellar cTBS decreased ABA reaction times, disclosing the current cerebellar recognition of sequences in which it is necessary to overcome previously inhibited events.
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http://dx.doi.org/10.1007/s12311-020-01115-9DOI Listing
June 2020

Investigating prismatic adaptation effects in handgrip strength and in plantar pressure in healthy subjects.

Gait Posture 2020 02 23;76:264-269. Epub 2019 Dec 23.

Department of Psychology, Educational Sciences and Human Movement, University of Palermo, Italy; NeuroTeam Life and Sciences, Palermo, Italy.

Background: Prismatic Adaptation (PA) is a visuomotor procedure inducing a shift of the visual field that has been shown to modulate activation of a number of brain areas, in posterior (i.e. parietal cortex) and anterior regions (i.e. frontal cortex). This neuromodulation could be useful to study neural mechanisms associated with either postural measures such as the distribution of plantar pressure or to the generation of muscle strength. Indeed, plantar pressure distribution is associated to activation of high-level cognitive mechanisms taking place within the posterior regions of the brain dorsal stream, especially of the right hemisphere. Conversely, hand force mostly rely on sensorimotor mechanisms, fulfilled by anterior regions of the brain and involving both hemispheres.

Research Question: Since PA effects have been reported to affect both sensorimotor and higher level cognitive processes, is it possible to hypothesize a modulation of both hands strenght and plantar pressure after PA?

Methods: Forty-six healthy subjects (male = 23; mean age = 25 ± 3 years) were randomly divided into two groups: a leftward prismatic adaptation group (l-PA) and a rightward prismatic adaptation group (r-PA). Hand strength and plantar pressure were assessed, immediately before and after PA, using the handgrip task and baropodometric measurement, respectively.

Results: Both l-PA and r-PA induced a significant decrease of strength in the hand contralateral to the lenses deviation side. Only r-PA was associated with an increase of the forefoot plantar pressure in both feet. Modulation of interhemispheric inhibitory processes at sensorimotor and higher cognitive level may account for the present results.

Significance: PA exerts effects on body posture and hand strength relying on different mechanisms. The PA effects on hand strength are probably related to the modulation of interhemispheric inhibition of sensorimotor processes, involving both hemispheres. The PA effects on body posture are probably related to modulation of body representation, involving mainly the right hemisphere.
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http://dx.doi.org/10.1016/j.gaitpost.2019.12.022DOI Listing
February 2020

Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex Enhances Recognition Memory in Alzheimer's Disease.

J Alzheimers Dis 2019 ;72(2):613-622

Department of Psychology, Educational Sciences and Human Movement, University of Palermo, Palermo, Italy.

Background: The lack of effective pharmacological or behavioral interventions for memory impairments associated with Alzheimer's disease (AD) emphasizes the need for the investigation of approaches based on neuromodulation.

Objective: This study examined the effects of inhibitory repetitive transcranial magnetic stimulation (rTMS) of prefrontal cortex on recognition memory in AD patients.

Methods: In a first experiment, 24 mild AD patients received sham and real 1Hz rTMS over the left and right dorsolateral prefrontal cortex (DLPFC), in different sessions, between encoding and retrieval phases of a non-verbal recognition memory task. In a second experiment, another group of 14 AD patients underwent sham controlled repeated sessions of 1Hz rTMS of the right DLPFC across a two week treatment. Non-verbal recognition memory task was performed at baseline, at the end of the two weeks period and at a follow up of 1 month.

Results: Right real rTMS significantly improved memory performance compared to right sham rTMS (p = 0.001). Left real rTMS left the memory performance unchanged as compared with left sham rTMS (p = 0.46). The two sham conditions did not differ between each other (p = 0.24). In the second experiment, AD patients treated with real rTMS showed an improvement of memory performance at the end of the two weeks treatment (p = 0.0009), that persisted at 1-month follow-up (p = 0.002).

Conclusion: These findings provide evidence that inhibitory rTMS over the right DLPFC can improve recognition memory function in AD patients. They also suggest the importance of a new approach of non-invasive brain stimulation as a promising treatment in AD.
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http://dx.doi.org/10.3233/JAD-190888DOI Listing
November 2020

Exploring the neural correlates of the reversed letter effect: Evidence from left and right parietal patients.

Neurosci Lett 2019 04 11;699:217-224. Epub 2019 Feb 11.

Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo, Italy; NeuroTeam Life and Science, Palermo, Italy; IRCCS Santa Lucia Foundation, Rome, Italy.

