Frontal Cortex Research Articles

Neuroanatomical alterations in brain disorder: A magnetic resonance imaging analysis

Background: Bipolar disorder is a serious mental disorder caused by strong mood fluctuations, affecting 2% of the world's population. People with bipolar disorder experience both manic and depressive episodes, which can lead to suicidal thoughts and changes in appetite, activity, and focus. There are different subtypes of bipolar disorder, with cyclothymic disorder being the milder of the two. Bipolar I is characterized by manic periods, while bipolar II is marked by hypomanic and significant depressive episodes. Bipolar disorder is a biological, genetic, and environmental condition that can affect anyone at any age. Methods: In this study, we enrolled a total of 49 bipolar disorder (BD) participants to 44 healthy control (HC) subjects. Bipolar disorder patients were enlisted with their consent using web portals, medical facilities, and local marketing. MRI contraindications, medical history, self-reported using a mood-altering medication, inadequate vision, and left-handedness were among the exclusion criteria. The various tissue structures which are: the gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were examined using voxel-based morphometry (VBM) to ascertain these changes. We employed statistical parametric mapping (SPM) for both image processing and statistical analysis. Results: Our findings demonstrate that individuals with bipolar disorder showed a substantial volume decrease in both gray matter (GM) and white matter (WM), with gray matter (GM) and white matter (WM) volume decreases being more noticeable in the frontal, temporal, parietal, and occipital lobes. Additionally, individuals with bipolar disorder showed no CSF volume in any of the brain regions. Conclusion: Our VBM research backs up earlier studies that link changes in brain structure, particularly gray matter and white matter, to bipolar disorder. These discoveries shed more information on the neurology of bipolar disorder and could guide the creation of more potent diagnostic and treatment modalities.

A case report of neonatal incontinentia pigmenti complicated by severe cerebrovascular lesions in one of the male monozygotic twins

BackgroundThis article reports a case of neonatal incontinentia pigmenti onset in only one male monozygotic twin with characteristic skin lesions after birth followed by severe cerebrovascular lesions.Case presentationA male infant, the first of monozygotic twins, was born with multiple yellow pustules all over his body, repeated new herpes at different sites during the course of the disease, aggravated by fusion, warty crusts, and hyperpigmentation; biopsy pathology suggested eosinophilic spongiform edema of the skin. Peripheral blood eosinophils were significantly elevated, and brain magnetic resonance imaging revealed diffuse multiple cystic and lamellar abnormal signal areas in the left frontal and parietal lobes. On day 30, the infant showed neurological symptoms, such as poor response and apnea, and an emergency cranial computed tomography scan revealed abnormal changes in the left cerebral hemisphere and bilateral cerebellum. After admission, he was given a potassium permanganate bath and topical mupirocin for 1 month, and the skin abnormalities improved. He was treated with mechanical ventilation and vasoactive drugs for 2 days after the cerebrovascular accident, and died the same day after the parents chose hospice care. No deletion variants or point mutations were detected in subsequent genetic tests, and chromosomal copy number variation tests revealed different degrees of chimeric duplications and deletions in different regions of chromosomes Y and 3. The parents were healthy, and his twin brother had normal growth and development with no abnormalities at multiple follow-up visits.ConclusionNeonatal incontinentia pigmenti in only one male monozygotic twin is extremely rare and the genetic diagnosis is challenging. Awareness of the combined cerebrovascular lesions needs to be enhanced, and potential prevention and treatment methods need to be explored to improve the prognosis.

Changes in the central nervous system in football players: an MRI study.

Football (soccer) is the world's most popular team sport. To comprehensively examine the brain in football (soccer) players, with the use of magnetic resonance imaging (MRI) techniques. The study involved 65 football players and 62 controls. The MR examinations were performed using MR 1.5-T system (Optima MR 360; GE Medical Systems). The examinations were carried out in the 3D Bravo, CUBE, FSEpropeller, and diffusion-weighted imaging (DWI) sequences. The 1HMRS signal was obtained from the volume of interest in the frontal and occipital lobes on both sides. The present study, based on structural MRI, shows some changes in the brains of the group of football players. The findings show asymmetry of the ventricular system in four football players, arachnoid cysts in the parieto-occipital region, and pineal cysts. NAA/Cr concentration in the right frontal lobe was lower in the football players than in the controls, and the Glx/Cr concentration in the right occipital lobe was higher. The apparent diffusion coefficient value is lower in football players in the occipital lobes. Playing football can cause measurable changes in the brain, known to occur in patients diagnosed with traumatic brain injury. The present findings fill the gap in the literature by contributing evidence showing that playing football may lead to changes in the brain, without clinical symptoms of concussion.

