Frontal allographic agraphia in a patient with behavioral variant frontotemporal dementia.

We report a patient with behavioral variant frontotemporal dementia who developed agraphia, irritability, perseverative and stereotyped behavior, and dietary changes. MRI revealed bilateral frontal convexity atrophy. Neuropsychological examination showed fluent aphasia with perseverative allographic agraphia, mild semantic impairment, and dysexecutive syndrome. Allographic agraphia featured unidirectional conversion from hiragana (cursive form of Japanese phonograms) and kanji (Japanese morphograms) to katakana (square form of Japanese phonograms), as opposed to mutual (bidirectional) conversion between hiragana and katakana in parieto-occipital gyri lesions. Furthermore, all letters of the word were converted and this whole-word conversion may be characteristic of perseverative behavior in frontotemporal dementia.

Serial position effects in graphemic buffer impairment: An insight into components of orthographic working memory.

This study investigated the nature of graphemic buffer functioning and impairment, through analysis of the spelling impairment shown by GEC, a man with acquired dysgraphia and clear characteristics of graphemic buffer impairment. We discuss GEC's error patterns in relation to different processes of orthographic working memory. This is the first study to show the contribution of these processes in one individual through performance on different spelling tasks. GEC's spelling errors in writing to dictation showed a linear serial position effect, including deletions of final letters. These "fragment errors" can be explained as the result of information rapidly decaying from the buffer (reduced temporal stability). However, in tasks that reduced working memory demands, GEC showed a different error distribution that may indicate impairment to a different buffer process (reduced representational distinctiveness). We argue that different error patterns can be a reflection of subcomponents of orthographic working memory that can be impaired separately.

Dystypia Associated with Diaschisis of the Middle Frontal Gyri after Left Angular Infarction.

Dystypia without aphasia, agraphia, or apraxia is a rare symptom and has been suggested to result from a lesion in the left middle frontal cortex. We herein describe a man with dystypia with agraphia due to infarction of the left angular gyrus. His dystypia seemed to result from the convergence failure of the kana into the alphabetical spellings. During dystypia, hypoperfusion of the bilateral middle frontal cortices was discovered. However, after his symptoms improved, blood flow in the middle frontal cortices returned to normal. This case suggests that the middle frontal cortex is downstream of the angular gyrus in the dictating pathway and a lesion in the left middle frontal cortex could cause pure dystypia.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Acquisition of handwriting in children with and without dysgraphia: A computational approach.

Handwriting is a complex skill to acquire and it requires years of training to be mastered. Children presenting dysgraphia exhibit difficulties automatizing their handwriting. This can bring anxiety and can negatively impact education. 280 children were recruited in schools and specialized clinics to perform the Concise Evaluation Scale for Children's Handwriting (BHK) on digital tablets. Within this dataset, we identified children with dysgraphia. Twelve digital features describing handwriting through different aspects (static, kinematic, pressure and tilt) were extracted and used to create linear models to investigate handwriting acquisition throughout education. K-means clustering was performed to define a new classification of dysgraphia. Linear models show that three features only (two kinematic and one static) showed a significant association to predict change of handwriting quality in control children. Most kinematic and statics features interacted with age. Results suggest that children with dysgraphia do not simply differ from ones without dysgraphia by quantitative differences on the BHK scale but present a different development in terms of static, kinematic, pressure and tilt features. The K-means clustering yielded 3 clusters (Ci). Children in C1 presented mild dysgraphia usually not detected in schools whereas children in C2 and C3 exhibited severe dysgraphia. Notably, C2 contained individuals displaying abnormalities in term of kinematics and pressure whilst C3 regrouped children showing mainly tilt problems. The current results open new opportunities for automatic detection of children with dysgraphia in classroom. We also believe that the training of pressure and tilt may open new therapeutic opportunities through serious games.

Dorsal type letter-by-letter reading accompanying alexia with agraphia due to a lesion of the lateral occipital gyri.

We report a patient with alexia with agraphia accompanied by letter-by-letter reading after hemorrhage in the left middle and inferior occipital gyri that spared the angular gyrus and the fusiform gyrus. Kanji (Japanese morphograms) and kana (Japanese phonetic writing) reading and writing tests revealed that alexia with agraphia was characterized by kana-predominant alexia and kanji-predominant agraphia. This type of "dorsal" letter-by-letter reading is discernable from conventional ventral type letter-by-letter reading that is observed in pure alexia in that (1) kinesthetic reading is less effective, (2) kana or literal agraphia coexists, and (3) fundamental visual discrimination is nearly normal.

