Dysgraphia disorder forecasting and classification technique using intelligent deep learning approaches.

Writing abilities are impacted by dysgraphia, a condition of learning disability. It might be challenging to diagnose dysgraphia at an initial point of a child's upbringing. Problematic abilities linked to Dysgraphia difficulties that is utilized in detecting the learning disorder. The features used in this research to identify dysgraphia include handwriting and geometric features that is reclaimed using kekre-discrete cosine mathematical model. The feature learning step of deep transfer learning makes good use of the obtained features to identify dysgraphia. The results of the data collection indicate that this study can use handwritten images to detect children who have dysgraphia. Compared to past investigations, this experiment has shown a significant improvement in the capacity to identify dysgraphia using handwritten drawings. The proposed approach is compared with the machine learning and deep learning approaches where the Kekre-Discrete Cosine Transform with Deep Transfer Learning (K-DCT-DTL) outperforms the existing approaches. The proposed K-DCT-DTL approach attains 99.75% of highest accuracy that exhibits the efficiency of the proposed method.

Asymmetry Matters: Diffusion Tensor Tractography of the Uncinate Fasciculus in Children with Verbal Memory Deficits.

BACKGROUND AND PURPOSE: Verbal declarative memory performance relies on frontotemporal connectivity. The uncinate fasciculus is a major association tract connecting the frontal and temporal lobes. Hemispheric asymmetries contribute to various cognitive and neurobehavioral abilities. Here we investigated microstructural alterations and hemispheric asymmetry of the uncinate fasciculus and their possible correlation to memory performance of children with learning disorders attributed to verbal memory deficits. MATERIALS AND METHODS: Two groups of right-handed children with learning disorders attributed to verbal memory deficits and typically developing children (n = 20 and 22, respectively) underwent DTI on a 1.5T scanner. Tractography of the uncinate fasciculus in both hemispheres was performed, and fractional anisotropy and diffusivity indices (radial diffusivity, axial diffusivity, and trace) were obtained. The asymmetry index was calculated. Verbal memory was assessed using subsets of the Stanford Binet Intelligence Scale, 4th edition, a dyslexia assessment test, and the Illinois test of Psycholinguistic Abilities. Correlation between diffusion metrics and verbal memory performance was investigated in the learning disorders group. Also, hemispheric differences in each group were tested, and between-group comparisons were performed. RESULTS: Children with learning disorders showed absence of the normal left-greater-than-right asymmetry of fractional anisotropy and the normal right-greater-than-left asymmetry of radial diffusivity seen in typically developing children. Correlation with verbal memory subsets revealed that the higher the fractional anisotropy and asymmetry index, the better the rapid naming performance (P <.05) was. CONCLUSIONS: These findings demonstrated microstructural aberrations with reduction of hemispheric asymmetry of the uncinate fasciculus, which could disrupt the normal frontotemporal connectivity in children with learning disorders attributed to verbal memory deficits. This outcome gives more understanding of pathologic mechanisms underlying this disorder.

Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability.

Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.

Spatial Network Connectivity and Spatial Reasoning Ability in Children with Nonverbal Learning Disability.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7-15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.

Visual paired associate learning deficits associated with elevated beta-amyloid in cognitively normal older adults.

OBJECTIVE: Previous studies have shown that paired associate learning (PAL), a type of episodic memory, is impaired in early Alzheimer's disease (AD). Such tasks require that a set of associations (e.g., pattern-location) be learned over several trials, and the objective is to reduce errors with each trial. Currently, the nature and magnitude of impairment and decline on PAL measures in cognitively normal (CN) older adults with elevated levels of beta-amyloid (Aß+) is unknown. METHOD: This study examined PAL errors in Aß+ and Aß - CN older adults, both within a single assessment and over time. Participants (210 Aß - CN, 146 Aß + CN) from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study underwent three assessments over 36-months (baseline, and 18- and 36-month follow-ups) using a computerized paired associate learning task (CPAL). Aß status was determined by positron emission tomography (PET) neuroimaging. RESULTS: No significant group differences in PAL were evident at baseline. Significant groupxtime interactions were observed, with the Aß - CN group, but not the Aß + CN group, evidencing improvement over time (Cohen's d = 0.30 [0.08, 0.51]). Despite this, no group differences were evident at 36-months. CONCLUSIONS: Results suggest that PAL dysfunction is evident over time in Aß + CNs. This indicates a lack of benefit from repeated exposure to the task over time associated with Aß+, which is not the case for Aß - CNs. Further, results suggest that assessing change in Aß+ related cognition over time, rather than at a single assessment, provides greater understanding of dysfunction in early AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Understanding the Learning Disabilities Linked to Sagittal Craniosynostosis.

