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2.
Bioorg Med Chem ; 28(20): 115700, 2020 10 15.
Article in English | MEDLINE | ID: mdl-33069076

ABSTRACT

The aggregation of ß-amyloid peptides is associated to neurodegeneration in Alzheimer's disease (AD) patients. Consequently, the inhibition of both oligomerization and fibrillation of ß-amyloid peptides is considered a plausible therapeutic approach for AD. Herein, the synthesis of new naphthalene derivatives and their evaluation as anti-ß-amyloidogenic agents are presented. Molecular dynamic simulations predicted the formation of thermodynamically stable complexes between the compounds, the Aß1-42 peptide and fibrils. In human microglia cells, these compounds inhibited the aggregation of Aß1-42 peptide. The lead compound 8 showed a high affinity to amyloid plaques in mice brain ex vivo assays and an adequate log Poct/PBS value. Compound 8 also improved the cognitive function and decreased hippocampal ß-amyloid burden in the brain of 3xTg-AD female mice. Altogether, our results suggest that 8 could be a novel therapeutic agent for AD.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/antagonists & inhibitors , Naphthalenes/pharmacology , Neuroprotective Agents/pharmacology , Peptide Fragments/antagonists & inhibitors , Protein Aggregates/drug effects , Protein Aggregation, Pathological/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Dose-Response Relationship, Drug , Mice , Mice, Inbred C57BL , Molecular Dynamics Simulation , Molecular Structure , Naphthalenes/chemical synthesis , Naphthalenes/chemistry , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Peptide Fragments/metabolism , Protein Aggregation, Pathological/metabolism , Structure-Activity Relationship , Thermodynamics
3.
Brain Sci ; 8(9)2018 Sep 10.
Article in English | MEDLINE | ID: mdl-30201924

ABSTRACT

Reading is essentially a two-channel function, requiring the integration of intact visual and auditory processes both peripheral and central. It is essential for normal reading that these component processes go forward automatically. Based on this model, Boder described three main subtypes of dyslexia: dysphonetic dyslexia (DD), dyseidetic, mixed and besides a fourth group defined non-specific reading delay (NSRD). The subtypes are identified by an algorithm that considers the reading quotient and the % of errors in the spelling test. Chiarenza and Bindelli have developed the Direct Test of Reading and Spelling (DTRS), a computerized, modified and validated version to the Italian language of the Boder test. The sample consisted of 169 subjects with DD and 36 children with NSRD. The diagnosis of dyslexia was made according to the DSM-V criteria. The DTRS was used to identify the dyslexia subtypes and the NSRD group. 2⁻5 min of artefact-free EEG (electroencephalogram), recorded at rest with eyes closed, according to 10⁻20 system were analyzed. Stability based Biomarkers identification methodology was applied to the DTRS and the quantitative EEG (QEEG). The reading quotients and the errors of the reading and spelling test were significantly different in the two groups. The DD group had significantly higher activity in delta and theta bands compared to NSRD group in the frontal, central and parietal areas bilaterally. The classification equation for the QEEG, both at the scalp and the sources levels, obtained an area under the robust Receiver Operating Curve (ROC) of 0.73. However, we obtained a discrimination equation for the DTRS items which did not participate in the Boder classification algorithm, with a specificity and sensitivity of 0.94 to discriminate DD from NSRD. These results demonstrate for the first time the existence of different neuropsychological and neurophysiological patterns between children with DD and children with NSRD. They may also provide clinicians and therapists warning signals deriving from the anamnesis and the results of the DTRS that should lead to an earlier diagnosis of reading delay, which is usually very late diagnosed and therefore, untreated until the secondary school level.

