Publications by authors named "Filippo Bianchini"

25 Publications

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Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease.

J Exp Med 2021 May;218(5)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.
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http://dx.doi.org/10.1084/jem.20210236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040517PMC
May 2021

Climate change and anthropogenic food manipulation interact in shifting the distribution of a large herbivore at its altitudinal range limit.

Sci Rep 2021 Apr 7;11(1):7600. Epub 2021 Apr 7.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.

Ungulates in alpine ecosystems are constrained by winter harshness through resource limitation and direct mortality from weather extremes. However, little empirical evidence has definitively established how current climate change and other anthropogenic modifications of resource availability affect ungulate winter distribution, especially at their range limits. Here, we used a combination of historical (1997-2002) and contemporary (2012-2015) Eurasian roe deer (Capreolus capreolus) relocation datasets that span changes in snowpack characteristics and two levels of supplemental feeding to compare and forecast probability of space use at the species' altitudinal range limit. Scarcer snow cover in the contemporary period interacted with the augmented feeding site distribution to increase the elevation of winter range limits, and we predict this trend will continue under climate change. Moreover, roe deer have shifted from historically using feeding sites primarily under deep snow conditions to contemporarily using them under a wider range of snow conditions as their availability has increased. Combined with scarcer snow cover during December, January, and April, this trend has reduced inter-annual variability in space use patterns in these months. These spatial responses to climate- and artificial resource-provisioning shifts evidence the importance of these changing factors in shaping large herbivore spatial distribution and, consequently, ecosystem dynamics.
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http://dx.doi.org/10.1038/s41598-021-86720-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027592PMC
April 2021

Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice.

Nature 2021 Mar 25. Epub 2021 Mar 25.

European Commission, Joint Research Centre, Ispra, Italy.

Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-19. A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-19. Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches.
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http://dx.doi.org/10.1038/s41586-021-03461-yDOI Listing
March 2021

Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease.

bioRxiv 2021 Jan 22. Epub 2021 Jan 22.

Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19) . We developed a bispecific, IgG1-like molecule based on two antibodies derived from COVID-19 convalescent donors, C121 and C135 . CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, completely prevents S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 recognizes a broad panel of RBD variants and neutralizes SARS-CoV-2 and the escape mutants generated by the single monoclonals at sub-nanomolar concentrations. In a novel model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.
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http://dx.doi.org/10.1101/2021.01.22.427567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836104PMC
January 2021

Convergent antibody responses to SARS-CoV-2 in convalescent individuals.

Nature 2020 08 18;584(7821):437-442. Epub 2020 Jun 18.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.

During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC values) as low as 2 ng ml. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
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http://dx.doi.org/10.1038/s41586-020-2456-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442695PMC
August 2020

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals.

bioRxiv 2020 May 22. Epub 2020 May 22.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (ICs) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
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http://dx.doi.org/10.1101/2020.05.13.092619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263513PMC
May 2020

Effects of oral contraceptives and natural menstrual cycling on environmental learning.

BMC Womens Health 2018 11 7;18(1):179. Epub 2018 Nov 7.

Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.

Background: Endogenous ovarian hormones as well as exogenous oestradiol and progesterone play an important role in cognitive processing. Specifically, these hormones play a role in different aspects of memory, both in terms of storage capacity and temporal duration of the mnemonic track. These hormones also have various effects on different types of memory (i.e., verbal, visuo-spatial, prospective). This study investigated the effects of hormones on topographic memory, a type of memory specifically needed to recall a pathway and to acquire spatial information about locations, distances, and directions.

Methods: We compared 25 naturally cycling women (NCW) in two different cycling phases, the early follicular phase (4th - 5th days) and the mid-luteal phase (20th-21st days), with 26 women taking oral contraceptives (OC) tested in the active pill phase (20th to 21st day of OC cycle) and the inactive pill phase (2nd to 4th day of OC cycle). Both groups performed the Walking Corsi Test to assess topographic memory in their respective cycling phases. Women were instructed to learn an eight-step sequence path and recall the path five minutes later.

Results: We found that the two groups differed in terms of learning the 8-step sequence path; OC users were always better (4-5 days vs. 20-21 days) than NCW. No differences emerged in the delayed recall of the same path.

