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Background The aim of this study was to use tractography and diffusion kurtosis imaging (DKI) to evaluate cerebral white matter (WM) changes in patients with cerebrotendinous xanthomatosis (CTX) after stopping chenodeoxycholic acid (CDCA) treatment. Material and methods Two siblings with CTX aged 40 and 38 years, respectively, who had been diagnosed with CTX for 16 years were enrolled. They had received CDCA treatment from 2005 until 2015, after which CDCA was no longer available in Taiwan. Serial brain magnetic resonance imaging (MRI) studies were used to record brain changes, and a seres of neuropsychiatric tests were used to evaluate cognitive changes 3 years after stopping CDCA treatment. Results The conventional MRI studies revealed progressive changes in dentate nuclei and surrounding cerebellar hemispheres, but no obvious changes in cerebral white matter (WM). Tractography captured in 2018 showed a general reduction in fiber density, especially involving frontal lobe fibers, compared to 2015. In addition, the DKI studies performed in 2018 showed a decreased axonal water fraction in diffuse WM structures and increased RadEAD in frontal WM. Comparisons of the neuropsychiatric test results between 2015 and 2018 showed a marked decline in executive function including design fluency, digit backward span and digit forward span, and this cognitive impairment highly suggested frontal lobe dysfunction. Conclusions This study may suggest that cerebral tractography and DKI study results can identify changes in cerebral WM in CTX patients shortly after stopping CDCA treatment, and that they may have a better correlation with the results of neuropsychiatric tests.

Introduction: The human brain shows modest traits of sexual dimorphism, with the female brain, on average, 10% smaller than the male brain. These differences do not imply a lowered cognitive performance, but suggest a more optimal brain organization in women. Here we evaluate the patterns of functional connectivity (FC) in women and men from the Connectomics of Brain Aging and Dementia sample. Methods: We used phase locking values to calculate FC from the magnetoencephalography time series in a sample of 138 old adults (87 females and 51 males). We compared the FC patterns between sexes, with the intention of detecting regions with different levels of connectivity. Results: We found a frontal cluster, involving anterior cingulate and the medial frontal lobe, where women showed higher FC values than men. Involved connections included the following: (1) medial parietal areas, such as posterior cingulate cortices and precunei; (2) right insula; and (3) medium cingulate and paracingulate cortices. Moreover, these differences persisted when considering only cognitively intact individuals, but not when considering only cognitively impaired individuals. Discussion: Increased anteroposterior FC has been identified as a biomarker for increased risk of developing cognitive impairment or dementia. In our study, cognitively intact women showed higher levels of FC than their male counterparts. This result suggests that neurodegenerative processes could be taking place in these women, but the changes are undetected by current diagnosis tools. FC, as measured here, might be valuable for early identification of this neurodegeneration.

ObjectiveWe present a semi-automated method for quantifying structural changes after epilepsy surgery that accounts for tissue deformation caused by resection. We demonstrate its utility by comparing the remote structural effects of two surgical approaches, the anterior temporal lobectomy (ATL) and the selective amygdalohippocampectomy (SAH).MethodsWe studied 37 temporal lobe epilepsy (TLE) patients who underwent resective surgery. Patients were treated with either an anterior temporal lobectomy (ATL, N=21) or a selective amygdalohippocampectomy (SAH, N=16). All patients received same-scanner MR imaging preoperatively and postoperatively (5+ months after surgery). To analyze structural changes in remote brain regions, we (1) implemented an automated method for segmenting resections with manual review, (2) applied cost function masking to the resection zone, and (3) estimated longitudinal cortical thickness changes using Advanced Normalization Tools (ANTs). We then compared post-operative changes in cortical thickness between the two surgical groups in brain regions outside the resected area.ResultsPatients treated with ATL exhibited significantly greater cortical thinning globally when compared to patients treated with SAH (p = 0.049). There were significant focal differences between the two treatment groups in the ipsilateral frontal lobe (superior medial and medial orbital regions) and insula (p > 0.001, α = 0.05 Bonferroni corrected). No significant effects were seen in the contralateral hemisphere.SignificanceWe present and share a semi-automated pipeline for quantifying remote longitudinal changes in cortical thickness after neurosurgery. The technique is applicable to a broad array of applications, including surgical planning and mapping neuropsychological function to brain structure. Using this tool, we demonstrate that patients treated with SAH for refractory temporal lobe epilepsy have less postoperative cortical thinning in remote brain regions than those treated with ATL. We share all algorithm code and results to accelerate collaboration and clinical translation of our work.KEY POINTS BOXDifferent epilepsy surgical approaches lead to distinct patterns of postoperative cortical atrophy in remote brain regionsPatients treated with SAH have less postoperative cortical thinning than patients treated with ATLThe insula and frontal lobe demonstrated the greatest focal differences in postoperative cortical thinning when comparing SAH and ATLPostoperative cortical thinning analyses may inform surgical planning and our understanding of cognitive sequelae