4.
Int J Psychophysiol ; 130: 9-20, 2018 08.
Article in English | MEDLINE | ID: mdl-29787785

ABSTRACT

Oppositional defiant disorder (ODD) is frequently associated with Attention Deficit Hyperactivity Disorder (ADHD) but no clear neurophysiological evidence exists that distinguishes the two groups. Our aim was to identify biomarkers that distinguish children with Attention Deficit Hyperactivity Disorder combined subtype (ADHD_C) from children with ADHD_C + ODD, by combining the results of quantitative EEG (qEEG) and the Junior Temperament Character Inventory (JTCI). 28 ADHD_C and 22 ADHD_C + ODD children who met the DSMV criteria participated in the study. JTCI and EEG were analyzed. Stability based Biomarkers identification methodology was applied to the JTCI and the qEEG separately and combined. The qEEG was tested at the scalp and the sources levels. The classification power of the selected biomarkers was tested with a robust ROC technique. The best discriminant power was obtained when TCI and qEEG were analyzed together. Novelty seeking, self-directedness and cooperativeness were selected as biomarkers together with F4 and Cz in Delta; Fz and F4 in Theta and F7 and F8 in Beta, with a robust AUC of 0.95 for the ROC. At sources level: the regions were the right lateral and medial orbito-frontal cortex, cingular region, angular gyrus, right inferior occipital gyrus, occipital pole and the left insula in Theta, Alpha and Beta. The robust estimate of the total AUC was 0.91. These structures are part of extensive networks of novelty seeking, self-directedness and cooperativeness systems that seem dysregulated in these children. These methods represent an original approach to associate differences of personality and behavior to specific neuronal systems and subsystems.


Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit and Disruptive Behavior Disorders/complications , Evoked Potentials/physiology , Personality Inventory , Temperament/physiology , Adolescent , Brain Mapping , Child , Electroencephalography , Female , Humans , Male , Neuropsychological Tests , ROC Curve , Statistics, Nonparametric
5.
Appl Psychophysiol Biofeedback ; 41(1): 27-37, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26294269

ABSTRACT

Children with learning disabilities (LD) frequently have an EEG characterized by an excess of theta and a deficit of alpha activities. NFB using an auditory stimulus as reinforcer has proven to be a useful tool to treat LD children by positively reinforcing decreases of the theta/alpha ratio. The aim of the present study was to optimize the NFB procedure by comparing the efficacy of visual (with eyes open) versus auditory (with eyes closed) reinforcers. Twenty LD children with an abnormally high theta/alpha ratio were randomly assigned to the Auditory or the Visual group, where a 500 Hz tone or a visual stimulus (a white square), respectively, was used as a positive reinforcer when the value of the theta/alpha ratio was reduced. Both groups had signs consistent with EEG maturation, but only the Auditory Group showed behavioral/cognitive improvements. In conclusion, the auditory reinforcer was more efficacious in reducing the theta/alpha ratio, and it improved the cognitive abilities more than the visual reinforcer.


Subject(s)
Alpha Rhythm/physiology , Learning Disabilities/rehabilitation , Neurofeedback/methods , Reinforcement, Psychology , Theta Rhythm/physiology , Acoustic Stimulation/methods , Child , Disabled Children , Humans , Photic Stimulation/methods , Random Allocation , Treatment Outcome
6.
Front Neurosci ; 9: 427, 2015.
Article in English | MEDLINE | ID: mdl-26582974

ABSTRACT

This study was a two-armed parallel group design aimed at testing real world effectiveness of a music therapy (MT) intervention for children with severe neurological disorders. The control group received only the standard neurorestoration program and the experimental group received an additional MT "Auditory Attention plus Communication protocol" just before the usual occupational and speech therapy. Multivariate Item Response Theory (MIRT) identified a neuropsychological status-latent variable manifested in all children and which exhibited highly significant changes only in the experimental group. Changes in brain plasticity also occurred in the experimental group, as evidenced using a Mismatch Event Related paradigm which revealed significant post intervention positive responses in the latency range between 308 and 400 ms in frontal regions. LORETA EEG source analysis identified prefrontal and midcingulate regions as differentially activated by the MT in the experimental group. Taken together, our results showing improved attention and communication as well as changes in brain plasticity in children with severe neurological impairments, confirm the importance of MT for the rehabilitation of patients across a wide range of dysfunctions.