Conclusions: As already observed in other memory domains (i.e., verbal memory, emotional memory), OC users showed an advantage in terms of topographic learning. Our results might be explained by hormonal mechanisms and may suggest the future application of OC in women with topographic disorders or visuo-spatial difficulties.
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http://dx.doi.org/10.1186/s12905-018-0671-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223061PMC
November 2018

Neuropsychology as a profession in Italy.

Appl Neuropsychol Adult 2019 Nov-Dec;26(6):543-557. Epub 2018 Sep 5.

BioCruces Health Research Institute, Cruces University Hospital , Barakaldo , Spain.

The purpose of this study was to analyze the characteristics of individuals working in the field of neuropsychology in Italy, as part of a larger study examining the practice of neuropsychology across various countries. They were asked about their background, professional training, current work situation, types of assessment, preferred diagnostic procedures, as well as the rehabilitation techniques, their targeted populations, teaching responsibilities, and research activities. A total of 154 professionals completed an online survey from April 28, 2016 through June 30, 2016. The majority of participants were women, with a mean age of 42.6 years. Participants reported working for the National Health System, in private practice, or in private rehabilitation facilities. Overall, they reported being very satisfied with their work. Those who identified themselves as neuropsychologists primarily assessed individuals with dementia, stroke, movement disorders, and traumatic brain injury. While the majority of participants declared no problems with the instruments they used, others reported complaints, including but not limited to the financial cost of current neuropsychological tests and the lack of psychometric support. The main perceived obstacles were the lack of willingness to collaborate among professionals, the scarcity of academic training programs, and the lack of clinical training opportunities.
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http://dx.doi.org/10.1080/23279095.2018.1466782DOI Listing
February 2020

Selective map-following navigation deficit: A new case of developmental topographical disorientation.

J Clin Exp Neuropsychol 2018 11 4;40(9):940-950. Epub 2018 Apr 4.

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

Introduction: Developmental topographical disorientation (DTD) is a lifelong condition in which affected individuals are selectively impaired in navigating space. Although it seems that DTD is widespread in the population, only a few cases have been studied from both a behavioral and a neuroimaging point of view. Here, we report a new case of DTD, never described previously, of a young woman (C.F.) showing a specific deficit in translating allocentrically coded information into egocentrically guided navigation, in presence of spared ability of constructing such representations.

Method: A series of behavioral experiments was performed together with a resting-state functional magnetic resonance imaging (fMRI).

Results: We demonstrated that C.F. was fully effective in learning and following routes and in building up cognitive maps as well as in recognizing landmarks. C.F.'s navigational skills, instead, dropped drastically in the map-following task when she was required to use a map to navigate in a novel environment. The rs-fMRI experiment demonstrated aberrant functional connectivity between regions within the default-mode network (DMN), and in particular between medial prefrontal cortex and posterior cingulate, medial parietal, and temporal cortices.

Discussion: Our results would suggest that, at least in C.F., dysfunctional coactivation of core DMN regions would interfere with the ability to exploit cognitive maps for real-life navigation even when these maps can be correctly built.
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http://dx.doi.org/10.1080/13803395.2018.1451493DOI Listing
November 2018

Does the cerebellum contribute to human navigation by processing sequential information?

Neuropsychology 2017 Jul 23;31(5):564-574. Epub 2017 Feb 23.

Department of Psychology, Sapienza University of Rome.

Objective: Several authors have proposed that the cerebellum has an important role in functions of higher order as a general mode of sequence detection, independently from the nature of the information. The aim of this study was to verify whether the cerebellum mediates the processing of navigational sequential information and to determine whether it is influenced by the modality of the stimuli presentation.

Method: We tested 12 cerebellar patients and 12 healthy age-matched participants in 2 comparable navigational tasks (Walking Corsi Test and the Magic Carpet) requiring to memorizing a sequence of spatial locations. The 2 tasks differ each other for the modality of stimuli presentation: in the Walking Corsi Test the sequence is shown by an examiner that walks on the carpet, whereas in the Magic Carpet it is shown by a computer that lights up the tiles in the sequence. We hypothesize that different mental processes are implicated between the Walking Corsi Test and the Magic Carpet. Indeed, whereas watching the examiner, who performs the sequence on the carpet, allows the patient to simulate the action mentally in the Walking Corsi Test, such simulation cannot be triggered in the Magic Carpet.