BACKGROUND Recent studies suggest gliomas location may be correlated with specific biological signatures. Our purpose was to focus on the possible correlation between MGMT metilation status and Ki67 positivity with patient age, glioma location and lateralization. METHODS We performed a retrospective evaluation to assess the correlation between MGMT metilation status and Ki67 index positivity with patient age, glioma location and lateralization. RESULTS The study included 174 supratentorial gliomas. Of these, 144 tumors were high grade gliomas (HGGs) and 30 tumors were low grade gliomas (LGGs). In HGG group we detected an association between tumor location and MGMT status. Those GBMs located in the frontal lobe were significantly associated with MGMT methylated status (MGMT+) and Ki67

Traumatic brain injury (TBI) is a leading cause of neurologic disability; the most common deficits affect prefrontal cortex-dependent functions such as attention, working memory, social behavior, and mental flexibility. Despite this prevalence, little is known about the pathophysiology that develops in frontal cortical microcircuits after TBI. We investigated whether alterations in subtype-specific inhibitory circuits are associated with cognitive inflexibility in a mouse model of frontal lobe contusion in both male and female mice that recapitulates aberrant mental flexibility as measured by deficits in rule reversal learning. Using patch-clamp recordings and optogenetic stimulation, we identified selective vulnerability in the non-fast-spiking and somatostatin-expressing (SOM+) subtypes of inhibitory neurons in layer V of the orbitofrontal cortex 2 months after injury. These subtypes exhibited reduced intrinsic excitability and a decrease in their synaptic output onto pyramidal neurons, respectively. By contrast, the fast-spiking and parvalbumin-expressing interneurons did not show changes in intrinsic excitability or synaptic output, respectively. Impairments in non-fast-spiking/SOM+ inhibitory circuit function were also associated with network hyperexcitability. These findings provide evidence for selective disruptions within specific inhibitory microcircuits that may guide the development of novel therapeutics for TBI. SIGNIFICANCE STATEMENT TBI frequently leads to chronic deficits in cognitive and behavioral functions that involve the prefrontal cortex, yet the maladaptive changes that occur in these cortical microcircuits are unknown. Our data indicate that alterations in subtype-specific inhibitory circuits, specifically vulnerability in the non-fast-spiking/somatostatin-expressing interneurons, occurs in the orbitofrontal cortex in the context of chronic deficits in reversal learning. These neurons exhibit reduced excitability and synaptic output, whereas the other prominent inhibitory population in layer V, the fast-spiking/parvalbumin-expressing interneurons as well as pyramidal neurons are not affected. Our work offers mechanistic insight into the subtype-specific function of neurons that may contribute to mental inflexibility after TBI.

Introduction The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP. Methods Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines. Results Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum. Conclusions While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation.

OBJECTIVE The postictal state after bilateral tonic-clonic seizures is often prolonged and can have significant impact on a patient's quality of life. Considerable variability exists in the magnitude of postictal agitation and in the speed of recovery, the determinants of which are not well understood. We studied postictal behavior after tonic-clonic seizures in various epilepsy localizations, focusing on postictal agitation and time to responsiveness. METHODS We retrospectively identified 15 adult patients each with idiopathic generalized, left temporal lobe, right temporal lobe and frontal lobe epilepsy. Localization in focal epilepsy was validated by good outcome after resective surgery at one-year of follow-up. The first tonic-clonic seizure with reliable video and EEG for each patient was analyzed by two reviewers, one of whom was blinded to clinical data. Clinical, ictal and postictal variables were collected for each patient and analyzed. Postictal agitation was classified as mild and marked. RESULTS We reviewed 60 tonic-clonic seizures, 15 in each of four patient groups. Postictal agitation was observed in 14 patients (23.3%; marked in one and mild in 13). Postictal agitation was most common in patients with left temporal (seven patients) and least common in idiopathic generalized epilepsy (one patient) groups (p=0.035). Based on subgroup analysis (n=28), time to responsiveness was 6.6 minutes for frontal, 7.2 minutes for generalized, 10 minutes for right temporal and 15.7 minutes for the left temporal groups (p

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = −0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.