Selective impairment of On-reading (Chinese-style pronunciation) in alexia with agraphia for kanji due to subcortical hemorrhage in the left posterior middle temporal gyrus.

We report a patient with alexia with agraphia for kanji after hemorrhage in the left posterior middle temporal gyrus. The results of single-character kanji reading and two-character on- (Chinese-style pronunciation), kun- (native Japanese pronunciation), and Jukujikun (irregular kun-) reading word tests revealed that the patient could not read kanji characters with on-reading but read the characters with kun-reading. We consider that this on-reading alexia was caused by disconnection between the posterior inferior temporal cortex (orthographic lexicon) and the posterior superior temporal gyrus (phonological lexicon), and preserved kun- and Jukujikun-reading was realized by bypassing the orthography-to-phonology route by the semantic route.

Proactive interference apraxic agraphia: a writing and drawing disorder associated with corticobasal syndrome.

Proactive interference is when a previously performed task impairs performance on a current task. It is often associated with memory tasks and has not been reported to interfere with writing or drawing. We evaluated a left-handed man diagnosed with corticobasal syndrome who had a two-year history of progressive agraphia. On the sentence writing and clock drawing tasks, he initially wrote letters and numbers correctly but revealed an increase of movement errors as the tasks progressed. We propose the term "proactive interference apraxic agraphia" for this novel disorder. Prefrontal dysfunction may cause an impairment in disengaging from previously activated motor programs.

Too harts, won sole: Using dysgraphia treatment to address homophone representation.

Previous spoken homophone treatment in aphasia found generalization to untreated homophones and interpreted this as evidence for shared phonological word form representations. Previous written treatment of non-homophones has attributed generalization to orthographic neighbours of treated items to feedback from graphemes to similarly spelled orthographic word forms. This feedback mechanism offers an alternative explanation for generalization found in treatment of spoken homophones. The aim of this study was to investigate the mechanism underpinning generalization (if any) from treatment of written homophones. To investigate this question a participant with acquired dysgraphia and impaired access to orthographic output representations undertook written spelling treatment. Generalization to untreated items with varying degrees of orthographic overlap was investigated. Three experimental sets included homographs (e.g., bank-bank), heterographs (e.g., sail-sale), and direct orthographic neighbours (e.g., bath-path). Treatment improved written picture naming of treated items. Generalization was limited to direct neighbours. Further investigation of generalization found that items with a greater number of close neighbours in the treated set showed greater generalization. This suggests that feedback from graphemes to orthographic word forms is the driving force of generalization. The lack of homograph generalization suggests homographs do not share a representation in the orthographic lexicon.

Re-learning to be different: Increased neural differentiation supports post-stroke language recovery.

Identifying the neural changes that support recovery of cognitive functions after a brain lesion is important to advance our understanding of human neuroplasticity, which, in turn, forms the basis for the development of effective treatments. To date, the preponderance of neuroimaging studies has focused on localizing changes in average brain activity associated with functional recovery. Here, we took a novel approach by evaluating whether cognitive recovery in chronic stroke is related to increases in the differentiation of local neural response patterns. This approach is supported by research indicating that, in the intact brain, local neural representations become more differentiated (dissimilar) with learning (Glezer et al., 2015). We acquired fMRI data before and after 21 individuals received approximately 12 weeks of behavioral treatment for written language impairment due to a left-hemisphere stroke. We used Local-Heterogeneity Regression Analysis (Purcell and Rapp, 2018) to measure local neural response differentiation associated with written language processing, assuming that greater heterogeneity in the pattern of activity across adjacent neural areas indicates more well-differentiated neural representations. First, we observed pre to post-treatment increases in local neural differentiation (Local-Hreg) in the ventral occipital-temporal cortex of the left hemisphere. Second, we found that, in this region, higher local neural response differentiation prior to treatment was associated with less severe written language impairment, and that it also predicted greater future responsiveness to treatment. Third, we observed that changes in neural differentiation were systematically related to performance changes for trained and untrained items. Fourth, we did not observe these brain-behavior relationships for mean BOLD responses, only for Local-Hreg. Thus, this is the first investigation to quantify changes in local neural differentiation in the recovery of a cognitive function and the first to demonstrate the clear behavioral relevance of these changes. We conclude that the findings provide strong support for the novel hypothesis that the local re-differentiation of neural representations can play a significant role in functional recovery after brain lesion.

