Cortical Abnormalities Research Articles

Association of reduced cortical thickness and psychopathological symptoms in patients with first-episode drug-naïve schizophrenia

Objective There is growing evidence that reduced cortical thickness has been considered to be a central abnormality in schizophrenia. Brain imaging studies have demonstrated that the cerebral cortex becomes thinner in patients with first-episode schizophrenia. This study aimed to examine whether cortical thickness is altered in drug-naïve schizophrenia in a Chinese Han population and the relationship between cortical thickness and clinical symptoms. Methods We compared cortical thickness in 41 schizophrenia patients and 30 healthy controls. Psychopathology of patients with schizophrenia was assessed using the Positive and Negative Syndrome Scale (PANSS). Results The cortical thickness of left banks of superior temporal sulcus, left lateral occipital gyrus, left rostral middle frontal gyrus, right inferior parietal lobule and right lateral occipital gyrus in schizophrenia patients was generally thinner compared with healthy controls. Correlation analysis revealed a negative correlation between cortical thickness of the left banks of superior temporal sulcus and general psychopathology of PANSS. Conclusions Our results suggest that cortical thickness abnormalities are already present early in the onset of schizophrenia and are associated with psychopathological symptoms, suggesting that it plays an important role in the pathogenesis and symptomatology of schizophrenia. Key points (1) The first-episode drug-naïve schizophrenia had reduced cortical thickness than the controls. (2) Cortical thickness was associated with psychopathological symptoms in patients with schizophrenia.

Magnetic resonance imaging features of isolated periventricular heterotopia in pediatric epilepsy: a comparative study

Periventricular nodular heterotopia is a neurodevelopmental disorder in which neurons fail to migrate to the cortical surface, forming discrete areas of grey matter adjacent to the lateral ventricles. Given that periventricular nodular heterotopia is seen as an incidental finding in patients without epilepsy, causality between periventricular nodular heterotopia and epilepsy cannot be assumed. Furthermore, the structural characteristics of periventricular nodular heterotopia in patients with epilepsy are poorly defined and can be misleading. In this article, we investigate whether structural radiological characteristics of heterotopia can predict epileptogenicity in pediatric patients. Pediatric patients with periventricular nodular heterotopia, but no other epilepsy-associated cortical abnormalities on magnetic resonance imaging, were identified and divided into two groups: with epilepsy and without epilepsy. Radiological characteristics of laterality, regionalization, largest dimension and number of nodules were compared between the two groups. Only periventricular nodular heterotopia spreading across several regions was associated with a statistically higher chance of epilepsy. Other features including laterality, individual region, number and largest dimension did not reliably predict epileptogenicity. Most radiological characteristics of periventricular nodular heterotopia are similar in patients with and without epilepsy. The involvement of multiple periventricular regions with heterotopia was the only feature that inferred a higher risk of epilepsy. Periventricular nodular heterotopia requires a comprehensive work-up and should be interpreted in the context of each individual patient and not assumed to be directly causative of epilepsy, nor unrelated to it. Therefore, further studies using additional structural and functional imaging modalities are needed to determine the radiological features of epileptogenic periventricular nodular heterotopia.

Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder.

Pediatric bipolar disorder (PBD) has been proven to be related to abnormal brain structural connectivity, but how the abnormalities in PBD correlate with gene expression is debated. This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD. Morphometric similarity networks (MSN) were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants (59 patients and 43 controls). Partial least squares (PLS) regression was used to calculate MSN differences related to transcriptomic data in AHBA. The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools. MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants. MSN differences were spatially correlated with the PBD-related weighted genes. The weighted genes were enriched for "trans-synaptic signaling" and "regulation of ion transport", and showed significant specific expression in excitatory and inhibitory neurons. This study identified the genes that contributed to structural network aberrations in PBD. It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison

Background & aimWe examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). MethodsWe recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. ResultsWe observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. ConclusionOur study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.

TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model

The precise development of the neocortex is a prerequisite for higher cognitive and associative functions. Despite numerous advances that have been made in understanding neuronal differentiation and cortex development, our knowledge regarding the impact of specific genes associated with neurodevelopmental disorders on these processes is still limited. Here, we show that Taok2, which is encoded in humans within the autism spectrum disorder (ASD) susceptibility locus 16p11.2, is essential for neuronal migration. Overexpression of de novo mutations or rare variants from ASD patients disrupts neuronal migration in an isoform-specific manner. The mutated TAOK2α variants but not the TAOK2β variants impaired neuronal migration. Moreover, the TAOK2α isoform colocalizes with microtubules. Consequently, neurons lacking Taok2 have unstable microtubules with reduced levels of acetylated tubulin and phosphorylated JNK1. Mice lacking Taok2 develop gross cortical and cortex layering abnormalities. Moreover, acute Taok2 downregulation or Taok2 knockout delayed the migration of upper-layer cortical neurons in mice, and the expression of a constitutively active form of JNK1 rescued these neuronal migration defects. Finally, we report that the brains of the Taok2 KO and 16p11.2 del Het mouse models show striking anatomical similarities and that the heterozygous 16p11.2 microdeletion mouse model displayed reduced levels of phosphorylated JNK1 and neuronal migration deficits, which were ameliorated upon the introduction of TAOK2α in cortical neurons and in the developing cortex of those mice. These results delineate the critical role of TAOK2 in cortical development and its contribution to neurodevelopmental disorders, including ASD.