7.
Epilepsy Res ; 108(4): 748-54, 2014 May.
Article in English | MEDLINE | ID: mdl-24661428

ABSTRACT

The purpose of this paper is to evaluate the effects of the anterior temporal lobectomy on the functional state of the auditory pathway in a group of drug-resistant epileptic patients, linking the electrophysiological results to the resection magnitude. Twenty-seven patients with temporal lobe epilepsy and a matched control group were studied. Auditory brainstem and middle latency responses (ABR and MLR respectively) were carried out before and after 6, 12 and 24 months surgical treatment. The volume and longitude of temporo-mesial resected structures were estimated on magnetic resonance images taken 6 months after surgery. Before the intervention the patients showed a significant delay of latency in waves III, V, Pa and Nb, with an increase in duration of I-V interval in comparison with healthy subjects (Mann-Whitney U-test, p<0.05). After resection, additional significant differences in waves I and Na latency were observed. Na and Pa waveforms showed a tendency to increase in amplitude, which became statistically significant 12 months after surgery for right hemisphere lobectomized patients in the midline electrode, and in Pa waveform for all patients in the temporal electrodes ipsilateral to resection (Wilcoxon test, p<0.05). In general, latency variations of MLR correlated with resection longitude, while changes in amplitude correlated with the volume of the resection in the middle temporal pole and amygdala (Pearson' correlation test, p<0.05). As a result, we assume that anterior temporal lobectomy provokes functional modifications into the auditory pathway, probably related to an indirect modulation of its activity by the temporo-mesial removed structures.


Subject(s)
Anterior Temporal Lobectomy , Auditory Pathways/physiopathology , Epilepsy, Temporal Lobe/surgery , Evoked Potentials, Auditory/physiology , Temporal Lobe/surgery , Adult , Epilepsy, Temporal Lobe/physiopathology , Female , Humans , Male , Reaction Time/physiology , Temporal Lobe/physiopathology , Treatment Outcome , Young Adult
8.
Int J Alzheimers Dis ; 2014: 180741, 2014.
Article in English | MEDLINE | ID: mdl-24551475

ABSTRACT

To evaluate the hypothesis that quantitative EEG (qEEG) analysis is susceptible to detect early functional changes in familial Alzheimer's disease (AD) preclinical stages. Three groups of subjects were selected from five extended families with hereditary AD: a Probable AD group (18 subjects), an asymptomatic carrier (ACr) group (21 subjects), with the mutation but without any clinical symptoms of dementia, and a normal group of 18 healthy subjects. In order to reveal significant differences in the spectral parameter, the Mahalanobis distance (D (2)) was calculated between groups. To evaluate the diagnostic efficiency of this statistic D (2), the ROC models were used. The ROC curve was summarized by accuracy index and standard deviation. The D (2) using the parameters of the energy in the fast frequency bands shows accurate discrimination between normal and ACr groups (area ROC = 0.89) and between AD probable and ACr groups (area ROC = 0.91). This is more significant in temporal regions. Theses parameters could be affected before the onset of the disease, even when cognitive disturbance is not clinically evident. Spectral EEG parameter could be firstly used to evaluate subjects with E280A Presenilin-1 mutation without impairment in cognitive function.

9.
PLoS One ; 8(6): e66271, 2013.
Article in English | MEDLINE | ID: mdl-23824339

ABSTRACT

Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.


