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Abstract Background Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. Methods We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. Results First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. Limitations We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. Conclusions Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

Abstract Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network – an early-emerging neural network involved in orienting attention to the most salient aspects of one’s internal and external environment – may predict the development of ASD symptoms such as reduced social attention and atypical sensory processing. Six-week-old infants at high likelihood of developing ASD based on family history exhibited stronger Salience Network connectivity with sensorimotor regions; infants at typical likelihood of developing ASD demonstrated stronger Salience Network connectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct tradeoff between attention to basic sensory versus socially-relevant information. Early alterations in Salience Network connectivity predicted subsequent ASD symptomatology, providing a plausible mechanistic account for the unfolding of atypical developmental trajectories associated with vulnerability to ASD.

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. Methods: We studied healthy older adult participants (N = 21, ages 48–79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Abstract Background Sensory over-responsivity (SOR) is an impairing sensory processing challenge in autism spectrum disorder (ASD) which shows heterogenous developmental trajectories and appears to improve into adulthood in some but not all autistic individuals. However, the neural mechanisms underlying interindividual differences in these trajectories are currently unknown. Methods Here, we used functional magnetic resonance imaging (fMRI) to investigate the association between age and neural activity linearly and nonlinearly in response to mildly aversive sensory stimulation as well as how SOR severity moderates this association. Participants included 52 ASD (14F) and 41 (13F) typically developing (TD) youth, aged 8.6–18.0 years. Results We found that in pre-teens, ASD children showed widespread activation differences in sensorimotor, frontal and cerebellar regions compared to TD children, while there were fewer differences between ASD and TD teens. In TD youth, older age was associated with less activation in the prefrontal cortex. In contrast, in ASD youth, older age was associated with more engagement of sensory integration and emotion regulation regions. In particular, orbitofrontal and medial prefrontal cortices showed a nonlinear relationship with age in ASD, with an especially steep increase in sensory-evoked neural activity during the mid-to-late teen years. There was also an interaction between age and SOR severity in ASD youth such that these age-related trends were more apparent in youth with higher SOR. Limitations The cross-sectional design limits causal interpretations of the data. Future longitudinal studies will be instrumental in determining how prefrontal engagement and SOR co-develop across adolescence. Conclusions Our results suggest that enhanced recruitment of prefrontal regions may underlie age-related decreases in SOR for a subgroup of ASD youth.

The cerebellum has been consistently shown to be atypical in autism spectrum disorder (ASD). However, despite its known role in sensorimotor function, there is limited research on its association with sensory over-responsivity (SOR), a common and impairing feature of ASD. Thus, this study sought to examine functional connectivity of the sensorimotor cerebellum in ASD compared to typically developing (TD) youth and investigate whether cerebellar connectivity is associated with SOR. Resting-state functional connectivity of the sensorimotor cerebellum was examined in 54 ASD and 43 TD youth aged 8-18 years. Using a seed-based approach, connectivity of each sensorimotor cerebellar region (defined as lobules I-IV, V-VI and VIIIA&B) with the whole brain was examined in ASD compared to TD youth, and correlated with parent-reported SOR severity. Across all participants, the sensorimotor cerebellum was functionally connected with sensorimotor and visual regions, though the three seed regions showed distinct connectivity with limbic and higher-order sensory regions. ASD youth showed differences in connectivity including atypical connectivity within the cerebellum and increased connectivity with hippocampus and thalamus compared to TD youth. More severe SOR was associated with stronger connectivity with cortical regions involved in sensory and motor processes and weaker connectivity with cognitive and socio-emotional regions, particularly prefrontal cortex. These results suggest that atypical cerebellum function in ASD may play a role in sensory challenges in autism.

Abstract Background Increased expression of the complement component 4A (C4A) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9–12 years to examine the relationship between genetically regulated expression (GREx) of C4A, childhood brain structure, cognition, and psychiatric symptoms. Results While C4A GREx is not related to childhood psychotic experiences, cognition, or global measures of brain structure, it is associated with a localized reduction in regional surface area (SA) of the entorhinal cortex. Furthermore, we show that reduced entorhinal cortex SA at 9–10 years predicts a greater number and severity of psychosis-like events at 1-year and 2-year follow-up time points. We also demonstrate that the effects of C4A on the entorhinal cortex are independent of genome-wide polygenic risk for schizophrenia. Conclusions Our results suggest neurodevelopmental effects of C4A on childhood medial temporal lobe structure, which may serve as a biomarker for schizophrenia risk prior to symptom onset.