To investigate the hemispheric lateralization of attentional processes during visual search tasks depending on the stimulus material embedding the target, twelve patients with unilateral left (n = 7) or right (n = 5) parietal lesions and 20 age and education matched healthy controls (HC) were recruited. We used a visual search task for a uniquely tilted oblique bar embedded in an object shape 'N' or in its mirror reversal 'И'. The accuracy and the averaged reaction times (RTs) in each stimulus type ('N' or 'И') were analysed. HC presented significantly longer RTs when the target bar was embedded in 'N' among its mirror reversed 'И' (p < .05). This "reversed letter effect" was also found in the right parietal patients (p < .001), while no evidence of a reversed letter effect was found in the left parietal patients.
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http://dx.doi.org/10.1016/j.neulet.2019.02.017DOI Listing
April 2019

Early detection of memory impairments in older adults: standardization of a short version of the verbal and nonverbal Recognition Memory Test.

Neurol Sci 2019 Jan 1;40(1):97-103. Epub 2018 Oct 1.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, viale delle Scienze, Ed.15, 90128, Palermo, Italy.

In several neurological conditions, in elderly and cognitively impaired subjects, memory functioning must be evaluated to early detect the cognitive deterioration processes. In particular, recognition memory assessment is an essential step in the clinical and neuropsychological evaluation of early memory impairments. The Recognition Memory Test (RMT) developed by Smirni et al. (G Ital Psicol XXXVII(1):325-343, 2010) is an effective instrument to assess verbal and nonverbal recognition memory in the Italian population. The current study provides a new, brief, and reliable RMT format to evaluate recognition memory on elderly subjects and it reports normative data in an older adult Italian population sample (including 100 participants well distributed across sex, education, and age categories). The shortened version of RMT keeps the administration procedures and materials of the original Italian RMT constant, i.e., words, faces, and buildings. Multiple regression analysis revealed significant effects of age and educational level on performance but no effect of sex. Inferential cutoffs have been determined and equivalent scores computed. The availability of equivalent scores for the Recognition Memory Test will prove useful in the clinical evaluation of patients' memory profiles.
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http://dx.doi.org/10.1007/s10072-018-3587-8DOI Listing
January 2019

Standardization and validation of a parallel form of the verbal and non-verbal recognition memory test in an Italian population sample.

Neurol Sci 2018 Aug 4;39(8):1391-1399. Epub 2018 May 4.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, viale delle Scienze, Ed.15, 90128, Palermo, Italy.

In the neuropsychological assessment of several neurological conditions, recognition memory evaluation is requested. Recognition seems to be more appropriate than recall to study verbal and non-verbal memory, because interferences of psychological and emotional disorders are less relevant in the recognition than they are in recall memory paradigms. In many neurological disorders, longitudinal repeated assessments are needed to monitor the effectiveness of rehabilitation programs or pharmacological treatments on the recovery of memory. In order to contain the practice effect in repeated neuropsychological evaluations, it is necessary the use of parallel forms of the tests. Having two parallel forms of the same test, that kept administration procedures and scoring constant, is a great advantage in both clinical practice, for the monitoring of memory disorder, and in experimental practice, to allow the repeated evaluation of memory on healthy and neurological subjects. First aim of the present study was to provide normative values in an Italian sample (n = 160) for a parallel form of a verbal and non-verbal recognition memory battery. Multiple regression analysis revealed significant effects of age and education on recognition memory performance, whereas sex did not reach a significant probability level. Inferential cutoffs have been determined and equivalent scores computed. Secondly, the study aimed to validate the equivalence of the two parallel forms of the Recognition Memory Test. The correlations analyses between the total scores of the two versions of the test and correlation between the three subtasks revealed that the two forms are parallel and the subtasks are equivalent for difficulty.
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http://dx.doi.org/10.1007/s10072-018-3433-zDOI Listing
August 2018

Benton visual form discrimination test in healthy children: normative data and qualitative analysis.

Neurol Sci 2018 May 24;39(5):885-892. Epub 2018 Feb 24.

Dipartimento di Scienze della Formazione, Università degli Studi di Catania, Catania, Italy.

The attention evaluation may be considered a crucial phase in neuropsychological assessment. It must take into account the systemic nature of the attentional functions and must use different reliable tests in relation to the neurological and attentional problems to be addressed. The aim of the study was to offer the clinician an effective tool for attention assessment and provide the normative data and performance analysis on the Benton Visual Form Discrimination Test on an Italian sample (number 323) of healthy school children, from ages 5 to 11. Performance on Visual Form Discrimination Test (VFDT) significantly increased with growing age. Performances were significantly different when the test was divided into four sets. All groups, especially the younger ones, showed some difficulty in maintenance and sustained attention. The correct answers were significantly more numerous when they were placed at the top quadrants. This effect was more marked in the younger groups. Sex was never a significantly influencing performance. Our data seem to indicate that the higher attentional frontoparietal network becomes more functionally organized around 9-10 years. VFDT appears as a discriminative task. In clinical practice, our normative data can be used both on complex visual attention skill evaluation in children and on the ability to maintain visual attention in time.
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http://dx.doi.org/10.1007/s10072-018-3297-2DOI Listing
May 2018

Prismatic Adaptation Modulates Oscillatory EEG Correlates of Motor Preparation but Not Visual Attention in Healthy Participants.