OBJECTIVE: The purpose of this study is to investigate further findings that corroborate similarities between corrected sagittal craniosynostosis and attention deficit hyperactivity disorder (ADHD). The aim is to further characterize the neurocognitive deficits seen in adolescents with corrected craniosynostosis by comparing it to established learning deficits such as ADHD. METHODS: A total of 30 functional magnetic resonance imaging (fMRI) of 10 sagittal nonsyndromic craniosynostosis (sNSC), 10 ADHD-combined, and 10 control adolescents were studied. The fMRI scans were analyzed utilizing Statistical Parametric Mapping (University College London, UK) and analyzed with BioImageSuite (Yale University, New Haven, CT). RESULTS: The ADHD has lower connectivity to Brodmann area (BA) 11 (Montreal Neurological Institution [MNI]: -12,26,-21), BA20 (MNI: 62,-24,-25), and BA21 (MNI: 62,-32,-23) compared to sNSC and controls (P < 0.001). The sNSC has a unique visuospatial defect, compared to ADHD, created by decreased connectivity to BA31 (MNI: -3,-68,37), BA7 (MNI: -4,-68,41), BA19 (MNI: 0,-83,31), visual association cortex (MNI: -4,-78,22), and primary visual cortex (MNI: 7,-74,21) (P < 0.001). CONCLUSION: Patients born with sNSC have different neural connections than children born with ADHD. Patients born with sNSC have decreased connections in areas of visual processing and increased connections in areas of attention and auditory processing than patients with ADHD. Therefore, children with sagittal craniosynsotosis may have learning difficulties that, similar, yet different from ADHD.

Brain SPECT scans in students with specific learning disability: Preliminary results.

Background and Objectives: Brain single-photon emission computed tomography (SPECT) assesses brain function through measurement of regional cerebral blood flow. This study was conducted to assess whether students with newly diagnosed specific learning disability (SpLD) show any abnormalities in cerebral cortex perfusion. Settings and Design: Cross-sectional single-arm pilot study in two tertiary care hospitals. Subjects and Methods: Nine students with SpLD were enrolled. Brain SPECT scan was done twice in each student. For the first or "baseline" scan, the student was first made to sit with eyes open in a quiet, dimly lit room for a period of 30-40 min and then injected intravenously with 20 mCi of 99mTc-ECD. An hour later, "baseline scan" was conducted. After a minimum gap of 4 days, a second or "test scan" was conducted, wherein the student performed an age-appropriate curriculum-based test for a period of 30-40 min to activate the areas in central nervous system related to learning before being injected with 20 mCi of 99mTc-ECD. Statistical Analysis Used: Cerebral cortex perfusion at rest and after activation in each student was compared qualitatively by visual analysis and quantitatively using NeuroGam™ software. Results: Visual analysis showed reduction in regional blood flow in temporoparietal areas in both "baseline" and "test" scans. However, when normalization was attempted and comparison done by Talairach analysis using NeuroGam software, no statistically significant change in regional perfusion in temporoparietal areas was appreciated. Conclusion: Brain SPECT scan may serve as a robust tool to identify changes in regional brain perfusion in students with SpLD.

Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder.

