Midtemporal Regions Research Articles

A Predictive Model of the Progression to Alzheimer's Disease in Patients with Mild Cognitive Impairment Based on the MRI Enlarged Perivascular Spaces.

Mild cognitive impairment (MCI) is a heterogeneous condition that can precede various forms of dementia, including Alzheimer's disease (AD). Identifying MCI subjects who are at high risk of progressing to AD is of major clinical relevance. Enlarged perivascular spaces (EPVS) on MRI are linked to cognitive decline, but their predictive value for MCI to AD progression is unclear. This study aims to assess the predictive value of EPVS for MCI to AD progression and develop a predictive model combining EPVS grading with clinical and laboratory data to estimate conversion risk. We analyzed 358 patients with MCI from the ADNI database, consisting of 177 MCI-AD converters and 181 non-converters. The data collected included demographic information, imaging data (including perivascular spaces grade), clinical assessments, and laboratory test results. Variable selection was conducted using the Least Absolute Shrinkage and Selection Operator (LASSO) method, followed by logistic regression to develop predictive model. In the univariate logistic regression analysis, both moderate (OR = 5.54, 95% CI [3.04-10.18]) and severe (OR = 25.04, 95% CI [10.07-62.23]) enlargements of the centrum semiovale perivascular space (CSO-PVS) were found to be strong predictors of disease progression. LASSO analyses yielded 12 variables, refined to six in the final model: APOE4 genotype, ADAS11 score, CSO-PVS grade, and volumes of entorhinal, fusiform, and midtemporal regions, with an AUC of 0.956 in the training and 0.912 in the validation cohort. Our predictive model, emphasizing EPVS assessment, provides clinicians with a practical tool for early detection and management of AD risk in MCI patients.

Brain perfusion single photon emission computed tomography abnormality in MRI-negative stroke-like patients post COVID-19 vaccination.

Stroke-like symptoms after COVID-19 vaccination was thought to be functional if there was no anatomical image abnormality. We aimed to analyze brain perfusion changes in these patients. A case-control study of brain perfusion single photon emission computed tomography (SPECT) of 12 vaccinated patients with left-sided stroke-like symptoms were compared with 12 age- and gender-matched normal interictal brain SPECTs using voxel-based analysis. Significant hyperperfusion was seen on the right side in postcentral, inferior parietal, mid temporal, parahippocampal, and caudate regions, and on the left side in the thalamus, hippocampus, and mid temporal areas. In addition, there were hypoperfused bilateral superior frontal gyri and right mid/posterior cingulate cortex (Family-wise-error corrected p-values < .05). Both hypoperfusion and hyperperfusion in the brain are demonstrated. We hypothesize that these findings might be the result of the functional neurological disorder. However, based on other previous studies, circulating spike protein in the patients' plasma early after vaccination might also be the cause.

Increased interictal synchronicity of respiratory related brain pulsations in epilepsy

Respiratory brain pulsations have recently been shown to drive electrophysiological brain activity in patients with epilepsy. Furthermore, functional neuroimaging indicates that respiratory brain pulsations have increased variability and amplitude in patients with epilepsy compared to healthy individuals. To determine whether the respiratory drive is altered in epilepsy, we compared respiratory brain pulsation synchronicity between healthy controls and patients. Whole brain fast functional magnetic resonance imaging was performed on 40 medicated patients with focal epilepsy, 20 drug-naïve patients and 102 healthy controls. Cerebrospinal fluid associated respiratory pulsations were used to generate individual whole brain respiratory synchronization maps, which were compared between groups. Finally, we analyzed the seizure frequency effect and diagnostic accuracy of the respiratory synchronization defect in epilepsy. Respiratory brain pulsations related to the verified fourth ventricle pulsations were significantly more synchronous in patients in frontal, periventricular and mid-temporal regions, while the seizure frequency correlated positively with synchronicity. The respiratory brain synchronicity had a good diagnostic accuracy (ROCAUC = 0.75) in discriminating controls from medicated patients. The elevated respiratory brain synchronicity in focal epilepsy suggests altered physiological effect of cerebrospinal fluid pulsations possibly linked to regional brain water dynamics involved with interictal brain physiology.

Altered Pain Processing Associated with Administration of Dopamine Agonist and Antagonist in Healthy Volunteers.

Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals’ ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.

Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study.

Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.

Spatial Distribution of the N2 and P300 Components of the Auditory Evoked Potential in Women with Arterial Hypertension: A study in the Russian Arctic

The aim of this study was to evaluate the spatial distribution of the latencies and amplitudes of the N2 and P3 (or P300) components of the AEP in the Russian Arctic working-age women with different levels of BP. Methods and Results: A total of 25 working-age women living in Nadym city for more than 20 years took part in this study. Group 1 (n=12, control group) consisted of women with BP within the normal range (&lt;130/90 mmHg); Group 2 (n=13) consisted of women with AH (AH duration from 1 to 10 years). The parameters of the N2 and P300) components of the AEP were evaluated using an electroencephalograph (Neuron-Spectrum-4/VPM, Russia). An auditory oddball paradigm was used to elicit the oddball ERPs. In Group 2, compared with Group 1, the N2 latency was more pronounced in the parietal (P4, P3), central (C4, C3), frontal (F4, F3), and left temporal (T3, F7) regions. The N2 amplitude in all studied brain regions in individuals of both groups was comparable. The P300 latency did not differ between the two groups. In Group 2, the P300 amplitude was significantly lower in the parietal region (P3) on the left, and in the central and temporal regions on the right (C4, T4). In Group 2, inverse correlations between DBP and the P3 amplitude were revealed in the central (C4: r=-0.88, P=0.001; C3: r=-0.86, P=0.001), frontal (F4: r=-0.76; P=0.01; F3: r=-0.93, P=0.001), and anterior-temporal cerebral regions (F8: r=-0.65, P=0.04; F7: r=-0.64, P=0.04). SBP correlated with the P3 amplitude in the right mid-temporal region (T4: r=0.64, P=0.04). Conclusion: The features of the spatial distribution of the N2 and P3 components of the AEP can be used for early diagnosis of the risk of developing cognitive disorders in AH patients.

The structural and functional corneal reinnervation mechanism at different regions after LASIK-an in vivo confocal microscopy study.

To determine the recovery of structural and functional corneal sensory nerves within the LASIK flap in order to provide insight to more proximal corneal reinnervation and symptoms post-LASIK. Twenty participants underwent femtosecond LASIK with a superior flap hinge. Ocular Comfort Index in Chinese (OCI-C), Cochet-Bonnet esthesiometry, and in vivo confocal microscopy were conducted before surgery and 1week, 1-, 3-, and 6-months post-LASIK to measure symptoms, corneal sensitivity, nerve fiberdensity, width, and the numberofinterconnections within the flap (central and mid-temporal regions), and next to the superior flap hinge. Linear mixed models were used to compare differences between corneal regions at each time point post-LASIK and changes over time post-LASIK. Spearman's correlation tests were used to examine the associations between variables post-LASIK. The least reduction in sensitivity (P < 0.03) and in nerve fiber density (P < 0.02) was found near the flap hinge compared to other regions, but no regional differences were found in nerve fiber width and interconnections. Nerve fiberdensity and the number of interconnections at all regions within the flap recovered over time (P < 0.02). The recovery of corneal sensitivity and nerve fiber width was only seen at the central and temporal regions (P < 0.04). No association was found between sensitivity and nerve parameters, but a higher OCI-C score was associated with a lower nerve fiber density near the hinge (r = - 0.43, P = 0.003) over time post-LASIK. Corneal sensitivity and density are preserved in the hinge, but this preservation of the corneal nerve damage does not affect the nerve morphology.

Differentiating Real-World Autobiographical Experiences without Recourse to Behaviour.