Subject(s)
Brain/diagnostic imaging , Neuromyelitis Optica/diagnostic imaging , Optic Neuritis/diagnostic imaging , Adolescent , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuromyelitis Optica/pathology , Recurrence , Young Adult
10.
MEDICC Rev ; 15(1): 16-22, 2013 01.
Article in English | MEDLINE | ID: mdl-23396237

ABSTRACT

INTRODUCTION: Cross-modal plasticity has been extensively studied in deaf adults with neuroimaging studies, yielding valuable results. A recent study in our laboratory with deaf-blind children found evidence of cross-modal plasticity, revealed in over-representation of median nerve somatosensory evoked potentials (SEP N20) in left hemisphere parietal, temporal and occipital regions. This finding led to asking whether SEP N20 changes are peculiar to deaf-blindness or are also present in sighted deaf children. OBJECTIVE: Assess cross-modal plasticity in deaf child cochlear implant candidates using neurophysiological techniques (visual evoked potentials and median nerve somatosensory evoked potentials). METHODS: Participants were 14 prelingually deaf children assessed in the Cuban Cochlear Implant Program. Flash visual-evoked potentials and SEP N20 were recorded at 19 scalp recording sites. Topographic maps were obtained and compared to those of control group children with normal hearing. Analysis took into account duration of hearing loss. RESULTS: Topographic maps of flash visual-evoked potentials did not show changes in deaf child cochlear implant candidates. However, SEP N20 from right median nerve stimulation did show changes from expansion of cortical activation into the left temporal region in deaf children aged ≥7 years, which was interpreted as neurophysiological evidence of cross-modal plasticity, not previously described for this technique and type of somatosensory stimulus. We interpret this finding as due in part to duration of deafness, particularly related to handedness, since expansion was selective for the left hemisphere in the children, who were all right-handed. CONCLUSIONS: Cortical over-representation of SEP N20 in the left temporal region is interpreted as evidence of cross-modal plasticity that occurs if the deaf child does not receive a cochlear implant early in life-before concluding the critical period of neural development-and relies on sign language for communication.


Subject(s)
Cochlear Implantation , Deafness/physiopathology , Evoked Potentials, Somatosensory/physiology , Evoked Potentials, Visual/physiology , Neuronal Plasticity/physiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Cuba , Deaf-Blind Disorders/physiopathology , Deep Brain Stimulation , Excitatory Postsynaptic Potentials/physiology , Female , Hearing Loss, Sensorineural/physiopathology , Humans , Male , Median Nerve/physiopathology , Prospective Studies
11.
MEDICC Rev ; 14(2): 23-9, 2012 04.
Article in English | MEDLINE | ID: mdl-22580550

ABSTRACT

INTRODUCTION: Studies of neuroplasticity have shown that the brain's neural networks change in the absence of sensory input such as hearing or vision. However, little is known about what happens when both sensory modalities are lost (deaf-blindness). Hence, this study of cortical reorganization in visually-impaired child cochlear implant (CI) candidates. OBJECTIVE: Assess cross-modal plasticity, specifically cortical reorganization for tactile representation in visually-impaired child CI candidates, through study of topography of somatosensory evoked potentials (SEP). METHODS: From April through September 2005, SEP from median and tibial nerve electrical stimulation were studied in 12 visually-impaired child CI candidates aged 3-15 years and 23 healthy controls. Following placement of 19 recording electrodes using the International 10-20 System , SEP were recorded and then processed. Topographic maps were obtained for SEP N20 (median nerve) and SEP P40 (tibial nerve), permitting assessment of cortical reorganization by comparing visually-impaired, deaf children's maps with those of healthy children by means of visual inspection and statistical comparison using a permutation test. RESULTS: SEP N20 topography was significantly more extensive in visually-impaired child CI candidates than in healthy children. An asymmetrical pattern occurred from the expansion of hand tactile activation into the temporal and occipital regions in the left hemisphere on right median nerve stimulation. This did not occur for SEP P40 on tibial nerve stimulation (right and left). Magnitude of expanded SEP N20 response was related to severity of visual impairment and longer duration of dual sensory loss. CONCLUSIONS: Changes in SEP N20 topography are evidence of cross-modal plasticity in visually-impaired child CI candidates, appearing to result from a complex interaction between severity of visual impairment and duration of multisensory deprivation.


