Left Occipitotemporal Region Research Articles

Task-related modulation of facial expression processing: An FPVS-EEG study.

In the current study, we examined the role of task-related top-down mechanisms in the recognition of facial expressions. An expression of increasing intensity was displayed at a frequency of 1.5 Hz among the neutral faces of the same model that was displayed at a frequency of 12 Hz (i.e., 12 frames per second, with the expression occurring every eight frames). Twenty-two participants were asked either to recognize the emotion at the expression-specific frequency (1.5 Hz) or to perform an orthogonal task in separate blocks, while a scalp electroencephalogram (EEG) was recorded. A significant 1.5 Hz response emerged with the increase in expressive intensity over the medial occipital, right and left occipitotemporal, and centro-frontal regions. In these three regions, the magnitude of this response was greater when participants were involved in expression recognition, especially when the intensity of expression was low and ambiguous. Time-domain analysis revealed that engagement in the explicit recognition of facial expression caused a modulation of the response even before the onset of the expression over centro-frontal regions. The response was then amplified over the medial occipital and right and left occipitotemporal regions. Overall, the procedure developed in the present study allowed us to document different stages of the voluntary recognition of facial expressions, from detection to recognition, through the implementation of task-related top-down mechanisms that modulated the incoming information flow. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dislexia e as vantagens de ser bilíngue: um estudo sobre a neurobiologia da leitura com o uso de RMf

The objective of the present study was to investigate reading performance and brain activation associated with reading for bilingual and monolingual dyslexics (DDB-DDM), and typical bilinguals as Controls (C). The behavioral results showed that DDB outperformed DDM in all reading components in Portuguese. In the tasks applied in English, there was no significant difference in the performance of DDB compared to C. The results of the brain imaging for the task in Portuguese showed C presented significant activation of the left occipitotemporal and left inferior frontal gyrus while reading words. DDB and DDM, in turn, showed deactivation of left temporoparietal region and no significant activation in the left occipitotemporal region or left inferior frontal gyrus. For the FAST LOC task, DDB showed hypoactivity in the Visual Word Form Area (VWFA) during word reading, both in English and Portuguese. The findings provide evidence for a possible positive impact of bilingualism on the reading performance of dyslexics.

Correlation of event-related potentials N170 with dysfunctional attitudes in patients with major depressive disorder

BackgroundCognitive impairment frequently accompanies first-episode major depressive disorder (MDD) in patients. Early detection and intervention for cognitive impairment can enhance the quality of life for individuals with depressive disorders. Impaired emotion recognition may serve as an initial manifestation of cognitive impairment in these patients. This study examines the characteristics of event-related potentials N170 and dysfunctional attitudinal questionnaire total scores, as well as each factor and their correlation, revealing characteristic electroencephalogram (EEG) changes associated with cognitive impairment in first-episode MDD patients. MethodA total of 88 patients experiencing first-episode MDD and 29 healthy volunteers from the same period participated in the study. They underwent event-related potential N170 measures to assess mood recognition function, the 17-item Hamilton depression scale (HAMD-17) to evaluate the severity of depressive disorder, and the Dysfunctional Attitudes Scales(DAS) to appraise cognitive function. ResultThe dysfunctional attitude questionnaire's total score and each factor score were higher in the MDD group compared to the healthy control (HC) group. The MDD group exhibited lower amplitudes than the HC group at CZ, PZ, POZ, P7, PO7, P8, and PO8 electrode points. A correlation was identified between the P7 and PO7 electrode points of the event-related potential N170 and cognitive function. LimitationThis study solely considered neutral face emotional stimuli and did not account for depressive disorder subtypes. ConclusionDifferences were observed between the MDD and HC groups in cognitive function and N170 amplitude in the central brain region (CZ, PZ, POZ), left posterior temporal region (P7), left occipitotemporal region (PO7), right posterior temporal region (P8), and right occipitotemporal region (PO8). Additionally, a correlation was found between N170 latency in the left posterior temporal region of the brain (P7) and the left occipitotemporal region (PO7) with cognitive function.

