White matter and task-switching in young adults: A Diffusion Tensor Imaging study

The capacity to flexibly switch between different task rules has been previously associated with distributed fronto-parietal networks, predominantly in the left hemisphere for phasic switching sub-processes, and in the right hemisphere for more tonic aspects of task-switching, such as rule maintenance and management. It is thus likely that the white matter (WM) connectivity between these regions is critical in sustaining the flexibility required by task-switching. This study examined the relationship between WM microstructure in young adults and task-switching performance in different paradigms: classical shape-color, spatial and grammatical tasks. The main results showed an association between WM integrity in anterior portions of the corpus callosum (genu and body) and a sustained measure of task-switching performance. In particular, a higher fractional anisotropy and a lower radial diffusivity in these WM regions were associated with smaller mixing costs both in the spatial task-switching paradigm and in the shape-color one, as confirmed by a conjunction analysis. No association was found with behavioral measures obtained in the grammatical task-switching paradigm. The switch costs, a measure of phasic switching processes, were not correlated with WM microstructure in any task. This study shows that a more efficient inter-hemispheric connectivity within the frontal lobes favors sustained task-switching processes, especially with task contexts embedding non-verbal components

Domain-independent neural underpinning of task-switching: an fMRI investigation

The ability to shift between different tasks according to internal or external demands, which is at the core of our behavioral flexibility, has been generally linked to the functionality of left fronto-parietal regions. Traditionally, the left and right hemispheres have also been associated with verbal and spatial processing, respectively. We therefore investigated with functional MRI whether the processes engaged during task-switching interact in the brain with the domain of the tasks to be switched, that is, verbal or spatial. Importantly, physical stimuli were exactly the same and participants\u2019 performance was matched between the two domains. The fMRI results showed a clearly left-lateralized involvement of fronto-parietal regions when contrasting task-switching vs. single task blocks in the context of verbal rules. A more bilateral pattern, especially in the prefrontal cortex, was instead observed for switching between spatial tasks. Moreover, while a conjunction analysis showed that the core regions involved in task-switching, independently of the switching context, were localized both in left inferior prefrontal and parietal cortices and in bilateral supplementary motor area, a direct analysis of functional lateralization revealed that hemispheric asymmetries in the frontal lobes were more biased toward the left side for the verbal domain than for the spatial one and vice versa. Overall, these findings highlight the role of left fronto-parietal regions in task-switching, above and beyond the specific task requirements, but also show that hemispheric asymmetries may be modulated by the more specific nature of the tasks to be performed during task-switching

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Verb generation for presurgical mapping: Gaining specificity

Verb generation is among the most frequently used tasks in presurgical mapping. Because this task involves many processes, the overall brain effects are not specific. While it is necessary to identify the whole network involving noun comprehension or semantic retrieval and lexical selection to produce the verb, isolation of those components is also crucial. Here, we present data from four patients undergoing presurgical brain mapping. The study implied a reanalysis of magnetoencephalography data with a recategorization of the used items. It aimed to extract the task component that relies on the inferior frontal gyrus (IFG). The task could be applied with higher specificity when targeting frontal areas. For that, we based item classification on the selection demands imposed by the noun. It is a robust finding that the IFG carries out this selection and that a quantitative index can be calculated for each noun, which depends on the selection effort (Proceedings of the National Academy of Sciences of the United States of America, 1997; 94(26):14792–14797, Proceedings of the National Academy of Sciences of the United States of America, 1998; 95(26):15855–15860). Data showed focality and specificity, with a correlation between this derived index and source activations in the inferior frontal gyrus for all patients. Strikingly, we detected when the right‐hemisphere homologue area was involved in the selection process in two patients showing reorganization or language right lateralization. The present data are a step towards a dissection of broad specific tasks frequently used in presurgical protocols

Thalamopeduncular Tumors in Pediatric Age: Advanced Preoperative Imaging to Define Safe Surgical Planning: A Multicentric Experience

