Bilateral Temporal Lobe Research Articles

Characterizing the effects of COVID‐19 on the brain using FDG PET imaging before and after COVID‐19 infection

AbstractBackgroundIndividuals diagnosed with COVID‐19 have been found to have changes in brain structure as well as dramatic neuropsychiatric effects such as dementia, Parkinsonism, and greater likelihood of stroke (Taquet, 2021). Infection has also been shown to result in hypometabolic changes on 18F ‐fluorodeoxyglucose positron emission tomography (FDG PET) when compared to normal controls (Guedj, 2021). This study will seek to determine which brain regions are most affected by COVID‐19 with FDG PET. To our knowledge, we are the first study to compare pre‐ and post‐infection FDG PET imaging within patients. These patients were coincidentally infected with COVID‐19 between standard of care longitudinal FDG PET imaging for cancer.MethodPatients with COVID‐19 who had FDG PET imaging that included the brain before and after serologic COVID‐19 diagnosis were identified from an internal COVID‐19 registry. Clinical data was mined from the electronic health record. Images were processed with well‐established SPM12 methods (Friston, 1995). A voxel‐wise ANCOVA was performed on FDG PET images before and after COVID‐19 infection, including covariates of age, sex, ethnicity, and time between chemotherapy and follow‐up imaging using p < 0.001 and voxel extent threshold of 10.Result29 patients met inclusion criteria (Table 1). Compared to baseline, 4 clusters of voxels were significantly decreased after COVID‐19 infection in the temporal lobes, anterior cingulate gyrus, and superior cerebellum (Table 2). In a post‐hoc analysis, spherical regions of interest (radius = 5 mm) surrounding these clusters were tested for post‐infection hypometabolism. The bilateral temporal lobes, anterior lobe of cerebellum, and right caudate head showed significant decrease in glucose metabolism following COVID‐19 infection (p < 0.05).ConclusionCurrently, this is the first study to leverage a pre‐COVID‐19 infection FDG PET for comparison to imaging post‐infection. We discovered regions in the temporal lobe, frontal lobe, and cerebellum that showed hypometabolic changes following infection, important for determining spatial localization of the effects of this viral infection.

A Preliminary Study of Brain Functional Magnetic Resonance Imaging in Text Reading and Comprehension.

Few studies have focused on the changes in human brain function activities caused by reading Chinese characters with different intelligibility and whether it can reflect the understanding and cognitive ability of the human brain. Task-fMRI based on Chinese character reading tasks with different intelligibility was used to explore activated brain regions and their cognitive changes. Volunteers were randomly recruited using advertisements. Forty volunteers were recruited based on strict inclusion and exclusion criteria, and 40 volunteers were recruited. Brain function data of 40 healthy right-handed volunteers in fuzzy/clear Chinese reading tasks were collected using a Siemens Skyra 3.0T magnetic resonance scanner. Data were preprocessed and statistically analyzed using the statistical software SPM12.0 to observe the activation of the cortex and analyze its characteristics and possible changes in cognitive function. Task-fMRI analysis: (1) The main brain regions activated in fuzzy/clear reading tasks were located in the occipital visual cortex (P < 0.001); (2) a paired sample t-test suggested that there was a significant difference in BOLD signals in the brain regions activated by fuzzy/clear reading tasks (P < 0.001, equiv Z = 4.25). Compared with the fuzzy reading task, the brain regions more strongly activated in the clear reading task were mainly located in the right superior frontal gyrus and the bilateral temporal lobe. Compared with the clear reading task, the brain region that was more strongly activated in the fuzzy reading task was mainly located in the right fusiform gyrus. Clear Chinese character information mainly activates the dorsal stream of the visual-spatial network. This reflects the information transmission of the brain after understanding the text content and is responsible for guiding and controlling attention. Fuzzy words that cannot provide clear text content activate the fusiform gyrus of the ventral stream of the visual-spatial network, strengthening the function of orthographic processing.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n =72) and non-Hispanic White (n =75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p<.001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Automated CT perfusion analysis reveals medial temporal perfusion abnormalities during transient global amnesia