Subthalamic nucleus–language network connectivity predicts dopaminergic modulation of speech function in Parkinson’s disease

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.

Trying harder: how cognitive effort sculpts neural representations during working memory.

While the exertion of mental effort improves performance on cognitive tasks, the neural mechanisms by which motivational factors impact cognition remain unknown. Here, we used fMRI to test how changes in cognitive effort, induced by changes in task difficulty, impacts neural representations of working memory. Participants (both sexes) were precued whether working memory difficulty would be hard or easy. We hypothesized that hard trials demanded more effort as a later decision required finer mnemonic precision. Behaviorally, pupil size was larger and response times were slower on hard compared to easy trials suggesting our manipulation of effort succeeded. Neurally, we observed robust persistent activity during delay periods in prefrontal cortex, especially during hard trials. Yet, details of the memoranda could not be decoded from patterns in prefrontal activity. In the patterns of activity in visual cortex, however, we found strong decoding of memorized targets, where accuracy was higher on hard trials. To potentially link these across-region effects, we hypothesized that effort, carried by persistent activity in prefrontal cortex, impacts the quality of working memory representations encoded in visual cortex. Indeed, we found that the amplitude of delay period activity in frontal cortex predicted decoded accuracy in visual cortex on a trial-wise basis. These results indicate that effort-related feedback signals sculpt population activity in visual cortex, improving mnemonic fidelity.Significance Statement A full understanding of the neural mechanisms underlying our cognitive abilities depends on understanding their interplay with factors such as cognitive effort. Here, we relied on the simple intuition that some tasks require more effort than others and success depends on how hard we try. We show how the exertion of cognitive effort - trying harder - improves the quality of working memory representations in visual cortex mediated by feedback from prefrontal cortex. Such a mechanism describes how the limited resources that support working memory are allocated and strategically controlled. These results have implications for psychiatric disorders, like schizophrenia, where motivational deficits may masquerade as cognitive dysfunction.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (β=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Automated Scoring of Alzheimer’s Disease Atrophy Scale with Subtype Classification Using Deep Learning-Based T1-Weighted Magnetic Resonance Image Segmentation

Background: Application of visual scoring scales for regional atrophy in Alzheimer’s disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets.

Brain Connectomics Improve the Prediction of High-Risk Depression Profiles in the First Year following Breast Cancer Diagnosis

Background. Prediction of high-risk depression trajectories in the first year following breast cancer diagnosis with fMRI-related brain connectomics is unclear. Methods. The Be Resilient to Breast Cancer (BRBC) study is a multicenter trial in which 189/232 participants (81.5%) completed baseline resting-state functional magnetic resonance imaging (rs-fMRI) and four sequential assessments of depression (T0-T3). The latent growth mixture model (LGMM) was utilized to differentiate depression profiles (high vs. low risk) and was followed by multivoxel pattern analysis (MVPA) to recognize distinct brain connectivity patterns. The incremental value of brain connectomics in the prediction model was also estimated. Results. Four depression profiles were recognized and classified into high-risk (delayed and chronic, 14.8% and 12.7%) and low-risk (resilient and recovery, 50.3% and 22.2%). Frontal medial cortex and frontal pole were identified as two important brain areas against the high-risk profile outcome. The prediction model achieved 16.82-76.21% in NRI and 12.63-50.74% in IDI when brain connectomics were included. Conclusion. Brain connectomics can optimize the prediction against high-risk depression profiles in the first year since breast cancer diagnoses.

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33years) for 20min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Exposure to hyperbaric O2 levels leads to blood-brain barrier breakdown in rodents

