Carotid Revascularization is Associated with Improved Mood in Patients with Advanced Carotid Disease.

OBJECTIVE: To investigate the impact of carotid interventions on patients' mental condition in patients with carotid stenosis. SUMMARY BACKGROUND DATA: Ongoing research highlights the impact of carotid interventions on neurocognitive function in patients with advanced carotid atherosclerosis. However, data regarding the impact of carotid revascularization on mood is scarce. METHODS: A total of 157 patients undergoing carotid revascularization were prospectively recruited. The primary outcome was depression, evaluated pre-operatively, and at 1-,6- and 12-month post-intervention using the long form of the geriatric depression scale (GDS-30) questionnaire. Other tests were also used to assess cognition at the respective timepoints. Statistical analyses were performed to assess the postoperative outcomes compared to baseline. RESULTS: Baseline depression (GDS>9) was observed in 49(31%) subjects, whereas 108(69%) patients were not depressed (GDS≤9). The average pre-operative GDS score was 15.42 ± 4.40(14.2-16.7) and 4.28 ±2.9(3.7-4.8) in the depressed and non-depressed groups, respectively. We observed a significant improvement in GDS scores within the depressed group at 1-month (P=0.002), 6-months (P=0.027), and 1-year (P<0.001) post-intervention compared to preop, whereas the non-depressed group had similar post-op GDS scores at all time points compared to baseline. Significant improvement in measures of executive function was seen in non-depressed patients at all three timepoints whereas depressed patients showed an improvement at 1-year follow-up. CONCLUSIONS: Our study highlights improvement in mood among patients with advanced carotid disease who screened positive for depression at baseline. Further studies with larger sample sizes are warranted to investigate the association between depression, carotid disease, and carotid intervention.

Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset.

INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.

Evidence of Impaired Remote Experience-near Semantic Memory in Medial Temporal Lobe Amnesia.

Neuropsychological research suggests that "experience-near" semantic memory, meaning knowledge attached to a spatiotemporal or event context, is commonly impaired in individuals who have medial temporal lobe amnesia. It is not known if this impairment extends to remotely acquired experience-near knowledge, which is a question relevant to understanding hippocampal/medial temporal lobe functioning. In the present study, we administered a novel semantic memory task designed to target knowledge associated with remote, "dormant" concepts, in addition to knowledge associated with active concepts, to four individuals with medial temporal lobe amnesia and eight matched controls. We found that the individuals with medial temporal lobe amnesia generated significantly fewer experience-near semantic memories for both remote concepts and active concepts. In comparison, the generation of abstract or "experience-far" knowledge was largely spared in the individuals with medial temporal lobe amnesia, regardless of whether the targets for retrieval were remote or active concepts. We interpret these findings as evidence that the medial temporal lobes may have a sustained role in the retrieval of semantic memories associated with spatiotemporal and event contexts, which are cognitive features often ascribed to episodic memory. These results align with recent theoretical models proposing that the hippocampus/medial temporal lobes support cognitive processes that are involved in, but not exclusive to, episodic memory.

Carotid Intervention Improves Cognitive Function in Patients With Severe Atherosclerotic Carotid Disease.

INTRODUCTION: Carotid revascularization procedures are effective in stroke prevention in appropriately selected patients. We sought to understand the effects of the carotid intervention on cognitive function in a well-defined cohort of prospectively recruited patients. METHODS: A total of 170 consecutive patients undergoing carotid intervention for severe carotid stenosis were recruited. Patients received neuropsychometric testing preintervention, and at 1, 6, and 12 months postoperative. Patients were screened with the Mini-Mental State Examination. Rey Auditory Verbal Learning test (RAVLT) test was the primary outcome measure and multiple cognitive tests were used to evaluate executive function. Paired t test and McNemar test were performed to compare age-adjusted and education-adjusted postoperative scores at the individual time point with the preoperative scores. RESULTS: Our patients had a high prevalence of cardiovascular risks and 51.2% of whom were symptomatic. The usages of statin and antiplatelet were high (88.8% and 69.4%, respectively). A total of 140 patients had 1 or more postoperative neuropsychometric tests in addition to their preoperative tests were included. The average RAVLT preoperative score was lower ( z =-0.79, SD=1.3, confidence interval: -1 to -0.53) than the age-adjusted norm. We observed a significant improvement in RAVLT memory scores at 1 and 6 months postoperative compared with preoperative. We also observed significant improvement in multiple executive functions measures up to 12 months postoperative. The improvement on patients with preoperative stroke symptoms was less consistent. CONCLUSIONS: This prospective study showed that carotid intervention improved memory and executive function in patients with the severe carotid occlusive disease. It highlights the cognitive benefit of the carotid intervention in appropriately selected patients.