Subject(s)
Cochlear Implants , Deaf-Blind Disorders/physiopathology , Evoked Potentials, Somatosensory/physiology , Neuronal Plasticity/physiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Cochlear Implants/psychology , Cuba , Deaf-Blind Disorders/rehabilitation , Female , Humans , Male , Prospective Studies , Tibial Nerve/physiopathology
12.
Sleep ; 35(4): 501-11, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22467988

ABSTRACT

INTRODUCTION: Cognitive and brain hyperactivation have been associated with trouble falling asleep and sleep misperception in patients with primary insomnia (PI). Activation and synchronization/temporal coupling in frontal and frontoparietal regions involved in executive control and endogenous attention might be implicated in these symptoms. METHODS: Standard polysomnography (PSG) and electroencephalogram (EEG) were recorded in 10 unmedicated young patients (age 19-34 yr) with PI with no other sleep/medical condition, and in 10 matched control subjects. Absolute power, temporal coupling, and topographic source distribution (variable resolution electromagnetic tomography or VARETA) were obtained for all time spent in waking, Stage 1 and Stage 2 of the wake-sleep transition period (WSTP), and the first 3 consecutive min of N3. Subjective sleep quality and continuity were evaluated. RESULTS: In comparison with control subjects, patients with PI exhibited significantly higher frontal beta power and current density, and beta and gamma frontoparietal temporal coupling during waking and Stage 1. CONCLUSION: These findings suggest that frontal deactivation and disengagement of brain regions involved in executive control, attention, and self-awareness are impaired in patients with PI. The persistence of this activated and coherent network during the wake-sleep transition period (WSTP) may contribute to a better understanding of underlying mechanisms involved in difficulty in falling asleep, in sleep misperception, and in the lighter, poorer, and nonrefreshing sleep experienced by some patients with PI.


Subject(s)
Arousal/physiology , Frontal Lobe/physiopathology , Parietal Lobe/physiopathology , Sleep Initiation and Maintenance Disorders/physiopathology , Sleep Stages/physiology , Adult , Case-Control Studies , Electroencephalography , Female , Humans , Male , Polysomnography , Young Adult
13.
J Alzheimers Dis ; 28(2): 357-67, 2012.
Article in English | MEDLINE | ID: mdl-22002790

ABSTRACT

In normal elderly subjects, the best electroencephalogram (EEG)-based predictor of cognitive impairment is theta EEG activity abnormally high for their age. The goal of this work was to explore the effectiveness of a neurofeedback (NFB) protocol in reducing theta EEG activity in normal elderly subjects who present abnormally high theta absolute power (AP). Fourteen subjects were randomly assigned to either the experimental group or the control group; the experimental group received a reward (tone of 1000 Hz) when the theta AP was reduced, and the control group received a placebo treatment, a random administration of the same tone. The results show that the experimental group exhibits greater improvement in EEG and behavioral measures. However, subjects of the control group also show improved EEG values and in memory, which may be attributed to a placebo effect. However, the effect of the NFB treatment was clear in the EG, although a placebo effect may also have been present.


Subject(s)
Brain Waves/physiology , Cognition Disorders/prevention & control , Cognition Disorders/physiopathology , Neurofeedback/methods , Aged , Aged, 80 and over , Analysis of Variance , Comprehension , Educational Status , Electroencephalography , Female , Humans , Male , Middle Aged , Neuropsychological Tests
14.
Neurosci Lett ; 492(2): 99-104, 2011 Apr 01.
Article in English | MEDLINE | ID: mdl-21291957