Anxiety is a complex emotional state that has a great impact on people's physical and mental health. Effectively identifying different anxiety states is very important. By inducing various anxiety states with electroencephalograph (EEG) recording, comprehensive EEG features (frequency and time domain features, statistical and nonlinear features) were extracted from different EEG bands and brain locations. Next, correlation analysis was performed for feature selection. And different classifiers were applied to classify four anxiety levels using different features alone or together to explore their anxiety recognition ability. Based on our dataset, the highest accuracy of identifying four anxiety states reached approximately 62.56% using the Support Vector Machine (SVM), which improved the classification accuracy compared with previous studies. The results also revealed the importance of EEG linear features (especially for features including total power, mean square and variance) in anxiety recognition. Furthermore, it suggested that EEG features in the beta band and the frontal lobe contributed to anxiety recognition more than the features in the other bands or other brain locations. In short, this study improves the accuracy of multi-level anxiety recognition and helps in choosing better features for anxiety recognition, which lay the foundation for the detection of continuous anxiety changes.

OBJECTIVE The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma. METHODS The study included all adult patients who underwent first-time glioblastoma surgery in 2012–2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival. RESULTS The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions. CONCLUSIONS Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

A 57-year-old male visited the hospital’s internal medicine department with a chief complaint of cognitive impairment for the past month. His Mini-Mental State Examination (MMSE) score was 23 points, exhibiting mild cognitive impairment. Brain magnetic resonance imaging (MRI) revealed no abnormalities; however, positive anti-SSA and anti-SSB antibodies were detected via bloodwork. To assess the patient for Sjogren’s syndrome (SS), the internal medicine department referred the patient to our department. Lip biopsy detected infiltrates of more than 50 lymphocytes surrounding the duct of the minor salivary gland. Furthermore, the patient’s brain single-photon emission computed tomography (SPECT) revealed a mild blood flow reduction within the frontal lobe, parietal lobe, and posterior cingulate gyrus on the right side. Findings from the patient’s bloodwork and histopathological examination led to a diagnosis of SS. Other autoimmune diseases did not complicated the diagnosis, and the diagnosis was primary Sjogren’s syndrome (pSS) accompanied by autoimmune encephalitis. After hospitalization by internal medicine physicians, pulse steroid therapy was initiated, and the patient displayed cognitive improvement, with an improvement in the MMSE score to 27 points.

Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract (PT), intratelencephalic (IT) and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scale. Cortical activity and optogenetic inactivation during an auditory decision task also revealed distinct functional roles: all PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, PT neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice-tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.

The electroencephalographic derived indices have been developed for adult patients, however these monitors have not been validated for infants.Frontal EEGs were recorded in 115 infants aged 1 year [0-3-months (N = 27), 4-6-months (N = 30), 7-9-months (N = 29) and 10-12-months (N = 29)] who received general anaesthesia with sevoflurane. Total power (µVNewborns show a mean relative δ-power at 80% in intraoperative EEG compared to infants (10-12 months) showing 47.5%. Relative β-power and α-power are low in newborns (mean 3.2% and 4.6%; respectively), with a marked increase in the older infants (4-6 months) (mean 10.9% and 14.4%; respectively). EEG dynamic in newborns from baseline (relative δ-power of 88%) to the intraoperative situation (80.5%) are discrete. In contrast infants 6-months have a strong reduction of relative δ-power from baseline to the intraoperative situation, which corresponds to an increase of faster frequencies.Age dependent perioperative EEG signatures can be demonstrated in infants younger than one year.We demonstrate significant differences in EEG readouts between newborns and infants which questions our monitoring systems in paediatric anaesthesia.

Orbital telorism, the interocular distance, is a clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We derived measures of orbital telorism from cranial magnetic resonance imaging (MRI) by calculating the distance between the eyeball center of gravity in two population-based datasets (N=5,653, N=29,824, Mean age 64.66, 63.75 years). This measure was found to be related grey matter tissue density within numerous regions of the brain, including, but surprisingly not limited to, the frontal regions, in both positive and negative directions. Additionally, telorism was related to several cognitive functions, such as Perdue Pegboard test (Beta, P-value, (CI95%) −0.02, 1.63×10-7(−0.03;-0.01)) and fluid intelligence (0.02, 4.75×10-06(0.01:0.02)), with some relationships driven by individuals with a smaller orbital telorism. This is reflective of the higher prevalence of hypo-telorism in developmental disorders, specifically those that accompany lower cognitive lower functioning. This study suggests, despite previous links only made in clinical extremes, that orbital telorism holds some relation to structural brain development and cognitive function in the general population. This relationship is likely driven by shared developmental periods.