Results: Our results showed that cerebellar patients obtained scores significantly lower than control participants only in the Magic Carpet.

Conclusions: We interpreted the patients' performance as a specific deficit in detecting and ordering single independent stimuli as a sequence, when the maintenance of stimulus-response associations is more demanding. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000354DOI Listing
July 2017

Cognitive Reserve in Healthy Aging and Alzheimer's Disease: A Meta-Analysis of fMRI Studies.

Am J Alzheimers Dis Other Demen 2016 08 14;31(5):443-9. Epub 2016 Jun 14.

Neuropsychology Unit, IRCCS Fondazione Santa Lucia of Rome, Rome, Italy Department of Life, Health and Environmental Sciences, L'Aquila University, L'Aquila, Italy.

Cognitive reserve (CR) has been defined as the ability to optimize or maximize performance through differential recruitment of brain networks. In the present study, we aimed at providing evidence for a consistent brain network underpinning CR in healthy and pathological aging. To pursue this aim, we performed a coordinate-based meta-analysis of 17 functional magnetic resonance imaging studies on CR proxies in healthy aging, Alzheimer's disease (AD), and mild cognitive impairment (MCI). We found that different brain areas were associated with CR proxies in healthy and pathological aging. A wide network of areas, including medial and lateral frontal areas, that is, anterior cingulate cortex and dorsolateral prefrontal cortex, as well as precuneus, was associated with proxies of CR in healthy elderly patients. The CR proxies in patients with AD and amnesic-MCI were associated with activation in the anterior cingulate cortex. These results were discussed hypothesizing the existence of possible compensatory mechanisms in healthy and pathological aging.
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http://dx.doi.org/10.1177/1533317516653826DOI Listing
August 2016

Cognitive-behavioural phenotype in a group of girls from 1.2 to 12 years old with the Incontinentia Pigmenti syndrome: Recommendations for clinical management.

Appl Neuropsychol Child 2017 Oct-Dec;6(4):327-334. Epub 2016 Jun 7.

e Institute of Genetics and Biophysics "Adriano Buzzati Traverso," Naples , Italy.

Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive-behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Five girls had severe to mild intellectual deficiencies and the remaining nine had a normal neurodevelopment. Four girls were of school age and two of these showed no intellectual disability, but had specific disabilities in calculation and arithmetic reasoning. This is the first description of the cognitive-behavioural profile in relation to developmental age. We stress the importance of an early assessment of learning abilities in individuals with IP without intellectual deficiencies to prevent the onset of any such deficit.
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http://dx.doi.org/10.1080/21622965.2016.1188388DOI Listing
May 2018

Gender differences in navigational memory: pilots vs. nonpilots.

Aerosp Med Hum Perform 2015 Feb;86(2):103-11

Introduction: The coding of space as near and far is not only determined by arm-reaching distance, but is also dependent on how the brain represents the extension of the body space. Recent reports suggest that the dissociation between reaching and navigational space is not limited to perception and action but also involves memory systems. It has been reported that gender differences emerged only in adverse learning conditions that required strong spatial ability.

Methods: In this study we investigated navigational versus reaching memory in air force pilots and a control group without flight experience. We took into account temporal duration (working memory and long-term memory) and focused on working memory, which is considered critical in the gender differences literature.

Results: We found no gender effects or flight hour effects in pilots but observed gender effects in working memory (but not in learning and delayed recall) in the nonpilot population (Women's mean = 5.33; SD= 0.90; Men's mean = 5.54; SD= 0.90). We also observed a difference between pilots and nonpilots in the maintenance of on-line reaching information: pilots (mean = 5.85; SD=0.76) were more efficient than nonpilots (mean = 5.21; SD=0.83) and managed this type of information similarly to that concerning navigational space. In the navigational learning phase they also showed better navigational memory (mean = 137.83; SD=5.81) than nonpilots (mean = 126.96; SD=15.81) and were significantly more proficient than the latter group.