ABSTRACT

Previous studies have investigated whether routine use of antiepileptic drugs is adequate to improve cognitive abilities in children who are learning disabled not otherwise specified (LD NOS) and who display interictal paroxysmal patterns in the electroencephalogram (EEG) but do not have epilepsy, and the findings of these studies have been controversial. In the current study, 112 LD children without epilepsy were assessed; however, only 18 met the strict inclusion/exclusion criteria in order to obtain a homogeneous sample. These children showed interictal paroxysmal patterns in the EEG, and a randomized, double-blind trial was carried out on them. The children were treated with either magnesium valproate (MgV; 20mg/kg/day) or a placebo for six months, and differences in WISC subtests, in a computerized reading skills battery (BTL) and EEG recordings were evaluated between groups before and after the treatment period. Performance IQ score and several items of the BTL (rhymes and ordering of words) improved in children who received MgV, whereas no changes were observed in the placebo group. No changes in the number of interictal paroxysmal patterns were observed in any group; however increased EEG currents at 10.92 and 12.87Hz (alpha band) in posterior regions and decreased currents in frequencies within the theta band (3.90, 4.29 and 5.07Hz) in frontal regions and at 4.68 and 5.46Hz in the parietal cortex were observed, suggesting an improvement in EEG maturation.


Subject(s)
Brain Mapping , Enzyme Inhibitors/therapeutic use , Learning Disabilities/drug therapy , Learning Disabilities/physiopathology , Valproic Acid/therapeutic use , Child , Electroencephalography/methods , Enzyme Inhibitors/pharmacology , Female , Humans , Male , Neuropsychological Tests , Photic Stimulation , Psychophysics , Valproic Acid/pharmacology
15.
Neuroimage ; 50(4): 1497-510, 2010 May 01.
Article in English | MEDLINE | ID: mdl-20083210

ABSTRACT

Recently, a related morphometry-based connection concept has been introduced using local mean cortical thickness and volume to study the underlying complex architecture of the brain networks. In this article, the surface area is employed as a morphometric descriptor to study the concurrent changes between brain structures and to build binarized connectivity graphs. The statistical similarity in surface area between pair of regions was measured by computing the partial correlation coefficient across 186 normal subjects of the Cuban Human Brain Mapping Project. We demonstrated that connectivity matrices obtained follow a small-world behavior for two different parcellations of the brain gray matter. The properties of the connectivity matrices were compared to the matrices obtained using the mean cortical thickness for the same cortical parcellations. The topology of the cortical thickness and surface area networks were statistically different, demonstrating that both capture distinct properties of the interaction or different aspects of the same interaction (mechanical, anatomical, chemical, etc.) between brain structures. This finding could be explained by the fact that each descriptor is driven by distinct cellular mechanisms as result of a distinct genetic origin. To our knowledge, this is the first time that surface area is used to study the morphological connectivity of brain networks.


Subject(s)
Brain/anatomy & histology , Cerebral Cortex/anatomy & histology , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aged , Brain Mapping , Cluster Analysis , Corpus Callosum/anatomy & histology , Cuba , Female , Humans , Male , Middle Aged , Nerve Fibers, Unmyelinated , Neural Pathways/anatomy & histology , Organ Size , Young Adult
16.
Stat Med ; 29(1): 63-74, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-19941298

ABSTRACT

Current analysis of event-related potentials (ERP) data is usually based on the a priori selection of channels and time windows of interest for studying the differences between experimental conditions in the spatio-temporal domain. In this work we put forward a new strategy designed for situations when there is not a priori information about 'when' and 'where' these differences appear in the spatio-temporal domain, simultaneously testing numerous hypotheses, which increase the risk of false positives. This issue is known as the problem of multiple comparisons and has been managed with methods that control the false discovery rate (FDR), such as permutation test and FDR methods. Although the former has been previously applied, to our knowledge, the FDR methods have not been introduced in the ERP data analysis. Here we compare the performance (on simulated and real data) of permutation test and two FDR methods (Benjamini and Hochberg (BH) and local-fdr, by Efron). All these methods have been shown to be valid for dealing with the problem of multiple comparisons in the ERP analysis, avoiding the ad hoc selection of channels and/or time windows. FDR methods are a good alternative to the common and computationally more expensive permutation test. The BH method for independent tests gave the best overall performance regarding the balance between type I and type II errors. The local-fdr method is preferable for high dimensional (multichannel) problems where most of the tests conform to the empirical null hypothesis. Differences among the methods according to assumptions, null distributions and dimensionality of the problem are also discussed.