Cognitive control and working memory (WM) processes are essential for goal-directed behaviour. Cognitive control and WM are probably based on overlapping neurophysiological mechanisms. For example, theta-band activity (TBA) plays an important role in both functions. For cognitive control processes, it is known that different aspects of information about stimulus content, motor processes and stimulus-response relationships are encoded simultaneously in the TBA. All this information is probably processed during WM gating processes and must be controlled during them. However, direct data for this are lacking. This question is investigated in this study by combining methods of EEG temporal signal decomposition, time-frequency decomposition and beamforming. We show that portions of stimulus-related information, motor response-related information and information related to the interaction between the stimulus and motor responses in the TBA are influenced in parallel and to a similar extent by WM gate opening and gate closing processes. Nevertheless, it is stimulus-related information in the theta signal in particular that modulates behavioural performance in WM-gating. The data suggest that the identified processes are implemented in specific neuroanatomical structures. In particular, the medial frontal cortex, temporal cortical regions and insular cortex are involved in these dynamics. The study shows that principles of information coding relevant to cognitive control processes are also crucial for understanding WM gating.

Agitation is a common neuropsychiatric symptom of Alzheimer’s disease (AD) that greatly impacts quality of life and amplifies caregiver burden. Agitation in AD may be associated with volume loss in the anterior cingulate cortex, posterior cingulate cortex, insula, amygdala, and frontal cortex, as well as with degeneration of monoaminergic neurotransmission, disrupted circadian rhythms, and frailty. Current pharmacological options have troubling safety concerns and only modest efficacy. There is increasing interest in cannabinoids as promising agents due to pre-clinical and early clinical research that suggest cannabinoids can elicit anxiolytic, antidepressant, and/or anti-inflammatory effects. Cannabinoids may relieve agitation by regulating neurotransmitters, improving comorbidities and circadian rhythms, and increasing cerebral circulation. Here we discuss the possible contributory mechanisms for agitation in AD and the therapeutic relevance of cannabinoids, including CBD and THC.

In drug-resistant temporal lobe epilepsy, precise predictions of drug response, surgical outcome and cognitive dysfunction at an individual level remain challenging. A possible explanation may lie in the dominant ‘one-size-fits-all’ group-level analytical approaches that does not allow parsing interindividual variations along the disease spectrum. Conversely, analysing inter-patient heterogeneity is increasingly recognized as a step towards person-centred care. Here, we used unsupervised machine learning to estimate latent relations (or disease factors) from 3 T multimodal MRI features [cortical thickness, hippocampal volume, fluid-attenuated inversion recovery (FLAIR), T1/FLAIR, diffusion parameters] representing whole-brain patterns of structural pathology in 82 patients with temporal lobe epilepsy. We assessed the specificity of our approach against age- and sex-matched healthy individuals and a cohort of frontal lobe epilepsy patients with histologically verified focal cortical dysplasia. We identified four latent disease factors variably co-expressed within each patient and characterized by ipsilateral hippocampal microstructural alterations, loss of myelin and atrophy (Factor 1), bilateral paralimbic and hippocampal gliosis (Factor 2), bilateral neocortical atrophy (Factor 3) and bilateral white matter microstructural alterations (Factor 4). Bootstrap analysis and parameter variations supported high stability and robustness of these factors. Moreover, they were not expressed in healthy controls and only negligibly in disease controls, supporting specificity. Supervised classifiers trained on latent disease factors could predict patient-specific drug response in 76 ± 3% and postsurgical seizure outcome in 88 ± 2%, outperforming classifiers that did not operate on latent factor information. Latent factor models predicted inter-patient variability in cognitive dysfunction (verbal IQ: r = 0.40 ± 0.03; memory: r = 0.35 ± 0.03; sequential motor tapping: r = 0.36 ± 0.04), again outperforming baseline learners. Data-driven analysis of disease factors provides a novel appraisal of the continuum of interindividual variability, which is probably determined by multiple interacting pathological processes. Incorporating interindividual variability is likely to improve clinical prognostics.

Thalamus and thalamocortical connectivity are crucial for consciousness; however, their microstructural changes in patients with a disorder of consciousness (DOC) have not yet been thoroughly characterized. In the present study, we applied the novel fixel-based analysis to comprehensively investigate the thalamus-related microstructural abnormalities in 10 patients with DOC using 7-T diffusion-weighted imaging data. We found that compared to healthy controls, patients with DOC showed reduced fiber density (FD) and fiber density and cross-section (FDC) in the mediodorsal, anterior, and ventral anterior thalamic nuclei, while fiber-bundle cross-section (FC) was not significantly altered in the thalamus. Impaired thalamocortical connectivity in the DOC cohort was mainly connected to the middle frontal gyrus, anterior cingulate gyrus, fusiform gyrus, and sensorimotor cortices, including the precentral gyrus and postcentral gyrus, with predominant microstructural abnormalities in FD and FDC. Correlation analysis showed that FC of the right mediodorsal thalamus was negatively correlated with the level of consciousness. Our results suggest that microstructural abnormalities of thalamus and thalamocortical connectivity in DOC were mainly attributed to axonal injury. In particular, the microstructural integrity of the thalamus is a vital factor in consciousness generation.