IntroductionThe underlying pathophysiology of Transient global amnesia (TGA) remains elusive. Reports of perfusion abnormalities in TGA were inconsistent, but semi-automated analysis of perfusion CT (CTP) may improve reliability and precision of perfusion deficit detection. MethodsPer institutional protocol, all TGA patients undergo multiphasic contrast-CT with arch to vertex CT angiography, intracranial CT venography, MRI, and EEG upon admission. During the study period consecutive patients diagnosed with TGA underwent CTP during the early acute amnestic phase. We retrospectively reviewed the clinical and radiological findings. ResultsFive patients (3 female. median age 71, range 47–74) fulfilled entry criteria. Automated CTP analysis revealed the absence of an ischemic core (defined by CBF < 30%) or conventionally defined clinically relevant hypoperfusion area (defined by Time-to-maximum (Tmax) >6 s) in any of the patients. However, four of the five patients demonstrated territories of benign oligemia defined as Tmax>4 s in areas supplied by the Posterior Cerebral Artery. Three of these four patients had clear involvement of the bilateral medial temporal lobes. None of the patients had epileptic activity on their EEG. Both CTA and MRI were normal apart for small foci of restricted diffusion in the hippocampus of four patients. DiscussionDeficits in perfusion were found in the hippocampi of 60% of patients in the acute phase of TGA using automated image analysis software. This method may provide a quick and simple method to detect these abnormalities. These perfusion abnormalities could help solidify the diagnosis at an early stage and may advance our understanding of this elusive syndrome.

Does right hemisphere compensate for the left in school-age children with large left middle fossa arachnoid cysts?

BackgroundTo assess the cognitive function changes and brain network neuroplasticity in school-age children having large (diameter > 5 cm) left middle fossa arachnoid cyst (MFACs).MethodsEleven patients and 22 normal controls (NC) between 6 and 14 years of age were included. The CNS Vital Signs (CNS VS) were administered for cognitive assessment. The differences of cognitive data and functional connectivity (FC) in resting-state functional magnetic resonance imaging (rs-fMRI) were compared between the patient group and the NC group. The correlations between the altered FC and cognitive data in the patient group were assessed.ResultsPatient group had significantly poorer attention (including Complex Attention, Sustained Attention, Simple Attention, Cognitive Flexibility, and Executive Function) and memory function (Visual Memory and Working Memory) than the NC group (uncorrected p-value, p-unc < 0.05). Whole-brain local correlation (LCOR) analysis showed an extensively lower LCOR in the patient group (voxel threshold p-unc < 0.001, cluster-size threshold of false discovery rate adjusted p (p-FDR) < 0.001). Functional connectivity (FC) analysis showed that bilateral frontal and temporal lobes connectivity in the patient group was significantly lower than the NC group (p-FDR < 0.05). Seed-based FC analysis indicated that there was altered FC between the right temporal lobe and the left temporal-parietal/temporal-occipital area (p-FDR < 0.05). In the patient group, most of the altered FC had a negative correlation to the cognitive score, while the FC in the right temporal lobe-left temporal-occipital area positively correlated to Verbal/Visual Memory (r = 0.41–0.60, p-FDR < 0.05). In correlation analysis between clinical data and cognitive score, the only significant result was a low correlation between cyst size and Reaction Time (-0.30–-0.36, P-FDR < 0.05).ConclusionsSchool-aged children with large left MFAC showed significantly lower cognitive performance primarily in attention and memory domains. Distinct from neuroplasticity in a unilateral brain lesion, compensation in the healthy hemisphere in MFAC patients was sparse.

56 Stereological Densities of Neuronal Tau Inclusions in Corticobasal Degeneration are Anatomically Distinct in PPA vs bvFTD