Discussion: There is no gender difference in a population of pilots in terms of navigational abilities, while it emerges in a control group without flight experience. We found also that pilots performed better than nonpilots. This study suggests that once selected, male and female pilots do not differ from each other in visuo-spatial abilities and spatial navigation.
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http://dx.doi.org/10.3357/AMHP.4024.2015DOI Listing
February 2015

Different neural modifications underpin PTSD after different traumatic events: an fMRI meta-analytic study.

Brain Imaging Behav 2016 Mar;10(1):226-37

Neuropsychology Unit, IRCCS Fondazione Santa Lucia of Rome, Rome, Italy.

Post-traumatic stress disorder (PTSD) is an anxiety condition that can develop after exposure to trauma such as physical or sexual assault, injury, combat-related trauma, natural disaster or death. Although an increasing number of neurobiological studies carried out over the past 20 years have allowed clarifying the neural substrate of PTSD, the neural modifications underpinning PTSD are still unclear. Here we used activation likelihood estimation meta-analysis (ALE) to determine whether PTSD has a consistent neural substrate. We also explored the possibility that different traumatic events produce different alterations in the PTSD neural network. In neuroimaging studies of PTSD, we found evidence of a consistent neural network including the bilateral insula and cingulate cortex as well as the parietal, frontal and limbic areas. We also found that specific networks of brain areas underpin PTSD after different traumatic events and that these networks may be related to specific aspects of the traumatic events. We discuss our results in light of the functional segregation of the brain areas involved in PTSD.
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http://dx.doi.org/10.1007/s11682-015-9387-3DOI Listing
March 2016

Finding my own way: an fMRI single case study of a subject with developmental topographical disorientation.

Neurocase 2015 3;21(5):573-83. Epub 2014 Oct 3.

a Neuropsychology Unit , Santa Lucia Foundation , Rome , Italy.

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai's abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.
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http://dx.doi.org/10.1080/13554794.2014.960424DOI Listing
March 2016

Deficits in visuo-spatial but not in topographical memory during pregnancy and the postpartum state in an expert military pilot: a case report.

BMC Res Notes 2014 Aug 13;7:524. Epub 2014 Aug 13.

Centro Sperimentale Volo - Reparto Medicina Aeronautica e Spaziale, Aeroporto "M, de Bernardi" Pratica di Mare Pomezia, Rome, Italy.

Background: It is well known that cognitive and emotional changes occur during pregnancy, but little is known about their magnitude or their time of occurrence and recovery. During pregnancy memory is one of the most impaired cognitive functions. Although long-term aspects of memory have been investigated, other aspects of memory have not yet been explored (i.e., navigational memory and reaching memory).

Case Presentation: Here we describe the changes in reaching and walking memory that occurred during pregnancy and one year after delivery in an Italian female military pilot (Case 1) with high spatial ability. In memory tests she showed a classical dissociation between performance in reaching and walking distance, which indicated a failure of working memory, learning, and storage in reaching space. This suggests that her expertise served as a protective factor mitigating her low walking memory performance, and saving the topographical component.We compared her performance with that of two non-pregnant control groups (i.e., women pilots and non-pilots) and found that Case 1's reaching memory performance was significantly worse than that of the control groups. Even one year postpartum, Case 1's performance was not yet the same as that of the other pilots.

Conclusions: These findings contribute to our knowledge of the specific, as yet unexplored, aspects of memory deficits in women pilots during pregnancy and postpartum and suggest the need for better neuropsychological assessment before these women return to work in operational environments.
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http://dx.doi.org/10.1186/1756-0500-7-524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138368PMC
August 2014

Looking for the compass in a case of developmental topographical disorientation: a behavioral and neuroimaging study.

J Clin Exp Neuropsychol 2014 17;36(5):464-81. Epub 2014 Apr 17.