Age-related differences in the functional hierarchical organization of the frontal lobe remain unclear. We adopted task-related functional magnetic resonance imaging (fMRI) to investigate age differences in the functional hierarchical organization of the frontal lobe. Behavioral results report both reaction time and efficiency declined as the levels of abstraction increased in the selection of a set of stimulus–response mappings in older adults compared with young adults. fMRI findings suggest trends of the hierarchical organization along the rostro–caudal axis in both groups, and brain–behavior correlation further suggests neural dedifferentiation in older adults when performing at the highest level of control demands experiment. Behavioral performances and age difference overactivations at the highest level of control demands were both associated with working memory capacity, suggesting the working memory capacity is important for processing the highest task demands. Region-of-interest analysis revealed age differences in brain overactivation and common activation across experiments in the primary motor cortex, parietal lobule, and the fusiform gyrus may serve as shared mechanisms underlying tasks that are required for the selection of stimulus–response mapping sets. Overall, older adults reflect maladaptive overactivation in task-irrelevant regions that are detrimental to performance with the highest control demands.

Background: The endogenous allocation of spatial attention to selected environmental stimuli is controlled by prefrontal (frontal eye fields [FEFs]) and parietal (superior parietal lobe [SPL] and intraparietal sulcus [IPS]) regions belonging to the dorsal attention network (DAN) with a subdivision in subsystems devoted to reorienting (or shifting) of attention between locations (SPL) or maintaining attention at contralateral versus ipsilateral locations (ventral IPS [vIPS]). Although previous studies suggested a leading role of prefrontal regions over parietal sites in orienting attention, the spectral signature of communication flow within the DAN for different attention processes is still debated. Methods: We used the directed transfer function (DTF) on magnetoencephalography (MEG) data to examine the causal interaction between prefrontal and parietal regions of the DAN when subjects shifted versus maintained attention to a stream of cued visual stimuli. Results: In the beta band, we found that shift versus stay cues induced stronger connectivity (DTF values) from right FEF to right SPL, in the early phase of reorienting. Conversely, when considering stay versus shift cues, an increase of DTF values and stronger directionality was observed between bilateral vIPS and from right vIPS to FEF. Similar analyses carried out in theta, alpha, and gamma showed no significant frontoparietal increases of DTF for shift versus stay cues, whereas the stay-related increase of DTF observed in beta between ventral parietal areas was preserved in the alpha band. Conclusions: These findings suggest that control processes in DAN regions (in particular between FEF and SPL) can be associated to a beta frequency channel during shift of attention. Impact statement In the present study, we compared the reorienting response to novel stimuli with respect to maintaining response. Results provided new insights into understanding the neural mechanisms of control attention processes by identifying the frequency-specific causal interactions between frontal and parietal regions belonging to the dorsal attention network supporting spatial reorienting response.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by excessive risky behavior, and an impulsive trait has been proposed to be associated with risk-taking. However, the aspect of the cognitive process that impulsivity influences is not well understood. We hypothesized that impulsivity could be related to an overhasty shifting of beliefs during risk learning, thereby resulting in enhanced risk-taking behavior. In this study, we tested our hypothesis using the Bayesian modeling approach and predicted overhasty learning by a data-driven approach. We used an openly available task-based functional magnetic resonance imaging (fMRI) dataset. Participants with adult ADHD (n = 42) completed the balloon analog risk task (BART). By fitting our computational model that encapsulates the degree of overhasty learning, we estimated the degree of learning bias and investigated its relationship with Barratt Impulsiveness Scale (BIS) outcomes. Moreover, we created a connectome-based predictive model (CPM) based on fMRI data to predict the degree of risk-learning bias. The degree of overhasty learning in ADHD patients was significantly correlated with the BIS score (r = 0.424, p = 0.009). The CPM predicted the ‘learning bias’ parameter using negatively correlated edges (r = 0.341, p = 0.041; q2 = 0.092). The ‘hub nodes’ in the predictive network were in the frontal lobe, including the orbitofrontal area. Our findings suggest that impulsivity in ADHD patients is associated with overhasty updating of beliefs during risk learning. Weak functional connectivity to the both dorso-lateral prefrontal and orbitofrontal lobes is predictive of the degree of overhasty learning.