Background: Childhood sleep problems are common and among the most frequent and impairing comorbidities of childhood psychiatric disorders. In adults, sleep disturbances are heritable and show strong genetic associations with brain morphology; however, little is known about the genetic architecture of childhood sleep and potential etiological links between sleep, brain development, and pediatric-onset psychiatric symptoms. Methods: Using data from the Adolescent Brain Cognitive Development Study (nPhenotype = 4428 for discovery/replication, nGenetics = 4728; age 9–10 years), we assessed phenotypic relationships, heritability, and genetic correlations between childhood sleep disturbances (insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area, cortical thickness, volume), and dimensional psychopathology. Results: Sleep disturbances showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain surface area. Among the sleep disturbances assessed, only insomnia showed significant heritability (h2SNP = 0.15, p < .05) and showed substantial genetic correlations with externalizing and attention-deficit/hyperactivity disorder symptomatology (rGs > 0.80, ps < .05). We found no evidence of genetic correlation between childhood insomnia and brain size. Furthermore, polygenic risk scores calculated from genome-wide association studies of adult insomnia and adult brain size did not predict childhood insomnia; instead, polygenic risk scores trained using attention-deficit/hyperactivity disorder genome-wide association studies predicted decreased surface area at baseline as well as insomnia and externalizing symptoms longitudinally. Conclusions: Findings demonstrate a distinct genetic architecture underlying childhood insomnia and brain size and suggest genetic overlap between childhood insomnia and attention-deficit/hyperactivity disorder symptomatology. Additional research is needed to examine how genetic risk manifests in altered developmental trajectories and comorbid sleep/psychiatric symptoms across adolescence.

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36–90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and atrophy in the medial temporal lobe (MTL) and subsequent brain regions. Structural magnetic resonance imaging (sMRI) has been widely used in research and clinical care for diagnosis and monitoring AD progression. However, atrophy patterns are complex and vary by patient. To address this issue, researchers have made efforts to develop more concise metrics that can summarize AD-specific atrophy. Many of these methods can be difficult to interpret clinically, hampering adoption.In this study, we introduce a novel index which we call an “AD-NeuroScore,” that uses a modified Euclidean-inspired distance function to calculate differences between regional brain volumes associated with cognitive decline. The index is adjusted for intracranial volume (ICV), age, sex, and scanner model. We validated AD-NeuroScore using 929 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, with a mean age of 72.7 years (SD = 6.3; 55.1–91.5) and cognitively normal (CN), mild cognitive impairment (MCI), or AD diagnoses.Our validation results showed that AD-NeuroScore was significantly associated with diagnosis and disease severity scores (measured by MMSE, CDR-SB, and ADAS-11) at baseline. Furthermore, baseline AD-NeuroScore was associated with both changes in diagnosis and disease severity scores at all time points with available data. The performance of AD-NeuroScore was equivalent or superior to adjusted hippocampal volume (AHV), a widely used metric in AD research. Further, AD-NeuroScore typically performed as well as or sometimes better when compared to other existing sMRI-based metrics.In conclusion, we have introduced a new metric, AD-NeuroScore, which shows promising results in detecting AD, benchmarking disease severity, and predicting disease progression. AD-NeuroScore differentiates itself from other metrics by being clinically practical and interpretable.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by social and communication differences. Recent research suggests ASD affects 1-in-44 children in the United States. ASD is diagnosed more commonly in males, though it is unclear whether this diagnostic disparity is a result of a biological predisposition or limitations in diagnostic tools, or both. One hypothesis centers on the ‘female protective effect,’ which is the theory that females are biologically more resistant to the autism phenotype than males. In this examination, phenotypic data were acquired and combined from four leading research institutions and subjected to multivariate linear discriminant analysis. A linear discriminant model was trained on the training set and then deployed on the test set to predict group membership. Multivariate analyses of variance were performed to confirm the significance of the overall analysis, and individual analyses of variance were performed to confirm the significance of each of the resulting linear discriminant axes. Two discriminant dimensions were identified between the groups: a dimension separating groups by the diagnosis of ASD (LD1: 87% of variance explained); and a dimension reflective of a diagnosis-by-sex interaction (LD2: 11% of variance explained). The strongest discriminant coefficients for the first discriminant axis divided the sample in domains with known differences between ASD and comparison groups, such as social difficulties and restricted repetitive behavior. The discriminant coefficients for the second discriminant axis reveal a more nuanced disparity between boys with ASD and girls with ASD, including executive functioning and high-order behavioral domains as the dominant discriminators. These results indicate that phenotypic differences between males and females with and without ASD are identifiable using parent report measures, which could be utilized to provide additional specificity to the diagnosis of ASD in female patients, potentially leading to more targeted clinical strategies and therapeutic interventions. The study helps to isolate a phenotypic basis for future empirical work on the female protective effect using neuroimaging, EEG, and genomic methodologies.