The role of the striatum in visuomotor integration during handwriting: an fMRI study.

This study investigates the role of the dorsal/sensorimotor striatum in visuomotor integration (i.e., the transformation of internal visual information about letter shapes into motor output) during handwriting. Twenty healthy participants underwent fMRI scanning with tasks consisting of self-paced handwriting of alphabetically ordered single letters and simple dots, with both tasks performed without visual feedback. Functional connectivity (FC) from these two tasks was compared to demonstrate the difference between coordinated activity arising during handwriting and the activity during a simpler motor condition. Our study focused upon the writing-specific cortico-striatal network of preselected regions of interest consisting of the visual word form area (VWFA), anterior intraparietal sulcus/superior parietal lobule, striatum, premotor cortex/Exner's area, and primary and supplementary motor regions. We observed systematically increased task-induced cortico-striatal and cortico-cortical FC. This increased synchronization of neural activity between the VWFA, i.e., the visual cortical area containing information about letter shapes, and the frontoparietal motor regions is mediated by the striatum. These findings suggest the involvement of the striatum in integrating stored letter-shape information with motor planning and execution during handwriting.

Face Recognition.

PURPOSE OF REVIEW: Functional imaging studies, intracranial recordings, and lesion-deficit correlations in neurological patients have produced unique insights into the cognitive mechanisms and neural substrates of face recognition. In this review, we highlight recent advances in the field and integrate data from these complementary lines of research to propose a functional neuroanatomical model of face identity recognition. RECENT FINDINGS: Rather than being localized to a single specialized cortical region, face recognition is supported by a distributed neural network. Core components of the network include face-selective visual areas in the ventral occipito-temporal cortex, whereas the extended network is comprised of anterior temporal lobe structures involved in the retrieval of multimodal identity-specific knowledge about familiar individuals, the amygdala responsible for generating emotional responses to faces, and prefrontal regions that provide top-down executive control of the recognition process. Damage to different network components results in neuropsychological disorders of face identity processing manifested either as impaired recognition of familiar faces (prosopagnosia, person recognition disorders) or as false recognition/misidentification of unfamiliar faces. Face identity recognition requires the coordinated activity of a large-scale neural network. Neurological damage can compromise the structural/functional integrity of specific network nodes or their connections and give rise to face recognition disorders with distinct clinical features and underlying cognitive mechanisms determined primarily by the location of the lesion.

The neural substrates of improved phonological processing following successful treatment in a case of phonological alexia and agraphia.

Phonological deficits are common in aphasia after left-hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals improve through treatment, the neural substrates supporting improvements are poorly understood. We measured brain activation during pseudoword reading in an individual through two treatment phases. Improvements were associated with greater activation in residual left dorsal language regions and bilateral regions supporting attention and effort. Gains were maintained, while activation returned to pre-treatment levels. This case demonstrates the neural support for improved phonology after damage to critical regions and that improvements may be maintained without markedly increased effort.

The nature and treatment of phonological text agraphia.

Phonological alexia and agraphia are written language disorders characterised by disproportionate difficulty reading and spelling nonwords in comparison to real words. In phonological alexia, it has been shown that, despite relatively accurate reading of words in isolation, text-level reading deficits are often marked and persistent. Specifically, some individuals demonstrate difficulty reading functors and affixes in sentences, a profile referred to as phonological text alexia. In this paper, we demonstrate an analogous manifestation of the phonological impairment on text-level writing and suggest the term "phonological text agraphia". We examined four individuals with phonological alexia/agraphia who also showed disproportionate difficulty writing well-formed sentences in comparison to their grammatical competence in spoken utterances. Implementation of a phonological treatment protocol resulted in significantly improved sublexical phonology skills as well as improvements in grammatical accuracy of written narratives. These findings support the notion of a common phonological impairment underlying nonword reading/spelling deficits and sentence-level difficulties.