J Neurosci 2018 01 18;38(5):1189-1201. Epub 2017 Dec 18.

Centre for Cognitive Neuroimaging, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QB, United Kingdom

Prismatic adaption (PA) has been proposed as a tool to induce neural plasticity and is used to help neglect rehabilitation. It leads to a recalibration of visuomotor coordination during pointing as well as to aftereffects on a number of sensorimotor and attention tasks, but whether these effects originate at a motor or attentional level remains a matter of debate. Our aim was to further characterize PA aftereffects by using an approach that allows distinguishing between effects on attentional and motor processes. We recorded EEG in healthy human participants (9 females and 7 males) while performing a new double step, anticipatory attention/motor preparation paradigm before and after adaptation to rightward-shifting prisms, with neutral lenses as a control. We then examined PA aftereffects through changes in known oscillatory EEG signatures of spatial attention orienting and motor preparation in the alpha and beta frequency bands. Our results were twofold. First, we found PA to rightward-shifting prisms to selectively affect EEG signatures of motor but not attentional processes. More specifically, PA modulated preparatory motor EEG activity over central electrodes in the right hemisphere, contralateral to the PA-induced, compensatory leftward shift in pointing movements. No effects were found on EEG signatures of spatial attention orienting over occipitoparietal sites. Second, we found the PA effect on preparatory motor EEG activity to dominate in the beta frequency band. We conclude that changes to intentional visuomotor, rather than attentional visuospatial, processes underlie the PA aftereffect of rightward-deviating prisms in healthy participants. Prismatic adaptation (PA) has been proposed as a tool to induce neural plasticity in both healthy participants and patients, due to its aftereffect impacting on a number of visuospatial and visuomotor functions. However, the neural mechanisms underlying PA aftereffects are poorly understood as only little neuroimaging evidence is available. Here, we examined, for the first time, the origin of PA aftereffects studying oscillatory brain activity. Our results show a selective modulation of preparatory motor activity following PA in healthy participants but no effect on attention-related activity. This provides novel insight into the PA aftereffect in the healthy brain and may help to inform interventions in neglect patients.
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http://dx.doi.org/10.1523/JNEUROSCI.1422-17.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792477PMC
January 2018

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

Neuropsychologia 2017 Jul 10;102:109-115. Epub 2017 Jun 10.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, Palermo, Italy; NeuroTeam Life and Science, Palermo, Italy; Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.

A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal patients.
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http://dx.doi.org/10.1016/j.neuropsychologia.2017.06.006DOI Listing
July 2017

Combining tDCS with prismatic adaptation for non-invasive neuromodulation of the motor cortex.

Neuropsychologia 2017 Jul 6;101:30-38. Epub 2017 May 6.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, Italy; NeuroTeam Life and Science, Palermo, Italy.

Background: Prismatic adaptation (PA) shifts visual field laterally and induces lateralized deviations of spatial attention. Recently, it has been suggested that prismatic goggles are also able to modulate brain excitability, with cognitive after-effects documented even in tasks not necessarily spatial in nature.

Objective: The aim of the present study was to test whether neuromodulatory effects obtained from tDCS and prismatic goggles could interact and induce homeostatic changes in corticospinal excitability.

Methods: Thirty-four subjects were submitted to single-pulse transcranial magnetic stimulation (TMS) over the right primary motor cortex to measure Input-Output (IO) curve as a measure of corticospinal excitability. Assessment was made in three experimental conditions: before and after rightward PA and anodal tDCS of the right motor cortex; before and after rightward PA; before and after anodal tDCS of the right motor cortex.

Results: A significant decrease of MEPs amplitude and of IO curve slope steepness was found after the combination of rightward PA and anodal tDCS; on the other hand, an increase of MEPs amplitude and of the steepness of IO curve slope on the right motor cortex was found following either rightward PA or anodal tDCS.

Conclusion: These findings suggest that priming of motor cortex excitability using PA could be an additional tool to modulate cortical metaplasticity.
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http://dx.doi.org/10.1016/j.neuropsychologia.2017.05.006DOI Listing
July 2017

Relationship between physiological excitatory and inhibitory measures of excitability in the left vs. right human motor cortex and peripheral electrodermal activity.