Cognitive dysfunction and cortical structural abnormalities in first-episode drug-naïve schizophrenia patients with auditory verbal hallucination.

ObjectiveThe current study aimed to examine the cognitive profiles and cortical structural alterations in first-episode drug-naïve schizophrenia with AVH (auditory verbal hallucination).MethodsCortical structural parameters including cortical thickness and local gyrification index (LGI) estimated using FreeSurfer as well as cognitive performance assessed on the MATRICS Consensus Cognitive Battery (MCCB) were acquired from 78 schizophrenia patients with AVH, 74 schizophrenia patients without AVH (non-AVH), and 76 healthy controls (HC). Hoffman Auditory Hallucination Rating Scale (HAHRS) was applied to assess the severity of AVH.ResultsThe results revealed extensive deficits in all cognitive domains among AVH, non-AVH, and HC groups. Compared to non-AVH group, the AVH group showed poorer performance on visual learning and verbal learning domains. There were six brain regions with cortical thinning in the right hemisphere of inferior temporal gyrus, superior temporal gyrus, lateral orbito frontal cortex, rostral anterior cingulate cortex, supramarginal gyrus and insula, and two brain regions with increased LGI in the left hemisphere of superior parietal gyrus and the right hemisphere of caudal anterior cingulate cortex on AVH group relative to non-AVH group. Correlation analysis revealed that the cortical thickness in the right hemisphere of lateral orbito frontal cortex was negatively correlated with the severity of AVH in schizophrenia patients with AVH.ConclusionVisual learning, verbal learning dysfunction, and specific disruption of cortical structure may characterize schizophrenia patients with AVH during early stages of the disorder. Right lateral orbito frontal cortical deficits may be the pathological mechanisms underlying AVH in first-episode drug-naïve schizophrenia.

Mapping structural covariance networks in children and adolescents with post-traumatic stress disorder after earthquake.

For children and adolescents, there is a high risk of developing post-traumatic stress disorder (PTSD) after suffering from catastrophic events. Previous studies have identified brain functionally and subcortical brain volumes structurally abnormalities in this population. However, up till now, researches exploring alterations of regional cortical thickness (CTh) and brain interregional structural covariance networks (SCNs) are scarce. In this cross-sectional study, CTh measures are derived from 3-Tesla Tl-weighted MRI imaging data in a well-characterized combined group of children and adolescents with PTSD after an earthquake (N = 35) and a traumatized healthy control group (N = 24). By using surface-based morphometry (SBM) techniques, the regional CTh analysis was conducted. To map interregional SCNs derived from CTh, twenty-five altered brain regions reported in the PTSD population were selected as seeds. Whole-brain SBM analysis discovered a significant thickness reduction in the left medial orbitofrontal cortex for the subjects with PTSD. Similarly, analysis of SCNs associated with “seed” regions primarily located in default mode network (DMN), midline cortex structures, motor cortex, auditory association cortex, limbic system, and visual cortex demonstrated that children and adolescents with PTSD are associated with altered structural covariance with six key regions. This study provides evidence for distinct CTh correlates of PTSD that are present across children and adolescents, suggesting that brain cortical abnormalities related to trauma exposure are present in this population, probably by driving specific symptom clusters associated with disrupted extinction recall mechanisms for fear, episodic memory network and visuospatial attention.

OP05.04: Expert neurosonography versus magnetic resonance imaging: comparison of techniques in detecting cortical abnormalities in a high‐risk population

OP05.04: Expert neurosonography versus magnetic resonance imaging: comparison of techniques in detecting cortical abnormalities in a high‐risk population