In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

Background High-positioned and/or superoposteriorly directed anterior communicating artery aneurysms can be treated by direct clipping using the pterional (fronto-temporo-sphenoidal) approach. This procedure, however, requires stronger retraction of the frontal lobe. Hence, preservation of the prominent frontal bridging veins (FBVs) draining into the sphenoparietal sinus (SPS) remains a significant challenge in preventing postoperative venous congestion. Methods We developed a technique to release the tension on the FBVs by pulling them together with the SPS epidurally. In 2 patients, who had presented with high-positioned and/or superoposteriorly directed anterior communicating artery aneurysms, we peeled off the arachnoid surrounding the FBVs and detached it from the brain surface. We further released the veins by moving them posteriorly, together with the SPS epidurally. Results Using this technique, we established a wide corridor through a more lateral transsylvian trajectory with effective posterior retraction of the frontal lobe and were successful in clipping and obliterating the aneurysms. Conclusions Open clipping of unruptured intracranial aneurysms requires accuracy to preserve higher brain function. Our technique was successful in both patients, and preserving the FBVs could be useful in the treatment of such aneurysms.

Background Focused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening has shown efficacy in removal of amyloid plaque and improvement of cognitive functions in preclinical studies, but this is rarely reported in clinical studies. This study was conducted to evaluate the safety, feasibility and potential benefits of repeated extensive BBB opening. Methods In this open-label, prospective study, six patients with Alzheimer’s disease (AD) were enrolled at Severance Hospital in Korea between August 2020 and September 2020. Five of them completed the study. FUS-mediated BBB opening, targeting the bilateral frontal lobe regions over 20 cm3, was performed twice at three-month intervals. Magnetic resonance imaging, 18F-Florbetaben (FBB) positron emission tomography, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) and comprehensive neuropsychological tests were performed before and after the procedures. Results FUS targeted a mean volume of 21.1 ± 2.7 cm3 and BBB opening was confirmed at 95.7% ± 9.4% of the targeted volume. The frontal-to-other cortical region FBB standardized uptake value ratio at 3 months after the procedure showed a slight decrease, which was statistically significant, compared to the pre-procedure value (− 1.6%, 0.986 vs1.002, P = 0.043). The CGA-NPI score at 2 weeks after the second procedure significantly decreased compared to baseline (2.2 ± 3.0 vs 8.6 ± 6.0, P = 0.042), but recovered after 3 months (5.2 ± 5.8 vs 8.6 ± 6.0, P = 0.89). No adverse effects were observed. Conclusions The repeated and extensive BBB opening in the frontal lobe is safe and feasible for patients with AD. In addition, the BBB opening is potentially beneficial for amyloid removal in AD patients.

Objective:Evidence from adult literature shows the involvement of cortical grey matter areas of the frontoparietal lobe and the white matter bundle, the superior longitudinal fasciculus (SLF) in motor planning. This is yet to be confirmed in children.Method:A multimodal study was designed to probe the neurostructural basis of childhood motor planning. Behavioural (motor planning), magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) data were acquired from 19 boys aged 8–11 years. Motor planning was assessed using the one and two colour sequences of the octagon task. The MRI data were preprocessed and analysed using FreeSurfer 6.0. Cortical thickness and cortical surface area were extracted from the caudal middle frontal gyrus (MFG), superior frontal gyrus (SFG), precentral gyrus (PcG), supramarginal gyrus (SMG), superior parietal lobe (SPL) and the inferior parietal lobe (IPL) using the Desikan–Killiany atlas. The DWI data were preprocessed and analysed using ExploreDTI 4.8.6 and the white matter tract, the SLF was reconstructed.Results:Motor planning of the two colour sequence was associated with cortical thickness of the bilateral MFG and left SFG, PcG, IPL and SPL. The right SLF was related to motor planning for the two colour sequence as well as with the left cortical thickness of the SFG.Conclusion:Altogether, morphology within frontodorsal circuity, and the white matter bundles that support communication between them, may be associated with individual differences in childhood motor planning.

OBJECTIVE Neurodevelopmental delays and frontal lobe cortical dysmaturation are widespread among children with congenital heart disease (CHD). The subventricular zone (SVZ) is the largest pool of neural stem/progenitor cells in the postnatal brain. Our aim is to determine the effects of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation in piglets whose SVZ development is similar to human infants. METHODS Three-week-old piglets (n = 29) were randomly assigned to control (no surgery), mild-CPB (34°C full flow for 60 minutes) and severe-CPB groups (25°C circulatory-arrest for 60 minutes). The SVZ and frontal lobe were analyzed with immunohistochemistry 3 days and 4 weeks postoperatively. MRI of the frontal lobe was used to assess cortical development. RESULTS SVZ neurogenic activity was reduced up to 4 weeks after both mild and severe CPB-induced insults. CPB also induced decreased migration of young neurons to the frontal lobe, demonstrating that CPB impairs postnatal neurogenesis. MRI 4 weeks after CPB displayed a decrease in gyrification index and cortical volume of the frontal lobe. Cortical fractional anisotropy was increased after severe CPB injury, indicating a prolonged deleterious impact of CPB on cortical maturation. Both CPB-induced insults displayed a significant change in densities of three major inhibitory neurons, suggesting excitatory-inhibitory imbalance in the frontal cortex. In addition, different CPB insults altered different subpopulations of inhibitory neurons. INTERPRETATION Our results provide novel insights into cellular mechanisms contributing to CHD-induced neurological impairments. Further refinement of CPB hardware and techniques is necessary to improve long-term frontal cortical dysmaturation observed in children with CHD. ANN NEUROL 2021;90:913-926.