Neurosci Lett 2017 02 16;641:45-50. Epub 2017 Jan 16.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, Italy; NeuroTeam Life and Science, Palermo, Italy. Electronic address:

The current study was aimed at investigating the relationships of excitatory and inhibitory circuits of the left vs. right primary motor cortex with peripheral electrodermal activity (EDA). Ten healthy subjects participated in two experimental sessions. In each session, EDA was recorded for 10min from the palmar surface of the left hand. Immediately after EDA recording, Transcranial Magnetic Stimulation (TMS) was used to probe excitatory and inhibitory circuits of the left or right primary motor cortex using two protocols of stimulation: the input-output curve for recording of motor evoked potentials, for testing excitatory circuits; the long-interval cortical inhibition (LICI) protocol, for testing inhibitory circuits. In both cases, motor evoked potentials were recorded with surface electrodes from a contralateral hand muscle. The main results showed that in the right motor cortex, excitatory circuits directly correlate and inhibitory circuits inversely correlate with sympathetic activation. In the left motor cortex, both excitatory and inhibitory circuits are inversely correlated with sympathetic activation. These findings may suggest a bi-hemispheric mode of control of vegetative system by motor cortices, with the right hemisphere mainly involved in sympathetic control.
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http://dx.doi.org/10.1016/j.neulet.2017.01.027DOI Listing
February 2017

Evidence for reading improvement following tDCS treatment in children and adolescents with Dyslexia.

Restor Neurol Neurosci 2016 ;34(2):215-26

Child Neuropsychiatric Unit, Bambino Gesù Children Hospital, Department of Neuroscience, Piazza Sant'Onofrio 4, Rome, Italy.

Purpose: There is evidence that non-invasive brain stimulation transitorily modulates reading by facilitating the neural pathways underactive in individuals with dyslexia. The study aimed at investigating whether multiple sessions of transcranial direct current stimulation (tDCS) would enhance reading abilities of children and adolescents with dyslexia and whether the effect is long-lasting.

Methods: Eighteen children and adolescents with dyslexia received three 20-minute sessions a week for 6 weeks (18 sessions) of left anodal/right cathodal tDCS set at 1 mA over parieto-temporal regions combined with a cognitive training. The participants were randomly assigned to the active or the sham treatment; reading tasks (text, high and low frequency words, non-words) were used as outcome measures and collected before treatment, after treatment and one month after the end of treatment. The tolerability of tDCS was evaluated.

Results: The active group showed reduced low frequency word reading errors and non-word reading times. These positive effects were stable even one month after the end of treatment. None reported adverse effects.

Conclusions: The study shows preliminary evidence of tDCS feasibility and efficacy in improving non-words and low frequency words reading of children and adolescents with dyslexia and it opens new rehabilitative perspectives for the remediation of dyslexia.
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http://dx.doi.org/10.3233/RNN-150561DOI Listing
December 2016

Reading changes in children and adolescents with dyslexia after transcranial direct current stimulation.

Neuroreport 2016 Mar;27(5):295-300

aChild Neuropsychiatric Unit, Department of Neuroscience, Bambino Gesù Children's Hospital bClinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy.

Noninvasive brain stimulation offers the possibility to induce changes in cortical excitability and it is an interesting option as a remediation tool for the treatment of developmental disorders. This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on reading and reading-related skills of children and adolescents with dyslexia. Nineteen children and adolescents with dyslexia performed different reading and reading-related tasks (word, nonword, and text reading; lexical decision; phonemic blending; verbal working memory; rapid automatized naming) in a baseline condition without tDCS and after 20 min of exposure to three different tDCS conditions: left anodal/right cathodal tDCS to enhance left lateralization of the parietotemporal region, right anodal/left cathodal tDCS to enhance right lateralization of the parietotemporal region, and sham tDCS. In text reading, results showed a significant reduction in errors after left anodal/right cathodal tDCS and an increase in errors after left cathodal/right anodal tDCS. No effect was found in the other reading and reading-related tasks. Our findings indicate for the first time that one session of tDCS modulates some aspects of reading performance of children and adolescents with dyslexia and that the effect is polarity dependent. These single-session results support a potential role of tDCS for developing treatment protocols and suggest possible parameters for tDCS treatment customization in children and adolescents with dyslexia.
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http://dx.doi.org/10.1097/WNR.0000000000000536DOI Listing
March 2016

The Remapping of Time by Active Tool-Use.

PLoS One 2015 30;10(12):e0146175. Epub 2015 Dec 30.

Department of Psychology, University of Bologna, Bologna, Italy.