Oscillatory reactivity to effortful cognitive processing in the subthalamic nucleus and internal pallidum: a depth electrode EEG study.

This study investigates how complex motor-cognitive activities are processed in the subthalamic nucleus (STN) and internal globus pallidum (GPi), as adverse neuropsychiatric effects may accompany deep brain stimulation (DBS), mainly in Parkinson's disease (PD) and STN-DBS. Dystonia patients with GPi-DBS electrodes (n = 5) and PD subjects (n = 5) with STN-DBS electrodes performed two tasks: (1) copying letters; and (2) writing any letter other than that appearing on the monitor. The cognitive load of the second task was greater than that of the first. Intracranial local field potentials (LFPs) were analysed. A beta power decrease was the main correlate of the enhanced cognitive load during the second task in both structures, with a lateralization to the left side, mainly in the GPi. A gamma power increase linked with the increased cognitive activity was observed only in the STN. Differences were also observed in the theta and alpha bandpasses. Beta ERD reactivity seems to be essential during the processing of complex motor-cognitive tasks, increases with enhanced cognitive effort, and was observed in both the STN and GPi. Oscillatory reactivity to effortful cognitive processing in other frequency bands was less consistent, with differences between the studied nuclei. Lateralization of activity related to cognitive factors was observed mainly in the GPi.

Bidirectional iterative parcellation of diffusion weighted imaging data: separating cortical regions connected by the arcuate fasciculus and extreme capsule.

This paper introduces a Bidirectional Iterative Parcellation (BIP) procedure designed to identify the location and size of connected cortical regions (parcellations) at both ends of a white matter tract in diffusion weighted images. The procedure applies the FSL option "probabilistic tracking with classification targets" in a bidirectional and iterative manner. To assess the utility of BIP, we applied the procedure to the problem of parcellating a limited set of well-established gray matter seed regions associated with the dorsal (arcuate fasciculus/superior longitudinal fasciculus) and ventral (extreme capsule fiber system) white matter tracts in the language networks of 97 participants. These left hemisphere seed regions and the two white matter tracts, along with their right hemisphere homologues, provided an excellent test case for BIP because the resulting parcellations overlap and their connectivity via the arcuate fasciculi and extreme capsule fiber systems are well studied. The procedure yielded both confirmatory and novel findings. Specifically, BIP confirmed that each tract connects within the seed regions in unique, but expected ways. Novel findings included increasingly left-lateralized parcellations associated with the arcuate fasciculus/superior longitudinal fasciculus as a function of age and education. These results demonstrate that BIP is an easily implemented technique that successfully confirmed cortical connectivity patterns predicted in the literature, and has the potential to provide new insights regarding the architecture of the brain.

Dysfunctional visual word form processing in progressive alexia.

Progressive alexia is an acquired reading deficit caused by degeneration of brain regions that are essential for written word processing. Functional imaging studies have shown that early processing of the visual word form depends on a hierarchical posterior-to-anterior processing stream in occipito-temporal cortex, whereby successive areas code increasingly larger and more complex perceptual attributes of the letter string. A region located in the left lateral occipito-temporal sulcus and adjacent fusiform gyrus shows maximal selectivity for words and has been dubbed the 'visual word form area'. We studied two patients with progressive alexia in order to determine whether their reading deficits were associated with structural and/or functional abnormalities in this visual word form system. Voxel-based morphometry showed left-lateralized occipito-temporal atrophy in both patients, very mild in one, but moderate to severe in the other. The two patients, along with 10 control subjects, were scanned with functional magnetic resonance imaging as they viewed rapidly presented words, false font strings, or a fixation crosshair. This paradigm was optimized to reliably map brain regions involved in orthographic processing in individual subjects. All 10 control subjects showed a posterior-to-anterior gradient of selectivity for words, and all 10 showed a functionally defined visual word form area in the left hemisphere that was activated for words relative to false font strings. In contrast, neither of the two patients with progressive alexia showed any evidence for a selectivity gradient or for word-specific activation of the visual word form area. The patient with mild atrophy showed normal responses to both words and false font strings in the posterior part of the visual word form system, but a failure to develop selectivity for words in the more anterior part of the system. In contrast, the patient with moderate to severe atrophy showed minimal activation of any part of the visual word form system for either words or false font strings. Our results suggest that progressive alexia is associated with a dysfunctional visual word form system, with or without substantial cortical atrophy. Furthermore, these findings demonstrate that functional MRI has the potential to reveal the neural bases of cognitive deficits in neurodegenerative patients at very early stages, in some cases before the development of extensive atrophy.