Objective:Primary progressive aphasia (PPA) is a dementia syndrome characterized early in its course by gradual dissolution of language and is associated with asymmetric atrophy in the language-dominant hemisphere (usually left). In contrast, behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by a progressive early decline in personality and comportment and is associated with relatively symmetric or rightward predominant bifrontal atrophy. This study analyzed the regional and hemispheric distributions of neuronal tau inclusions of the corticobasal degeneration variant of FTLD-tau pathology (FTLD-CBD) in individuals with PPA or bvFTD. The goal was to establish clinicopathologic concordance between FTLD-CBD and behavioral/comportmental vs aphasic dementia syndromes.Participants and Methods:Seven participants were clinically diagnosed with PPA and 6 were diagnosed with bvFTD. All had FTLD-CBD as the principal neuropathologic diagnosis at postmortem study. Sections from the following cortical regions were stained immunohistochemically with AT-8 to visualize neuronal tau inclusions: bilateral middle frontal gyrus (MFG), inferior parietal lobule (IPL), superior temporal gyrus (STG); and unilateral occipital cortex (OCC). Bilateral anterior temporal lobes (ATL) were analyzed in PPA cases only. Unbiased stereological analysis was performed to compare regional and hemispheric distributions between and within PPA vs. bvFTD groups.Results:Overall neocortical (MFG+STG+IPL) tau densities were significantly greater in the PPA group compared to the bvFTD group (p&lt;0.05). Within the bvFTD group, the highest densities of tau inclusions were observed in the right MFG (mean=6,871.17; SD=3,220). In the PPA group, highest densities were observed in the left ATL (mean=9,901.81; SD=6,871). There was leftward hemispheric asymmetry of tau inclusions in IPL, STG and ATL which trended towards significance in the latter (p=0.083). Cortical distributions were symmetric or rightward predominant within the bvFTD group. Occipital cortex was devoid of inclusions.Conclusions:Preliminary stereological findings of FTLD-CBD tau inclusions suggest that the distributions of pathologic tau are different across two distinct clinical dementia phenotypes. The presence of left-sided neuronal tau inclusions in PPA is concordant with the aphasic phenotype whereas symmetric and frontal-predominant densities in bvFTD are consistent with comportmental dysfunction.

Medial Temporal Lobe Tau Aggregation Relates to Divergent Cognitive and Emotional Empathy Abilities in Alzheimer's Disease.

In Alzheimer's disease (AD), the gradual accumulation of amyloid-β (Aβ) and tau proteins may underlie alterations in empathy. To assess whether tau aggregation in the medial temporal lobes related to differences in cognitive empathy (the ability to take others' perspectives) and emotional empathy (the ability to experience others' feelings) in AD. Older adults (n = 105) completed molecular Aβ positron emission tomography (PET) scans. Sixty-eight of the participants (35 women) were Aβ positive and symptomatic with diagnoses of mild cognitive impairment, dementia of the Alzheimer's type, logopenic variant primary progressive aphasia, or posterior cortical atrophy. The remaining 37 (22 women) were asymptomatic Aβ negative healthy older controls. Using the Interpersonal Reactivity Index, we compared current levels of informant-rated cognitive empathy (Perspective-Taking subscale) and emotional empathy (Empathic Concern subscale) in the Aβ positive and negative participants. The Aβ positive participants also underwent molecular tau-PET scans, which were used to investigate whether regional tau burden in the bilateral medial temporal lobes related to empathy. Aβ positive participants had lower perspective-taking and higher empathic concern than Aβ negative healthy controls. Medial temporal tau aggregation in the Aβ positive participants had divergent associations with cognitive and emotional empathy. Whereas greater tau burden in the amygdala predicted lower perspective-taking, greater tau burden in the entorhinal cortex predicted greater empathic concern. Tau burden in the parahippocampal cortex did not predict either form of empathy. Across AD clinical syndromes, medial temporal lobe tau aggregation is associated with lower perspective-taking yet higher empathic concern.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

A - 114 Long Term Cognitive Sequela of Intracranial Radiation Therapy in a Pediatric Cerebellar Medulloblastoma Survivor.