Multiple, action-based space representations are each based on the extent to which action is possible toward a specific sector of space, such as near/reachable and far/unreachable. Studies on tool-use revealed how the boundaries between these representations are dynamic. Space is not only multidimensional and dynamic, but it is also known for interacting with other dimensions of magnitude, such as time. However, whether time operates on similar action-driven multiple representations and whether it can be modulated by tool-use is yet unknown. To address these issues, healthy participants performed a time bisection task in two spatial positions (near and far space) before and after an active tool-use training, which consisted of performing goal-directed actions holding a tool with their right hand (Experiment 1). Before training, perceived stimuli duration was influenced by their spatial position defined by action. Hence, a dissociation emerged between near/reachable and far/unreachable space. Strikingly, this dissociation disappeared after the active tool-use training since temporal stimuli were now perceived as nearer. The remapping was not found when a passive tool-training was executed (Experiment 2) or when the active tool-training was performed with participants' left hand (Experiment 3). Moreover, no time remapping was observed following an equivalent active hand-training but without a tool (Experiment 4). Taken together, our findings reveal that time processing is based on action-driven multiple representations. The dynamic nature of these representations is demonstrated by the remapping of time, which is action- and effector-dependent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146175PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696728PMC
July 2016

Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex.

PLoS One 2015 17;10(12):e0144838. Epub 2015 Dec 17.

Dipartimento di Scienze Psicologiche, Pedagogiche e della Formazione, Università degli Studi di Palermo, Palermo, Italy.

Objective: The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task.

Method: 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS.

Results: Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance.

Conclusion: Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144838PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682999PMC
June 2016

Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening.

Front Hum Neurosci 2015 26;9:158. Epub 2015 Mar 26.

Clinical and Behavioral Neurology Laboratory, Non-Invasive Brain Stimulation Unit, IRCCS "Santa Lucia" Foundation Rome, Italy ; Department of Psychology, University of Palermo Palermo, Italy ; NeuroTeam Life and Science Institute Palermo, Italy.

Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS) pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT). The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect). Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning) and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.
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http://dx.doi.org/10.3389/fnhum.2015.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374462PMC
April 2015

Repetitive transcranial magnetic stimulation over the left parietal cortex facilitates visual search for a letter among its mirror images.

Neuropsychologia 2015 Apr 3;70:196-205. Epub 2015 Mar 3.

Dipartimento di Scienze Psicologiche Pedagogiche e della Formazione, Università di Palermo, Edificio 15, 90128 Palermo, Italy; Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.

Interference by task irrelevant information is seen in visual search paradigms using letters. Thus, it is harder to find the letter 'N' among its mirror reversals 'И' than vice versa. This observation, termed the reversed letter effect, involves both a linguistic association and an interference of task irrelevant information—the shape of 'N' or 'И' is irrelevant, the search requires merely distinguishing the tilts of oblique bars. We adapted the repetitive transcranial magnetic stimulation (rTMS) methods that we previously used, and conducted three rTMS experiments using healthy subjects. The first experiment investigated the effects of rTMS on the left and right posterior parietal cortex (PPC) on the search performance. The second experiment focused on the role of the left PPC. The third experiment explored whether another left posterior region, known to be involved in word reading (ventral occipito-temporal cortex, vOTC), plays a role. We found that rTMS on right PPC and left VOTC had no effect on the speed and accuracy of the visual search regardless of whether the target is 'N' or its mirror reversal. In contrast, rTMS on the left PPC speeded up the search on finding target 'N' among its mirror images. We suggest that left PPC is involved in letter recognition, and that rTMS on left PPC facilitated our visual search task by reducing task interference triggered by task irrelevant letter recognition.
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http://dx.doi.org/10.1016/j.neuropsychologia.2015.03.002DOI Listing
April 2015

Processing past tense in the left cerebellum.

Neurocase 2015 6;21(2):185-9. Epub 2014 Feb 6.

a Dipartimento di Psicologia , Università di Palermo , Palermo , Italy.

We report the case of a patient with ischemic lesion of the left cerebellum, who showed specific deficits in processing past versus future tense of action verbs. These findings confirm, in the presence of cerebellar damage, previous results obtained with transcranial magnetic stimulation in healthy subjects and suggest a specificity of the left cerebellum for preparation of responses to the past tense of action verbs. As part of the procedural brain, the cerebellum could play a role in applying the linguistic rules for selection of morphemes typical of past and future tense formation.
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http://dx.doi.org/10.1080/13554794.2013.878730DOI Listing
December 2015

The temporoparietal junction modulates self-other motor representations during online and offline social motor conflict: an rTMS study.

Neuroreport 2015 Jan;26(1):1-5

aSanta Lucia Foundation IRCCS bNeurology Clinic, University of Rome Tor Vergata cDepartment of Psychological and Pedagogical Sciences, University of Palermo, Palermo, Italy.