Early Visual Deprivation Impairs Functional Development of the Visual Ventral Stream.

To probe the dynamic alternations of neural networks in real-time visual processing after visual deprivation (VD) removal. A prospective cross-sectional study was conducted. Twenty children with a history of early binocular VD caused by congenital cataracts and 20 matched typically developing (TD) children were enrolled. The event-related potential (ERP) data were obtained via high-density electroencephalography. ERP data were analyzed based on three components (P1, N170, and P2), three test conditions (objects, human faces, and Chinese characters), and peak time and region of interest (ROI) chosen on a grand average head map collapsed from the averaged waveform of each group. Source localization and alpha power spectrum density were applied to define the functional pattern of brain areas and evaluate the attention function. The VD group showed significantly lower P1 amplitudes than the TD group under all conditions in peak ROIs, which were situated in the left occipito-temporal region. For both VD and TD groups, there were strong N170 effects in the character and human face conditions in the component's peak ROIs. Furthermore, source mapping indicated that the VD group generally showed significantly lower activation in the visual cortex and ventral stream, whereas the beyond network areas (mostly frontal areas) intensively participated in functional compensation in the VD group. The VD group showed significant poststimulus alpha desynchronization in object recognition. Our research described the mechanisms of visual networks after early binocular VD removal. Our findings may provide a new basis for the poor visual recovery after early binocular VD removal and offer clues for visual recovery strategies.

Relationships between reading performance and regional spontaneous brain activity following surgical removal of primary left-hemisphere tumors: A resting-state fMRI study

Left-hemisphere intraparenchymal primary brain tumor patients are at risk of developing reading difficulties that may be stable, improve or deteriorate after surgery. Previous studies examining language organization in brain tumor patients have provided insights into neural plasticity supporting recovery. Only a single study, however, has examined the role of white matter tracts in preserving reading ability post-surgery and none have examined the functional reading network. The current study aimed to investigate the regional spontaneous brain activity associated with reading performance in a group of 36 adult patients 6–24 months following left-hemisphere tumor resection. Spontaneous brain activity was assessed using resting-state fMRI (rs-fMRI) regional homogeneity (ReHo) and fractional amplitude low frequency fluctuation (fALFF) metrics, which measure local functional connectivity and activity, respectively. ReHo in the left occipito-temporal and right superior parietal regions was negatively correlated with reading performance. fALFF in the putamen bilaterally and the left cerebellum was negatively correlated with reading performance, and positively correlated in the right superior parietal gyrus. These findings are broadly consistent with reading networks reported in healthy participants, indicating that reading ability following brain tumor surgery might not involve substantial functional re-organization.

Reduced pattern similarity in brain activation during orthographic processing in children with developmental dyslexia

Intra-individual variability of neural response has been found to be negatively associated with cognitive proficiency and automaticity. However, whether developmental dyslexia (DD) is marked by greater intra-individual neural variability remains unclear. Using a multivariate approach and dual-control group design, the current study aims to examine whether the pattern similarity of brain activation during a visual spelling task is abnormal in children with DD compared to age control and reading control children. We found that there was reduced intra-subject pattern similarity at the left occipito-temporal regions in children with DD than both control groups, suggesting a neural signature of DD. Furthermore, we found that pattern similarity was positively associated with stability of reaction time and reading fluency in both children with DD and typical control children, suggesting that neural stability supports behavioral stability and automaticity during reading.

Evaluating interhemispheric connectivity during midline object recognition using EEG.