Efficient visual object and word recognition relies on high spatial frequency coding in the left posterior fusiform gyrus: evidence from a case-series of patients with ventral occipito-temporal cortex damage.

Recent visual neuroscience investigations suggest that ventral occipito-temporal cortex is retinotopically organized, with high acuity foveal input projecting primarily to the posterior fusiform gyrus (pFG), making this region crucial for coding high spatial frequency information. Because high spatial frequencies are critical for fine-grained visual discrimination, we hypothesized that damage to the left pFG should have an adverse effect not only on efficient reading, as observed in pure alexia, but also on the processing of complex non-orthographic visual stimuli. Consistent with this hypothesis, we obtained evidence that a large case series (n = 20) of patients with lesions centered on left pFG: 1) Exhibited reduced sensitivity to high spatial frequencies; 2) demonstrated prolonged response latencies both in reading (pure alexia) and object naming; and 3) were especially sensitive to visual complexity and similarity when discriminating between novel visual patterns. These results suggest that the patients' dual reading and non-orthographic recognition impairments have a common underlying mechanism and reflect the loss of high spatial frequency visual information normally coded in the left pFG.

Cognitive effects of carotid revascularization in octogenarians.

BACKGROUND: Cognitive impairment is the epitome of cerebrovascular diseases, causing a significant economic burden on our health care system. Growing evidence has indicated the benefits of carotid interventions in patients with severe carotid atherosclerosis. However, the neurocognitive outcome of carotid revascularization in octogenarians is not clearly understood. We aim to evaluate postintervention cognitive changes in seniors older than 80 years. METHODS: We prospectively recruited 170 patients undergoing carotid interventions. Neurocognitive testing was performed preoperatively and at 1, 6, and 12 months postoperatively. Episodic memory was assessed with Rey's Auditory Verbal Learning Test. Other executive functions and language measures were also evaluated at individual time points. Raw test scores were converted to z-scores or scaled scores adjusted for age and education. The sample was divided into 2 groups based on age: octogenarian (≥80 years) and nonoctogenarian (<80 years old). Postoperative cognitive scores were compared to baseline within each subcohort. RESULTS: A total of 23 subjects (13%) were octogenarians, and 147 (87%) were younger than 80 years. Younger patients demonstrated significant cognitive improvements up to 12 months postop compared to the baseline. However, octogenarians exhibited a lack of improvement in verbal memory, measures of executive function, and language at all 3 postintervention time points. CONCLUSION: Carotid interventions improve cognitive functions in younger patients with carotid occlusive atherosclerosis. However, no cognitive benefits were seen in male seniors older than 80 years. Further investigations are warranted to better understand the postinterventional cognitive changes in octogenarians.

Written language impairments in primary progressive aphasia: a reflection of damage to central semantic and phonological processes.

Connectionist theories of language propose that written language deficits arise as a result of damage to semantic and phonological systems that also support spoken language production and comprehension, a view referred to as the "primary systems" hypothesis. The objective of the current study was to evaluate the primary systems account in a mixed group of individuals with primary progressive aphasia (PPA) by investigating the relation between measures of nonorthographic semantic and phonological processing and written language performance and by examining whether common patterns of cortical atrophy underlie impairments in spoken versus written language domains. Individuals with PPA and healthy controls were administered a language battery, including assessments of semantics, phonology, reading, and spelling. Voxel-based morphometry was used to examine the relation between gray matter volumes and language measures within brain regions previously implicated in semantic and phonological processing. In accordance with the primary systems account, our findings indicate that spoken language performance is strongly predictive of reading/spelling profile in individuals with PPA and suggest that common networks of critical left hemisphere regions support central semantic and phonological processes recruited for spoken and written language.

Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.

BACKGROUND: The APOE epsilon4 allele is associated with the risk of late-onset Alzheimer's disease. The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown. METHODS: Using local advertisements, we recruited cognitively normal subjects between the ages of 21 and 97 years, who were grouped according to their APOE epsilon4 status. We then followed the subjects with longitudinal neuropsychological testing. Anyone in whom mild cognitive impairment or dementia developed during follow-up was excluded. We compared the rates of decline in predetermined cognitive measures between carriers and noncarriers of the APOE epsilon4 allele, using a mixed model for longitudinal change with age. RESULTS: We analyzed 815 subjects: 317 APOE epsilon4 carriers (79 who were homozygous for the APOE epsilon4 allele and 238 who were heterozygous) and 498 noncarriers. Carriers, as compared with noncarriers, were generally younger (mean age, 58.0 vs. 61.4 years; P<0.001) and were followed for a longer period (5.3 vs. 4.7 years, P=0.01), with an equivalent duration of formal education (15.4 years) and proportion of women (69%). Longitudinal decline in memory in carriers began before the age of 60 years and showed greater acceleration than in noncarriers (P=0.03), with a possible allele-dose effect (P=0.008). We observed similar although weaker effects on measures of visuospatial awareness and general mental status. CONCLUSIONS: Age-related memory decline in APOE epsilon4 carriers diverges from that of noncarriers before the age of 60 years, despite ongoing normal clinical status.

Common predictors of spoken and written language performance in aphasia, alexia, and agraphia.

Language performance requires support from central cognitive/linguistic abilities as well as the more peripheral sensorimotor skills to plan and implement spoken and written communication. Both output modalities are vulnerable to impairment following damage to the language-dominant hemisphere, but much of the research to date has focused exclusively on spoken language. In this study we aimed to examine an integrated model of language processing that includes the common cognitive processes that support spoken and written language, as well as modality-specific skills. To do so, we evaluated spoken and written language performance from 87 individuals with acquired language impairment resulting from damage to left perisylvian cortical regions that collectively constitute the dorsal language pathway. Comprehensive behavioral assessment served to characterize the status of central and peripheral components of language processing in relation to neurotypical controls (n = 38). Performance data entered into principal components analyses (with or without control scores) consistently yielded a strong five-factor solution. In line with a primary systems framework, three central cognitive factors emerged: semantics, phonology, and orthography that were distinguished from peripheral processes supporting speech production and allographic skill for handwriting. The central phonology construct reflected performance on phonological awareness and manipulation tasks and showed the greatest deficit of all the derived factors. Importantly, this phonological construct was orthogonal to the speech production factor that reflected repetition of words/non-words. When entered into regression analyses, semantics and phonological skill were common predictors of language performance across spoken and written modalities. The speech production factor was also a strong, distinct predictor of spoken naming and oral reading, in contrast to allographic skills which only predicted written output. As expected, visual orthographic processing contributed more to written than spoken language tasks and reading/spelling performance was strongly reliant on phonological and semantic abilities. Despite the heterogeneity of this cohort regarding aphasia type and severity, the marked impairment of phonological skill was a unifying feature. These findings prompt greater attention to clinical assessment and potential treatment of underlying phonological skill in individuals with left perisylvian damage.

Autobiographical memory unknown: Pervasive autobiographical memory loss encompassing personality trait knowledge in an individual with medial temporal lobe amnesia.

Autobiographical memory consists of distinct memory types varying from highly abstract to episodic. Self trait knowledge, which is considered one of the more abstract types of autobiographical memory, is thought to rely on regions of the autobiographical memory neural network implicated in schema representation, including the ventromedial prefrontal cortex, and critically, not the medial temporal lobes. The current case study introduces an individual who experienced bilateral posterior cerebral artery strokes resulting in extensive medial temporal lobe damage with sparing of the ventromedial prefrontal cortex. Interestingly, in addition to severe retrograde and anterograde episodic and autobiographical fact amnesia, this individual's self trait knowledge was impaired for his current and pre-morbid personality traits. Yet, further assessment revealed that this individual had preserved conceptual knowledge for personality traits, could reliably and accurately rate another person's traits, and could access his own self-concept in a variety of ways. In addition to autobiographical memory loss, he demonstrated impairment on non-personal semantic memory tests, most notably on tests requiring retrieval of unique knowledge. This rare case of amnesia suggests a previously unreported role for the medial temporal lobes in self trait knowledge, which we propose reflects the critical role of this neural region in the storage and retrieval of personal semantics that are experience-near, meaning autobiographical facts grounded in spatiotemporal contexts.