The aim of this study was to investigate the role of the temporoparietal junction (TPJ) during tasks of imitation and counter-imitation of observed actions. Twenty individuals participated in two experiments. One experiment was an imitation/counter-imitation task, requiring the participant to imitate or counter-imitate an observed movement. The second experiment required the participant to plan a movement, then to imitate an observed movement that could be either the same or different from that planned. In both experiments, participants executed the task in a baseline session and in a session following inhibitory trains of repetitive transcranial magnetic stimulation on the right TPJ and on the right ventral premotor cortex. In both experiments, repetitive transcranial magnetic stimulation of the right TPJ decreased reaction times of incongruent responses--that is, it facilitated the execution of movements different from those previously observed or planned. These findings provide an example of modulation of self-other interactions using noninvasive neuromodulation of the right TPJ.
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http://dx.doi.org/10.1097/WNR.0000000000000282DOI Listing
January 2015

Disrupting SMA activity modulates explicit and implicit emotional responses: an rTMS study.

Neurosci Lett 2014 Sep 17;579:30-4. Epub 2014 Jul 17.

Department of Psychological, Pedagogical and Education Sciences, University of Palermo, Fondazione Santa Lucia IRCCS, Roma, Italy. Electronic address:

Supplementary Motor Area (SMA) has been considered as an interface between the emotional/motivational system and motor effector system. Here, we investigated whether it is possible to modulate emotional responses using non-invasive brain stimulation of the SMA. 1Hz repetitive transcranial magnetic stimulation (rTMS) trains were applied over the SMA of healthy subjects performing a task requiring to judge the valence and arousal of emotional stimuli. rTMS trains over the SMA increased the perceived valence of emotionally negative visual stimuli, while decreasing the perceived valence of emotionally positive ones. The modulatory effect on emotional valence was specific for stimuli with emotional content, since it was not observed for neutral visual stimuli. The effect was also specific for the site of stimulation, since rTMS of the visual cortex failed to modulate either perceived valence or arousal. These findings provide the first example of neuromodulation of emotional responses based on non-invasive brain stimulation.
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http://dx.doi.org/10.1016/j.neulet.2014.07.012DOI Listing
September 2014

Exploring the reciprocal modulation of time and space in dancers and non-dancers.

Exp Brain Res 2014 Oct 17;232(10):3191-9. Epub 2014 Jun 17.

Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, 00143, Rome, Italy,

We explored whether time and space representations modulate each other in subjects that are trained to integrate time and space dimensions, i.e., professional dancers. A group of dancers, and one of non-dancers, underwent two different tasks employing identical stimuli. A first static central line could last one of three possible durations and could have one of three possible lengths. A second growing line appeared from the left or right of the screen and grew up toward the opposite direction at constant velocity. In the Spatial task, subjects encoded the length of the static line and stopped the growing line when it had reached half the length of the static one, regardless of time travel. In the Temporal task, subjects encoded the duration of the static line and stopped the growing line when it had lasted half the duration of the static one, regardless of space traveled. Dancers, differently from non-dancers, anticipated time in the Temporal task. However, both dancers and non-dancers were biased by the stimulus length when performing the Temporal task, while they were not biased by the stimulus duration when performing the Spatial task. Concluding, this study underlines the plasticity of time dimension that can be influenced by spatial information and by sensorimotor training for the synchronization in space and time.
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http://dx.doi.org/10.1007/s00221-014-4005-yDOI Listing
October 2014

Prismatic adaptation as a novel tool to directionally modulate motor cortex excitability: evidence from paired-pulse TMS.

Brain Stimul 2014 Jul-Aug;7(4):573-9. Epub 2014 Apr 13.

Fondazione "Santa Lucia" IRCCS, Roma, Italy; Department of Psychology, University of Palermo, Palermo, Italy.

Background: The prismatic adaptation (PA) is a visuo-motor procedure that has captured the attention of neuroscientists in the last decades, hence it seems to affect high-order cognition. However, the basic neural processes related to PA and its effects on cortical plasticity are not clear yet.

Objective/hypothesis: The aim of the present study is to explore whether PA induces a direct effect on the motor cortices (M1) excitability.

Methods: Fourteen healthy participants were submitted to paired-pulse TMS to measure short-intracortical-inhibition (SICI) and intracortical-facilitation (ICF) on both the left and the right M1, before and after PA, that could induce a leftward or rightward after-effect.

Results: An increase of intracortical-facilitation was found in the M1 contralateral to the after-effect direction. Moreover the extent of facilitation and of the after-effect were correlated to each others.

