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Neuropsychologia Jul 2018The neural basis of reading and writing has been a source of inquiry as well as controversy in the neuroscience literature. Reading has been associated with both left...
The neural basis of reading and writing has been a source of inquiry as well as controversy in the neuroscience literature. Reading has been associated with both left posterior ventral temporal zones (termed the "visual word form area") as well as more dorsal zones, primarily in left parietal cortex. Writing has also been associated with left parietal cortex, as well as left sensorimotor cortex and prefrontal regions. Typically, the neural basis of reading and writing are examined in separate studies and/or rely on single case studies exhibiting specific deficits. Functional neuroimaging studies of reading and writing typically identify a large number of activated regions but do not necessarily identify the core, critical hubs. Last, due to constraints on the functional imaging environment, many previous studies have been limited to measuring the brain activity associated with single-word reading and writing, rather than sentence-level processing. In the current study, the brain correlates of reading and writing at both the single- and sentence-level were studied in a large sample of 111 individuals with a history of chronic stroke using voxel-based lesion symptom mapping (VLSM). VLSM provides a whole-brain, voxel-by-voxel statistical analysis of the role of distinct regions in a particular behavior by comparing performance of individuals with and without a lesion at every voxel. Rather than comparing individual cases or small groups with particular behavioral dissociations in reading and writing, VLSM allowed us to analyze data from a large, well-characterized sample of stroke patients exhibiting a wide range of reading and writing impairments. The VLSM analyses revealed that reading was associated with a critical left inferior temporo-occipital focus, while writing was primarily associated with the left supramarginal gyrus. Separate VLSM analyses of single-word versus sentence-level reading showed that sentence-level reading was uniquely associated with anterior to mid-portions of the middle and superior temporal gyri. Both single-word and sentence-level writing overlapped to a great extent in the left supramarginal gyrus, but sentence-level writing was associated with additional underlying white matter pathways such as the internal capsule. These findings suggest that critical aspects of reading and writing processes diverge, with reading relying critically on the ventral visual recognition stream and writing relying on a dorsal visuo-spatial-motor stream.
Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Mapping; Female; Functional Laterality; Humans; Imaging, Three-Dimensional; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Reading; Stroke; Writing
PubMed: 29572061
DOI: 10.1016/j.neuropsychologia.2018.03.021 -
Pharmaceuticals (Basel, Switzerland) May 2024Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B... (Review)
Review
Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients.
PubMed: 38794161
DOI: 10.3390/ph17050591 -
Frontiers in Neuroinformatics 2022Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a...
Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages. This study aims to compare classification performance based on two types of features: features automatically extracted by a pretrained convolutional neural network (CNN) and HF designed by human experts. Both approaches are evaluated on a multilingual dataset collected from 143 PD patients and 151 healthy controls in the Czech Republic, United States, Colombia, and Hungary. The subjects performed the spiral drawing task (SDT; a language-independent task) and the sentence writing task (SWT; a language-dependent task). Models based on logistic regression and gradient boosting were trained in several scenarios, specifically single language (SL), leave one language out (LOLO), and all languages combined (ALC). We found that the HF slightly outperformed the CNN-extracted features in all considered evaluation scenarios for the SWT. In detail, the following balanced accuracy (BACC) scores were achieved: SL-0.65 (HF), 0.58 (CNN); LOLO-0.65 (HF), 0.57 (CNN); and ALC-0.69 (HF), 0.66 (CNN). However, in the case of the SDT, features extracted by a CNN provided competitive results: SL-0.66 (HF), 0.62 (CNN); LOLO-0.56 (HF), 0.54 (CNN); and ALC-0.60 (HF), 0.60 (CNN). In summary, regarding the SWT, the HF outperformed the CNN-extracted features over 6% (mean BACC of 0.66 for HF, and 0.60 for CNN). In the case of the SDT, both feature sets provided almost identical classification performance (mean BACC of 0.60 for HF, and 0.58 for CNN).
PubMed: 35722168
DOI: 10.3389/fninf.2022.877139 -
JMIR Serious Games May 2021Specific learning difficulties (SpLD) include several disorders such as dyslexia, dyscalculia, and dysgraphia, and the children with these SpLD receive special...
BACKGROUND
Specific learning difficulties (SpLD) include several disorders such as dyslexia, dyscalculia, and dysgraphia, and the children with these SpLD receive special education. However, the studies and the educational material so far focus mainly on one specific disorder.
OBJECTIVE
This study's primary goal is to develop comprehensive training material for different types of SpLD, with five serious games addressing different aspects of the SpLD. The second focus is measuring the impact of adaptive difficulty level adjustment in the children's and their educators' usability and technology acceptance perception. Receiving feedback from the children and their educators, and refining the games according to their suggestions have also been essential in this two-phase study.