A-266 Neuropsychological Profile of a 5-Year-Old Boy with Gould Syndrome

Abstract Objective: Gould syndrome (COL4A1/A2-related disorders) is an extremely rare, genetic disorder characterized by cerebral vasculature defects, ocular dysgenesis, myopathy, and cerebral cortical abnormalities. Many individuals with COL4A1 mutations exhibit seizures, stroke, visual field defects, and hydrocephalus. To date, research regarding neuropsychological sequelae of Gould syndrome has been sparse. Therefore, this presentation aims to present clinical considerations for pediatric patients with Gould syndrome. Method: Patient is a 5-year-old Hispanic boy born at 35-weeks following perinatal stroke, pre-term birth, and suspected cyanosis. After birth, genetic testing revealed a COL4A1p.G1234R gene mutation (i.e., Gould syndrome). Patient’s medical history is also notable for cerebral palsy, epilepsy, encephalopathy, hypertonia, global developmental delays with language regression, and attention-deficit/hyperactivity disorder. Previous brain MRIs have found decreased white matter density in both cerebral hemispheres. Abbreviated neuropsychological testing was completed during an inpatient pre-surgical epilepsy evaluation. Patient was non-verbal. Results: Non-verbal intellectual ability was Below Average (IQ=74). Receptive language was Average (SS=93). Further, bilateral fine-motor speed and dexterity and visual motor integration were Exceptionally Low. Standardized questionnaires revealed ongoing concerns related to attention, hyperactivity, and poor adaptive functioning. Diagnostic impressions included Global Developmental Delay. Conclusion: Gould syndrome can include a variety of neurological sequelae depending on neurological defects and incidents. These findings are consistent with the “early vulnerability” position of brain development, which proposes that earlier age at brain insult may result in greater impairments in cognitive functioning (Jacomb et al., 2018). Therefore, early intervention and targeted long-term interventions appears imperative to improve function outcomes for pediatric patients with Gould syndrome.

A morphological study of schizophrenia with magnetic resonance imaging, advanced analytics, and machine learning.

We have performed a morphological analysis of patients with schizophrenia and compared them with healthy controls. Our analysis includes the use of publicly available automated extraction tools to assess regional cortical thickness (inclusive of within region cortical thickness variability) from structural magnetic resonance imaging (MRI), to characterize group-wise abnormalities associated with schizophrenia based on a publicly available dataset. We have also performed a correlation analysis between the automatically extracted biomarkers and a variety of patient clinical variables available. Finally, we also present the results of a machine learning analysis. Results demonstrate regional cortical thickness abnormalities in schizophrenia. We observed a correlation (rho = 0.474) between patients’ depression and the average cortical thickness of the right medial orbitofrontal cortex. Our leading machine learning technology evaluated was the support vector machine with stepwise feature selection, yielding a sensitivity of 92% and a specificity of 74%, based on regional brain measurements, including from the insula, superior frontal, caudate, calcarine sulcus, gyrus rectus, and rostral middle frontal regions. These results imply that advanced analytic techniques combining MRI with automated biomarker extraction can be helpful in characterizing patients with schizophrenia.

Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

Absence-like Seizures, Cortical Oscillations Abnormalities and Decreased Anxiety-like Behavior in Wistar Audiogenic Rats with Cortical Microgyria

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach to increment epileptogenesis and SES is to use a second insult to be added to the genetic background. Here, we used adult naïve WARs with microgyria induced by neonatal cortical freeze-lesion (FL) to evaluate the occurrence of SES and the modification in cortical oscillation patterns and behavior. The neonatal cortical FL was performed in Wistar and naïve WARs (Wis-FL and WAR-FL). Sham animals were used as controls (Wistar-S and WAR-S). Video-EEG recordings and behavioral tasks were performed during adulthood. Surprisingly, spike-waive discharges (SWD) events associated with behavior arrest were detected in WAR-S rats. Those events increased in duration and number in WAR-FL animals. The EEG quantitative analysis showed decreased power of cortical delta, theta and beta oscillations in WAR-S, decreased power of cortical fast gamma (FG) oscillations in WARs, independent of microgyria, and decreased interhemispheric synchrony for delta and FG with stronger coupling in delta and theta-FG oscillations in FL animals. The WARs, regardless of microgyria, had reduced locomotor activity, but only WAR-FL animals had reduced anxiety-like behavior. Microgyria in naïve WARs intensified SWD events associated with behavior arrest that could reflect absence-like seizures and abnormal cortical oscillations, and reduced anxiety-like behavior indicating that WAR-FL could be a reliable model to study epileptogenesis.

Cortical Abnormalities in Patients with Fibromyalgia: A Pilot Study of Surface-Based Morphometry Analysis.

Although neuroanatomical studies correlated to fibromyalgia (FM) are gaining increasing interest, the cortical morphology of patients are largely unknown, and data on cortical gyrification are scarce. The objective of the present study is to assess the cortical morphology in female patients with FM compared with healthy controls (HC) using surface-based morphometry (SBM) analysis of magnetic resonance imaging (MRI). T1-MRIs and clinical data of 20 FM patients and 20 HC subjects were obtained from a public data set via OpenNeuro. For each subject, surface parameters including cortical thickness, local gyrification index (LGI), sulcal depth, and fractal dimensionality were estimated using SBM analysis. These data were compared between two groups controlled by age. The correlations between regional SBM parameters showing group differences and clinical profiles were analyzed. Compared with HC subjects, FM patients showed reduced cortical thickness in right primary motor cortex, lower LGI in right rostral anterior cingulate and higher sulcal depth in right precuneus (P < 0.05 cluster level family- wise error corrected). In FM patients, correlation analysis showed that the cortical thickness in right primary motor cortex were inversely correlated with scores of pain catastrophizing scale (r = -0.498, P = 0.030) and pain self-perception scale (r = -0.527, P = 0.020), and disease duration (r = -0.488, P = 0.034), respectively. Our findings provide evidence of neuroanatomical aberrations in FM patients, which may provide insight into the neuropathology of FM.