Conclusion: This finding reveals that PA influences M1 cortices directly, raising their excitability. The present investigation represents an innovative step for the understanding of neurophysiological processes by which PA affects brain functions.
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http://dx.doi.org/10.1016/j.brs.2014.03.005DOI Listing
April 2015

Impairments in top down attentional processes in right parietal patients: paradoxical functional facilitation in visual search.

Vision Res 2014 Apr 28;97:74-82. Epub 2014 Feb 28.

Dipartimento di Psicologia, Università di Palermo, Palermo, Italy; Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.

It is well known that the right posterior parietal cortex (PPC) is involved in attentional processes, including binding features. It remains unclear whether PPC is implicated in top-down and/or bottom-up components of attention. We aim to clarify this by comparing performance of seven PPC patients and healthy controls (HC) in a visual search task involving a conflict between top-down and bottom-up processes. This task requires essentially a bottom-up feature search. However, top-down attention triggers feature binding for object recognition, designed to be irrelevant but interfering to the task. This results in top-down interference, prolonging the search reaction time. This interference was indeed found in our HCs but not in our PPC patients. In contrast to HC, the PPC patients showed no evidence of prolonged reactions times, even though they were slower than the HCs in search tasks without the conflict. This finding is an example of paradoxical functional facilitation (PFF) by brain damage. The PFF effect enhanced our patients' performance by reducing the top down interference. Our finding supports the idea that right PPC plays a crucial role in top-down attentional processes. In our search tasks, right PPC induces top-down interference either by directing spatial attention to achieve viewpoint invariance in shape recognition or by feature binding.
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http://dx.doi.org/10.1016/j.visres.2014.02.002DOI Listing
April 2014

Left insular cortex and left SFG underlie prismatic adaptation effects on time perception: evidence from fMRI.

Neuroimage 2014 May 24;92:340-8. Epub 2014 Jan 24.

Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK.

Prismatic adaptation (PA) has been shown to affect left-to-right spatial representations of temporal durations. A leftward aftereffect usually distorts time representation toward an underestimation, while rightward aftereffect usually results in an overestimation of temporal durations. Here, we used functional magnetic resonance imaging (fMRI) to study the neural mechanisms that underlie PA effects on time perception. Additionally, we investigated whether the effect of PA on time is transient or stable and, in the case of stability, which cortical areas are responsible of its maintenance. Functional brain images were acquired while participants (n=17) performed a time reproduction task and a control-task before, immediately after and 30 min after PA inducing a leftward aftereffect, administered outside the scanner. The leftward aftereffect induced an underestimation of time intervals that lasted for at least 30 min. The left anterior insula and the left superior frontal gyrus showed increased functional activation immediately after versus before PA in the time versus the control-task, suggesting these brain areas to be involved in the executive spatial manipulation of the representation of time. The left middle frontal gyrus showed an increase of activation after 30 min with respect to before PA. This suggests that this brain region may play a key role in the maintenance of the PA effect over time.
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http://dx.doi.org/10.1016/j.neuroimage.2014.01.028DOI Listing
May 2014

How to improve reading skills in dyslexics: the effect of high frequency rTMS.

Neuropsychologia 2013 Dec 31;51(14):2953-9. Epub 2013 Oct 31.

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, I-00165 Rome, Italy.

The latest progress in understanding remediation of dyslexia underlines how some changes in brain are a necessary mechanism of improvement. We wanted to determine whether high frequency repetitive transcranial magnetic stimulation (hf-rTMS) over areas that are underactive during reading in dyslexics, would improve reading of dyslexic adults. We applied 5Hz-TMS over both left and right inferior parietal lobule (IPL) and superior temporal gyrus (STG) prior to word, non-word and text reading aloud. Results show that hf-rTMS stimulation over the left IPL improves non-word reading accuracy and hf-rTMS stimulation over the left STG increases word reading speed and text reading accuracy. Moreover after right IPL stimulation, non-word reading accuracy also improves. These findings indicate that in dyslexics, L-STG and L-IPL have a differential role in word, non-word and text reading. Even if we would normally expect left-lateralized improvements only, the finding of a right IPL involvement suggests that there is additional compensatory recruitment of this region in dyslexics. In conclusion, we provide the first evidence that distinctive facilitation of neural pathways known to be underactive in dyslexics transitorily improves their reading performance. Such ameliorative effect may open new perspectives for the development of long-term specific treatments for dyslexia.
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http://dx.doi.org/10.1016/j.neuropsychologia.2013.10.018DOI Listing
December 2013

The role of posterior parietal cortices on prismatic adaptation effects on the representation of time intervals.

Neuropsychologia 2013 Nov 13;51(13):2825-32. Epub 2013 Aug 13.