Alexia and Agraphia from 1861 to 1965.

Studies of alexia and agraphia have played historically important roles in efforts to understand the relation between brain and behavior. In the second half of the 19th century, works by Paul Broca and Carl Wernicke led to the concept of delimited cortical centers in the left cerebral hemisphere concerned with discrete aspects of spoken and written language. These specialized centers were linked by white matter pathways. Charlton Bastian, Jean-Martin Charcot, Sigmund Exner, and Jules Dejerine championed center-pathway models of reading and writing. Dejerine played a dominant role, rejecting the idea of a left frontal lobe center that mediated writing and proposing a unique, specialized role for the left angular gyrus in both reading and writing. In 1891 and 1892, he detailed the symptoms of alexia and agraphia that resulted from injury to the left angular gyrus and from the isolation of the left angular gyrus from visual input required for reading. During the early 20th century, his work and that of other so-called diagram makers was confronted and largely discredited by Pierre Marie, joined later by Henry Head and Kurt Goldstein. In the 1960s, the center-pathway model was resurrected and refined by Norman Geschwind. He drew upon foundational works of Dejerine, Hugo Liepmann, and others to describe syndromes resulting from cortical disconnections and, in doing so, helped to establish a framework for the modern discipline of behavioral neurology.

Representations of grapho-motor patterns unique to Chinese character writing: evidence from a patient with mirror writing.

This study investigated the grapho-motor patterns used in writing Chinese characters. A Chinese patient, CSC, who demonstrated post-brain-injury mirror writing, was recruited. In Experiment 1, non-mirrored writing responses were obtained when CSC was instructed to copy asymmetrical non-verbal symbols and pictures. Resembling the patterns observed in a patient's writing reported in a previous study, it was hypothesized that CSC's mirror writing was a result of untransformed preserved grapho-motor patterns. In Experiments 2 and 3, CSC was further instructed to copy real Chinese characters, pseudo-characters with authentic radicals and logographemes (i.e., stroke clusters that frequently occur in radicals), and Hangul characters with stroke clusters resembling the shapes of authentic logographemes. The results showed that CSC demonstrated mirror writing only when authentic Chinese orthographic units were involved. Non-mirrored writing responses were obtained from stimuli without authentic Chinese orthographic units. In sum, CSC's performance supported the existence of grapho-motor patterns of Chinese orthographic units represented in the brain. Theoretical implications were discussed.

The effects of lesion and treatment-related recovery on functional network modularity in post-stroke dysgraphia.

A better understanding of the neural network properties that support cognitive recovery after a brain lesion is important for our understanding of human neuroplasticity and may have valuable clinical implications. In fifteen individuals with chronic, acquired written language deficits subsequent to left-hemisphere stroke, we used task-based functional connectivity to evaluate the relationship between the graph-theoretic measures (modularity, participation coefficient and within-module degree z-score) and written language production accuracy before and after behavioral treatment. A reference modular structure and local and global hubs identified from healthy controls formed the basis of the analyses. Overall, the investigation revealed that less modular networks with greater global and lower local integration were associated with greater deficit severity and lower response to treatment. Furthermore, we found treatment-induced increases in modularity and local integration measures. In particular, local integration within intact ventral occipital-temporal regions of the spelling network showed the greatest increase in local integration following treatment. This investigation significantly extends previous research by using task-based (rather than resting-state) functional connectivity to examine a larger set of network characteristics in the evaluation of treatment-induced recovery and by including comparisons with control participants. The findings demonstrate the relevance of network modularity for understanding the neuroplasticity supporting functional neural reorganization.

Sensory trick in upper limb dystonia.