Intracranial radiation therapy (IRT) for pediatric brain tumors is associated with late delayed brain injury due to cerebrovascular abnormality, white matter necrosis, demyelination, and gliosis which are irreversible. As a result, persistent cognitive deficits in adulthood emerge which are aggravated by younger age at diagnosis, higher radiation dose, whole brain radiation (WBR), and concurrent chemotherapy. The case is a childhood brain tumor survivor seen 18years post treatment who displayed cognitive deficits reflecting the cognitive sequela of WBR that overlapped with the anatomical distribution of white matter damage sustained. 23-year-old Black male with a history of childhood cerebellar medulloblastoma diagnosed at age 4, tumor resection, WBR, chemotherapy, more recent seizure disorder and medullary stroke, diabetes, and hypertension was seen for a neuropsychological evaluation due to memory complaints. His neuroimaging showed white matter hyperintensities in bilateral temporal and occipital lobes, bilateral cerebellar hemispheres, bilateral frontal lobes, medial posterior right cerebellar cyst, and 10 x 5mm cyst in the left temporal lobe. Results showed FSIQ = 59 and deficits in language, processing speed, visuospatial abilities, executive functioning, and verbal memory. His auditory working memory and visual memory were preserved. Based on his numerous adaptive limitations, moderate intellectual development disorder diagnosis was given. Deficits across several cognitive domains were consistent with multi-focal white matter lesions seen in patient's neuroimaging which reflect radiographic findings related to long-term sequela of previous intracranial radiation. A unique finding was relatively preserved visual memory as findings related to asymmetrical memory dysfunction in childhood medulloblastoma survivors are scarce.

SAT531 Thyroid Metastasis From Non-small Cell Lung Cancer: An Unusual Case Presentation

Abstract Disclosure: E.Y. Ibrahim: None. I. Guillen Alvarez: None. I. Hulinsky: None. D. Regelmann: None. C. Janowiecki: None. Background: Cases of thyroid tumors metastasizing from the lungs are rare, and their diagnosis is often challenging and can be mistaken for primary thyroid tumors or subacute thyroiditis. Thyroid function tests are typically normal and not helpful in establishing the diagnosis. Ultrasonography commonly shows focal or diffuse hypoechoic lesions. Correspondingly, heterogeneous hypodense areas with mild contrast enhancement are seen on CT scans. Clinical Case: Our patient is a 61-year-old male with a history of diabetes mellitus and 40 years tobacco use, who presented with a 1-week history of right-sided weakness and 3-weeks of dry cough. The weakness of his leg progressed to the point he could not ambulate. Initially, he was evaluated for a stroke and underwent CT imaging showing extensive lesions of the bilateral frontal, temporal, and parietal lobes. These findings were suspicious, and confirmed by MRI, to reflect multifocal metastatic lesions with vasogenic edema. Initial physical examination revealed a palpable thyroid nodule in the right lobe with bilateral cervical lymphadenopathy. CT of the neck demonstrated lymphadenopathy as well as multiple bilateral hypoechoic thyroid nodules, the largest of which measured 0.8 cm in the right thyroid lobe. TSH was 0.34 (0.48-4.17mU/L) with Free T4 at 1.39 (0.8-1.90ng/dL). The patient had denied symptoms of heat intolerance, tremor, or palpitations. A CT chest with contrast found a 3.5 cm cavitary lesion in the right upper lobe concerning for a primary lung neoplasm, as well as multiple bilateral lung nodules, mediastinal and hilar lymphadenopathy, and bilateral adrenal masses. Subsequent ultrasound-guided biopsy of the thyroid tumor revealed histologic features of a poorly differentiated non-small cell carcinoma, with features of a primary lung origin. These features were also present on a concurrent fine needle biopsy of an enlarged cervical lymph node. Immunohistochemistry staining showed the tumor was highly expressive for PDL1, focally positive for p40, pancytokeratin AE1/AE3, and negative for TTF-1 and thyroglobulinDue to the vasogenic cerebral edema, he was given dexamethasone with good response, and his weakness improved to the point that patient was able to ambulate. Treatment also included radiation therapy with subsequent pembrolizumab upon completion of radiotherapy. Conclusion: Several thyroid lesions representing metastases may go unnoticed because the physician’s attention toward lesions at other, more common sites, and detailed thyroid examination can be commonly overlooked. Patients with newly diagnosed malignancies should also be screened for thyroid involvement, including detailed physical, radiographic, and histologic examination of pathologic findings. Presentation Date: Saturday, June 17, 2023

Nonfluent Variant Primary Progressive Aphasia on FDG, 11 C-PIB, and 18 F-APN-1607 PET Imaging.