The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an ‘arrest’ pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a ‘clumsy’ pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

Cerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer’s disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aβ burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.

Supplementary motor area (SMA) syndrome refers to varying degrees of transient hemiparesis and mutism following insult to the medial posterior frontal lobe. We describe a rare case of an isolated lower limb SMA deficit with associated pre- and post-operative multimodality neurophysiological monitoring data. We review the literature on SMA somatotopy and the prognostic abilities of intraoperative motor evoked potentials in suspected SMA dysfunction. A 45-year-old male underwent staged resection of a complex parasagittal WHO grade II meningioma involving the posterior superior frontal gyrus bilaterally. Intraoperative neurophysiological monitoring with transcranial motor evoked potentials (TCMEP) and direct cortical motor evoked potentials (DCMEP) were used during both stages of resection. The patient developed an isolated left foot drop despite unchanged DCMEP and TCMEP data obtained during the first stage of the procedure. During the second stage of resection 3 days later, repeat neurophysiological monitoring confirmed intact corticospinal tracts. Deep peroneal somatosensory evoked potentials (SSEPs) revealed good morphology, appropriate latency and amplitudes during the second stage of resection. These results suggested a diagnosis of focal SMA dysfunction. Left foot drop persisted 7 days post-operatively. At one month follow up, the patient was neurologically intact with full strength noted in all muscle groups of the left lower extremity. An improved understanding of the somatotopic organization of the SMA with additional neuromonitoring data can allow neurosurgeons to better predict and understand perioperative SMA dysfunctions.

There is considerable individual variability in second language (L2) learning abilities in adulthood. The inferior parietal lobule, important in L2 learning success, is anatomically connected to language areas in the frontal lobe via the superior longitudinal fasciculus (SLF). The second and third branches of the SLF (SLF II and III) have not been examined separately in the context of language, yet they are known to have dissociable frontoparietal connections. Studying these pathways and their functional contributions to L2 learning is thus of great interest. Using diffusion MRI tractography, we investigated individuals undergoing language training to explore brain structural predictors of L2 learning success. We dissected SLF II and III using gold-standard anatomical definitions and related prelearning white matter integrity to language improvements corresponding with hypothesized tract functions. SLF II properties predicted improvement in lexical retrieval, while SLF III properties predicted improvement in articulation rate. Finer grained separation of these pathways enables better understanding of their distinct roles in language, which is essential for studying how anatomical connectivity relates to L2 learning abilities.

In contrast to the traditional definition of the disorder, many individuals with aphasia exhibit non-linguistic cognitive impairments, including executive control deficits. Classic lesion studies cite frontal lobe damage in executive dysfunction, but more recent lesion symptom-mapping studies in chronic aphasia present mixed results. In this study, we compared executive control abilities of acute stroke survivors with and without aphasia and investigated lesion correlates of linguistic and non-linguistic cognitive tasks. Twenty-nine participants with acute left hemisphere stroke resulting in aphasia (n = 14) or no aphasia (n = 15) completed clinical MRI and testing, including three NIH Toolbox Cognition Batteries (Pattern Comparison Processing Speed, Flanker Inhibitory Control and Attention, and Dimensional Change Card Sort Tests) and the Boston Naming Test. We compared performance between groups using Wilcoxon rank sum tests. We used Least Absolute Shrinkage and Selection Operator Regression to identify neural markers (percent regional damage, hypoperfusion within vascular territories, and total lesion volume) of executive control deficits and anomia. Group performance was comparable on the Pattern Comparison Processing Speed Test, but people with aphasia had poorer standard scores, lower accuracy, and slower response times on the Dimensional Change Card Sort Test than people without aphasia. Damage to extrasylvian regions (dorsolateral prefrontal cortex, intraparietal sulcus) was related to executive control deficits, whereas language network damage (to inferior frontal and superior and posterior middle temporal gyri) was linked to naming impairments. These results suggest people with aphasia can exhibit comorbid executive control impairments linked to damage outside classic language network areas. Supplementary Information The online version contains supplementary material available at 10.1007/s11682-021-00580-y.

