Left Hemisphere Lateralization Research Articles

Hemispheric dominance in reading system alters contribution to face processing lateralization across development

Face processing dominates the right hemisphere. This lateralization can be affected by co-lateralization within the same system and influence between different systems, such as neural competition from reading acquisition. Yet, how the relationship pattern changes through development remains unknown. This study examined the lateralization of core face processing and word processing in different age groups. By comparing fMRI data from 36 school-aged children and 40 young adults, we investigated whether there are age and regional effects on lateralization, and how relationships between lateralization within and between systems change across development. Our results showed significant right hemispheric lateralization in the core face system and left hemispheric lateralization in reading-related areas for both age groups when viewing faces and texts passively. While all participants showed stronger lateralization in brain regions of higher functional hierarchy when viewing faces, only adults exhibited this lateralization when viewing texts. In both age cohorts, there was intra-system co-lateralization for face processing, whereas an inter-system relationship was only found in adults. Specifically, functional lateralization of Broca’s area during reading negatively predicted functional asymmetry in the FFA during face perception. This study initially provides neuroimaging evidence for the reading-induced neural competition theory from a maturational perspective in Chinese cohorts.

Precision fMRI reveals that the language network exhibits adult-like left-hemispheric lateralization by 4 years of age.

Language is the most canonical function that shows a strong hemispheric asymmetry in adult brains. However, whether the language system is already lateralized to the left hemisphere early in development has long been debated, given that early left-hemisphere damage often leaves language processing unimpaired. We examined the developmental trajectory of language lateralization in two large-scale pediatric datasets using robust individual-subject fMRI approaches. We found that the language system exhibits adult-like left-hemispheric lateralization by age 4, although other aspects of the neural infrastructure for language show a clear change between age 4 and late childhood. These findings challengethe claim that the language system is bilateral during early development and call for alternative accounts of early hemispheric equipotentiality for language.

RETRACTED: Left hemisphere lateralization of the limbic system and frontoparietal network (FPN) correlates with positive and negative symptom improvement following cannabidiol (CBD) administration in psychosis and ultra-high risk (UHR) populations: A voxel-wise meta-analysis

This voxel-wise meta-analysis assesses current findings about the neural correlates of cannabidiol on the positive and negative symptoms among individuals with psychosis or ultra-high risk (UHR) for psychosis. We used PubMed, EMBASE, and ScienceDirect as primary databases and initially retrieved 157 studies. After applying our eligibility criteria, 13 studies remained for inclusion. Ten studies focused on psychosis. Three studies focused on UHR. Quality assessment was performed for included articles using the RoB2 instrument. Statistical analysis implicated a voxel-wise meta-analysis of different task paradigms (emotion recognition, verbal memory recall, and inhibitory control) with a jackknife sensitivity measure, Egger's test of random effects, and a meta-regression with relevant covariates. Article quality was determined to be primarily low risk of bias, with some elements of unclear bias figuring across studies. Our results showed robust, convergent correlations between CBD administration and left hemisphere lateralization of limbic system and frontoparietal network (FPN) subregions across task paradigms in psychosis and UHR populations. Our meta-regression revealed that decreased limbic system activity correlated with positive symptom improvements, and decreased FPN activity correlated with negative symptom improvements. Lastly, sensitivity analyses determined that there was minimal risk bias or risk of confounding variables unduly influencing our meta-analyses (p > 0.05).

Effect of γ-tACS on prefrontal hemodynamics in bipolar disorder: A functional near-infrared study

ObjectivesTranscranial alternating current stimulation (tACS) is a potential therapeutic psychiatric tool that has been shown to modulate clinical symptoms and brain function by inducing brain oscillations. However, direct evidence on the effects of gamma-tACS (γ-tACS) on Bipolar I Disorder (BD-I) is limited. In the present study we used functional near-infrared spectroscopy to explore prefrontal hemodynamic changes in BD-I patients receiving combined γ-tACS intervention in addition to pharmacological treatment. MethodsOnly 39 male patients with BD-I in the acute manic phase were included, and they were randomly divided into an intervention group (n = 18) and a control group (n = 21). The intervention group received γ-tACS treatment on a weekday for a total of 10 sessions in the right prefrontal cortex and left prefrontal cortex. All participants were pretested (baseline) and posttested (2 weeks after) with questionnaires to assess clinical symptoms and cognitive abilities, and with functional near infrared spectroscopy (fNIRS) to assess spontaneous cortical hemodynamic activities. ResultsCompared to the control group, the intervention group had greater increases in Montreal Cognitive Assessment (MoCA) scores, and greater decreases in Bech-Rafaelsen Mania Rating Scale (BRMS) scores. In the intervention group, functional connectivity (FC) was significantly greater in the left hemisphere. γ-tACS treatment resulted in a left hemispheric lateralization effect of resting state FC in BD-I patients, increasing the hemodynamic activity of the patient's left prefrontal cortex. Conclusionsγ-tACS can improve cognitive impairment and mood symptoms with BD-I patients in an acute manic episode by enhancing FC in the patients' left prefrontal cortex.