Subject(s)
Data Interpretation, Statistical , Evoked Potentials/physiology , Computer Simulation , False Positive Reactions , Humans
17.
Hum Brain Mapp ; 31(2): 247-65, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19650138

ABSTRACT

Although subtle anatomical anomalies long precede the onset of clinical symptoms in Alzheimer's disease, their impact on the reorganization of brain networks underlying cognitive functions has not been fully explored. A unique window into this reorganization is provided by presymptomatic cases of familial Alzheimer's disease (FAD). Here we studied neural circuitry related to semantic processing in presymptomatic FAD cases by estimating the intracranial sources of the N400 event-related potential (ERP). ERPs were obtained during a semantic-matching task from 24 presymptomatic carriers and 25 symptomatic carriers of the E280A presenilin-1 (PS-1) mutation, as well as 27 noncarriers (from the same families). As expected, the symptomatic-carrier group performed worse in the matching task and had lower N400 amplitudes than both asymptomatic groups, which did not differ from each other on these variables. However, N400 topography differed in mutation carrier groups with respect to the noncarriers. Intracranial source analysis evinced that the presymptomatic-carriers presented a decrease of N400 generator strength in right inferior-temporal and medial cingulate areas and increased generator strength in the left hippocampus and parahippocampus compared to the controls. This represents alterations in neural function without translation into behavioral impairments. Compared to controls, the symptomatic-carriers presented a similar anatomical shift in the distribution of N400 generators to that found in presymptomatic-carriers, albeit with a larger reduction in generator strength. The redistribution of N400 generators in presymptomatic-carriers indicates that early focal degeneration associated with the mutation induces neural reorganization, possibly contributing to a functional compensation that enables normal performance in the semantic task.


Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Brain/physiopathology , Evoked Potentials , Presenilin-1/genetics , Presenilin-1/metabolism , Adult , Brain Mapping , Electroencephalography , Heterozygote , Humans , Middle Aged , Mutation, Missense , Neuropsychological Tests , Semantics , Young Adult
18.
Span J Psychol ; 12(2): 441-53, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19899646

ABSTRACT

Learning to read is one of the most important cognitive milestones in the human social environment. One of the most accepted models explaining such process is the Double-Route Cascaded Model. It suggests the existence of two reading strategies: lexical and sublexical. In the Spanish language there are some contradictions about how these strategies are applied for reading. In addition, there are only a few studies dealing with the analysis of shifts between them, achieving a fluent reading process. In this paper we use a reading task including words and pseudowords for characterizing the cost of shifting between reading strategies in children with developmental dyslexia and normal controls. Our results suggest the presence of both strategies in these two experimental groups. In controls, both strategies become more efficient in correspondence to the increased exposition to written material. However, in children with developmental dyslexia only the lexical strategy exhibits such improvement. Their also point to a low cost for shifting between strategies in controls and a much more significant one in children with developmental dyslexia, differentiating subgroups with distinct shifting patterns.


