Biology subjects

Miserocchi, A.

Publications and source records attributed to Miserocchi, A..

5 recordsLinked to original sources

bioRxiv2026

Histological morphometric correlates of MRI-defined cortical thinning in temporal lobe epilepsy

Large-scale MRI studies have consistently demonstrated progressive and age-accelerated neocortical thinning in temporal lobe epilepsy (TLE). These findings are frequently interpreted as evidence of cumulative neurodegeneration. However, the histopathological substrates underlying MRI-confirmed cortical thinning in epilepsy remain poorly defined. In particular, it is unknown whether cortical thinning reflects irreversible neuronal loss or potentially reversible epilepsy-related network alterations in cortical microstructure. We analysed the resected middle temporal gyrus from 117 individuals undergoing surgery for temporal lobe epilepsy, including cases with (n= 74) or without hippocampal sclerosis (HS) and 12 cases with additional temporal lobe sclerosis (TLS, or Focal Cortical Dysplasia IIIa), defined by a distinct pattern of cytoarchitectural reorganisation and gliosis involving superficial layers. All cases were stratified by the presence or absence of pre-operative MRI-defined cortical thinning of the middle temporal gyrus, quantified using CAT12 relative to healthy controls. On NeuN-immuno-labelled sections using automated image analysis we assessed neuronal spatial distributions relative to their size and packing density; relative cortical layer thickness and sulcal-gyral cytoarchitectural variation were also quantified. MRI-defined cortical thinning was not associated with diffuse neuronal loss. Instead, thinning correlated with increased neuronal density and altered cell-size spatial organisation in superficial and deep layers, particularly in right temporal lobe epilepsy cases with HS. There was limited evidence of layer-specific laminar thinning, being confined to layer VI in the right TLE/HS group only. Of note, TLS cases did not show either cortical thinning on MRI or laminar thinning on histology compared to cases without TLS but altered neuronal densities and composition that was not confined to the superficial cortex. MRI cortical thinning was also characterised by attenuation of normal sulcal/gyral cytoarchitectural variations suggesting disruption of cortical architectural gradients. In contrast, cases with HS but without MRI cortical thinning demonstrated loss of the expected inter-hemispheric cytoarchitectural asymmetry, indicating a distinct pathological process dissociated from thinning. Clinical-pathological correlations were lateralised, including age of onset, further supporting distinct mechanisms contributing to MRI cortical thinning between left and right TLE. These findings challenge the prevailing assumption that MRI-defined cortical thinning in epilepsy reflects progressive neuronal degeneration. Rather than laminar neuronal loss and atrophy, thinning was associated with altered neuronal packing and cell-size distributions between layers. This points towards altered neuropil volumes, including myelin content and dendritic remodelling, in turn suggesting potentially reversible dynamic seizure- or network-related processes.

pathology↗

bioRxiv2026

An Implantable Wireless Battery-Free Selective Vagus Nerve Stimulator

Objective. Vagus nerve stimulation (VNS) is an established clinical therapy for drug-resistant epilepsy and other inflammatory conditions. However, off-target stimulation can produce unwanted side effects that limit therapeutic stimulation and hinder the development of new neuromodulation therapies. Selective VNS (sVNS) offers a strategy to reduce off-target organ activation; however, this approach is not available in humans, and no implantable or portable devices exist to trial sVNS in the clinical setup. This work aimed to design, manufacture, and validate an implantable wireless, battery-free stimulator with a selectively addressable output stage for targeted current delivery to specific regions of the human vagus nerve (VN). Approach. We developed a near-field communication-controlled, wirelessly powered, battery-free, temporary implantable multichannel stimulation device, compatible with a 15-channel sVNS cuff electrode (14 selective electrode pairs and one circumferential whole-nerve channel). The device was encapsulated for short-term implantation and evaluated through benchtop characterisation, accelerated ageing, and validation in an acute porcine and a pilot human study. Main result. The sVNS device was evaluated in a porcine (n = 4) trial and a first-in-human pilot study (n = 1). Selective bradycardia of 23.28 {+/-} 12.91% was observed in pigs and 7.5% in the human participant. In the human, a clear separation of bradycardic and tachycardic effects was observed, with additional selectivity in laryngeal activity. Cardiac and laryngeal responses were separated by 231{degrees} around the circumference of the nerve. Significance. This work demonstrates the feasibility of wireless battery-free sVNS for cardiac applications using a temporary implantable device. Geometrically selective stimulation has the potential to improve therapeutic efficacy while reducing stimulation-related side effects, and may facilitate future therapies for heart failure and other autonomic disorders.

bioengineering↗

bioRxiv2026

Fast-ripples are emergent properties of neuronal networks

Fast-ripples (250-500 Hz) have been proposed as a promising biomarker in epilepsy, but their specificity remains unclear. In particular, it is uncertain whether they reflect chance coincident neural activity or distinctly generated pathological entities. We combined in silico simulations, neuronal cultures, the intra-hippocampal kainate rat model of hippocampal epilepsy, and human microwire recordings to investigate whether fast-ripples occur more frequently than expected by the chance aggregation of action potentials. Our simulations showed that chance aggregation can generate fast-ripples and that their incidence changes depending on brain state, an observation that we confirmed in our rodent data. The likelihood of exceeding chance depended on biological system complexity and vigilance state: fast-ripples in neuronal cultures did not surpass chance levels, whereas those in awake - but not sleeping - rodents did. Similarly, the incidence of fast-ripples in awake human recordings was ~30% greater than expected by chance. As such, our findings suggest that most fast-ripples reflect stochastic network activity rather than distinctly generated pathological entities. This work does not rule out FRs as potential indicators of epileptogenic tissue, but it does challenge prevailing assumptions about their generation and specificity. Their higher prevalence in epileptogenic tissue is likely primarily due to increased excitation and/or neural synchronization, rather than peculiar abnormalities in network behavior.

neuroscience↗

bioRxiv2019

Node abnormality predicts seizure outcome and relates to long-term relapse after epilepsy surgery

ObjectiveWe assessed pre-operative structural brain networks and clinical characteristics of patients with drug resistant temporal lobe epilepsy (TLE) to identify correlates of post-surgical seizure outcome at 1 year and seizure relapses up to 5 years.\n\nMethodsWe retrospectively examined data from 51 TLE patients who underwent anterior temporal lobe resection (ATLR) and 29 healthy controls. For each patient, using the pre-operative structural, diffusion, and post-operative structural MRI, we generated two networks: pre-surgery network and surgically-spared network. The pre-surgery network is the whole-brain network before surgery and the surgically-spared network is a subnetwork of the pre-surgery network which is expected to remain unaffected by surgery and hence present post-operatively. Standardising these networks with respect to controls, we determined the number of abnormal nodes before surgery and expected to remain after surgery. We incorporated these 2 abnormality measures and 13 commonly acquired clinical data from each patient in a robust machine learning framework to estimate patient-specific chances of seizures persisting after surgery.\n\nResultsPatients with more abnormal nodes had lower chance of seizure freedom at 1 year and even if seizure free at 1 year, were more likely to relapse within five years. In the surgically-spared networks of poor outcome patients, the number of abnormal nodes was greater and their locations more widespread than in good outcome patients. We achieved 0.84 {+/-} 0.06 AUC and 0.89 {+/-} 0.09 specificity in detecting unsuccessful seizure outcomes at 1-year. Moreover, the model-predicted likelihood of seizure relapse was significantly correlated with the grade of surgical outcome at year-one and associated with relapses up-to five years post-surgery.\n\nConclusionNode abnormality offers a personalised non-invasive marker, that can be combined with clinical data, to better estimate the chances of seizure freedom at 1 year, and subsequent relapse up to 5 years after ATLR.

neuroscience↗

bioRxiv2019

Theta power and theta-gamma coupling support spatial memory retrieval

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands ( low 2-5Hz and high 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between low theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.

neuroscience↗