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

Developmental topographical disorientation (DTD) is the presence of navigational deficits in the context of normal intellectual ability and in the absence of any perinatal, neurological, or psychiatric disorder. As only three cases of DTD have been fully described thus far, we are still unable to draw definitive conclusions about its nature and relationship with other visuospatial competencies, such as mental rotation. The case of Mr. L.A., a 38-year-old man with no history of neurological or psychiatric disorders, sheds some light on these open questions. A neuropsychological assessment including IQ, memory, visuospatial, visuoconstructive, and navigational tests showed that Mr. L.A. has pure navigational deficits affecting both route knowledge and cognitive map processing. Unlike previously described cases of DTD, Mr. L.A. was not affected by any other visuospatial or visuoconstructive deficits. In a functional magnetic resonance imaging (fMRI) task involving the recall of route knowledge, Mr. L.A. showed activation in the occipital areas, involved in low-level perceptual analysis of the stimuli, and showed no activation in the areas activated in controls with regard to route knowledge. The present case suggests that different types of DTD exist, which are characterized by different navigational difficulties and anomalous/lacking functional brain activities in specific navigational networks.
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http://dx.doi.org/10.1080/13803395.2014.904843DOI Listing
January 2015

Incontinentia pigmenti: learning disabilities are a fundamental hallmark of the disease.

PLoS One 2014 29;9(1):e87771. Epub 2014 Jan 29.

Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Naples, Italy ; Fondazione IRCCS SDN, Naples, Italy.

Studies suggest that genetic factors are associated with the etiology of learning disabilities. Incontinentia Pigmenti (IP, OMIM#308300), which is caused by mutations of the IKBKG/NEMO gene, is a rare X-linked genomic disorder (1:10000/20:000) that affects the neuroectodermal tissues. It always affects the skin and sometimes the hair, teeth, nails, eyes and central nervous system (CNS). Data from IP patients demonstrate the heterogeneity of the clinical phenotype; about 30% have CNS manifestations. This extreme variability suggests that IP patients might also have learning disabilities. However, no studies in the literature have evaluated the cognitive profile of IP patients. In fact, the learning disability may go unnoticed in general neurological analyses, which focus on major disabling manifestations of the CNS. Here, we investigated the neuropsychological outcomes of a selected group of IP-patients by focusing on learning disabilities. We enrolled 10 women with IP (7 without mental retardation and 3 with mild to severe mental retardation) whose clinical diagnosis had been confirmed by the presence of a recurrent deletion in the IKBKG/NEMO gene. The participants were recruited from the Italian patients' association (I.P.A.SS.I. Onlus). They were submitted to a cognitive assessment that included the Wechsler Adult Intelligence scale and a battery of tests examining reading, arithmetic and writing skills. We found that 7 patients had deficits in calculation/arithmetic reasoning and reading but not writing skills; the remaining 3 had severe to mild intellectual disabilities. Results of this comprehensive evaluation of the molecular and psychoneurological aspects of IP make it possible to place "learning disabilities" among the CNS manifestations of the disease and suggest that the IKBKG/NEMO gene is a genetic determinant of this CNS defect. Our findings indicate the importance of an appropriate psychoneurological evaluation of IP patients, which includes early assessment of learning abilities, to prevent the onset of this deficit.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906222PMC
October 2014

Mental rotation task in a pilot during and after pregnancy.

Aviat Space Environ Med 2013 Oct;84(10):1092-4

Experimental Flight Center, Aerospace Medicine Department, Pratica Di Mare AFB, Pomezia, Rome, Italy.

Introduction: Discordant findings have been reported about the change in pregnant women's cognitive test performance. Visuo-spatial abilities, which are crucial in terrestrial/flight navigation, could be influenced by hormonal variations.

Case Report: A 32-yr-old Italian Air Force pilot underwent a 2-D Mental Rotation Task (MRT) and hormonal assessment in the second trimester of pregnancy and 1 yr after delivery. Her performance was compared with that of two nonpregnant groups of women: one with flying experience and the other without. Estradiol and progesterone were significantly higher in pregnancy compared with postpartum, while testosterone was almost unchanged. During pregnancy, we observed a significant difference in the subject's response time compared with pilots (she was slower) and nonpilots (she was faster). One year after delivery, her performance was still better than the nonpilot group and was almost the same as the pilot group.

Discussion: Our data are consistent with an effect of pregnancy on visuo-spatial ability that can last for some time after delivery, even with the early recovery of the hormonal levels. MRT smoothly changed in our subject, supporting previous findings that women who are experts in flight navigation are less sensitive to hormonal fluctuations.