A 61-year-old right-handed man presented with decreased cognitive function, short-term memory, fluent speech disorders, and grammatical errors for 1 year. The patient underwent PET imaging with 11 C-PIB, 18 F-FDG, and 18 F-APN-1607. The 11 C-PIB PET showed no amyloid accumulation; the 18 F-FDG PET showed hypometabolism in the bilateral frontal lobe, temporal lobe, and midbrain; and the 18 F-APN-1607 PET showed tau accumulation in the brainstem, basal ganglia, and left inferior frontal gyrus. These findings suggested a diagnosis of nonfluent variant primary progressive aphasia. This case emphasizes the value of combined imaging of glucose metabolism, Aβ, and tau PET in the diagnosis of nonfluent variant primary progressive aphasia.

Elucidating individual differences in chronic pain and whole person health with allostatic load biomarkers

Chronic pain is a stressor that affects whole person functioning. Persistent and prolonged activation of the body's stress systems without adequate recovery can result in measurable physiological and neurobiological dysregulation recognized as allostatic load. We and others have shown chronic pain is associated with measures of allostatic load including clinical biomarker composites, telomere length, and brain structures. Less is known regarding how different measures of allostatic load align. The purpose of the study was to evaluate relationships among two measures of allostatic load: a clinical composite and pain-related brain structures, pain, function, and socioenvironmental measures. Participants were non-Hispanic black and non-Hispanic white community-dwelling adults between 45 and 85 years old with knee pain. Data were from a brain MRI, questionnaires specific to pain, physical and psychosocial function, and a blood draw. Individuals with all measures for the clinical composite were included in the analysis (n = 175). Indicating higher allostatic load, higher levels of the clinical composite were associated with thinner insula cortices with trends for thinner inferior temporal lobes and dorsolateral prefrontal cortices (DLPFC). Higher allostatic load as measured by the clinical composite was associated with greater knee osteoarthritis pathology, pain disability, and lower physical function. Lower allostatic load as indicated by thicker insula cortices was associated with higher income and education, and greater physical functioning. Thicker insula and DLPFC were associated with a lower chronic pain stage. Multiple linear regression models with pain and socioenvironmental measures as the predictors were significant for the clinical composite, insular, and inferior temporal lobes. We replicate our previously reported bilateral temporal lobe group difference pattern and show that individuals with high chronic pain stage and greater socioenvironmental risk have a higher allostatic load as measured by the clinical composite compared to those individuals with high chronic pain stage and greater socioenvironmental buffers. Although brain structure differences are shown in individuals with chronic pain, brain MRIs are not yet clinically applicable. Our findings suggest that a clinical composite measure of allostatic load may help identify individuals with chronic pain who have biological vulnerabilities which increase the risk for poor health outcomes.

Regional Cortical Thickness Correlates of Intellectual Abilities Differ in Children With Traumatic Brain Injury Versus Those With Orthopedic Injury in the Chronic Post-Injury Phase.

A decline in intellectual functioning (intelligence quotient [IQ]) is often observed following more severe forms of traumatic brain injury (TBI) and is a useful index for long-term outcome. Identifying brain correlates of IQ can serve to inform developmental trajectories of behavior in this population. Using magnetic resonance imaging (MRI), we examined the relationship between intellectual abilities and patterns of cortical thickness in children with a history of TBI or with orthopedic injury (OI) in the chronic phase of injury recovery. Participants were 47 children with OI and 58 children with TBI, with TBI severity ranging from complicated-mild to severe. Ages ranged from 8 to 14 years old, with an average age of 10.47 years, and an injury-to-test range of ∼1-5 years. The groups did not differ in age or sex. The intellectual ability estimate (full-scale [FS]IQ-2) was derived from a two-form (Vocabulary and Matrix Reasoning subtests) Wechsler Abbreviated Scale of Intelligence (WASI). MRI data were processed using the FreeSurfer toolkit and harmonized across data collection sites using neuroComBat procedures, while holding demographic features (i.e., sex, socioeconomic status [SES]), TBI status, and FSIQ-2 constant. Separate general linear models per group (TBI and OI) and a single interaction model with all participants were conducted with all significant results withstanding correction for multiple comparisons via permutation testing. Intellectual ability was higher (p < 0.001) in the OI group (FSIQ-2 = 110.81) than in the TBI group (FSIQ-2 = 99.81). In children with OI, bi-hemispheric regions, including the right pre-central gyrus and precuneus and bilateral inferior temporal and left occipital areas were related to IQ, such that higher IQ was associated with thicker cortex in these regions. In contrast, only cortical thickness in the right pre-central gyrus and bilateral cuneus positively related to IQ in children with TBI. Significant interaction effects were found in the bilateral temporal, parietal, and occipital lobes and left frontal regions, indicating that the relationship between IQ and cortical thickness differed between groups in these regions. Changes in cortical associations with IQ after TBI may reflect direct injury effects and/or adaptation in cortical structure and intellectual functioning, particularly in the bilateral posterior parietal and inferior temporal regions. This suggests that the substrates of intellectual ability are particularly susceptible to acquired injury in the integrative association cortex. Longitudinal work is needed to account for normal developmental changes and to investigate how cortical thickness and intellectual functioning and their association change over time following TBI. Improved understanding of how TBI-related cortical thickness alterations relate to cognitive outcome could lead to improved predictions of outcome following brain injury.