Indirect Exposure to Atrocities and Post-Traumatic Stress Disorder Symptoms among Aid Workers: Hemispheric Lateralization Matters.

Background: Humanitarian aid workers (HAWs) are indirectly exposed to atrocities relating to people of concern (POC). This may result in a risk of secondary traumatization demonstrated by post-traumatic stress symptoms (PTSSs). Previous studies have demonstrated that hemispheric lateralization (HL) moderates the relationship between threat exposure and post-traumatic stress symptoms (PTSSs). Aims: We hypothesized that indirect exposure to atrocities (IETA) would be positively correlated with PTSSs among HAWs with right and not left HL. Method: Fifty-four HAWs from several countries that provided humanitarian support in Greece and Colombia participated in this correlational and cross-sectional observation study. They completed scales relating to IETA, PTSSs were assessed using a brief, valid scale, and HL was measured. Results: IETA was positively and significantly related to PTSSs (r = 0.39, p < 0.005). Considering HL, IETA was unrelated to PTSSs among people with right HL (r = 0.29, p = 0.14), while IETA was related to PTSSs among people with left HL (r = 0.52, p = 0.008). Right HL emerged as a protective factor in the relationship between IETA and PTSS. Conclusions: An assessment of dominant HL can serve as one consideration among others when deploying HAWs in specific locations and roles, vis à vis IETA. Moreover, those found to have a higher risk for PTSSs based on their HL could be monitored more closely to prevent adverse reactions to IETA.

Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression.

Frontal alpha asymmetry (FAA) is an electroencephalography (EEG) measure that quantifies trait-like left versus right hemisphere lateralization in alpha power. Increased FAA indicates relatively greater left than right frontal cortex activation and is associated with enhanced reward-related approach behaviors rather than avoidance or withdrawal. Studies dating back several decades have often suggested that having greater FAA supports enhanced positive affect and protection against major depressive disorder (MDD), whereas having greater right frontal activation (i.e., reduced FAA) is associated with negative affect and risk for MDD. While this hypothesis is widely known, a number of other studies instead have found increased FAA in MDD, or evidence that either leftward or rightward bias in FAA is associated with depression. Here we briefly review the literature on leftward or rightward lateralization in FAA in MDD, and find much evidence that MDD is not always characterized by reduced FAA. We also review the limited literature on FAA and monoaminergic neurotransmitter systems, including pharmacologic agents that act on them. Studies of serotonin in particular provide genetic and pharmacologic evidence for modulation of FAA, where some of these data may suggest that serotonin reduces FAA. In a synthesis of the collective literature on FAA and the monoamines, we suggest that serotonin and norepinephrine may differentially affect FAA, with serotonin tending to promote right frontal activation and norepinephrine biased toward left frontal activation. These putative differences in frontal lateralization may influence MDD phenotypes or potential subtypes of the disorder, and suggest pharmacologic treatment strategies.

Effects of different frequencies music on cortical responses and functional connectivity in patients with minimal conscious state.

The objective of this study was to investigate brain activation and functional network patterns during musical interventions in different frequency bands using functional near-infrared spectroscopy, and to provide a basis for more effective music therapy strategy selection for patients in minimally conscious state (MCS). Twenty six MCS patients and 20 healthy people were given music intervention with low frequency (31-180 Hz), medium frequency (180-4k Hz), and high frequency (4k-22k Hz) audio. In MCS patients, low frequency music intervention induced activation of left prefrontal cortex and left primary sensory cortex (S1), also a left-hemisphere lateralization effect of dorsolateral prefrontal cortex (DLPFC). And the functional connectivity of right DLPFC-right S1 was significantly improved by high frequency music intervention. The low frequency and high frequency music may contribute more than medium frequency music to the recovery of consciousness. This study also validated the effectiveness of fNIRS in studies of brain function in MCS patients.