Cortical thickness abnormalities in attention deficit hyperactivity disorder revealed by structural magnetic resonance imaging: Newborns to young adults.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition for which we have an incomplete understanding, and so brain imaging methods, such as magnetic resonance imaging (MRI), may be able to assist in characterising and understanding the presentation of the brain in an ADHD population. Statistical and computational methods were used to compare participants with ADHD and neurotypical controls at a variety of developmental stages to assess detectable abnormal neurodevelopment potentially associated with ADHD and to assess our ability to diagnose and characterise the condition from real-world clinical MRI examinations. T1-weighted structural MRI examinations (n =993; 0-31 years old [YO]) were obtained from neurotypical controls, and 637 examinations were obtained from patients with ADHD (0-26 YO). Measures of average (mean) regional cortical thickness were acquired, alongside the first reporting of regional cortical thickness variability (as assessed with the standard deviation [SD]) in ADHD. A comparison between the inattentive and combined (inattentive and hyperactive) subtypes of ADHD is also provided. A preliminary independent validation was also performed on the publicly available ADHD200 dataset. Relative to controls, subjects with ADHD had, on average, lowered SD of cortical thicknesses and increased mean thicknesses across several key regions potentially linked with known symptoms of ADHD, including the precuneus and supramarginal gyrus.

The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients.

Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC). Methods Twenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant ) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between and FA in each group were evaluated using Spearman’s rho correlation coefficients. Results Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384). Conclusion Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.

Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications

PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.

Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients.

To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively. Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV.

Long-term brain changes in bipolar disorder

IntroductionThe term “neuroprogression” imply that bipolar disorder (BD) progressively worsens for some patients and accompanying neuroanatomical changes. BD has indeed been associated with cortical and subcortical brain abnormalities. But cross-sectional studies cannot determine whether the observed brain alterations reflect static premorbid traits or whether they result from progressive changes during the course of illness.ObjectivesThe aims of this series of studies were to determine if progressive brain changes occur in bipolar disorder, and if so, what the drivers of these changes are.MethodsWe addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.ResultsWe addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.ConclusionsBD is associated with some (accelerated ventricular enlargement) but not global progressive brain changes (change in cortical structures do not differ from controls). Occurrence of manic episodes is, however, associated with accelerated cortical thinning over time. These results highlight the importance of preventing the potentially toxic effects of manic episodes and might explain why some patients experience worsening cognitive function.DisclosureML has received lecture honoraria (unrelated to this topic) from Lundbeck pharmaceuticals.

Increased spectral power of theta rhythm is not associated with decreased supragranular thickness in first-episode schizophrenia

IntroductionSchizophrenia is associated with disturbances in neurophysiological processes. However, the relation of EEG and ERP parameters to structural supragranular cortical abnormalities, observed in schizophrenia, remains unclear.ObjectivesThe purpose was to characterize EEG and ERP disturbances and their relationship to changes occurring in supragranular cortical layers in subjects with schizophrenia.Methods43 first-episode schizophrenia (FES) male patients and 43 matched healthy controls (HC) underwent background EEG and standard two-tones oddball ERP recording and structural MRI at 3T Philips scanner. MRI images were processed via FreeSurfer and MATLAB to derive two markers specific to supragranular thickness change: gyral-sulcal thickness differences (GSTD) and gyral-sulcal intrinsic curvature differences on pial surface (GSCD) (github.com/kwagstyl/schizophrenia_gyral_sulcal).ResultsTheta rhythm spectral power was increased in FES while P300 amplitudes and latencies, N100 (to non-targets) amplitudes, alpha rhythm spectral power were not altered compared to HC. GSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES. No correlations between altered EEG and supragranular thickness markers survived correction for multiple comparisons.ConclusionsPresumably, theta rhythm has a widespread circuit of generators, including the cortical ones. However, we have not found correlations between EEG and supragranular markers in FES. Considering an absence of correlations between theta and hippocampal volumes (Lebedeva et al., 2020), a speculative interpretation is that the neurophysiological disturbances may be associated with a more complex patterns of more localized structural and functional impairments.DisclosureThe work was supported by RFBR grant 20-013-00748.