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Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.

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Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia.

Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness may be associated with dysregulation of core intracellular processes such as signaling pathways that underlie the regulation and integration of these systems. The AKT-mTOR signaling cascade has been implicated in SZ by gene association, postmortem brain and animal studies. AKT and mTOR are serine/threonine kinases which play important roles in cell growth, proliferation, survival, and differentiation. Both AKT and mTOR require phosphorylation at specific sites for their complete activation. mTOR forms two functionally distinct multiprotein complexes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2). mTORC1 mediates ribosome biogenesis, protein translation, and autophagy, whereas mTORC2 contributes to actin dynamics. Altered protein synthesis and actin dynamics can lead to an abnormal neuronal morphology resulting in deficits in learning and memory. Currently, there is a lack of direct evidence to support the hypothesis of disrupted mTOR signaling in SZ, and we have addressed this by characterizing this signaling pathway in SZ brain. We found a reduction in AKT and mTOR protein expression and/or phosphorylation state in dorsolateral prefrontal cortex (DLPFC) from 22 pairs of SZ and matched comparison subjects. We also found reduced protein expression of GβL, a subunit protein common to both mTOR complexes. We further investigated mTOR complex-specific subunit composition and phosphorylation state, and found abnormal mTOR expression in both complexes in SZ DLPFC. These findings provide evidence that proteins associated with the AKT-mTOR signaling cascade are downregulated in SZ DLPFC.

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Mental state space visualization for interactive modeling of personalized BCI control strategies.

Numerous studies in the area of BCI are focused on the search for a better experimental paradigm -- a set of mental actions that a user can evoke consistently and a machine can discriminate reliably. Examples of such mental activities are motor imagery, mental computations, etc. We propose a technique that instead allows the user to try different mental actions in the search for the ones that will work best.

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Cushing's dogged struggle against death: the astonishing case of a patient under cardiac arrest surviving craniopharyngioma surgery.

The decisive role Dr. Harvey Cushing (1869-1939) played in medicine goes far beyond the development of neurosurgery. His scientific devotion and commitment to patient care made him an ethical model of strict professionalism. This paper seeks to analyze the decisions Cushing made with the challenging case of HW, an adolescent boy with a craniopharyngioma (CP) involving the third ventricle. Cushing's earlier failure to successfully remove two similar lesions alerted him to the proximity of HW's tumor and the hypothalamus. Consequently, he decided to use the chiasm-splitting technique for the first time, with the aim of dissecting the CP-hypothalamus boundaries under direct view. Unexpectedly, HW suffered cardiac arrest during the surgery, but Cushing did not give up. He continued with the operation while his assistants performed resuscitation maneuvers. Such determined and courageous action allowed Cushing to succeed in an apparently hopeless case. Cushing's unwavering willingness to save patients' lives, even under extreme circumstances, was a fundamental trait defining his identity as a neurosurgeon. Analyzing the way Cushing dealt with HW's case provides valuable lessons for neurosurgeons today, particularly the importance of assuming proactive attitudes and, in certain cases, making painstaking efforts to overcome daunting situations to save a life.

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Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study.

Extensive resection of a tumor in the posterior fossa in children is associated with the risk of neurological deficits. The objective of this study was to prospectively evaluate the short-term neurological morbidity in children after medulloblastoma surgery and relate this to the tumor's growth pattern and to the extent of resection.

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Occipital nerve stimulation and deep brain stimulation for refractory cluster headache: a prospective analysis of efficacy over time.

Occipital nerve stimulation (ONS) and deep brain stimulation (DBS) are widely used surgical treatments for chronic refractory cluster headache (CH). However, there is little literature regarding long-term follow-up of these treatments.

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Letter to the Editor. ClearPoint versus frame-based MRI-guided and MRI-verified deep brain stimulation.


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Rapid evacuation of chronic subdural hematoma - A possible traumatic brain injury (TBI).

The chronic subdural hematoma is an entity, which affects mainly the elderly patients. According to literature, the complication rate was up to 22,7%, including recurrence of hematoma, worsening of the neurological status, postoperative delirium, etc. Treating of a chronic subdural hematoma could be conservative and operative, including twist drill craniostomy, single or multiple burr hole drainage, and craniotomy. In the patients who underwent a decompression of the hematoma a postoperative hyperperfusion syndrome could be observed, according to literature up to 51,4%. This syndrome is associated risk of postoperative delirium and neurological deterioration. The hyperperfusion syndrome is also observed in traumatic brain injury. A rapid decompression of a subdural hematoma leads to a brain shifting to the skull bones and thus a traumatic brain injury due to decompression. The development of the hyperperfusion syndrome could be related to the decompression of the subdural hematoma in a rapid fashion.

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Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice.

This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1β level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.

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Forced conceptual thought induced by electrical stimulation of the left prefrontal gyrus involves widespread neural networks.

Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM).

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