Background: Thalamopeduncular tumors are challenging lesions arising at the junction between the thalamus and the cerebral peduncle. They represent 1-5% of pediatric brain tumors, are mainly pilocytic astrocytoma and occur within the first two decades of life. To date, the optimal treatment remains unclear. Methods: We retrospectively reviewed pediatric patients who underwent surgery for thalamopeduncular tumors in the Academic Pediatric Neurosurgery Unit of Padova and Verona from 2005 to 2022. We collected information on age, sex, symptoms, preoperative and postoperative neuroradiological studies, histological specimens, surgical approaches, and follow-up. Results: We identified eight patients with a mean age of 9 years. All lesions were pilocytic astrocytoma. The main symptoms were spastic hemiparesis, cranial nerve palsy, headache, and ataxia. The corticospinal tract was studied in all patients using diffusion-tensor imaging brain MRI and in two patients using navigated transcranial magnetic stimulation. The transsylvian approach was the most frequently used. A gross total resection was achieved in two patients, a subtotal resection in five and a partial resection in one. In three patients, a second treatment was performed due to the regrowth of the tumor, performing an additional surgery in two cases and a second-look surgery followed by adjuvant therapy in one. After the surgery, four patients maintained stability in their postoperative neurological exam, two patients improved, and two worsened but in one of them, an improvement during recovery occurred. At the last follow-up available, three patients were disease-free, four had a stable tumor residual, and only one patient died from the progression of the disease. Conclusions: Advanced preoperative tools allow one to define a safe surgical strategy. Due to the indolent behavior of thalamopeduncular tumors, surgery should be encouraged

Bovine herpesvirus 4 based vector as a potential oncolytic-virus for treatment of glioma

The application of gene therapy for malignant gliomas is still under study and the use of specific vectors represents an important contribution. Here, we investigated bovine herpesvirus 4 (BoHV-4), which is non-pathogenic if injected into the rodent brain. We show that the vector can infect mouse, rat and human glioma cell lines and primary cultures obtained from human glioblastoma in vitro. BoHV-4 was injected into a tumour grown in rat brain. Although virus expression was scattered across the tumour mass, it was mainly located in the peripheral area of larger gliomas. These data support BoHV-4 as a candidate vector for glioma treatment

Disc Regeneration Using MSC Transplanted via the Endplate Route

IntroductionStem cell based intervertebral disc (IVD) regeneration is quickly moving toward clinical applications.1 However, many aspects need to be investigated to routinely translate this therapy..

Reproducible Disc Degeneration Scale in a Large Animal Model

IntroductionTo study the efficacy of novel regenerative strategies is necessary to develop new models that do not implement annulus fibrosus (AF) damage. We hypothesize an ideal preclinical model t..

Molecular Mechanisms of HIF-1α Modulation Induced by Oxygen Tension and BMP2 in Glioblastoma Derived Cells

BACKGROUND: Glioblastoma multiforme (GBM) is one of most common and still poorly treated primary brain tumors. In search for new therapeutic approaches, Bone Morphogenetic Proteins (BMPs) induce astroglial commitment in GBM-derived cells in vitro. However, we recently suggested that hypoxia, which is characteristic of the brain niche where GBM reside, strongly counter-acts BMP effects. It seems apparent that a more complete understanding of the biology of GBM cells is needed, in particular considering the role played by hypoxia as a signaling pathways regulator. HIF-1alpha is controlled at the transcriptional and translational level by mTOR and, alike BMP, also mTOR pathway modulates glial differentiation in central nervous system (CNS) stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigate the role of mTOR signaling in the regulation of HIF-1alpha stability in primary GBM-derived cells maintained under hypoxia (2% oxygen). We found that GBM cells, when acutely exposed to high oxygen tension, undergo Akt/mTOR pathway activation and that BMP2 acts in an analogous way. Importantly, repression of Akt/mTOR signaling is maintained by HIF-1alpha through REDD1 upregulation. On the other hand, BMP2 counter-acts HIF-1alpha stability by modulating intracellular succinate and by controlling proline hydroxylase 2 (PHD2) protein through inhibition of FKBP38, a PHD2 protein regulator. CONCLUSIONS/SIGNIFICANCE: In this study we elucidate the molecular mechanisms by which two pro-differentiating stimuli, BMP2 and acute high oxygen exposure, control HIF-1alpha stability. We previously reported that both these stimuli, by inducing astroglial differentiation, affect GBM cells growth. We also found differences in high oxygen and BMP2 sensitivity between GBM cells and normal cells that should be further investigated to better define tumor cell biology