Investigating human consciousness based on brain activity alone is a key challenge in cognitive neuroscience. One of its central facets, the ability to form autobiographical memories, has been investigated through several fMRI studies that have revealed a pattern of activity across a network of frontal, parietal, and medial temporal lobe regions when participants view personal photographs, as opposed to when they view photographs from someone else’s life. Here, our goal was to attempt to decode when participants were re-experiencing an entire event, captured on video from a first-person perspective, relative to a very similar event experienced by someone else. Participants were asked to sit passively in a wheelchair while a researcher pushed them around a local mall. A small wearable camera was mounted on each participant, in order to capture autobiographical videos of the visit from a first-person perspective. One week later, participants were scanned while they passively viewed different categories of videos; some were autobiographical, while others were not. A machine-learning model was able to successfully classify the video categories above chance, both within and across participants, suggesting that there is a shared mechanism differentiating autobiographical experiences from non-autobiographical ones. Moreover, the classifier brain maps revealed that the fronto-parietal network, mid-temporal regions and extrastriate cortex were critical for differentiating between autobiographical and non-autobiographical memories. We argue that this novel paradigm captures the true nature of autobiographical memories, and is well suited to patients (e.g., with brain injuries) who may be unable to respond reliably to traditional experimental stimuli.

Neuroinflammation is highest in areas of disease progression in semantic dementia.

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. We also tested the hypothesis that inflammation, by providing non-specific binding targets, could explain the 18F-flortaucipir signal in semantic variant primary progressive aphasia. Eight amyloid-PET-negative patients with semantic variant primary progressive aphasia underwent 11C-PBR28 and 18F-flortaucipir PET. Healthy controls underwent 11C-PBR28 PET (n = 12) or 18F-flortaucipir PET (n = 12). Inflammation in PET with 11C-PBR28 was analysed using Logan graphical analysis with a metabolite-corrected arterial input function. 18F-flortaucipir standardized uptake value ratios were calculated using the cerebellum as the reference region. Since monoamine oxidase B receptors are expressed by astrocytes in affected tissue, selegiline was administered to one patient with semantic variant primary progressive aphasia before repeating 18F-flortaucipir scanning to test whether monoamine oxidase B inhibition blocked flortaucipir binding, which it did not. While 11C-PBR28 uptake was mostly cortical, 18F-flortaucipir uptake was greatest in the white matter. The uptake of both tracers was increased in the left temporal lobe and in the right temporal pole, as well as in regions adjoining the left temporal pole such as insula and orbitofrontal cortex. However, peak uptake of 18F-flortaucipir localized to the left temporal pole, the epicentre of pathology, while the peak of inflammation 11C-PBR28 uptake localized to a more posterior, mid-temporal region and left insula and orbitofrontal cortex, in the periphery of the damage core. Neuroinflammation, greatest in the areas of progression of the pathological process in semantic variant primary progressive aphasia, should be further studied as a possible therapeutic target to slow disease progression.

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

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

Abnormalities of Alpha Activity in Frontocentral Region of the Brain as a Biomarker to Diagnose Adolescents With Bipolar Disorder.

Objectives. To investigate brain abnormalities in adolescents with new-onset bipolar disorder (BD) during acute hypomanic and depressive episodes using electroencephalogram (EEG) analysis and to derive a computer-based method for diagnosis of the disorder. Methods. EEG spectral power and entropy of 21 adolescents with BD (included 11 patients in the hypomanic episode and 10 patients in the depressive episode) and 18 healthy adolescents were compared. Moreover, using significant differences and K-nearest-neighbors (KNN) classifier, it was attempted to distinguish the BD adolescents from normal ones. Results. The BD adolescents had higher values of spectral power in all frequency bands, particularly in the frontocentral, mid-temporal, and right parietal regions. Also, spectral entropy had significantly increased in delta, alpha, and gamma frequency bands for BD. A high accuracy of 95.8% was achieved by all significant differences in the alpha band in discriminating adolescents with BD. The depressive state showed higher values of spectral power and entropy in low-frequency bands (delta and theta) compared to the hypomanic state. Conclusion. Based on BD symptoms, especially inattention, increased alpha power is a rational finding which is associated with thalamus dysfunction. Thus, it seems that EEG alpha oscillation is the main source of abnormality in BD. Furthermore, EEG slowing in the depressive episode is related to inhibition of electrical activity and reduced cognitive functions.

Functional Connectivity of Cortical Fields at Rest as a Mechanism of Brain Preparation to Purposeful Activity

The relationship between individual characteristics of spontaneous electrical activity of the brain and concentration of attention was studied using the analysis of accuracy in the “Bourdon test” for voluntary attention. The accuracy of test performance was found to correlate with the spectral power and index of the α and θ bands in the left mid-temporal cortical area, as well as an increase in signal connectivity between the mid-temporal and other EEG sites. An increase in the spectral power of the θ band and a decrease in α index led to an increase in the number of errors in the test. On the one hand, the findings possibly indicate that the left mid-temporal region plays a special role organizing the coordinated systemic spatiotemporal interaction of cortical fields, which is necessary for efficient test performance. On the other hand, the findings raise the question as to whether a reorganization of background brain activity is of importance as a precondition of local processes to facilitate further cognitive performance.