Functional integration between two hemispheres is crucial for perceptual binding to occur when visual stimuli are presented in the midline of the visual field. Mima and colleagues (2001) showed using EEG that midline object recognition was associated with task-related decrease in alpha band power (alpha desynchronisation) and a transient increase in interhemispheric coherence. Our objective in the current study was to replicate the results of Mima et al. and to further evaluate interhemispheric effective connectivity during midline object recognition in source space. We recruited 11 healthy adult volunteers and recorded EEG from 64 channels while they performed a midline object recognition task. Task-related power and coherence were estimated in sensor and source spaces. Further, effective connectivity was evaluated using Granger causality. While we were able to replicate the alpha desynchronisation associated with midline object recognition, we could not replicate the coherence results of Mima et al. The data-driven approach that we employed in our study localised the source of alpha desynchronisation over the left occipito-temporal region. In the alpha band, we further observed significant increase in imaginary part of coherency between bilateral occipito-temporal regions during object recognition. Finally, Granger causality analysis between the left and right occipito-temporal regions provided an insight that even though there is bidirectional interaction, the left occipito-temporal region may be crucial for integrating the information necessary for object recognition. The significance of the current study lies in using high-density EEG and applying more appropriate and robust measures of connectivity as well as statistical analysis to validate and enhance our current knowledge on the neural basis of midline object recognition.

The Functional Neuroanatomy of Reading Intervention.

The present article reviews the literature on the brain mechanisms underlying reading improvements following behavioral intervention for reading disability. This includes evidence of neuroplasticity concerning functional brain activation, brain structure, and brain connectivity related to reading intervention. Consequently, the functional neuroanatomy of reading intervention is compared to the existing literature on neurocognitive models and brain abnormalities associated with reading disability. A particular focus is on the left hemisphere reading network including left occipito-temporal, temporo-parietal, and inferior frontal language regions. In addition, potential normalization/compensation mechanisms involving right hemisphere cortical regions, as well as bilateral sub-cortical and cerebellar regions are taken into account. The comparison of the brain systems associated with reading intervention and the brain systems associated with reading disability enhances our understanding of the neurobiological basis of typical and atypical reading development. All in all, however, there is a lack of sufficient evidence regarding rehabilitative brain mechanisms in reading disability, which we discuss in this review.

The spatiotemporal characteristics of N170s for faces and words: A meta-analysis study.

N170 is a negative event-related potential (ERP) component in response to visual stimuli, such as faces. It remains controversial whether N170 reflects the specific processing of faces or can also be elicited by objects of expertise (e.g., words). In this research, we conducted a meta-analysis for the spatiotemporal characteristics of N170 of face and word stimuli from 24 studies in which both stimuli were presented for each subject. We observed that (1) both face and word stimuli can elicit conspicuous N170s and that there was no difference between the amplitude of face-N170 and word-N170; (2) there is no difference in the latencies between the two N170s; and (3) both N170s are distributed in the occipitotemporal regions but with a reversed hemispheric distribution pattern-face-N170 is more negative in the right than left occipitotemporal regions, while word-N170 is the opposite. These results showed that the face- and word-N170s are qualitatively the same but have different hemispheric lateralization advantages-N170 might be a general neural index of the expertise-dependent object-recognition process in occipitotemporal regions.

Implicit, automatic semantic word categorisation in the left occipito-temporal cortex as revealed by fast periodic visual stimulation

Conceptual knowledge allows the categorisation of items according to their meaning beyond their physical similarities. This ability to respond to different stimuli (e.g., a leek, a cabbage, etc.) based on similar semantic representations (e.g., belonging to the vegetable category) is particularly important for language processing, because word meaning and the stimulus form are unrelated. The neural basis of this core human ability is debated and is complicated by the strong reliance of most neural measures on explicit tasks, involving many non-semantic processes. Here we establish an implicit method, i.e., fast periodic visual stimulation (FPVS) coupled with electroencephalography (EEG), to study neural conceptual categorisation processes with written word stimuli. Fourteen neurotypical participants were presented with different written words belonging to the same semantic category (e.g., different animals) alternating at 4 Hz rate. Words from a different semantic category (e.g., different cities) appeared every 4 stimuli (i.e., at 1 Hz). Following a few minutes of recording, objective electrophysiological responses at 1 Hz, highlighting the human brain's ability to implicitly categorize stimuli belonging to distinct conceptual categories, were found over the left occipito-temporal region. Topographic differences were observed depending on whether the periodic change involved living items, associated with relatively more ventro-temporal activity as compared to non-living items associated with relatively more dorsal posterior activity. Overall, this study demonstrates the validity and high sensitivity of an implicit frequency-tagged marker of word-based semantic memory abilities.