Left-dominance for resting-state temporal low-gamma power in children with impaired word-decoding and without comorbid ADHD.

One theory of the origins of reading disorders (i.e., dyslexia) is a language network which cannot effectively 'entrain' to speech, with cascading effects on the development of phonological skills. Low-gamma (low-γ, 30-45 Hz) neural activity, particularly in the left hemisphere, is thought to correspond to tracking at phonemic rates in speech. The main goals of the current study were to investigate temporal low-γ band-power during rest in a sample of children and adolescents with and without reading disorder (RD). Using a Bayesian statistical approach to analyze the power spectral density of EEG data, we examined whether (1) resting-state temporal low-γ power was attenuated in the left temporal region in RD; (2) low-γ power covaried with individual reading performance; (3) low-γ temporal lateralization was atypical in RD. Contrary to our expectations, results did not support the hypothesized effects of RD status and poor decoding ability on left hemisphere low-γ power or lateralization: post-hoc tests revealed that the lack of atypicality in the RD group was not due to the inclusion of those with comorbid attentional deficits. However, post-hoc tests also revealed a specific left-dominance for low-γ rhythms in children with reading deficits only, when participants with comorbid attentional deficits were excluded. We also observed an inverse relationship between decoding and left-lateralization in the controls, such that those with better decoding skills were less likely to show left-lateralization. We discuss these unexpected findings in the context of prior theoretical frameworks on temporal sampling. These results may reflect the importance of real-time language processing to evoke gamma rhythms in the phonemic range during childhood and adolescence.

Interdependency in lateralization of written word and face processing in right-handed individuals

It has been suggested that the right hemisphere lateralization typically observed for face processing may depend on lateralization of written word processing to the left hemisphere; a pattern referred to as the causal complementary principle of lateralization. According to a strong version of this principle, a correlation should be found between the degree of left and right hemisphere lateralization for word and face processing respectively. This has been observed in two studies, but only for left-handed individuals. The present study tested whether a similar lateralization pattern could be found in a relatively large sample of right-handed individuals (N = 210) using behavioral measures (divided visual field paradigms). It was also tested whether the degree of right hemisphere lateralization for face and global shape processing would correlate positively, as predicted by a strong version of the input asymmetry principle of lateralization. This was tested in a subsample (n = 189). Bayesian analyses found no evidence for lateralization interdependency as the observed data were 4–17 times more likely under the null hypothesis. Unfortunately, the reliabilities of the lateralization measures were found to be poor. While this dampens the firmness of the conclusions that can be drawn, it is argued that at present there is no positive evidence for strong interdependency between written word and face processing in right-handed individuals.

The efficiency of using the “Stupalka-LOGOS” simulator in improving the psycho-speech development of preschool children

The article presented the authors’ simulator "Stupalki-LOGOS" (authors: M. M. Yefymenko, M. D. Moga) and considered the possibilities of its use in improving (correcting) the psycho-speech development of preschoolers with general underdevelopment of speech. The design of the simulator and the purpose of its three removable parts (handgrip handle, base platform, supporting surface of the simulator) are described. A brief classification of the main types of children’s hand disorders (hypotonic, hypertonic, dystonic, asymmetric) is made, and an algorithm for overcoming hand disorders according to each of the listed types is given. The main power hand functions that can be formed with the help of the Stupalki-LOGOS simulator (grab, supports, springs, rolling, balancing, stepping, etc.) are listed. The special role of the two-handed coordination function, which is formed due to this simulator, is emphasized. The cross-coordination of the upper and lower (when crawling) limbs forms the internal hemispheric neural networks necessary for brain activity for further left-hemisphere lateralization of the brain. The practical aspect of the research is presented in the article with sets of special exercises on the Stupalki-LOGOS simulator to improve the motor and psycho-speech development of preschoolers with general speech underdevelopment. The performed pedagogical observations proved that the "Stupalki-LOGOS" simulator improves the indicators of psycho-speech development: two-handed coordination improved, the basic power functions of the hand were formed (capture, supports, springs, rolling, stepping, pushing away), the state of mental well-being improved, as well as certain indicators of speech development (articulatory motor skills, phonetics, vocabulary).

Studying hemispheric lateralization of 4-month-old infants from different language groups through near-infrared spectroscopy-based connectivity.