Fondazione "Santa Lucia" IRCCS, 00179 Roma, Italy; Department of Psychology, University of Bologna, 40127 Bologna, Italy. Electronic address:

Previous studies provided evidence of an ascending left-to-right spatial representation of time durations by using a technique affecting high levels of spatial cognition, i.e. prismatic adaptation (PA). Indeed, PA that induced a leftward aftereffect distorted time representation toward an underestimation, while PA that induced a rightward aftereffect distorted time representation toward an overestimation. The present study advances previous findings on the effects of PA on time by investigating the neural basis subtending these effects. We focused on the posterior parietal cortex (PPC) since it is involved in the PA procedure and also in the formulation of the spatial representation of time. We conducted two experiments where right-handed healthy adults were submitted to a time task, before and after PA, that could induce a leftward or rightward aftereffect. Repetitive TMS (rTMS) was used to inhibit the left or right PPC before PA administration. In a first experiment the time task consisted of reproducing an half duration (time bisection task) by pressing a key and the participants responded and adapted to prisms with their right hand. In a second experiment the time task consisted of reproducing a whole duration (time reproduction task) by pressing a key and the participants responded and adapted to prisms with their left hand. We found an abolition of the effects of PA on time when rTMS was delivered on the left and not on the right PPC, regardless of the task and moreover, when the participants responded and adapted with the right hand and also with the left hand. This result suggests a direct involvement of the left PPC in the interactive process, between spatial modulations induced by PA and the spatial representation of time, that does not depend on motor processes. This study provides useful results for future investigations on the neural mechanisms subtending the effects of PA on spatial representations.
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http://dx.doi.org/10.1016/j.neuropsychologia.2013.08.006DOI Listing
November 2013

Cerebellar contribution to mental rotation: a cTBS study.

Cerebellum 2013 Dec;12(6):856-61

Department of Psychology, University "Sapienza", Rome, Italy,

A cerebellar role in spatial information processing has been advanced even in the absence of physical manipulation, as occurring in mental rotation. The present study was aimed at investigating the specific involvement of left and right cerebellar hemispheres in two tasks of mental rotation. We used continuous theta burst stimulation to downregulate cerebellar hemisphere excitability in healthy adult subjects performing two mental rotation tasks: an Embodied Mental Rotation (EMR) task, entailing an egocentric strategy, and an Abstract Mental Rotation (AMR) task entailing an allocentric strategy. Following downregulation of left cerebellar hemisphere, reaction times were slower in comparison to sham stimulation in both EMR and AMR tasks. Conversely, identical reaction times were obtained in both tasks following right cerebellar hemisphere and sham stimulations. No effect of cerebellar stimulation side was found on response accuracy. The present findings document a specialization of the left cerebellar hemisphere in mental rotation regardless of the kind of stimulus to be rotated.
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http://dx.doi.org/10.1007/s12311-013-0494-7DOI Listing
December 2013

Continuous theta burst stimulation (cTBS) on left cerebellar hemisphere affects mental rotation tasks during music listening.

PLoS One 2013 28;8(5):e64640. Epub 2013 May 28.

IRCCS Santa Lucia Foundation, Rome, Italy.

Converging evidence suggests an association between spatial and music domains. A cerebellar role in music-related information processing as well as in spatial-temporal tasks has been documented. Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a "Mozart Effect". Cerebellar cTBS applied before musical listening made subjects faster (P = 0.005) and less accurate (P = 0.005) in performing the EMR but not the AMR task. Thus, cerebellar inhibition by TBS unmasked the effect of musical listening on motor imagery. These data support a coupling between music listening and sensory-motor integration in cerebellar networks for embodied representations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064640PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665687PMC
January 2014

The right frontopolar cortex is involved in visual-spatial prospective memory.

PLoS One 2013 13;8(2):e56039. Epub 2013 Feb 13.

Clinical and Behavioural Neurology Laboratory, Istituto Di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.

The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10, right BA10 and CZ (control condition). In the prospective memory procedure, sequences of four spatial positions (black squares) each were presented. During the inter-sequence delay, subjects had to reproduce the sequence in the observed order (ongoing task forward) or the reverse order (backward). At the occurrence of a target position, subjects had to press a key on the keyboard (prospective memory score). Recall and recognition of the target positions were also tested. We found that prospective memory accuracy was lower after theta-burst stimulation over right BA10 than CZ (p<0.01), whereas it was comparable in left BA10 and CZ conditions. No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance. Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospective memory. In the context of previous data providing evidence for left BA 10 involvement in verbal prospective memory, our results also suggest material-specific lateralization of prospective memory processes in BA 10.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056039PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572161PMC
August 2013