OBJECTIVE: Nonverbal learning disability (NVLD) is a putative neurodevelopmental disorder characterized by spatial processing deficits as well as social deficits similar to those characteristic of autism spectrum disorder (ASD). Nonetheless, NVLD may be a distinct disorder that is differentially associated with the functioning and connectivity of the salience (SN) and default mode (DMN) networks that support social processing. Thus, we sought to assess and compare connectivity across these networks in children with NVLD, ASD, and typically developing children. METHOD: Resting-state fMRI data were examined in 17 children with NVLD, 17 children with ASD selected from the Autism Brain Imaging Data Exchange (ABIDE), and 40 TD children (20 from ABIDE). Average DMN and SN functional connectivity and pairwise region-to-region connectivity were compared across groups. Associations with social impairment and IQ were assessed. RESULTS: Children with NVLD showed reduced connectivity between SN regions (anterior insula to anterior cingulate and to rostral prefrontal cortex [rPFC]), whereas children with ASD showed greater connectivity between SN regions (supramarginal gyrus to rPFC) relative to the other groups. Both clinical groups showed higher levels of parent-reported social problems, which related to altered SN connectivity in the NVLD group. No differences were detected in overall average connectivity within or between networks. CONCLUSIONS: The social deficits common across children with NVLD and ASD may derive from distinct alterations in connectivity within the SN. Such findings represent the first step toward identifying a neurobiological signature of NVLD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Characterizing the nature of emotional-associative learning deficits in panic disorder: An fMRI study on fear conditioning, extinction training and recall.

Emotional-associative learning represents a translational model for the development, maintenance and treatment of anxiety disorders such as panic disorder (PD). The exact nature of the underlying fear learning and extinction deficits however, remains under debate. Using a three-day paradigm to separate the distinct learning and consolidation processes, we aimed to gain insights into the neurofunctional substrates of altered fear conditioning, extinction training and recall in PD. In contrast to studies employing one-session fear conditioning paradigms, a differential fear conditioning and delayed extinction task was conducted for the purpose of disentangling neural networks involved in fear acquisition, extinction training and recall of extinction memories. Using functional magnetic resonance imaging (fMRI), quality-controlled datasets from 10 patients with PD and 10 healthy controls were available from three consecutive days (day 1: acquisition; day 2: extinction training; day 3: extinction recall) with neutral faces serving as CSs and an aversive auditory stimulus (panic scream) as US. PD patients showed heightened fear circuitry (e.g. right amygdala and left insula) activation during early acquisition and prolonged activation in the right insula, left inferior frontal operculum and left inferior frontal gyrus during extinction recall compared to healthy controls. Stronger neural activation in structures conferring defensive reactivity during early acquisition and extinction recall may indicate the accelerated acquisition of conditioned responses, while extinction recall may be attenuated as a function of PD pathophysiology. Future studies should investigate the predictive value of experimental measures of extinction recall for clinical relapse.

Learning Processes and Brain Connectivity in A Cognitive-Motor Task in Neurodegeneration: Evidence from EEG Network Analysis.

Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions.

A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality.

We describe four unrelated patients with the same de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene. We found a high phenotype-genotype correlation with all four patients having early childhood-onset predominant lower limb muscle weakness and wasting which was slowly progressing and later-onset mild upper extremities proximal weakness. All four patients presented minor cognitive dysfunction with learning difficulty and developmental behavioural comorbidities with mild abnormalities in the brain MRI. The leg muscle MRI findings are highly consistent in DYN1CH1-related spinal muscular atrophy with lower limb predominance (SMALED) with relative sparing of biceps femoris and semitendinosus, and hypertrophy of adductor longus in the thighs; and sparing the anterior and medial muscles in the calves. This report provides important clinical evidence indicating the de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene is pathogenic causing SMALED. Muscle MRI is more specific than muscle biopsy in the diagnosis of SMALED.

Episodic Memory and Learning Dysfunction Over an 18-Month Period in Preclinical and Prodromal Alzheimer's Disease.

Recent meta-analyses suggest that episodic memory impairment associated with preclinical Alzheimer's disease (AD) equates to 0.15-0.24 standard deviations below that of cognitively healthy older adults. The current study aimed to characterize impairments in verbal acquisition and recall detectable at a single assessment, and investigate how verbal learning and episodic memory deteriorates in preclinical AD. A verbal list-learning task, the International Shopping List Test (ISLT), was administered multiple times over an 18-month period, to three groups of participants: amyloid-beta negative healthy older adults (Aß- CN; n = 50); Aß+ positive healthy older adults (preclinical AD; n = 25); and Aß+ positive individuals diagnosed with mild cognitive impairment (prodromal AD; n = 22). At baseline, there was no significant difference between the preclinical AD and control groups rate of acquisition, or total and delayed recall, however all indices were impaired in prodromal AD. Performance on ISLT total score improved in the control group over the 18-month period, but showed a moderate magnitude decline in the preclinical AD group (Cohen's d = - 0.63, [- 1.12, - 0.14]) and the prodromal AD group (Cohen's d = - 0.36, [- 0.94, 0.22]). No significant impairment in acquisition associated with preclinical AD was seen at baseline. Individuals with preclinical AD showed a significantly different performance on the ISLT total score over an 18-month period, compared to those without abnormal Aß. Individuals with prodromal AD showed substantial impairment on the ISLT at baseline and declined to a greater extent over time.