Increased early motivational response to food in adolescent anorexia nervosa revealed by magnetoencephalography.

It remains unclear to what extent reduced nutritional intake in anorexia nervosa (AN) is a consequence of a reduced motivational response to food. Although self-reports typically suggest AN patients have a reduced appetitive response, behavioral and neurophysiological measures have revealed evidence for both increased and reduced attentional biases towards food stimuli. The mechanisms influencing food perception in AN, might be clarified using time-sensitive magnetoencephalography (MEG) to differentiate the early (more automatic processing) stages from the late (more controlled) stages. MEG was recorded in 22 partially weight-restored adolescent AN patients and 29 age- and gender-matched healthy control (HC) participants during a rapid serial visual presentation paradigm using 100 high-calorie food, 100 low-calorie food, and 100 non-food pictures. Neural sources of event-related fields were estimated using the L2-Minimum-Norm method and analyzed in early (50-300 ms) and late (350-500 ms) time intervals. AN patients rated high-calorie food as less palatable and reported overall less food craving than HC participants. Nevertheless, in response to food pictures AN patients showed relative increased neural activity in the left occipito-temporal and inferior frontal regions in the early time interval. No group differences occurred in the late time interval. MEG results speak against an overall reduced motivational response to food in AN. Instead, relative increased early food processing in the visual cortex suggests greater motivated attention. A greater appetitive response to food might be an adaptive mechanism in a state of undernourishment. Yet, this relative increased food processing in AN was no longer present later, arguably reflecting rapid downregulation.

Recent update on reading disability (dyslexia) focused on neurobiology.

Reading disability (dyslexia) refers to an unexpected difficulty with reading for an individual who has the intelligence to be a much better reader. Dyslexia is most commonly caused by a difficulty in phonological processing (the appreciation of the individual sounds of spoken language), which affects the ability of an individual to speak, read, and spell. In this paper, I describe reading disabilities by focusing on their underlying neurobiological mechanisms. Neurobiological studies using functional brain imaging have uncovered the reading pathways, brain regions involved in reading, and neurobiological abnormalities of dyslexia. The reading pathway is in the order of visual analysis, letter recognition, word recognition, meaning (semantics), phonological processing, and speech production. According to functional neuroimaging studies, the important areas of the brain related to reading include the inferior frontal cortex (Broca’s area), the midtemporal lobe region, the inferior parieto-temporal area, and the left occipitotemporal region (visual word form area). Interventions for dyslexia can affect reading ability by causing changes in brain function and structure. An accurate diagnosis and timely specialized intervention are important in children with dyslexia. In cases in which national infant development screening tests have been conducted, as in Korea, if language developmental delay and early predictors of dyslexia are detected, careful observation of the progression to dyslexia and early intervention should be made.

Distinct neural substrates of individual differences in components of reading comprehension in adults with or without dyslexia

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the Simple View framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia.

Differential activation of the visual word form area during auditory phoneme perception in youth with dyslexia

Developmental dyslexia is a learning disorder characterized by difficulties reading words accurately and/or fluently. Several behavioral studies have suggested the presence of anomalies at an early stage of phoneme processing, when the complex spectrotemporal patterns in the speech signal are analyzed and assigned to phonemic categories. In this study, fMRI was used to compare brain responses associated with categorical discrimination of speech syllables (P) and acoustically matched nonphonemic stimuli (N) in children and adolescents with dyslexia and in typically developing (TD) controls, aged 8–17 years. The TD group showed significantly greater activation during the P condition relative to N in an area of the left ventral occipitotemporal cortex that corresponds well with the region referred to as the “visual word form area” (VWFA). Regression analyses using reading performance as a continuous variable across the full group of participants yielded similar results. Overall, the findings are consistent with those of previous neuroimaging studies using print stimuli in individuals with dyslexia that found reduced activation in left occipitotemporal regions; however, the current study shows that these activation differences seen during reading are apparent during auditory phoneme discrimination in youth with dyslexia, suggesting that the primary deficit in at least a subset of children may lie early in the speech processing stream and that categorical perception may be an important target of early intervention in children at risk for dyslexia.