Increased food choice-evoked brain activation in adolescents with excess weight: Relationship with subjective craving and behavior

ObjectiveWe used functional magnetic resonance imaging (fMRI) to assess brain regions associated with food choices between appetizing (i.e., high sugar, high fat) and plain food in adolescents with excess weight and those with normal weight. The associations between choice-evoked brain activation and subjective food craving and behavioral food choices were also evaluated. MethodsSeventy-three adolescents (aged 14–19 years), classified into excess weight (n = 38) or normal weight (n = 39) groups, participated in the study. We used a food-choice fMRI task, between appetizing and plain food, to analyse brain activation differences between groups. Afterwards, participants assessed their "craving" for each food presented in the scanner. ResultsAdolescents with excess weight showed higher brain activation in frontal, striatal, insular and mid-temporal regions during choices between appetizing and standard food cues. This pattern of activations correlated with behavioral food choices and subjective measures of craving. ConclusionsOur findings suggest that adolescents with excess weight have greater food choice-related brain reactivity in reward-related regions involved in motivational and emotional responses to food. Increased activation in these regions is generally associated with craving, and increased dorsolateral prefrontal cortex is specifically associated with appetizing food choices among adolescents with excess weight, which may suggest greater conflict in these decisions. These overweight- and craving-associated patterns of brain activation may be relevant to decision-making about food consumption.

Neural representation of word categories is distinct in the temporal lobe: An activation likelihood analysis

The distinction between nouns and verbs is a language universal. Yet, functional neuroimaging studies comparing noun and verb processing have yielded inconsistent findings, ranging from a complete frontal(verb)-temporal(noun) dichotomy to a complete overlap in activation patterns. The current study addressed the debate about neural distinctions between nouns and verbs by conducting an activation likelihood estimation (ALE) meta-analysis of probabilistic cytoarchitectonic maps. Two levels of analysis were conducted: simple effects (Verbs vs. Baseline, Nouns vs. Baseline), and direct comparisons (Verbs vs. Nouns, Nouns vs. Verbs). Nouns were uniquely associated with a left medial temporal cluster (BA37). Activation foci for verbs included extensive inferior frontal (BA44-47) and mid-temporal (BA22, 21) regions in the left hemisphere. These findings confirm that the two grammatical classes have distinct neural architecture in supra-modal brain regions. Further, nouns and verbs overlapped in a small left lateral inferior temporal activation cluster (BA37), which is a region for modality-independent, grammatical class-independent lexical representations. These findings are most consistent with the view that as one acquires language, linguistic representations for a lexical category shift from the modality specific cortices which represent prototypical members of that category (e.g., motion for verbs) to abstract amodal representations in close proximity to modality specific cortices.

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth (P = .05) and trended lower in preterm infants with brain injury (P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons (P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions (P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury (P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery (P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry.

S06. A case of linear scleroderma en coup de sabre and epilepsy: Manage the sabre to control the seizures