Early monolingual versus bilingual experience affects linguistic and cognitive processes during the first months of life, as well as functional activation patterns. The previous study explored the influence of a bilingual environment in the first months of life on resting-state functional connectivity and reported no significant difference between language groups. To further explore the influence of a bilingual environment on brain development function, we used the resting-state functional near-infrared spectroscopy public dataset of the 4-month-old infant group in the sleep state (30 Spanish; 33 Basque; 36 bilingual). Wavelet Transform Coherence, graph theory, and Granger causality methods were performed on the functional connectivity of the frontal lobes. The results showed that functional connectivity strength was significantly higher in the left hemisphere than that in the right hemisphere in both monolingual and bilingual groups. The graph theoretic analysis showed that the characteristic path length was significantly higher in the left hemisphere than in the right hemisphere for the bilingual infant group. Contrary to the monolingual infant group, the left-to-right direction of information flow was found in the frontal regions of the bilingual infant group in the effective connectivity analysis. The results suggested that the left hemispheric lateralization of functional connectivity in frontal regions is more pronounced in the bilingual group compared to the monolingual group. Furthermore, effective connectivity analysis may be a useful method to investigate the resting-state brain networks of infants.

Hand Preference in Children’s Referential Gestures During Storytelling: Testing for Effects of Bilingualism, Language Ability, Age, and Sex

Adults, preschool children, and infants gesture more with their right hand than with their left hand. Since gestures and speech are related in production, it is possible that this right-hand preference reflects left-hemisphere lateralization for gestures and speech. The primary purpose of the present study was to test if children between the ages of 6 and 10 years show a right-hand preference in referential gestures while telling a story. We also tested four predictors of children’s degree of right-hand preference: 1) bilingualism, 2) language proficiency, 3) age, and 4) sex. Previous studies have shown that these variables are related to the degree of speech lateralization. Twenty-five English monolingual (17 girls; Mage = 8.0, SDage = 1.4), 21 French monolingual (12 girls; Mage = 7.3, SDage = 1.4,) and 25 French-English bilingual (11 girls; Mage = 8.5, SDage = 1.4) children watched a cartoon and told the story back. The bilinguals did this once in each language. The referential gestures were coded for handedness. Most of the participants showed a right-hand preference for gesturing. In English, none of the predictor variables was clearly related to right-hand preference. In French, the monolinguals showed a stronger right-hand preference than the bilinguals. These inconsistent findings across languages raise doubts as to whether the right-hand preference is linked to lateralization for speech.

Effective connectivity of the left-ventral occipito-temporal cortex during visual word processing: Direct causal evidence from TMS-EEG co-registration

As an interface between the visual and language system, the left ventral occipito-temporal cortex (left-vOT) plays a key role in reading. This functional role is supported by anatomical and functional connections between the area and other brain regions within and outside the language network. Nevertheless, only a few studies have investigated how the functional state of this area, which is dependent upon the nature of the task demand and the stimulus being processed, could influence the activity of the connected brain regions. In the present combined TMS-EEG study, we studied the left-vOT effective connectivity by adopting a direct, causal intervention approach. Using TMS, we probed left-vOT activation in different processing contexts and measured the neural propagation of activity from this area to other brain regions. A comparison of neural propagation measured during low-level visual detection of language versus non-language stimuli showed that processing language stimuli reduced neural propagation from the left-vOT to the right occipital cortex. Additionally, compared to the low-level visual detection of language stimuli, performing semantic judgments on the same stimuli further reduced neural propagation to the posterior part of the corpus callosum, right superior parietal lobule and the right anterior temporal lobe. This reduction of cross-hemispheric neural propagation was accompanied by an increase in the collaboration between areas within the left-hemisphere language network. Together, this first evidence from a direct causal intervention approach suggests that processing language stimuli and performing a high-level language task reduce effective connectivity from the left-vOT to the right hemisphere, and may contribute to the left-hemisphere lateralization typically observed during language processing.

Cognitive, academic, executive and psychological functioning in children with spastic motor type cerebral palsy: Influence of extent, location, and laterality of brain lesions.

To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions. The semi-quantitative scale for MRI (sqMRI) was scored for 101 children with cerebral palsy. Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling, numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores' laterality index. Verbal-related outcomes were compared between participants with left-sided versus bilateral brain lesions. Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables. The laterality of early-life lesions influences the development of verbal-related cognitive functions.

Interhemispheric functional brain connectivity predicts new language learning success in adults.