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally followed a linear decline from 5 to 21 years of age, except for three functional networks that displayed nonlinear trajectories. We found no main effect of sex or age by sex interaction for any network. Earlier pubertal timing was associated with reduced mean CT and CT in seven networks. We also found a significant age by maternal education interaction for mean CT across cortex and CT in the dorsal attention network, where higher levels of maternal education were associated with steeper age-related decreases in CT. Taken together, our results suggest that these biological and environmental variations may impact the emerging functional connectome.

Abstract Background Social interaction often occurs in noisy environments with many extraneous sensory stimuli. This is especially relevant for youth with autism spectrum disorders (ASD) who commonly experience sensory over-responsivity (SOR) in addition to social challenges. However, the relationship between SOR and social difficulties is still poorly understood and thus rarely addressed in interventions. This study investigated the effect of auditory sensory distracters on neural processing of emotion identification in youth with ASD and the effects of increasing attention to social cues by priming participants with their own emotional faces. Methods While undergoing functional magnetic resonance imaging (fMRI), 30 youth with ASD and 24 typically developing (TD) age-matched controls (ages 8–17 years) identified faces as happy or angry with and without simultaneously hearing aversive environmental noises. Halfway through the task, participants also viewed videos of their own emotional faces. The relationship between parent-rated auditory SOR and brain responses during the task was also examined. Results Despite showing comparable behavioral performance on the task, ASD and TD youth demonstrated distinct patterns of neural activity. Compared to TD, ASD youth showed greater increases in amygdala, insula, and primary sensory regions when identifying emotions with noises compared to no sounds. After viewing videos of their own emotion faces, ASD youth showed greater increases in medial prefrontal cortex activation compared to TD youth. Within ASD youth, lower SOR was associated with reduced increased activity in subcortical regions after the prime and greater increased activity in the ventromedial prefrontal cortex after the prime, particularly in trials with noises. Conclusions The results suggest that the sensory environment plays an important role in how ASD youth process social information. Additionally, we demonstrated that increasing attention to relevant social cues helps ASD youth engage frontal regions involved in higher-order social cognition, a mechanism that could be targeted in interventions. Importantly, the effect of the intervention may depend on individual differences in SOR, supporting the importance of pre-screening youth for sensory challenges prior to social interventions.

Abstract Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = −0.48, p

Abstract Introduction Studying neuro‐structural markers of intellectual giftedness (IG) will inform scientific understanding of the processes helping children excel academically. Methods Structural and diffusion‐weighted MRI was used to compare regional brain shape and connectivity of 12 children with average to high average IQ and 18 IG children, defined as having IQ greater than 145. Results IG had larger subcortical structures and more robust white matter microstructural organization between those structures in regions associated with explicit memory. TD had more connected, larger subcortical structures in regions associated with implicit memory. Conclusions It was found that the memory systems within brains of children with exceptional intellectual abilities are differently sized and connected compared to the brains of typically developing children. These different neurodevelopmental trajectories suggest different learning strategies. A spectrum of intelligence types is envisioned, facilitated by different ratios of implicit and explicit system, which was validated using a large external dataset.