Introduction Linear scleroderma en coup de sabre (ECS) is a rare form of localized scleroderma (0.4–2.7/100,000 people) ( Peterson et al., 1997 ) that has characteristic cutaneous involvement of the forehead and scalp ( Holland et al., 2006 ) and is named in reference to its “stroke of a sabre”-like appearance. It typically has onset in the pediatric population and has a higher association with extracutaneous manifestations than other forms of localized scleroderma. Focal epilepsy is the most commonly reported extracutaneous manifestation of ECS, seen in 42% of reported cases ( Doolittle et al., 2015 ). In one study, 7 of 7 patients with ECS associated epilepsy had abnormal brain imaging ( Amaral et al., 2013 ). Methods Ms. J is a 24 year old right handed woman with history of ECS diagnosed in 2007 involving the left forehead, refractory left temporal lobe epilepsy with onset in 2008, and a left anterior temporal lobe lesion that was resected in 2008 with reported pathology of arteriovenous malformation (AVM). Ms. J has undergone extensive evaluation by physicians in the departments of neurology and rheumatology at the Mayo Clinic since 2013, including two epilepsy monitoring unit (EMU) evaluations, ictal-SPECT scan, serial brain MRI and head and neck MRA studies, serological testing, and CSF testing. She has been treated with various antiepileptic medications, and methotrexate and mycophenolate mofetil have been used to manage her ECS. Results Preoperative imaging of the left anterior temporal lobe lesion was retrospectively reviewed by the Mayo Clinic neuroradiology department and is not suggestive of AVM; request for pathology slides from the outside facility has been unsuccessful. Serial imaging since the resection shows new T2 hyperintensity, microhemorrages on susceptibility sequences, and scattered enhancement in the mid and posterior left temporal region, identical in appearance to the resected anterior temporal lobe lesion. Ms. J enjoyed 2 extended periods of seizure freedom, 2008 – May, 2011, and November, 2013 – November, 2016. Her seizure control correlated with treatment of her ECS: she reliably took methotrexate from 2008 – February, 2011 and mycophenolate mofetil from September, 2013 – August, 2016. She restarted mycophenolate mofetil in Jaunary, 2017 and has been seizure free since July (except for an EMU admission October, 2017 on reduced antiepileptic medications). She has been treated with a combination of lamotrigine, levetiracetam, and oxcarbazepine, currently all three, and was maintained on antiepileptic medications since 2008. Conclusion This case illustrates the importance to recognize ECS as a cause of focal epilepsy and brain imaging lesions, and suggests a need for ECS management for seizure control. Proper diagnosis is needed to avoid ineffective brain surgery and to prompt appropriate ECS treatment.

Quantitative electroencephalographic changes in children with autism spectrum disorders

Background Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by impairment of social interaction, communication, and behavior. It has been recently suggested that ASD are characterized by abnormal brain networks and connectivity, which was studied using neuroimaging modalities. Objective The aim of this study is to assess the quantitative electroencephalographic (QEEG) findings in children with ASD compared with age-matched children and to assess if QEEG analysis is a sensitive and simple method to aid in the diagnosis of ASD in children. Patients and methods QEEG recordings of 50 children with ASD between the ages of 2 and 6 years were compared with those of 50 age-matched controls under eyes-closed condition. Brain functioning and its connectivity were examined using measurements of spectral analysis of both absolute and relative power and interhemispheric coherence. Results There were statistically significant differences in electroencephalogram spectral power and coherence between the study and control groups. It revealed an increased absolute delta power in the frontal, anterior temporal, midtemporal, central, and parietal regions and an increase of absolute alpha power mainly in the prefrontal and frontal regions. There was a greater beta power in midtemporal and posterior temporal regions. In addition, interhemispheric coherence showed a pattern of frontal overconnectivity and temporal underconnectivity with the other brain areas in children with ASD in comparison with the control group. Moreover, statistical differences in electroencephalogram spectral power and coherence between the different grades of children with ASD were noticed. Conclusion These results suggested that children with ASD have QEEG dysfunctions that underlie their symptomatology. Hence, QEEG provides a useful method that aids in the diagnosis of children with ASD.

Refractory chronic epilepsy associated with neuronal auto-antibodies: could perisylvian semiology be a clue?

We report a case series of 10 patients with chronic medically refractory antibody-positive autoimmune epilepsy and assess their common clinical features. Immune-mediated seizures are most commonly reported in the context of encephalitis or encephalopathy, with few reports focusing on lone, chronic epilepsy in the outpatient setting. Our aim was to define the potential diagnostic clues that might be present in these cases, leading to consideration of an autoimmune cause of the epilepsy. We performed a retrospective review of all patients presenting to the outpatient department of our unit who underwent autoimmune screening. All patients with chronic epilepsy and a positive result for an antibody known to be associated with epilepsy were included. Sixty-three patients underwent testing. Thirteen returned a positive result, however, only 10 of these were patients which chronic epilepsy who did not present with an acute illness. Common features in these cases included: perisylvian semiology, EEG abnormalities in the mid temporal region, normal or non-specific MRI findings, depression, and head injury. In cases of medically refractory, lesion-negative epilepsy, with predominantly perisylvian semiology, clinicians should have a high level of suspicion for the diagnosis of autoimmune aetiologies and a low threshold to perform autoantibody screening. This is especially true if there are atypical electrographic findings, a previous history of head injury, or co-morbid depression.