Objectives We investigated peripheric smell regions of olfactory bulb (OB) volume and olfactory sulcus (OS) depth in temporal and frontal lobe epilepsy patients by cranial magnetic resonance imaging (MRI). Methods In this retrospective study, cranial MRI images of 150 adult patients were included. Group 1 was consisted of 50 adult patients with temporal lobe epilepsy (TLE). Group 2 was consisted of 50 adult patients with frontal lobe epilepsy (FLE). The control group (Group 3) was consisted of 50 healthy subjects without epilepsy. OB volume and OS depth were measured in all groups. Results OB volumes of the temporal and frontal epilepsy groups were significantly lower than those of the control group (padjusted 0.05). In the temporal and frontal epilepsy groups, there were positive correlations between OB volumes; OS depths; left OB volume and bilateral OS depths p 0.05). Conclusion We concluded that temporal and frontal epilepsy maybe related to decrease in OB volume and may cause olfactory impairment. Olfactory deficit maybe related to central epileptic focus. Therefore, early diagnosis and appropriate treatment of epilepsy are important to prevent olfactory impairment.

Many patients with glioma experience surgery-related language impairment. This study developed a classification system to predict postoperative language prognosis. Sixty-eight patients were retrospectively reviewed. Based on their location, tumors were subtyped as follows: (I) inferior frontal lobe or precentral gyrus; (II) posterior central gyrus or supramarginal gyrus (above the lateral fissure level); (III) posterior region of the superior or middle temporal gyri or supramarginal gyrus (below the lateral fissure level); and (IV) insular lobe. The distance from the tumor to the superior longitudinal fasciculus/arcuate fasciculus was calculated. The recovery of language function was assessed using the Western Aphasia Battery before surgery, and a comprehensive language test was conducted on the day of surgery; 3, 7, and 14 days after surgery. Our follow-up information of was the comprehensive language test from telephone interviews in 3 months after surgery. Thirty-three patients experienced transient language impairment within 1 week of surgery. Fourteen patients had permanent language impairment. Type II tumors, shorter distance from the tumor to the posterior superior longitudinal fasciculus/arcuate fasciculus, and isocitrate dehydrogenase mutations were risk factors for surgery-related language impairment. Regarding the presence or absence of permanent surgery-related language impairments, the cut-off distance between the tumor and posterior superior longitudinal fasciculus/arcuate fasciculus was 2.75 mm. According to our classification, patients with type II tumors had the worst language prognosis and longest recovery time. Our classification, based on tumor location, can reliably predict postoperative language status and may be used to guide tumor resection.

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.

Across species, adolescence is a period of growing independence that is associated with the maturation of cognitive, social, and affective processing. Reorganization of neural circuits within the frontal cortex is believed to contribute to the emergence of adolescent changes in cognition and behavior. While puberty coincides with adolescence, relatively little is known about which aspects of frontal cortex maturation are driven by pubertal development and gonadal hormones. In this review, we highlight existing work that suggests puberty plays a role in the maturation of specific cell types in the medial prefrontal cortex (mPFC) of rodents, and highlight possible routes by which gonadal hormones influence frontal cortical circuit development.

Brain-age (BA) estimates based on deep learning are increasingly used as neuroimaging biomarker for brain health; however, the underlying neural features have remained unclear. We combined ensembles of convolutional neural networks with Layer-wise Relevance Propagation (LRP) to detect which brain features contribute to BA. Trained on magnetic resonance imaging (MRI) data of a population-based study (n=2637, 18-82 years), our models estimated age accurately based on single and multiple modalities, regionally restricted and whole-brain images (mean absolute errors 3.37-3.86 years). We find that BA estimates capture aging at both small and large-scale changes, revealing gross enlargements of ventricles and subarachnoid spaces, as well as white matter lesions, and atrophies that appear throughout the brain. Divergence from expected aging reflected cardiovascular risk factors and accelerated aging was more pronounced in the frontal lobe. Applying LRP, our study demonstrates how superior deep learning models detect brain-aging in healthy and at-risk individuals throughout adulthood.

Ageing is associated with endothelial dysfunction and reduced cerebral blood flow and oxygenation. The present study aimed to investigate whether turmeric supplementation could improve cerebral oxygenation and blood volume during brain activation via dynamic handgrip exercise in older males and females. Twelve older males and females were studied using a double-blind, placebo-controlled, cross-over design. Participants ingested turmeric root extract or placebo. Heart rate and blood pressure were measured before and 2 hours after supplementation. Afterward, the exercise protocol was started, and cerebral oxygenation and blood volume were evaluated. During exercise, changes in cerebral oxygenation were higher after turmeric extract supplementation, as was blood volume compared to placebo. Changes in heart rate, systolic blood pressure, and diastolic blood pressure were not significant. The current findings indicate the potential for curcumin as an intervention for improving cerebral oxygenation and blood volume changes in older males and females.