Prior studies have demonstrated that infants and toddlers who later go on to develop autism spectrum disorder (ASD) show atypical functional connectivity as well as altered neural processing of language and other auditory stimuli, but the timeline underlying the emergence of these altered developmental trajectories is still unclear. Here we used resting-state fMRI (rsfMRI) during natural sleep to examine the longitudinal development of functional connectivity in language-related networks from 1.5 to 9 months of age. We found that functional connectivity of networks that underlie the integration of sensory and motor representations, which is crucial for language development, is disrupted in infants at high familial risk (HR) for developing ASD as early as 1.5 months of age. By 9 months of age, HR infants showed hyperconnectivity between auditory and somatosensory regions whereas low risk (LR) infants displayed greater intrahemispheric connectivity between auditory cortex and higher-order temporal regions as well as the hippocampus. Furthermore, while LR infants showed robust changes in functional connectivity during the first year of life with increasing long-range connectivity accompanied by decreasing short-range connectivity over time, HR infants displayed limited developmental changes. Our findings demonstrate that early disruptions in the development of language-related network connectivity may provide an early marker for the later emergence of ASD symptomatology.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by lack of attention to social cues in the environment, including speech. Hypersensitivity to sensory stimuli, such as loud noises, is also extremely common in youth with ASD. While a link between sensory hypersensitivity and impaired social functioning has been hypothesized, very little is known about the neural mechanisms whereby exposure to distracting sensory stimuli may interfere with the ability to direct attention to socially-relevant information. Here, we used functional magnetic resonance imaging (fMRI) in youth with and without ASD (N=54, age range 8–18 years) to (1) examine brain responses during presentation of brief social interactions (i.e., two-people conversations) shrouded in ecologically-valid environmental noises, and (2) assess how brain activity during encoding might relate to later accuracy in identifying what was heard. During exposure to conversation-in-noise (vs. conversation or noise alone), both neurotypical youth and youth with ASD showed robust activation of canonical language networks. However, the extent to which youth with ASD activated temporal language regions, including voice-selective cortex (i.e., posterior superior temporal sulcus), predicted later discriminative accuracy in identifying what was heard. Further, relative to neurotypical youth, ASD youth showed significantly greater activity in left-hemisphere speech-processing cortex (i.e., angular gyrus) while listening to conversation-in-noise (vs. conversation or noise alone). Notably, in youth with ASD, increased activity in this region was associated with higher social motivation and better social cognition measures. This heightened activity in voice-selective/speech-processing regions may serve as a compensatory mechanism allowing youth with ASD to hone in on the conversations they heard in the context of non-social distracting stimuli. These findings further suggest that focusing on social and non-social stimuli simultaneously may be more challenging for youth with ASD requiring the recruitment of additional neural resources to encode socially-relevant information.

Sensory over-responsivity (SOR) is a common condition in autism spectrum disorders (ASD) that is associated with greater social impairment. However, the mechanisms through which sensory stimuli may affect social functioning are not well understood. This study used fMRI to examine brain activity while interpreting communicative intent in 15 high-functioning youth with ASD and 16 age- and IQ-matched typically-developing (TD) controls. Participants completed the task with and without a tactile sensory distracter, and with and without instructions directing their attention to relevant social cues. When completing the task in the presence of the sensory distracter, TD youth showed increased activity in auditory language and frontal regions whereas ASD youth showed decreased activation in these areas. Instructions mitigated this effect such that ASD youth did not decrease activation during tactile stimulation; instead, the ASD group showed increased medial prefrontal activity. SOR severity modulated the effect of the tactile stimulus on social processing. Results demonstrate for the first time a neural mechanism through which sensory stimuli cause disruption of social cognition, and that attentional modulation can restore neural processing of social cues through prefrontal regulation. Findings have implications for novel, integrative interventions that incorporate attentional directives to target both sensory and social symptoms. Keywords: Autism, fMRI, Sensory over-responsivity, Social cognition