IntroductionHyperbaric oxygen has been used as a medical treatment tool in hyperbaric chambers and is an integral part of professional and combat divers’ activity. In extreme cases, exposure to hyperbaric oxygen can develop central nervous system oxygen toxicity (CNS-OT), which leads to seizures and eventually death. CNS-OT is caused by neuronal hyperactivity due to high oxygen levels, potentially damaging brain cells including the blood-brain barrier (BBB). However, the effect of hyperbaric oxygen levels on the healthy BBB has not been characterized directly yet.MethodsSix or three different groups of ~ eight rats or mice, respectively, were exposed to increasing levels of partial pressure of oxygen (0.21 to 5 ATA) in a hyperbaric chamber, followed by MRI scanning with gadolinium. Statistical significance (adjusted p-value ≤ 0.05) was assessed using linear regression and ordinary one-way (rats) or two-way (mice) ANOVA with correction of multiple comparison tests. In rats, the effect of 100% oxygen at 5 ATA was independently validated using FITC-Dextran (5 kDa). Statistical significance (p-value ≤ 0.05) was assessed using Welch’s t-test and effect size was calculated by Cohen’s D.ResultsIn rats, analyzed MRI scans showed a significant trend of increase in the % gadolinium in brain tissues as a result of hyperbaric oxygen pressures (p-value = 0.0079). The most significant increase was measured at 4 ATA compared to air (adjusted p-value = 0.0461). Significant increased FITC-Dextran levels were measured in the rats’ brains under 100% oxygen at 5 ATA versus air (p-value = 0.0327; Effect size = 2.0). In mice, a significant increase in gadolinium penetration into the hippocampus and frontal cortex was measured over time (adjusted p-value < 0.05) under 100% oxygen at 3 and 5 ATA versus air, and between the treatments (adjusted p-value < 0.0001).ConclusionsThe BBB is increasingly disrupted due to higher levels of hyperbaric oxygen in rodents, indicating a direct relation between hyperbaric oxygen and BBB dysregulation for the first time. We suggest considering this risk in different diving activities, and protocols using a hyperbaric chamber. On the other hand, this study highlights the potential therapeutic usage of hyperbaric oxygen for controlled drug delivery through the BBB into brain tissues in different brain-related diseases.

Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial

BackgroundResearch on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS:...

Transcranial direct current stimulation in the treatment of alcohol, tobacco and opioid use disorder in clinical studies

Transcranial direct current stimulation (tDCS) is a promising research tool to address substance abuse, including alcohol, tobacco, opioid, and drug use disorders. The present literature review compared previous studies conducted with various current intensities, application regions, durations of stimulations, and different region targets of the brain. Studies based on the analyses conducted after tDCS administration in substance use disorder were promising for the use of tDCS as adjunctive therapy to reduce visible psychological and neurological symptoms of the addiction. Therefore, we aimed to provide an insight into the current state of research on tDCS as a therapeutic intervention in substance use disorders, identify gaps in the literature, and emphasize future investigation areas. Ultimately, the review sought to contribute to the understanding of the role of tDCS in addressing the complex challenges posed by substance use disorder, and its potential as a complementary or adjunctive treatment modality in addiction care. The present study identified that the left dlPFC and brain regions were effective targets for 1 mA and 2 mA tDCS current density in tobacco/nicotine use disorder. Also, the left dlPFC and 2 mA current density were identified as effective targets for tDCS in alcohol use disorder. Furthermore, left dlPFC and 2 mA current density were identified as effective targets for tDCS in opioid use disorder. Additionally, the right/left dlPFC, orbital frontal cortex, thalamus, and 2 mA current density were identified as effective targets for tDCS in other drug or substance use disorders. Animal studies demonstrated that tDCS was promising in reducing neuropathic pain, modulating neuropeptide Y activity, and reducing the redevelopment of ethanol consumption in animal models. However, further research is required to fully understand the optimal tDCS application parameters.

Association between electroencephalogram alpha-band oscillations and executive and processing functions in patients with cerebral small vessel diseases.

Electroencephalogram (EEG) alpha-band oscillations may reflect executive and processing function in patients with cerebral small vessel disease (CSVD). We aimed to assess such association and its relationship with CSVD severity, and to identify specific alpha-band parameters and the cut-off values for cognitive screening. We analysed the dispersion of amplitude-frequency characteristics of EEG alpha-band and different alpha-band parameters (PFα , ΔPFα , PPα , NCL) in different brain locations. We also assessed patients' executive and processing functions using verbal fluency test (VFT) and color trails test (CTT), and CSVD severity using total burden and Fazekas scores. 129 patients were recruited in the study. After adjusting for age, gender and education, PFα(F3), PFα(F4) and NCL were significantly associated with VFT-composite performance (p < 0.05). CTT-1 time and error were associated with PFα(F3), PFα(F4), ΔPFα(O1;F3) and CSVD severity (p < 0.05), whereas CTT-2 time was only associated with CSVD severity. Moreover, the correlations between alpha-band oscillations and cognitive function were higher in low than in high disease-severity group (ρ: -0.58 vs. -0.38, p < 0.05). The AUC of selected alpha-band parameters were higher than 0.8 for VFT and CTT. Specific alpha-band parameters in the frontal lobe were identified to correspond to executive and processing function. Assessing EEG alpha-band oscillations may assist in screening cognitive impairment.

Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging.

Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics. The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics. Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics. Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology. This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

Robot-assisted treatment of secondary epilepsy caused by parasitic infection: a case report

BackgroundCerebral sparganosis represents the most severe manifestation of sparganosis, with a relatively low global incidence. For cases of secondary epileptic seizures caused by sparganosis infection in the functional areas of the brain, what advanced neurosurgical techniques should be employed to precisely identify and excise the epileptic lesions in the deep functional areas of the brain, aiming to achieve maximal removal while minimising the risk of neurological deficits? This remains a current challenge for epilepsy surgeons.Case presentationA 24-year-old Chinese male was admitted to our hospital, presenting with a history of left limb twitching persisting for over a year. His main clinical symptoms presented twitching and numbness of his left limb without loss of consciousness. Under the premise of inappropriate anti-seizure treatment, recurrent epilepsy attacked persist. The patient's diagnosis was considered as “space-occupying lesions in the several lobes of brain, secondary epilepsy” after comprehensive assessment and discussion. And experts considered that the patient's space-occupying lesions in the right frontal and parietal lobes were highly suspected to be infected by parasites. This report delved into the application of neurosurgery robot-assisted frameless stereotaxic technology and intraoperative stereotactic electroencephalography (SEEG) monitoring technology to accurately locate and optimize removal of parasite-related epileptic lesions situated in functional areas of the brain. As a result, the patient had achieved seizure freedom, leaving no symptoms of neurological deficit.ConclusionsWith the highly integrated development of imaging technology, mechanical technology, computer control technology, and artificial intelligence, surgical robots are poised to play a larger role across various neurosurgical specialties in the future. Considering benefits for patients and the promising application of this technology, its utilization holds significant value.

Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases

We present the case of a 33-year-old male referred across several hospitals because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). Initially admitted in October 2022 for a recurrent, severe cough and diagnosed with CTEPH, he received anticoagulant therapy. However, his symptoms worsened, necessitating a transfer to another facility for thrombolysis treatment. Following an episode of syncope, an MRI scan revealed a metastatic brain tumor. Subsequently, he experienced a third transfer to our hospital, emergency surgery was performed to alleviate cerebral edema and excise a lesion in the left frontal lobe. Postoperative pathology was inconclusive, but a multidisciplinary team meeting, aided by experienced radiologists, eventually confirmed a diagnosis of pulmonary artery sarcoma (PAS) with systemic metastases. This case underscores the necessity of promptly ruling out PAS in patients presenting with significant emboli in the central pulmonary arteries and suggests early referral to specialized centers for suspected cases.

"Witzelsucht". On the introduction and meaning of the term by Hermann Oppenheim in 1890 and its distinction from "moria"

Hermann Oppenheim (1858-1919) was a German neurologist without an academic career, who in his productive period around 1900 made aname for himself during his lifetime as amajor player in the history of German neurology with his many contributions to multiple sclerosis, syphilis and the controversial study of traumatic neurosis; however, it is almost unknown that in 1890 he introduced the term "witzelsucht", which is still used internationally today. Moritz Jastrowitz dealt with behavioral abnormalities due to frontal brain injuries 1year earlier and used the term "moria" for aform of mental disorder associated with akind of childish behavior and inappropriate jocularity. Oppenheim was critical of this and differentiated his "witzelsucht" from this. With this term he wanted to describe humoristic feeble-mindedness in a much narrower sense, which stands in striking contrast to the usual symptoms in cases of cerebral tumors. Oppenheim recognized the frontal brain, particularly the right brain, to be an important functional unit for humorous behavior. Modern research has confirmed that the processing of humor requires a complex interaction of multiple brain regions. Damage to the right frontal lobe or to connecting structures can lead to the disorder "witzelsucht". Whether asimultaneous damage to the left hemisphere must be present or if this is dependent on the individual dominant hemisphere, needs further research.

Comparing mouse and human cingulate cortex organization using functional connectivity.