Investigating interhemispheric interactions between homologous cortical regions during language processing is of interest. Despite prevalent left hemisphere lateralization of language, the right hemisphere also plays an important role and interhemispheric connectivity is influenced by language experience and is implicated in second language (L2) acquisition. Regions involved in language processing have differential connectivity to other cortical regions and to each other, and play specific roles in language. We examined the interhemispheric interactions of subregions of the inferior frontal gyrus (areas 44 and 45), the adjacent area 9/46v in the middle frontal gyrus, the superior temporal gyrus (STG), and the posterior inferior parietal lobule (pIPL) in relation to distinct and specific aspects of L2 learning success. The results indicated that the connectivity between left and right areas 44 and 9/46v predicted improvement in sentence repetition, connectivity between left and right area 45 and mid-STG predicted improvement in auditory comprehension, and connectivity between left and right pIPL predicted improvement in reading speed. We show interhemispheric interactions in the specific context of facilitating performance in adult L2 acquisition that follow an anterior to posterior gradient in the brain, and are consistent with the respective roles of these regions in language processing.

HEMISPHERE LATERALIZATION IN PATIENTS WITH CHRONIC VENOUS CEREBRAL DYSFUNCTION SYNDROME AND EMOTIONAL-VOLUNTARY DISORDERS.

Relevance: The problem of treatment of cerebrovascular diseases is one of the leading in modern medicine. The combination of this nosology in patients with emotional and volitional disorders acquires a special shade. Features of neurochemical transmission of impulses in different hemispheres of the brain provide greater opportunities for improving the treatment of patients with chronic cerebral venous dysfunction syndrome (SCVD).&#x0D; Objective: To study the features of hemispheric lateralization of the brain in patients with SCVD and indicators of anxiety on the Spielberger-Khanin scale and depression on the Beck scale. Materials and methods: 153 patients tested on the scale of reactive (RT) and personal (LT) anxiety Spielberger-YL Khanin and Beck depression. 125 people with signs of SCCVD and various levels of BP. Mean age of patients: 53.60 ± 10.27 years, 115 women, 38 men. All underwent clinical and neurological examination, testing to determine hemispheric dominance on the scale of NP Rebrova and MP Chernysheva. Statistics were calculated using the Medstat program. The comparison was performed according to the criterion of W. Kruskal-A. Wallis, the criterion of J. Dunn and the chi-square. Results: It was found that the presence of SCCVD did not depend on hemispheric dominance. In patients with SCVD with left hemisphere lateralization, there was a statistically significant increase in personal anxiety on the Spielberger-Khanin scale (p&lt;0.001). The patients with SCVD and right-hemispheric lateralization had a statistically significant increase in depression on the Beck scale (p &lt;0.001). Patients of the control group did not show a statistically significant relationship between the types of hemispheric dominance and indicators of personal anxiety and depression.

Magic Hats and Teddy Bear picnics: Language and visuospatial lateralisation tasks for children

ABSTRACT The behavioural outcomes associated with atypical cerebral lateralization during the early stages of cognitive development is an interesting research venture. However, there are few tasks for assessing lateralization in young children. The current study describes the Magic Hat task and the Teddy Bear Picnic task, which were designed to measure the lateralization of language and visuospatial attention, respectively, in children as young as three years old. Forty-five adults were recruited to complete the child-friendly tasks as well as the Word Generation and Landmark tasks whilst functional Transcranial Doppler ultrasound (fTCD) measured cerebral blood flow velocity. As expected, at the group level, the Magic Hat task produced left hemisphere lateralization, and the Teddy Bear Picnic task produced right hemisphere lateralization. Both tasks demonstrated high internal reliability (α > .80). The laterality indices produced by the Magic Hat task correlated with the Word Generation task, ρ = .52, p = .001. Likewise, the laterality indices produced by the Teddy Bear Picnic task correlated with the Landmark task, ρ = .45, p = .028. Thus, the Magic Hat and Teddy Bear Picnic tasks are reliable and valid measures of language and visuospatial lateralization, suitable for toddlers and young children using fTCD.