INTRODUCTION: Sensory trick is a specific maneuver that temporarily improves dystonia that is usually observed in 44%-89% of patients with cranial-cervical dystonia and in 20% of patients with upper limb dystonia. This study aimed to assess the prevalence of sensory trick in a cohort of 37 patients with idiopathic adult-onset upper limb dystonia and to determine whether sensory trick can be a useful tool to distinguish dystonic and non-dystonic tremor. METHODS: Thirty-seven right-handed patients with idiopathic upper limb dystonia and disturbed handwriting and 19 patients with non-dystonic action tremor in the upper limb causing writing disturbances participated into the study. Patients were asked to write a standard sentence twice, before and after applying a standardized sensory trick (gently grabbing right wrist with his left hand). Readability of the two sentences was assessed by three observers blinded to diagnosis. RESULTS: Five/37 patients (13%) self-discovered ST over disease history, while performing the standardized trick maneuver improved handwriting in 14/37 patients (38%). Interobserver agreement on the effectiveness of sensory trick among the three observers yielded a kappa value of 0.86 (p < 0.0001). The standardized trick was effective in 8/19 patients with dystonic tremor (42%) and in 0/19 patients with non-dystonic tremor (p = 0.003). CONCLUSION: The results of applying a standardized non-spontaneous trick demonstrated that, in upper limb dystonia, ST may be more frequent than usually observed. Effective sensory trick, when present, may be a hallmark of idiopathic dystonia. The lack of effective sensory trick may help to identify non dystonic upper limb tremor.

Maximising recovery from aphasia with central and peripheral agraphia: The benefit of sequential treatments.

Maximal recovery from acquired language impairment may require progression from one behavioural treatment protocol to the next in order to build upon residual and relearned cognitive-linguistic and sensory-motor processes. We present a five-stage treatment sequence that was initiated at one year post stroke in a woman with acquired impairments of spoken and written language. As is typical of individuals with left perisylvian damage, she demonstrated marked impairment of phonological retrieval and sublexical phonology, but she also faced additional challenges due to impaired letter shape knowledge and visual attention. The treatment sequence included (1) written spelling of targeted words, (2) retraining sublexical sound-to-letter correspondences and phonological manipulation skills, (3) training strategic approaches to maximise interactive use of lexical, phonological, and orthographic knowledge, (4) lexical retrieval of spoken words, and finally (5) sentence-level stimulation to improve grammatical form of written narratives. This Phase II clinical study documented positive direct treatment outcomes along with evidence of a significant reduction in the underlying deficits and generalisation to untrained items and language tasks. Improvements on a comprehensive assessment battery were realised as functional gains in everyday written and spoken communication, including improved lexical retrieval and grammatical complexity of written narratives. This case provides a valuable example of the cumulative therapeutic benefit of sequential application of theoretically motivated treatment protocols.

Agraphia with reversible splenial corpus callosum lesion caused by hypoglycemia.

BACKGROUND: Neurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare. SUBJECT AND METHODS: We examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone. CONCLUSION: This rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.

Inter-relationships between objective handwriting features and executive control among children with developmental dysgraphia.

OBJECTIVE: To describe handwriting and executive control features and their inter-relationships among children with developmental dysgraphia, in comparison to controls. METHOD: Participants included 64 children, aged 10-12 years, 32 with dysgraphia based on the Handwriting Proficiency Screening Questionnaire (HPSQ) and 32 matched controls. Children copied a paragraph onto paper affixed to a digitizer that supplied handwriting process objective measures (Computerized Penmanship Evaluation Tool (ComPET). Their written product was evaluated by the Hebrew Handwriting Evaluation (HHE). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire about their child's executive control abilities. RESULTS: Significant group differences were found for handwriting performance measures (HHE and ComPET) and executive control domains (BRIEF). Based on one discriminate function, including handwriting performance and executive control measures, 98.4% of the participants were correctly classified into groups. Significant correlations were found in each group between working memory and legibility as well as for other executive domains and handwriting measures. Furthermore, twenty percent of the variability of the mean pressure applied towards the writing surface among children with was explained by their 'emotional control' (BRIEF). CONCLUSION: The results strongly suggest consideration of executive control domains to obtain better insight into handwriting impairment characteristics among children with dysgraphia to improve their identification, evaluation and the intervention process.

Revival of Historical Kana Orthography in a Patient with Allographic Agraphia.

Japanese people born before World War II learned Japanese kana (Japanese syllabograms) writing in a style that is not currently used. These individuals had to learn the current style of kana orthography after the war. An 85-year-old man was taken to our hospital by his family who were surprised by his diary. It was written with kanji (Japanese ideograms) and katakana using the prewar style. A neuropsychological examination revealed impaired recall of hiragana. Neuroimaging studies revealed atrophy of the left fronto-parietal lobe and hypoperfusion of the left frontal lobe. His allographic agraphia might have resulted from the disturbance of the current style of kana orthography.