Mapping the Proxies of Memory and Learning Function in Senior Adults with High-performing, Normal Aging and Neurocognitive Disorders.

BACKGROUND: Memory and learning, as the core brain function, shows controversial results across studies focusing on aging and dementia. One of the reasons is because of the multi-faceted nature of memory and learning. However, there is still a dearth of comparable proxies with psychometric and morphometric portrait in clinical and non-clinical populations. OBJECTIVE: We aim to investigate the proxies of memory and learning function with direct and derived measures and examine their associations with morphometric features in senior adults with different cognitive status. METHODS: Based on two modality-driven tests, we assessed the component-specific memory and learning in the individuals with high performing (HP), normal aging, and neurocognitive disorders (NCD) (n = 488). Structural magnetic resonance imaging was used to measure the regional cortical thickness with surface-based morphometry analysis in a subsample (n = 52). METHODS: Compared with HP elderly, the ones with normal aging and minor NCD showed declined recognition memory and working memory, whereas had better learning performance (derived scores). Meanwhile, major NCD patients showed more breakdowns of memory and learning function. The correlation between proxies of memory and learning and cortical thickness exhibited the overlapped and unique neural underpinnings. CONCLUSIONS: The proxies of memory and learning could be characterized by component-specific constructs with psychometric and morphometric bases. Overall, the constructs of memory are more likely related to the pathological changes, and the constructs of learning tend to reflect the cognitive abilities of compensation.

Altered neural encoding of prediction errors in assault-related posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is widely associated with deficits in extinguishing learned fear responses, which relies on mechanisms of reinforcement learning (e.g., updating expectations based on prediction errors). However, the degree to which PTSD is associated with impairments in general reinforcement learning (i.e., outside of the context of fear stimuli) remains poorly understood. Here, we investigate brain and behavioral differences in general reinforcement learning between adult women with and without a current diagnosis of PTSD. 29 adult females (15 PTSD with exposure to assaultive violence, 14 controls) underwent a neutral reinforcement-learning task (i.e., two arm bandit task) during fMRI. We modeled participant behavior using different adaptations of the Rescorla-Wagner (RW) model and used Independent Component Analysis to identify timecourses for large-scale a priori brain networks. We found that an anticorrelated and risk sensitive RW model best fit participant behavior, with no differences in computational parameters between groups. Women in the PTSD group demonstrated significantly less neural encoding of prediction errors in both a ventral striatum/mPFC and anterior insula network compared to healthy controls. Weakened encoding of prediction errors in the ventral striatum/mPFC and anterior insula during a general reinforcement learning task, outside of the context of fear stimuli, suggests the possibility of a broader conceptualization of learning differences in PTSD than currently proposed in current neurocircuitry models of PTSD.

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy.

Importance: Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. Objective: To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). Design, Setting, and Participants: This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. Main Outcomes and Measures: Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. Results: A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy. Conclusions and Relevance: Nonlanguage mathematical and visuospatial LDs were associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.

Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury.

This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ -0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.

Electroencephalographic characterization of subgroups of children with learning disorders.