METHODS
A total of 10 SpLD educators and 23 children with different types of SpLD tested the prototypes of the five serious games (ie, Word game, Memory game, Category game, Space game, and Math game), gave detailed feedback, answered the System Usability Scale and Technology Acceptance Model (TAM) questionnaires, and applied think-aloud protocols during game play.
RESULTS
The games' standard and adaptive versions were analyzed in terms of average playtime and the number of false answers. Detailed analyses of the interviews, with word clouds and player performances, were also provided. The TAM questionnaires' average and mean values and box plots of each data acquisition session for the children and the educators were also reported via System Usability Scale and TAM questionnaires. The TAM results of the educators had an average of 8.41 (SD 0.87) out of 10 in the first interview and an average of 8.71 (SD 0.64) out of 10 in the second interview. The children had an average of 9.07 (SD 0.56) out of 10 in the first interview.
CONCLUSIONS
Both the educators and the children with SpLD enjoyed playing the games, gave positive feedback, and suggested new ways for improvement. The results showed that these games provide thorough training material for different types of SpLD with personalized and tailored difficulty systems. The final version of the proposed games will become a part of the special education centers' supplementary curriculum and training materials, making new enhancements and improvements possible in the future.
PubMed: 34057415
DOI: 10.2196/25997 -
Learning Disabilities (Pittsburgh, Pa.) 2018Movement, which draws on motor skills and executive functions for managing them, plays an important role in literacy learning (e.g., movement of mouth during oral...
Movement, which draws on motor skills and executive functions for managing them, plays an important role in literacy learning (e.g., movement of mouth during oral reading and movement of hand and fingers during writing); but relatively little research has focused on movement skills in students with specific learning disabilities as the current study did. Parents completed normed (ABC-2), ratings and their children in grades 4 to 9 ( = 11 years, 11 months; 94 boys, 61 girls) completed diagnostic assessment used to assign them to diagnostic groups: control typical language learning ( = 42), dysgraphia (impaired handwriting) ( = 29), dyslexia (impaired word decoding/reading and spelling) ( = 65), or oral and written language learning disability (OWL LD) (impaired syntax in oral and written language) ( = 19). The research aims were to (a) correlate the parent ratings for Scale A Static/Predictable Environment (15 items) and Scale B Dynamic/Unpredictable Environment (15 items) with reading and writing achievement in total sample varying within and across different skills; and (b) compare each specific learning disability group with the control group on parent ratings for Scale A, Scale B, and Scale C Movement-Related (Non-Motor Executive Functions, or Self-Efficacy, or Affect) (13 items). At least one parent rating was correlated with each assessed literacy achievement skill. Each of three specific learning disability groups differed from the control group on two Scale A (static/predictable environment) items (fastens buttons and forms letters with pencil or pen) and on three Scale C items (distractibility, overactive, and underestimates own ability); but only OWL LD differed from control on Scale B (dynamic/unpredictable environment) items. Applications of findings to assessment and instruction for students ascertained for and diagnosed with persisting specific learning disabilities in literacy learning, and future research directions are discussed.
PubMed: 29606845
DOI: 10.18666/LDMJ-2018-V23-I1-8449 -
Journal of Writing Research Feb 2015Although handwriting is typically taught during early childhood and keyboarding may not be taught explicitly, both may be relevant to writing development in the later...
Although handwriting is typically taught during early childhood and keyboarding may not be taught explicitly, both may be relevant to writing development in the later grades. Thus, Study 1 investigated automatic production of the ordered alphabet from memory for manuscript (unjoined), cursive (joined), and keyboard letter modes (alphabet 15 sec) and their relationships with each other and spelling and composing in typically developing writers in grades 4 to 7 ( = 113). Study 2 compared students with dysgraphia (impaired handwriting, =27), dyslexia (impaired word spelling, =40), or oral and written language learning disability (OWL LD) (impaired syntax composing, =11) or controls without specific writing disabilities (=10) in grades 4 to 9 (=88) on the same alphabet 15 modes, manner of copying (best or fast), spelling, and sentence composing. In Study 1, sequential multilevel model regressions of predictor alphabet 15 letter production/selection modes on spelling and composition outcomes, measured annually from grade 4 to grade 7 (ages 9 to 13 years), showed that only the cursive mode , positively, and consistently predicted both spelling and composing in each grade. For composing, in grade 4 manuscript mode was positively predictive and in grades 5-7 keyboard selection was. In Study 2 all letter production modes correlated with each other and one's best and fast sentence copying, spelling, and timed sentence composing. The groups with specific writing disabilities differed from control group on alphabet 15 manuscript mode, copy fast, and timed sentence composing. The dysgraphia and dyslexia groups differed on copying sentences in one's best handwriting, with the dysgraphia group scoring lower. The educational and theoretical significance of the findings are discussed for multiple modes and manners of letter production/selection of the alphabet that support spelling and composing beyond the early grades in students with and without specific writing disabilities.
PubMed: 25984288
DOI: 10.17239/jowr-2015.06.03.1 -
Children (Basel, Switzerland) May 2023In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To...