Structural language impairment in Autism Spectrum Disorder versus Loss of Autism Diagnosis: Behavioral and neural characteristics

This study probed for structural language impairment using behavioral and functional neuroimaging methods in individuals with Autism Spectrum Disorder (ASD) and those diagnosed with ASD in childhood who no longer meet criteria for ASD, referred to as Loss of Autism Diagnosis (LAD1). Participants were drawn from Fein et al. (2013): ASD (n = 35), LAD (n = 31), and Neurotypical (NT; n = 34). Criteria for structural language impairment were: Scores ≤ 82 on Clinical Evaluation of Language Fundamentals-4 (CELF) Core Language, an omnibus measure of language; and scores ≤ 7 on CELF Recalling Sentences, a clinical marker of structural language impairment. Task-based fMRI examined lateralization of significantly activated language-related brain regions in groups with structural language impairment (LI2) versus normal-range language (LN3), collapsed across ASD, LAD1, and NT status. Results showed no ASD versus LAD group differences in the proportion of participants with structural language impairment according to either metric (Recalling Sentences or Core Language). Functional MRI results indicated greater left hemisphere lateralization within significantly activated regions in the LI2 group. Structural language abilities were not meaningfully associated with either social abilities or lifetime ADHD symptoms in LI2 subgroups, further suggesting the presence of structural language impairment. Findings indicate the presence of persistent structural language difficulty even in the absence of ASD symptoms in some individuals within the LAD1 group and unique patterns of language-related neural specialization for language function in LI2 relative to LN3.

Activating the Right Hemisphere Through Left-Hand Muscle Contraction Improves Novel Metaphor Comprehension.

The neurotypical brain is characterized by left hemisphere lateralization for most language processing. However, the right hemisphere plays a crucial part when it is required to bring together seemingly unrelated concepts into meaningful expressions, such as in the case of novel metaphors (unfamiliar figurative expressions). The aim of the current study was to test whether it is possible to enhance novel metaphor comprehension through an easy, efficient, and non-invasive method – intentional contraction of the left hand’s muscles, to activate the motor and sensory areas in the contralateral hemisphere. One hundred eighteen neurotypical participants were asked to perform a semantic judgment task involving two-word expressions of four types: literal, conventional metaphors, novel metaphors, or unrelated, while squeezing a rubber ball with their right hand, left hand, or not at all. Results demonstrated that left-hand contraction improved novel metaphor comprehension, as participants were more accurate and quicker in judging them to be meaningful. The findings of the present work provide a simple and efficient method for boosting right hemisphere activation, which can be used to improve metaphoric language comprehension. This method can aid several populations in which right hemisphere function is not fully established, and who struggle with processing figurative language, such as adolescents and individuals on the autistic spectrum.

Posterior cortical atrophy phenotypic heterogeneity revealed by decoding 18F-FDG-PET.

Posterior cortical atrophy is a neurodegenerative syndrome with a heterogeneous clinical presentation due to variable involvement of the left, right, dorsal and ventral parts of the visual system, as well as inconsistent involvement of other cognitive domains and systems. 18F-fluorodeoxyglucose (FDG)-PET is a sensitive marker for regional brain damage or dysfunction, capable of capturing the pattern of neurodegeneration at the single-participant level. We aimed to leverage these inter-individual differences on FDG-PET imaging to better understand the associations of heterogeneity of posterior cortical atrophy. We identified 91 posterior cortical atrophy participants with FDG-PET data and abstracted demographic, neurologic, neuropsychological and Alzheimer’s disease biomarker data. The mean age at reported symptom onset was 59.3 (range: 45–72 years old), with an average disease duration of 4.2 years prior to FDG-PET scan, and a mean education of 15.0 years. Females were more common than males at 1.6:1. After standard preprocessing steps, the FDG-PET scans for the cohort were entered into an unsupervised machine learning algorithm which first creates a high-dimensional space of inter-individual covariance before performing an eigen-decomposition to arrive at a low-dimensional representation. Participant values (‘eigenbrains’ or latent vectors which represent principle axes of inter-individual variation) were then compared to the clinical and biomarker data. Eight eigenbrains explained over 50% of the inter-individual differences in FDG-PET uptake with left (eigenbrain 1) and right (eigenbrain 2) hemispheric lateralization representing 24% of the variance. Furthermore, eigenbrain-loads mapped onto clinical and neuropsychological data (i.e. aphasia, apraxia and global cognition were associated with the left hemispheric eigenbrain 1 and environmental agnosia and apperceptive prosopagnosia were associated with the right hemispheric eigenbrain 2), suggesting that they captured important axes of normal and abnormal brain function. We used NeuroSynth to characterize the eigenbrains through topic-based decoding, which supported the idea that the eigenbrains map onto a diverse set of cognitive functions. These eigenbrains captured important biological and pathophysiologic data (i.e. limbic predominant eigenbrain 4 patterns being associated with older age of onset compared to frontoparietal eigenbrain 7 patterns being associated with younger age of onset), suggesting that approaches that focus on inter-individual differences may be important to better understand the variability observed within a neurodegenerative syndrome like posterior cortical atrophy.