Electroencephalographic alterations have been reported in subjects with learning disorders, but there is no consensus on what characterizes their electroencephalogram findings. Our objective was to determine if there were subgroups within a group of scholars with not otherwise specified learning disorders and if they had specific electroencephalographic patterns. Eighty-five subjects (31 female, 8-11 years) who scored low in at least two subscales -reading, writing and arithmetic- of the Infant Neuropsychological Evaluation were included. Electroencephalograms were recorded in 19 leads during rest with eyes closed; absolute power was obtained every 0.39 Hz. Three subgroups were formed according to children's performance: Group 1 (G1, higher scores than Group 2 in reading speed and reading and writing accuracy), Group 2 (G2, better performance than G1 in composition) and Group 3 (G3, lower scores than Groups 1 and 2 in the three subscales). G3 had higher absolute power in frequencies in the delta and theta range at left frontotemporal sites than G1 and G2. G2 had higher absolute power within alpha frequencies than G3 and G1 at the left occipital site. G3 had higher absolute power in frequencies in the beta range than G1 in parietotemporal areas and than G2 in left frontopolar and temporal sites. G1 had higher absolute power within beta frequencies than G2 in the left frontopolar site. G3 had lower gamma absolute power values than the other groups in the left hemisphere, and gamma activity was higher in G1 than in G2 in frontopolar and temporal areas. This group of children with learning disorders is very heterogeneous. Three subgroups were found with different cognitive profiles, as well as a different electroencephalographic pattern. It is important to consider these differences when planning interventions for children with learning disorders.

Category learning in Alzheimer's disease and normal cognitive aging depends on initial experience of feature variability.

Semantic category learning is dependent upon several factors, including the nature of the learning task, as well as individual differences in the quality and heterogeneity of exemplars that an individual encounters during learning. We trained healthy older adults (n=39) and individuals with a diagnosis of Alzheimer's disease or Mild Cognitive Impairment (n=44) to recognize instances of a fictitious animal, a "crutter". Each stimulus item contained 10 visual features (e.g., color, tail shape) which took one of two values for each feature (e.g., yellow/red, curly/straight tails). Participants were presented with a series of items (learning phase) and were either told the items belonged to a semantic category (explicit condition) or were told to think about the appearance of the items (implicit condition). Half of participants saw learning items with higher similarity to an unseen prototype (high typicality learning set), and thus lower between-item variability in their constituent features; the other half learned from items with lower typicality (low typicality learning set) and higher between-item feature variability. After the learning phase, participants were presented with test items one at a time that varied in the number of typical features from 0 (antitype) to 10 (prototype). We examined between-subjects factors of learning set (lower or higher typicality), instruction type (explicit or implicit), and group (patients vs. elderly control). Learning in controls was aided by higher learning set typicality: while controls in both learning set groups demonstrated significant learning, those exposed to a high-typicality learning set appeared to develop a prototype that helped guide their category membership judgments. Overall, patients demonstrated more difficulty with category learning than elderly controls. Patients exposed to the higher-typicality learning set were sensitive to the typical features of the category and discriminated between the most and least typical test items, although less reliably than controls. In contrast, patients exposed to the low-typicality learning set showed no evidence of learning. Analysis of structural imaging data indicated a positive association between left hippocampal grey matter density in elderly controls but a negative association in the patient group, suggesting differential reliance on hippocampal-mediated learning. Contrary to hypotheses, learning did not differ between explicit and implicit conditions for either group. Results demonstrate that category learning is improved when learning materials are highly similar to the prototype.

A method for integrating neuroimaging into genetic models of learning performance.

Specific learning disorders (SLD) are an archetypal example of how clinical neuropsychological (NP) traits can differ from underlying genetic and neurobiological risk factors. Disparate environmental influences and pathologies impact learning performance assessed through cognitive examinations and clinical evaluations, the primary diagnostic tools for SLD. We propose a neurobiological risk for SLD with neuroimaging biomarkers, which is integrated into a genome-wide association study (GWAS) of learning performance in a cohort of 479 European individuals between 8 and 21 years of age. We first identified six regions of interest (ROIs) in temporal and anterior cingulate regions where the group diagnosed with learning disability has the least overall variation, relative to the other group, in thickness, area, and volume measurements. Although we used the three imaging measures, the thickness was the leading contributor. Hence, we calculated the Euclidean distances between any two individuals based on their thickness measures in the six ROIs. Then, we defined the relative similarity of one individual according to the averaged ranking of pairwise distances from the individuals to those in the SLD group. The inverse of this relative similarity is called the neurobiological risk for the individual. Single nucleotide polymorphisms in the AGBL1 gene on chromosome 15 had a significant association with learning performance at a genome-wide level. This finding was supported in an independent cohort of 2,327 individuals of the same demographic profile. Our statistical approach for integrating genetic and neuroimaging biomarkers can be extended into studying the biological basis of other NP traits.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings.

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated.