Biology subjects

Hadi, Z.

Publications and source records attributed to Hadi, Z..

5 recordsLinked to original sources

bioRxiv2026

Conventional dendritic cells type I with an enhanced type-I-IFN signaling underpin anti-tumor immune responses in brain metastases

Brain metastases are associated with poor prognosis. A better understanding of anti-tumor immune responses in the context of immune specialized microenvironment of the brain is required to develop improved therapeutic strategies for this disease. We demonstrate that the conventional dendritic cells type 1 (cDC1) gene signature positively correlates with a prolonged BrM-dependent survival in melanoma and breast cancer patients. Furthermore, intracranial anti-tumor immune responses in preclinical BrM models consistently rely on cDC1s for tumor growth control, BrM-dependent survival and maintenance of the intra-tumoral CD8+ T cell pool, in contrast to variable, cancer type-dependent cDC1 roles in extracranial tumors. This is underpinned by tumor site-specific cDC1 molecular profiles with distinct Toll like receptor repertoires, upregulation of co-stimulatory molecules and IL-12, and enhanced type-I-IFN signaling in intracranial cDC1s, with the latter driving increased cDC1 activation. cDC1s also promote the conversion of progenitor exhausted CD8+ T cells to transient effectors, which is further enhanced by immune checkpoint blockade therapy. These findings pinpoint cDC1s as a major cell population of interest in the development of future immunotherapies for BrM. Significance statementCharacteristics of immune cells and tumor microenvironment in brain metastases (BrM) are distinct to extracranial tumor sites and characterized by special immunological barriers and suppressive stroma. Conventional dendritic cells type 1 (cDC1s), which are key regulators of anti-tumor immunity, remain largely unexplored in this context. This study deepens our understanding of how anti-tumor immune responses differ between BrM and extracranial tumors by revealing BrM-specific phenotype and function of cDC1s, with the latter being critical for anti-tumor immunity in BrM even in cancer models where extracranial cDC1s demonstrate pro-tumorigenic function, highlighting cDC1s as universal regulators of intracranial anti-tumor immunity. Our study suggests that tumor site-specific augmentation of cDC1s should be pursued to enhance the efficacy of immunotherapies in BrM.

cancer biology↗

bioRxiv2024

Vestibular prepulse inhibition of the human blink reflex

ObjectiveAuditory and somatosensory prepulses are commonly used to assess prepulse inhibition (PPI). The effect of a vestibular prepulse upon blink reflex (BR) excitability has not been hitherto assessed. MethodsTwenty-two healthy subjects and two patients with bilateral peripheral vestibular failure took part in the study. Whole body yaw rotation in the dark provided a vestibular inertial prepulse. BR was electrically evoked after the end of the rotation. The area-under-the-curve (area) of the BR responses (R1, R2, and R2c) was recorded and analysed. ResultsA vestibular prepulse inhibited the R2 (p < 0.001) and R2c area (p < 0.05). Increasing the angular acceleration did not increase the R2/R2c inhibition (p>0.05). Voluntary suppression of the vestibular-ocular reflex did not affect the magnitude of inhibition (p>0.05). Patients with peripheral vestibular failure did not show any inhibition. ConclusionsOur data support a vestibular-gating mechanism in humans. SignificanceThe main brainstem nucleus mediating PPI - the pedunculopontine nucleus (PPN) - is heavily vestibular responsive, which is consistent with our findings of a vestibular-mediated PPI. Our technique may be used to interrogate the fidelity of brain circuits mediating vestibular-related PPN functions. Given the PPNs importance in human postural control, our technique may also provide a neurophysiological biomarker of balance. HighlightsO_LIThis is the first report of a vestibular prepulse inhibition of the blink reflex. C_LIO_LIA vestibular prepulse inhibits the R2/R2c area in healthy subjects but not in patients with bilateral peripheral vestibular failure. C_LIO_LIVestibular PPI is a potential neurophysiological marker of vestibular-motor integration at the brainstem level. C_LI

neuroscience↗

bioRxiv2021

Vestibular Agnosia is linked to abnormal functional brain networks

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinsons Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Whole-brain rsfMRI was acquired from 39 prospectively recruited acute TBI patients with preserved peripheral vestibular function, along with self-motion perceptual thresholds during passive yaw rotations in the dark. Following quality-control checks, 25 patient scans were analyzed. TBI patients were classified as having vestibular agnosia (n = 11) or not (n = 14) via laboratory testing of self-motion perception. Using independent component analysis, we found altered functional connectivity in the right superior longitudinal fasciculus and left rostral prefrontal cortex in vestibular agnosia. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

neuroscience↗

bioRxiv2021

The Effects of Unilateral Transcranial Direct Current Stimulation on Unimanual Laparoscopic Peg-Transfer Task

IntroductionEfficient training methods are required for laparoscopic surgical skills training to reduce the time needed for proficiency. Transcranial direct current stimulation (tDCS) is widely used to enhance motor skill acquisition and can be used to supplement the training of laparoscopic surgical skill acquisition. The aim of this study was to investigate the effect of anodal tDCS over the primary motor cortex (M1) on the performance of a unimanual variant of the laparoscopic peg-transfer task. MethodsFifteen healthy subjects participated in this randomized, double-blinded crossover study involving an anodal tDCS and a sham tDCS intervention separated by 48 hours. On each intervention day, subjects performed a unimanual variant of laparoscopic peg-transfer task in three sessions (baseline, tDCS, post-tDCS). The tDCS session consisted of 10 minutes of offline tDCS followed by 10 minutes of online tDCS. The scores based on the task completion time and the number of errors in each session were used as a primary outcome measure. A linear mixed-effects model was used for the analysis. ResultsWe found that the scores increased over sessions (p<0.001). However, we found no effects of stimulation (anodal tDCS vs. sham tDCS) and no interaction of stimulation and sessions. ConclusionThis study suggests that irrespective of the type of current stimulation (anodal and sham) over M1, there was an improvement in the performance of the unimanual peg-transfer task, implying that there was motor learning over time. The results would be useful in designing efficient training paradigms and further investigating the effects of tDCS on laparoscopic peg-transfer tasks.

neuroscience↗

bioRxiv2019

The effect of single-task training on learning transfer to a novel bimanual task

BackgroundThe contextual interference effect suggests that the random practice of multiple-tasks is more beneficial for the retention and transfer of the learning as compared to blocked practice. Therefore, the transfer of learning is usually attributed to the contextual interference effect and is studied in a multi-task setting. ObjectiveThe goals of this study were to evaluate whether the transfer of learning (i) can occur when a single bimanual task is practiced, (ii) is affected by the knowledge of results (feedback), and (iii) sustains over an extended number of trials. MethodsFifty-two healthy subjects were equally divided into four groups. Before the transfer test, two groups practiced a bimanual finger-tapping task with feedback (EF) and without feedback (ENF). The third group (IM) practiced the same task using the kinesthetic motor imagery, whereas the last group acted as a control (CTRL) and performed only a bimanual button-pressing task used for the transfer test. ResultsLinear mixed-model showed that in the transfer test, groups EF, ENF and IM had similar performance but significantly higher scores compared to the CTRL group. Compared to the CTRL, the EF and IM groups showed significantly improved performance in most of the sessions but group ENF had similar results. ConclusionThis study suggests that the single-task practice of a discrete bimanual task can facilitate the learning transfer to a novel task and knowledge of results (feedback) have no significant impact on the transfer of learning. Moreover, the transfer of learning effect does not disappear in extended trials. HighlightsO_LISingle-task practice of a discrete bimanual task can facilitate the learning of a novel bimanual task C_LIO_LIKnowledge of results (feedback) does not improve learning transfer in single-task setting C_LIO_LITransfer of learning effect does not disappear in extended trials C_LI

neuroscience↗