The Effective Brain Areas in Recognition of Dyslexia

Background: The brain has four lobes consist of frontal, parietal, occipital, and temporal. Most researchers have reported that the left occipitotemporal region of the brain, which is the combined region of the occipital and temporal lobes, is less active in children with dyslexia like Sklar, Glaburda, Ashkenazi and Leisman. Methods: There are different methods and tools to investigate how the brain works, such as magnetic resonance imaging (MRI), positron emission tomography (PET), magneto-encephalography (MEG) and electroencephalography (EEG). Among these, EEG determines the electrical activity of the brain with the electrodes placed on the special areas on the scalp. In this research, we processed the EEG signals of dyslexic children and healthy ones to determine what the areas of the brain are most likely to cause the disease. Results: For this purpose, we extracted 43 features, including relative spectral power (RSP) features, mean, standard deviation, skewness, kurtosis, Hjorth, and AR parameters. Then an SVM classifier is used to separate two classes. Finally, we show the particular brain activation pattern by calculating the correlation coefficients and co-occurrence matrices, which suggests the activation of the working memory region as an active area. Conclusion: By identifying the brain areas involved in reading activity, it has expected that psychologists and physicians will be able to design the therapeutic exercises to activate this part of the brain.

Left-Hemispheric Asymmetry for Object-Based Attention: an ERP Study.

It has been shown that selective attention enhances the activity in visual regions associated with stimulus processing. The left hemisphere seems to have a prominent role when non-spatial attention is directed towards specific stimulus features (e.g., color, spatial frequency). The present electrophysiological study investigated the time course and neural correlates of object-based attention, under the assumption of left-hemispheric asymmetry. Twenty-nine right-handed participants were presented with 3D graphic images representing the shapes of different object categories (wooden dummies, chairs, structures of cubes) which lacked detail. They were instructed to press a button in response to a target stimulus indicated at the beginning of each run. The perception of non-target stimuli elicited a larger anterior N2 component, which was likely associated with motor inhibition. Conversely, target selection resulted in an enhanced selection negativity (SN) response lateralized over the left occipito-temporal regions, followed by a larger centro-parietal P300 response. These potentials were interpreted as indexing attentional selection and categorization processes, respectively. The standardized weighted low-resolution electromagnetic tomography (swLORETA) source reconstruction showed the engagement of a fronto-temporo-limbic network underlying object-based visual attention. Overall, the SN scalp distribution and relative neural generators hinted at a left-hemispheric advantage for non-spatial object-based visual attention.

A mesial-to-lateral dissociation for orthographic processing in the visual cortex

Efficient reading requires a fast conversion of the written word to both phonological and semantic codes. We tested the hypothesis that, within the left occipitotemporal cortical regions involved in visual word recognition, distinct subregions harbor slightly different orthographic codes adapted to those 2 functions. While the lexico-semantic pathway may operate on letter or open-bigram information, the phonological pathway requires the identification of multiletter graphemes such as "ch" or "ou" in order to map them onto phonemes. To evaluate the existence of a specific stage of graphemic encoding, 20 adults performed lexical decision and naming tasks on words and pseudowords during functional MRI. Graphemic encoding was facilitated or disrupted by coloring and spacing the letters either congruently with multiletter graphemes (ch-ai-r) or incongruently with them (c-ha-ir). This manipulation affected behavior, primarily during the naming of pseudowords, and modulated brain activity in the left midfusiform sulcus, at a site medial to the classical visual word form area (VWFA). This putative grapheme-related area (GRA) differed from the VWFA in being preferentially connected functionally to dorsal parietal areas involved in letter-by-letter reading, while the VWFA showed effects of lexicality and spelling-to-sound regularity. Our results suggest a partial dissociation within left occipitotemporal cortex: the midfusiform GRA would encode orthographic information at a sublexical graphemic level, while the lateral occipitotemporal VWFA would contribute primarily to direct lexico-semantic access.