In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To investigate the effectiveness of PMT, we conducted a randomised field trial (RFT). The sample consisted of 121 first and second graders with graphomotor impairments, some of whom met the criteria of developmental coordination disorder, while the remaining suffered from developmental dysgraphia. The treatments lasted over 5 months. Handwriting fluency and consistency were measured five times on a digitising tablet. All participating children completed a self-concept interview, and a standardised fine motor performance test twice. Psychomotor therapy significantly improved the fine motor skills of the therapy group compared to those of the waiting group. However, there was no evidence that the treated children improved more than the waiting children in terms of their graphomotor skills such as frequency, automaticity, and consistency of forming letters. Finally, the children of the therapy group showed partial improvements in their handwriting self-concept, while those of the waiting group children remained stable. This short-term RFT demonstrated the effectiveness of PMT in terms of fine motor skills and some aspects of the handwriting self-concept but showed no effects on handwriting fluency and consistency.
PubMed: 37371196
DOI: 10.3390/children10060964 -
PloS One 2016Patients with Parkinson's disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This... (Comparative Study)
Comparative Study
BACKGROUND
Patients with Parkinson's disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation.
OBJECTIVE
To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting.
METHODS
Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes.
RESULTS
Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group.
CONCLUSIONS
Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols.
Topics: Aged; Agraphia; Auditory Perception; Biomechanical Phenomena; Cues; Female; Gait Disorders, Neurologic; Hand; Humans; Learning Disabilities; Male; Memory Disorders; Middle Aged; Motor Skills; Parietal Lobe; Parkinson Disease; Psychomotor Performance; Retention, Psychology; Writing
PubMed: 26862915
DOI: 10.1371/journal.pone.0148933 -
Journal of Alzheimer's Disease : JAD 2022The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer's disease (AD) patients. Of the identified variants, the PSEN2...
BACKGROUND
The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer's disease (AD) patients. Of the identified variants, the PSEN2 mutations are even less common.
OBJECTIVE
With the genetic study from the dementia cohort of Peking Union Medical College Hospital (PUMCH), we aim to illustrate the PSEN2 mutation spectrum and novel functionally validated mutations in Chinese AD patients.
METHODS
702 AD participants, aged 30-85, were identified in PUMCH dementia cohort. They all received history inquiry, physical examination, biochemical test, cognitive evaluation, brain CT/MRI, and next-generation DNA sequencing. Functional analysis was achieved by transfection of the HEK293 cells with plasmids harboring the wild-type PSEN2 or candidate mutations.
RESULTS
Nine PSEN2 rare variants were found, including two reported (M239T, R62C) and seven novel variants (N141S, I368F, L396I, G117X, I146T, S147N, H220Y). The HEK293 cells transfected with the PSEN2 N141S, M239T, I368F plasmids showed higher Aβ42 and Aβ42/Aβ40 levels relative to the wild-type PSEN2. The PSEN2 L396I, G117X, S147N, H220Y, and R62C did not alter Aβ42, Aβ40 levels, or Aβ42/Aβ40 ratio. 1.9%,(13/702) subjects harbored rare PSEN2 variants. 0.4%,(3/702) subjects carried pathogenic/likely pathogenic PSEN2 mutations. The three subjects with the functionally validated PSEN2 mutations were all familial early-onset AD patients. The common symptoms included amnesia and mental symptom. Additionally, the M239T mutation carrier presented with dressing apraxia, visuospatial agraphia, dyscalculia and visual mislocalization.
CONCLUSION
The PSEN2 N141S, M239T, and I368F are functionally validated mutations.
Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; HEK293 Cells; Humans; Mutation; Presenilin-2
PubMed: 35491795
DOI: 10.3233/JAD-220194 -
Cureus Jun 2017Pure alexia refers to an acquired disorder associated with the damage to medial occipitotemporal gyrus in the dominant hemisphere, which is also known as visual word...
Pure alexia refers to an acquired disorder associated with the damage to medial occipitotemporal gyrus in the dominant hemisphere, which is also known as visual word form area (VWFA). VWFA is involved in rapid word recognition and fluent reading. Alexia without agraphia is a disconnection syndrome that occurs when the splenium is also damaged with the occipital lobe on a dominant side. We report a case of a 72-year-old right-handed male who presented with alexia without agraphia accompanied by right homonymous hemianopia resulting from acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus that probably occurred on the previous day. During the evaluation, he exhibited marked impairment in the ability to read with the vision being grossly normal. Magnetic resonant imaging (MRI) revealed an acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus. A computerized tomography angiogram (CTA) revealed left posterior cerebral artery (PCA) territory infarct without any evidence of hemorrhagic conversion. Infarction of the occipital lobe on the dominant side (left) in a right-handed individual may cause a disruption in the visual word form area and is manifested by an inability to read with no abnormalities in visual acuity.
PubMed: 28690938
DOI: 10.7759/cureus.1304