The subdivisions of the extended cingulate cortex of the human brain are implicated in a number of high-level behaviors and affected by a range of neuropsychiatric disorders. Its anatomy, function, and response to therapeutics are often studied using non-human animals, including the mouse. However, the similarity of human and mouse frontal cortex, including cingulate areas, is still not fully understood. Some accounts emphasize resemblances between mouse cingulate cortex and human cingulate cortex while others emphasize similarities with human granular prefrontal cortex. We use comparative neuroimaging to study the connectivity of the cingulate cortex in the mouse and human, allowing comparisons between mouse 'gold standard' tracer and imaging data, and, in addition, comparison between the mouse and the human using comparable imaging data. We find overall similarities in organization of the cingulate between species, including anterior and midcingulate areas and a retrosplenial area. However, human cingulate contains subareas with a more fine-grained organization than is apparent in the mouse and it has connections to prefrontal areas not present in the mouse. Results such as these help formally address between-species brain organization and aim to improve the translation from preclinical to human results.

Schizencephaly: Etiopathogenesis, Classification, Therapeutic, and Rehabilitative Approach

AbstractSchizencephaly is an uncommon anomaly in neuronal migration characterized by complete clefts that extend from the pia mater to the ependymal surface of the ventricular system. These clefts are encompassed by displaced gray matter and filled with cerebrospinal fluid. Typically, they are found most often in the frontal lobe or the area around the lateral sulcus and can occur on one or both sides. The size, location, and type of these clefts carry significant clinical and prognostic implications. Moreover, they are frequently associated with other central nervous system malformations, including the absence of the septum pellucidum, septo-optic dysplasia, optic nerve hypoplasia, pachygyria, polymicrogyria, cortical dysplasia, heterotopia, and dysplasia of the corpus callosum. Occurrence of schizencephaly is almost always sporadic but its etiopathogenesis is yet to be fully understood. Most likely environmental factors, including exposure to teratogens, viral infections, and maternal factors, operate jointly with genetic defects. To date COL4A1, EMX2, SHH, and SIX3 are the genes identified as possible pathogenetic target. It is interesting to notice that schizencephaly is commonly seen in abandoned or adopted children, as proof of causative effect of intrautero insults. Clinical presentations widely vary and symptoms include a spectrum of cognitive impairment, limb paresis/tetraparesis, and epileptic seizures either with early or late onset; anyway, none of these symptoms is ever-present and patients with schizencephaly can also have normal neurocognitive and motor development. Diagnostic gold standard for schizencephaly is magnetic resonance imaging, which allows to identify and characterize typical clefts. Treatment of schizencephaly is symptomatic and supportive and depends on the severity of morbidity resulting from the malformation. Therapy includes antiepileptic drugs, psychomotor rehabilitation, and in selected cases surgical approach.

Holoprosencephaly: The Disease and Its Related Disabilities

AbstractHoloprosencephaly (HPE), the most prevalent developmental anomaly affecting the forebrain in humans, occurs in ∼1 in 16,000 liveborn neonates, with an incidence reaching 1 in 250 in conceptuses. This condition is distributed worldwide. HPE is etiologically heterogeneous, and its pathogenesis is variable. Environmental, teratogenic, genetic, or metabolic factors can contribute to the development of HPE. Notably, maternal insulin-dependent diabetes mellitus and maternal alcoholism are among the primary causative factors. HPE may be linked to various well-defined multiple malformation syndromes characterized by a normal karyotype, such as Smith–Lemli–Opitz's, Pallister–Hall's, or velocardiofacial syndrome. Alternatively, it can be associated with chromosomal abnormalities. (i.e., Patau's syndrome and, less frequently, Edwards' syndrome or Down's syndrome). The major genes implicated in HPE are SHH, ZIC2, SIX3, and TGIF. The range of HPE is extensive, covering diverse neuropathological phenotypes of varying severity. Three classical types of HPE can be distinguished in increasing order of severity: lobar HPE, characterized by separated right and left ventricles with some continuity across the frontal cortex; semilobar HPE, featuring a partial separation; and the most severe form, alobar HPE, where there is a single brain ventricle and the absence of an interhemispheric fissure. Additionally, there are other variations of HPE, ranging in severity, including the less severe interhemispheric median HPE (also known as middle interhemispheric variant). The phenotypic spectrum of HPE is highly extensive, encompassing severe cerebral malformations to microforms. Children with HPE often encounter numerous medical challenges; among them neurological disorders, craniofacial malformations, endocrine disorders, oral and motor dysfunction, and dysfunction of the autonomic nervous system. Neurologic problems, such as cerebral palsy and seizures, are common. The diagnosis of HPE is typically made prenatally, relying primarily on ultrasound and magnetic resonance imaging examinations. The prognosis for individuals with HPE is largely dependent on its underlying causes. Those with cytogenetic abnormalities, in particular, face a significantly poorer prognosis, with only 2% surviving beyond 1 year.