The neural correlates of word position and lexical predictability during sentence reading: evidence from fixation-related fMRI

ABSTRACTBy means of combining eye-tracking and fMRI, the present study aimed to investigate aspects of higher linguistic processing during natural reading which were formerly hard to assess with traditional paradigms. Specifically, we investigated the haemodynamic effects of incremental sentence comprehension – as operationalised by word position – and its relation to context-based word-level effects of lexical predictability. We observed that an increasing amount of words being processed was associated with an increase in activation in the left posterior middle temporal and angular gyri. At the same time, left occipito-temporal regions showed a decrease in activation with increasing word position. Region of interest (ROI) analyses revealed differential effects of word position and predictability within dissociable parts of the semantic network – showing that it is expedient to consider these effects conjointly.

Measuring face-name integration with fast periodic visual stimulation

Associating specific names to faces of familiar identity is crucial for social interactions. This is a difficult process, which can be severely disrupted in neurodegenerative disorders such as Alzheimer's disease or temporal epilepsy. An outstanding issue is whether face and name representations are kept separated in the human brain and associated through re-entrant interactions, or if they are integrated into common representation at higher stages. Here we addressed this issue with fast periodic stimulation in EEG. Healthy subjects (n=12) were exposed to randomly alternating face photographs and written names of a famous identity (base stimuli) at a fast rate (3.999 Hz, about 4 images per second) while recording their brain activity with high density (128 channels) scalp EEG. A change in identity (either presented as a face or a name) occurred every seven stimuli (i.e., 0.5713 Hz; oddball stimuli). Following a few minutes of recordings, there were significant electrophysiological responses at the frequency of a face identity change (i.e., 0.5713 and harmonics), suggesting integrated representations of faces and names. Experiment 2 (n=20) replicated these findings and added two control conditions: A face only condition in which the specific identity names presented at the base rate were replaced by other famous names, and a name only condition which followed the same principle for names. There were much weaker amplitudes at the periodic change of identity in control conditions. Most importantly, the sum of the two control conditions' activation was weaker than the effect found in the main condition, in particular over the left medial occipital region and extending to the posterior part of the left occipito-temporal region. Overall, these observations provide evidence for integrated face/name representations in the human brain, with a left occipito-temporal locus.

The relationship between CSF biomarkers and cerebral metabolism in early-onset Alzheimer's disease.

One can reasonably suppose that cerebrospinal spinal fluid (CSF) biomarkers can identify distinct subgroups of Alzheimer's disease (AD) patients. In order to better understand differences in CSF biomarker patterns, we used FDG PET to assess cerebral metabolism in CSF-based subgroups of AD patients. Eighty-five patients fulfilling the criteria for probable early-onset AD (EOAD) underwent lumbar puncture, brain 18F-FDG PET and MRI. A cluster analysis was performed, with the CSF biomarkers for AD as variables. Vertex-wise, partial-volume-corrected metabolic maps were computed for the patients and compared between the clusters of patients. Linear correlations between each CSF biomarker and the metabolic maps were assessed. Three clusters emerged. The "Aβ42" cluster contained 32 patients with low levels of Aβ42, while tau and p-tau remained within the normal range. The "Aβ42 + tau" cluster contained 41 patients with low levels of Aβ42 and high levels of tau and p-tau. Lastly, the "tau" cluster contained 12 patients with very high levels of tau and p-tau and low-normal levels of Aβ42. There were no inter-cluster differences in age, sex ratio, educational level, APOE genotype, disease duration or disease severity. The "Aβ42 + tau" and "tau" clusters displayed more marked frontal hypometabolism than the "Aβ42" cluster did, and frontal metabolism was significantly negatively correlated with the CSF tau level. The "Aβ42" and "Aβ42 + tau" clusters displayed more marked hypometabolism in the left occipitotemporal region than the "tau" cluster did, and metabolism in this region was significantly and positively correlated with the CSF Aβ42 level. The CSF biomarkers can be used to identify metabolically distinct subgroups of patients with EOAD. Future research should seek to establish whether these biochemical differences have clinical consequences.