Largely intact memory for spatial locations during navigation in an individual with dense amnesia.

Spatial navigation and event memory (termed episodic memory) are thought to be heavily intertwined, both in terms of their cognitive processes and underlying neural systems. Some theoretical models posit that both memory for places during navigation and episodic memory depend on highly overlapping brain systems. Here, we assessed this relationship by testing navigation in an individual with severe retrograde and anterograde amnesia; the amnesia stemmed from bilateral lesions in the medial temporal lobes from two separate strokes. The individual with amnesia and age-matched controls were tested on their memories for the locations of previously seen objects relative to distal mountain cues in an immersive virtual environment involving free ambulation. All participants were tested from both repeated and novel start locations and when a single distal mountain cue was unknowingly moved to determine if they relied on a single (beacon) cue to a greater extent than the collection of all distal cues. Compared to age-matched controls, the individual with amnesia showed no significant deficits in navigation from either the repeated or novel start points, although both the individual with amnesia and controls performed well above chance at placing objects near their correct locations. The individual with amnesia also relied on a combination of distal cues in a manner comparable to age-matched controls. Despite largely intact memory for locations using distal cues, the individual with amnesia walked longer paths, rotated more, and took longer to complete trials. Our findings suggest that memory for places during navigation and episodic memory may involve partially dissociable brain circuits and that other brain regions outside of the medial temporal lobe partially support some aspects of navigation. At the same time, the fact that the individual with amnesia walked more circuitous paths and had dense amnesia for autobiographic events supports the idea that the hippocampus may be important for binding information as part of a larger role in memory.

Functional neuroanatomy of reading in Czech: Evidence of a dual-route processing architecture in a shallow orthography.

Introduction: According to the strong version of the orthographic depth hypothesis, in languages with transparent letter-sound mappings (shallow orthographies) the reading of both familiar words and unfamiliar nonwords may be accomplished by a sublexical pathway that relies on serial grapheme-to-phoneme conversion. However, in languages such as English characterized by inconsistent letter-sound relationships (deep orthographies), word reading is mediated by a lexical-semantic pathway that relies on mappings between word-specific orthographic, semantic, and phonological representations, whereas the sublexical pathway is used primarily to read nonwords. Methods: In this study, we used functional magnetic resonance imaging to elucidate neural substrates of reading in Czech, a language characterized by a shallo worthography. Specifically, we contrasted patterns of brain activation and connectivity during word and nonword reading to determine whether similar or different neural mechanisms are involved. Neural correlates were measured as differences in simple whole-brain voxel-wise activation, and differences in visual word form area (VWFA) task-related connectivity were computed on the group level from data of 24 young subject. Trial-to-trial reading reaction times were used as a measure of task difficulty, and these effects were subtracted from the activation and connectivity effects in order to eliminate difference in cognitive effort which is naturally higher for nonwords and may mask the true lexicality effects. Results: We observed pattern of activity well described in the literature mostly derived from data of English speakers - nonword reading (as compared to word reading) activated the sublexical pathway to a greater extent whereas word reading was associated with greater activation of semantic networks. VWFA connectivity analysis also revealed stronger connectivity to a component of the sublexical pathway - left inferior frontal gyrus (IFG), for nonword compared to word reading. Discussion: These converging results suggest that the brain mechanism of skilled reading in shallow orthography languages are similar to those engaged when reading in languages with a deep orthography and are supported by a universal dual-pathway neural architecture.

Comparison of CNN-Learned vs. Handcrafted Features for Detection of Parkinson's Disease Dysgraphia in a Multilingual Dataset.

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).