Study on neural entrainment to continuous speech using dynamic source connectivity analysis

Objective. Many recent studies investigating the processing of continuous natural speech have employed electroencephalography (EEG) due to its high temporal resolution. However, most of these studies explored the response mechanism limited to the electrode space. In this study, we intend to explore the underlying neural processing in the source space, particularly the dynamic functional interactions among different regions during neural entrainment to speech. Approach. We collected 128-channel EEG data while 22 participants listened to story speech and time-reversed speech using a naturalistic paradigm. We compared three different strategies to determine the best method to estimate the neural tracking responses from the sensor space to the brain source space. After that, we used dynamic graph theory to investigate the source connectivity dynamics among regions that were involved in speech tracking. Main result. By comparing the correlations between the predicted neural response and the original common neural response under the two experimental conditions, we found that estimating the common neural response of participants in the electrode space followed by source localization of neural responses achieved the best performance. Analysis of the distribution of brain sources entrained to story speech envelopes showed that not only auditory regions but also frontoparietal cognitive regions were recruited, indicating a hierarchical processing mechanism of speech. Further analysis of inter-region interactions based on dynamic graph theory found that neural entrainment to speech operates across multiple brain regions along the hierarchical structure, among which the bilateral insula, temporal lobe, and inferior frontal gyrus are key brain regions that control information transmission. All of these information flows result in dynamic fluctuations in functional connection strength and network topology over time, reflecting both bottom-up and top-down processing while orchestrating computations toward understanding. Significance. Our findings have important implications for understanding the neural mechanisms of the brain during processing natural speech stimuli.

The effect of repetition on intersubject synchrony assessed with fMRI

We investigated how repeated exposure to a stimulus affects intersubject synchrony in the brains of young and older adults. We used functional magnetic resonance imaging (fMRI) to measure brain responses to familiar and novel stimuli. Young adults participated in a familiarization paradigm designed to mimic ‘natural’ exposure while older adults were presented with stimuli they had known for more than 50 years. Intersubject synchrony was calculated to detect common stimulus-driven brain activity across young and older adults as they listened to the novel and familiar stimuli. Contrary to our hypotheses, synchrony was not related to the amount of stimulus exposure; both young and older adults showed more synchrony to novel than to familiar stimuli regardless of whether the stimuli had been heard once, known for a few weeks, or known for more than 50 years. In young adults these synchrony differences were found across the brain in the bilateral temporal lobes, and in the frontal orbital cortex. In older adults the synchrony differences were found only in the bilateral temporal lobes. This reduction may be related to an increase in idiosyncratic responses after exposure to a stimulus but does not seem to be related to how well the stimuli are learned or to differences in attention. Until the effects of repeated exposure on synchrony are fully understood, future studies using intersubject synchrony, where the novelty of the stimuli cannot be guaranteed, may consider exposing all of their participants to the stimuli once before data are collected to mitigate the effects of any systematic differences in stimulus exposure.

Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T. Twenty-one refractory DLCBLs underwent whole-body and brain [18 F]-fluorodeoxyglucose (FDG) PET before and 30days after treatment with CAR-T. Five patients did not develop inflammatory-related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post-CAR-T brain FDG-PET were compared with a local controls dataset to identify hypometabolic patterns both at single-patient and group levels (p<.05 after correction for family-wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG-PET and compared between patients' subgroups (t-test). ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p<.003 FWE-corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p<.002 FWE-corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p<.002 FWE-corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p<.02). Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine-induced inflammation.

ID: 218087 RNS for Medically Uncontrolled Bilateral Neocortical Temporal Lobe Epilepsy Confers Favorable Long-Term Seizure Control

Patients with refractory neocortical temporal lobe epilepsy are challenging surgical candidates. Preoperative evaluation often fails to accurately localize SOZs, which necessitates the use of intracranial electroencephalography (iEEG). Furthermore, once SOZ can be defined, patients are typically not candidates for resective surgery. We present a retrospective case series of our experience with diagnosis and management of “bilateral neocortical temporal lobe epilepsy” (bnTLE) treated with responsive neurostimulation (RNS).?

Exploring the association between tau‐PET and Aβ‐amyloid Centiloid value using deep learning

AbstractBackgroundThe study of how extracellular Aβ‐amyloid (Aβ) drives intracellular, heterogeneous tau accumulation in Alzheimer’s disease has been approached using linear models under an implicit assumption of regionally independent tau accumulation (Lockhart et al, 2017; Iaccarino et al, 2017). Multivariate, non‐linear models which enable relaxation of this assumption can be used; we employed a convolutional neural network (CNN) to identify critical tau topographic changes associated with Aβ‐burden in a cohort with a range of Aβ values, and compared results with linear analyses.Method134 subjects with [NAV4694 (Aβ) and [MK6240 (tau) scans were considered. A CNN was trained to map normalised tau (input) to Aβ Centiloid values (CL). CNN models were interpreted using saliency maps, denoting the importance of corresponding voxels to the output. The CNN approach was compared with linear analysis by testing the following voxel‐wise models: estimating tau SUVR from Aβ CL, and saliency from Aβ CL. All models were tested with minimum cluster extent of 200 after controlling for age and sex. Occlusion analysis was used to assess the importance of CNN‐identified salient clusters, which quantified the change in output after removing salient clusters from the input tau images.ResultThe Aβ CL values were well predicted by tau topography using the CNN (training R2 = 0.86, validation R2 = 0.75, testing R2 = 0.72). Linear analysis identified widespread correlation between Aβ CL and tau‐SUVR in the brain, while CNN analysis demonstrated focal clusters in frontal lobes, middle cingulate, precuneus, postcentral gyrus and bilateral medial temporal lobes. At low Aβ levels, information from the frontal lobe, middle cingulate and precuneus regions was more predictive of Aβ CL while the information from medial temporal lobes was more predictive of high Aβ levels.ConclusionThe nonlinear data‐driven CNN approach, relaxing the assumption of independent regional tau accumulation, has revealed new associations between tau topography and Aβ burden.

Vasospasm secondary to responsive neurostimulator placement: a previously unreported complication. Illustrative case.

The Responsive Neurostimulation (RNS) system is an implantable device for patients with drug-resistant epilepsy who are not candidates for resection of a seizure focus. As a relatively new therapeutic, the full spectrum of adverse effects has yet to be determined. A literature review revealed no previous reports of cerebral vasospasm following RNS implantation. A 35-year-old man developed severe angiographic and clinical vasospasm following bilateral mesial temporal lobe RNS implantation. He initially presented with concerns for status epilepticus 8 days after implantation. On hospital day 3, a decline in his clinical examination prompted imaging studies that revealed a left middle cerebral artery (MCA) stroke with angiographic evidence of severe vasospasm of the left internal carotid artery (ICA), MCA, anterior cerebral artery (ACA), and right ICA and ACA. Despite improvements in angiographic vasospasm after appropriate treatment, a thrombus developed in the posterior M2 branch, requiring mechanical thrombectomy. Ultimately, the patient was stabilized and discharged to a rehabilitation facility with residual cognitive and motor deficits. Cerebral vasospasm as a cause of ischemic stroke after uneventful RNS implantation is exceedingly rare, yet demands particular attention given the potential for severe consequences and the growing number of patients receiving RNS devices.