Conclusion: In this case, visuospatial ability requiring effortful processing underwent variations during pregnancy and postpartum. Further studies are needed in order to confirm our observations in a wider population.
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http://dx.doi.org/10.3357/asem.3629.2013DOI Listing
October 2013

Gender effects on mental rotation in pilots vs. nonpilots.

Aviat Space Environ Med 2013 Jul;84(7):726-9

Experimental Flight Center, Aerospace Medicine Department, Mario de Bernardi Airport, Pratica di Mare Pomezia (Rome), Italy.

Introduction: Mental rotation ability has an important role in human navigation and, together with other cognitive abilities such as processing speed, working memory, and attention, is crucial for aircraft navigation. In the human performance literature, mental rotation tasks have consistently yielded reports of gender differences favoring men. The aim of this study was to compare the gender difference measured in a specialized population of aviators vs. a matched population of nonpilots.

Methods: : Studied were 41 pilots (20 men and 21 women) and 38 nonpilots (20 men and 18 women) matched for age and education. Pilots were stratified for flying hours. Participants performed a mental rotation task (MRT) in which accuracy and response time were recorded, and also completed sense-of-direction (SOD) and spatial cognitive styles self-evaluation scales.

Results: Men had significantly smaller response time in the MRT (men 279.6 +/- 147.0 s, women 401.6 +/- 361.3) and greater SOD (men's score 49.1 +/- 8.6, women's score 46.6 +/- 7.8), but these differences were absent among pilots. A positive relationship was also identified between pilots' response times and their flight hours.

Conclusion: These data suggest that the effect of gender on the speed of cognitive spatial processing is absent in a population with aviation experience. Gender effects may be associated with a low spatial cognitive style, whereas in groups such as aviators, who are expected to have high spatial cognitive style, other factors such as experience may come into play.
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http://dx.doi.org/10.3357/asem.3466.2013DOI Listing
July 2013

Where Am I? A new case of developmental topographical disorientation.

J Neuropsychol 2014 Mar 21;8(1):107-24. Epub 2013 Jan 21.

Dipartimento Psicologia 39, Sapienza Università di Roma, Italy; I.R.C.C.S. Fondazione Santa Lucia, Rome, Italy.

Recently, developmental topographical disorientation (DTD) was described (Bianchini et al., 2010, J Clin Exp Neuropsychol, 20, 807-27; Iaria & Barton, 2010, Exp Brain Res, 206, 189-96; Iaria, Bogod, Fox, & Barton, 2009, Neuropsychologia, 47, 30-40) as a navigational deficit in the absence of neurological or psychiatric disorders. Here, we reported the case of a healthy subject who presented this disorder. Dr. WAI was a 29-year-old right-handed man with normal development and no clinical history of neurological or psychiatric diseases who was affected by a very pervasive topographical orientation and navigational disorder. A neuroradiological exam confirmed the absence of structural and anatomical alterations of the brain. Dr. WAI was submitted to an extensive neuropsychological examination and to a battery of tests specifically developed to assess developmental topographical disorder. Using this battery, we analysed Dr. WAI's acquisition of navigational information and re-orientation processes. He showed severe DTD accompanied by deficits of different cognitive processes directly or indirectly involved in navigational skills. Dr. WAI showed a deficit in developing cognitive maps, already found in previous cases, plus difficulties in evaluating distances and computing metric environmental features. He represents a further confirmation of the existence of DTD suggesting dissociations within the disorder related to the level of development of the ability to build cognitive maps and the association of different imagery deficits. Dr. WAI can help in shedding some light on the mechanisms underlying lack of development of navigational skills.
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http://dx.doi.org/10.1111/jnp.12007DOI Listing
March 2014

Role of visuo-spatial working memory in path integration disorders in neglect.

Cortex 2013 Apr 27;49(4):920-30. Epub 2012 Mar 27.

Dipartimento di Psicologia, Università Sapienza di Roma, Italy.