Subject(s)
Dyslexia/diagnosis , Language , Models, Educational , Reading , Achievement , Child , Cuba , Dyslexia/psychology , Education, Special , Female , Humans , Male , Phonetics , Reaction Time , Reference Values , Semantics , Verbal Learning , Vocabulary
19.
Span. j. psychol ; 12(2): 441-453, nov. 2009. tab, ilus
Article in English | IBECS | ID: ibc-74923

ABSTRACT

Learning to read is one of the most important cognitive milestones in the human social environment.One of the most accepted models explaining such process is the Double-Route Cascaded Model. It suggests the existence of two reading strategies: lexical and sublexical. In the Spanish language there are some contradictions about how these strategies are applied for reading. In addition, there are only a few studies dealing with the analysis of shifts between them, achieving a fluent reading process. In this paper we use a reading task including words and pseudowords for characterizing the cost of shifting between reading strategies in children with developmental dyslexia and normal controls. Our results suggest the presence of both strategies in these two experimental groups. In controls, both strategies become more efficient in correspondence to the increased exposition to written material. However, in children with developmental dyslexia only the lexical strategy exhibits such improvement. Their also point to a low cost for shifting between strategies in controls and a much more significant one in children with developmental dyslexia, differentiating subgroups with distinct shifting patterns (AU)


El aprendizaje de la lectura constituye uno de los hitos cognitivos más importantes del entorno social humano. Uno de los modelos de lectura más aceptados ha sido el Modelo de Doble Ruta en Cascada que sugiere la existencia de dos estrategias de lectura: lexical y sublexical. En el idioma español existen datos contradictorios acerca de cómo se aplican estas estrategias y no hay estudios que describan cómo se realizan los cambios de una a otra para lograr una lectura fluida. En este trabajo utilizamos una tarea de lectura de palabras y pseudopalabras para caracterizar el costo de cambio de una a otra estrategia en niños buenos lectores y niños con dislexia del desarrollo. Nuestros resultados sugieren la presencia de ambas estrategias en los dos grupos. En los niños buenos lectores ambas estrategias se hacen más eficientes con el grado de exposición a la lectura. Sin embargo, en los niños disléxicos esto solo ocurre en la estrategia lexical. Además, indican que los niños buenos lectores desarrollan un bajo costo en el cambio de estrategia de lectura mientras que un subgrupo de niños disléxicos presenta un costo mayor, conformándose subgrupos con patrones diferentes de afectación selectiva (AU)


Subject(s)
Humans , Male , Female , Child , Dyslexia/diagnosis , Language , Models, Educational , Reading , Verbal Learning , Cuba/epidemiology , Dyslexia/psychology , Education, Special/methods , Achievement , Phonetics , Reaction Time , Reference Values , Semantics , Vocabulary
20.
Neuropsychologia ; 47(1): 41-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18789956

ABSTRACT

Rightward shifts in attention are a common consequence of brain injury. A growing body of evidence appears to suggest that increases in attentional load, and decreases in alertness can lead to rightward shifts in attention in healthy and patient populations. It is unclear however whether these factors affect spatial biases in attention at the level of preparatory control processes or at the level of stimulus driven expression mechanisms. Whilst such effects cannot easily be dissociated behaviourally, the robust association between changes in alpha-band activity and shifts in visual attention provides a neural marker by which the temporal dynamics of effects of attentional load on spatial processing might be examined. Here we use electroencephalography to examine the relationship between modulations in alpha-band activity and behavioural outcome on a dual task paradigm comprising a detection task (t1), closely followed by a temporal order judgment task (t2). We examine the effects of high (respond to t1 and t2) and low (t2 only) attentional load conditions on spatial bias and changes in lateralization of alpha-band activity over the course of the trial. As anticipated a rightward bias in detecting target onsets was observed in the temporal order judgment task (t2) under conditions of high attentional load. This rightward shift in attention was associated with changes in the lateralization of alpha-band activity that occurred only after the presentation of t2, suggesting that attentional load may primarily influence expression mechanisms.


Subject(s)
Alpha Rhythm , Attention/physiology , Functional Laterality/physiology , Judgment/physiology , Visual Perception/physiology , Adolescent , Adult , Brain Mapping , Electroencephalography/methods , Female , Humans , Male , Photic Stimulation , Statistics as Topic , Young Adult
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