The Neurobiology of Agrammatic Sentence Comprehension: A Lesion Study.

Broca's area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of "agrammatic comprehension" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared with canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Broca's area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. This study investigates these seemingly conflicting findings in 66 left-hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Broca's area (but excluding the temporal lobe; n = 11) on average did not exhibit the expected agrammatic comprehension pattern-for example, their performance was >80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage ( n = 18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion-symptom mapping, we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Broca's area. Notably, however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Broca's area, suggesting that the contribution of Broca's area to sentence comprehension may be related to task-related cognitive demands.

WHITE MATTER MICROSTRUCTURAL AND EXTRACELLULAR FREE-WATER CHANGES ASSOCIATED WITH COGNITION IN AMNESTIC MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE

Alzheimer's Disease (AD) and amnestic Mild Cognitive Impairment (aMCI) are associated with white matter (WM) microstructure abnormalities revealed by diffusion tensor imaging (DTI) methods (Acosta-Cabronero et al., 2010). However, the current DTI model suffers from partial volume effects, therefore preventing accurate quantification of WM abnormalities and their roles in cognitive deficits in the prodromal and clinical stages of AD (Metzler-Baddeley et al., 2012). Free-water (FW) imaging method can resolve this problem by differentiating the water compartment in the extracellular space from tissue in a voxel-based manner (Pasternak et al., 2009). We hypothesized that aMCI would have widespread FW increase and temporal WM microstructural damage whereas AD would have further deterioration. Moreover, we sought to investigate the association of FW increases and WM microstructural changes with memory impairment. 39 healthy controls (HC), 41 aMCI, and 36 AD patients underwent MR imaging (Siemens Tim Trio, 3T). The FW method was applied to derive individual FW and tissue compartment fractional anisotropy (FAT) maps. To assess group differences, we carried out voxel-wise statistical analyses on the FW and FAT images using two-sample t-tests. To assess region-specific WM changes underlying cognitive decline across aMCI and AD subjects, we built voxel-wise general linear models (GLM) with the skeletonized FW/DTI indices as the dependent variable, visual/verbal memory performance z-scores as the independent variables. All analyses were controlled for age, gender, handedness, and ethnicity. aMCI had widespread FW increases compared to HC. FW was further increased in AD compared with aMCI (Fig. 1A & C). Moreover, aMCI only had focal FAT reductions in frontal, hippocampal-temporal regions. FAT was further reduced in frontal, parietal, and occipital regions in AD (Fig. 1B & D). More importantly, visual/verbal memory impairment in aMCI and AD patients were associated with FW increases in several WM regions, but not in the body of the fornix. In contrast, visual/verbal memory decline was associated with FAT reductions in the body of the fornix (Fig. 2). Our findings suggest that FW correction isolates vascular damage from WM microstructural alterations and characterize their differential contributions to cognitive impairment in AD. Increased free-water (FW) and reduced tissue compartment fractional anisotropy (FAT) alone AD progression. (A) aMCI had widespread FW increase than HC. The FW level further increased when they reached the AD stage. White matter skeleton is highlighted in green color. (B) FAT reduced in frontal, mid-temporal and parietal regions in aMCI. Then, it further reduced in frontal and occipital parts in AD stage. All results are reported at the threshold of p < 0.05, TFCE and FWE corrected. (C) Mean FW (derived from group difference mask) increase in AD progression (D) Mean FAT (derived from group difference mask) reduce in AD progression. ‘**’ indicates p<0.05. Free-water (FW) increase and tissue compartment fractional anisotropy (FAT) deterioration correlated with verbal memory deficits. (A) Whole-brain voxel-wise linear regression indicated that increased FW values in widespread brain regions were associated with worse verbal memory. (B) Region-specific FAT reduce was associated with verbal memory deficits only in the body of fornix. White matter skeleton is highlighted in green color. All results are reported at the threshold of p < 0.05, TFCE and FWE corrected.