This paper investigates the relationship between memory deficits and navigational ability in neglect. In recent studies (Piccardi et al., 2008a, 2010; Bianchini et al., 2010), a dissociation was found in visuo-spatial memory for peripersonal/reaching space and visuo-spatial memory for navigational space, suggesting that the latter is processed by a specific system devoted to storing environmental information for navigational purposes (Piccardi et al., 2010). Specific deficits have also been described in neglect patients in navigational tasks requiring to memorize and retrieve a target location in a real environment. In order to analyze the relation between visuo-spatial memory for different type of space (reaching vs navigational) and its relation with navigational processes, in the present study, we compared the performance of right brain-damaged patients with and without neglect on visuo-spatial memory both in peripersonal/reaching (Corsi Block-Tapping test) and in navigational (Walking Corsi test Laser) space with performances on navigational tests (a human version of the Morris Water Maze). Results indicate that a specific deficit in navigational working memory affects navigational ability in neglect patients. Indeed, neglect patients' difficulty in using path integration to navigate in the environment is directly correlated with a deficit in visuo-spatial working memory. These results support the existence of a specific memory system devoted to representing environmental information for navigational purposes and separate from visuo-spatial memory systems, which stores information in peripersonal/reaching space.
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http://dx.doi.org/10.1016/j.cortex.2012.03.009DOI Listing
April 2013

Assessing topographical orientation skills in cannabis users.

ScientificWorldJournal 2012 3;2012:137071. Epub 2012 Jan 3.

Dipartimento di Psicologia, "Sapienza" Università di Roma, 00185 Rome, Italy.

The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks.
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http://dx.doi.org/10.1100/2012/137071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259701PMC
May 2012

Sex differences in a landmark environmental re-orientation task only during the learning phase.

Neurosci Lett 2011 Oct 24;503(3):181-5. Epub 2011 Aug 24.

Dipartimento di Scienze della Salute, Università degli Studi dell'Aquila, Via Vetoio, Coppito 2, 67010 Coppito (AQ), Italy.

Sex differences are consistently reported in human navigation. Indeed, to orient themselves during navigation women are more likely to use landmark-based strategies and men Euclidean-based strategies. The difference could be due to selective social pressure, which fosters greater spatial ability in men, or biological factors. And the great variability of the results reported in the literature could be due to the experimental setting more than real differences in ability. In this study, navigational behaviour was assessed by means of a place-learning task in which a modified version of the Morris water maze for humans was used to evaluate sex differences. In using landmarks, sex differences emerged only during the learning phase. Although the men were faster than the women in locating the target position, the differences between the sexes disappeared in delayed recall.
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http://dx.doi.org/10.1016/j.neulet.2011.08.031DOI Listing
October 2011

Walking in the Corsi test: which type of memory do you need?

Neurosci Lett 2008 Feb 15;432(2):127-31. Epub 2008 Jan 15.

Facoltà Psicologia, Università dell'Aquila, L'Aquila, Italy.

Sex differences are often reported in spatial abilities. However, some studies show conflicting results, which can be ascribed to the complexity of the variables involved in the visuo-spatial domain. Until a few years ago, it was widely accepted that men outperformed women on almost all spatial tasks. However, recently some studies [A. Postma, G. Jager, R.P.C. Kessels, H.P.F. Koppeschaar, J. van Honk, Sex differences for selective forms of spatial memory, Brain Cogn. 54 (2004) 24-34; D.H. McBurney, S.J.C. Gaulin, T. Devineni, C. Adams, Superior spatial memory of women: stronger evidence for the gathering hypothesis, Evol. Hum. Behav. 18 (1997) 165-174; Q. Rahman, G.D. Wilson, S. Abrahams, Sexual orientation related differences in spatial memory, J. Int. Neuropsychol. Soc. 9 (2003) 376-383] found sex differences for selective forms of spatial memory and described a female advantage in specific spatial abilities. In this paper, we studied sex differences by testing object locations and route memories with the Corsi Block-Tapping test (CBT), one of the non-verbal tasks most used in clinical settings, and its modified, large-scale version. Our results showed a performance advantage for males in both tests and a more homogeneous pattern of memory in females.
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http://dx.doi.org/10.1016/j.neulet.2007.12.044DOI Listing
February 2008