Introduction: Attention-deficit hyperactive disorder (ADHD) is the most common neurodevelopmental disorder in children. Diagnosis is currently based on behavioral criteria, but magnetic resonance imaging (MRI) of the brain is increasingly used in ADHD research. To date however, MRI studies have provided mixed results in ADHD patients, particularly with respect to the laterality of findings. Methods: We studied 849 children and adolescents (ages 6–21 y.o.) diagnosed with ADHD (n = 341) and age-matched typically developing (TD) controls with structural brain MRI. We calculated volumetric measures from 34 cortical and 14 non-cortical brain regions per hemisphere, and detailed shape morphometry of subcortical nuclei. Diffusion tensor imaging (DTI) data were collected for a subset of 104 subjects; from these, we calculated mean diffusivity and fractional anisotropy of white matter tracts. Group comparisons were made for within-hemisphere (right/left) and between hemisphere asymmetry indices (AI) for each measure. Results: DTI mean diffusivity AI group differences were significant in cingulum, inferior and superior longitudinal fasciculus, and cortico-spinal tracts (p

Neurosurgery on individuals with lesions around language areas becomes even more complicated when the patient is bilingual. It is thus important to understand the principles that predict the likelihood of convergent versus separate neuroanatomical organization of the first (L1) and the second language (L2) in these individuals. We reviewed all English-language publications on neurosurgical language mapping in bilinguals before January 2020 in three databases (e.g., PubMed). Our search yielded 28 studies with 207 participants. The reviewed data suggest several principles of language organization in bilingual neurosurgical patients: (1) separate cortical areas uniquely dedicated to each language in both anterior and posterior language sites are the rule rather than occasional findings, (2) In cases where there was a convergent neuroanatomical representation for L1 and L2, two factors explained the overlap: an early age of L2 acquisition and a small linguistic distance between L1 and L2 and (3) When L1 and L2 diverged neuroanatomically, more L1-specific sites were identified for early age of L2 acquisition, high L2 proficiency and a larger linguistic distance. This work provides initial evidence-based principles predicting the likelihood of converging versus separate neural representations of L1 and L2 in neurosurgical patients.

Background: Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal–striatal functions and may worsen with immunosuppression. Coupling frontal–striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. Objective: We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV+ individuals would demonstrate greater brain activity in frontal–subcortical regions despite minimal differences between groups on neuropsychological testing. Within the HIV+ sample, we examined associations between indices of immunosuppression (recent and nadir CD4+ count) and task-related signal change in frontostriatal structures.Method16 HIV+ participants and 12 HIV− controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency Results: HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV+ individuals demonstrating significantly greater activation in BG structures than HIV− individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV+ group, current CD4+ count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. Conclusion: During phonemic fluency performance, HIV+ patients recruit subcortical structures to a greater degree than HIV− controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV+ individuals, reduced activity in the frontal–subcortical structures was associated with lower CD4+ count.

Background: Management of language difficulties is an important aspect of clinical care for glioma patients, and accurately identifying the possible language deficits in patients based on lesion location would be beneficial to clinicians. To that end, we examined the relationship between lesion presence and language performance on tests of receptive language and expressive language using a highly specific voxel-based lesion–symptom mapping (VLSM) approach in glioma patients. Methods: 98 adults with primary glioma, who were pre-surgical candidates, were administered seven neurocognitive tests within the domains of receptive language and expressive language. The association between language performance and lesion presence was examined using VLSM. Statistical parametric maps were created for each test, and composite maps for both receptive language and expressive language were created to display the significant voxels common to all tests within these language domains. Results: We identified clusters of voxels with a significant relationship between lesion presence and language performance. All tasks were associated with several white matter pathways. The receptive language tasks were additionally all associated with regions primarily within the lateral temporal lobe and medial temporal lobe. In contrast, the expressive language tasks shared little overlap, despite each task being independently associated with large anatomic areas. Conclusions: Our findings identify the key anatomic structures involved in language functioning in adult glioma patients using an innovative lesion analysis technique and suggest that expressive language abilities may be more task-dependent and distributed than receptive language abilities.