Davide Giampiccolo

Introduction: The pallidothalamic tract (PTT), formed by convergence of the ansa lenticularis and fasciculus lenticularis at Forel's field H1, is a major basal ganglia efferent pathway and an emerging functional neurosurgical target. No systematic review has previously synthesised outcomes across PTT-targeted interventions. Methods: This PRISMA 2020-compliant systematic review was registered on PROSPERO (CRD420251248260). PubMed, OVID, and Web of Science were searched for studies reporting functional neurosurgical outcomes targeting the PTT or Forel's fields. Prospective and retrospective studies, case series, and case reports were eligible. Methodological quality was assessed using design-appropriate risk-of-bias tools. Results: Forty studies encompassing 483 patients (1966–2025) were included across five modalities: MR-guided focused ultrasound (n = 143), radiofrequency ablation (n = 167), deep brain stimulation (n = 40), cryogenic lesioning (n = 82), and oil-wax injection (n = 52). Mean follow-up was 21 months. In Parkinson disease (PD; 11 studies; n = 135), mean Unified Parkinson's Disease Rating Scale-III improvement was 39%, with reductions in dyskinesia (Unified Dyskinesia Ratings Scale 90%) and tremor (75%). In dystonia (12 studies; n = 87), Burke Fahn Marsden Dystonia Rating Scale and TWSTRS improved by 57% and 47%, respectively. Dual-target strategies, particularly PTT-VIM combinations, showed additive effects, including greater tremor reduction (77%) and improved rigidity. In drug-resistant epilepsy (6 studies; n = 157), seizure reduction occurred in 71% and seizure freedom in 33%. Conclusion: PTT-targeted interventions yield meaningful motor improvements in PD and dystonia, with preliminary evidence supporting additive dual-target benefits. Seizure-reducing effects in refractory epilepsy have been reported. Evidence remains limited by small uncontrolled studies, heterogeneous outcomes, and inconsistent adverse-event reporting. Prospective trials will elucidate the efficacy, safety, and clinical role of the PTT in neurosurgery.

Piriform seizures mediated by the piriform-entorhino-dentate circuit induce brainwide functional reorganization in mice Yan Tao, Yuxin Zhao, Wenqi Zhong, Jiajia Zhang, Hongyan Zhu, Xutao Zhu, Zikun Wang, Na Wang, Liqin Yang, Fuqiang Xu, Ruiqi Wu. PLoS Biol. 24(2): e3003577 (2026). Systematic identification of global epileptic reorganization and critical seizure-controlling circuits is essential for comprehending epilepsy pathophysiology and for developing network-guided targeted therapies. The piriform cortex (PC) is a recognized epileptogenic region, but how its hyperactivity reshapes whole-brain dynamics and which specific circuits mediate seizures remains unclear. Through multimodal integration of optogenetics, fMRI, electrophysiology, Ca2 + imaging, neural tracing, and circuit-specific manipulation, we mapped the whole-brain dynamics following optogenetic stimulation of PC and identified the fundamental circuit governing piriform seizures. We observed pronounced generalized seizures in mice via repeated optogenetic stimulation of PC Vglut1 + neurons. Optogenetic kindling of PCVglut1 induced widespread blood-oxygen-level-dependent (BOLD) signal hyperactivation and resting-state functional connectivity (rsFC) alterations, notably sustained hyper­activation in the lateral entorhinal cortex (Lent) and enhanced PC-Lent rsFC. Chronic elimination of Lent neurons receiving PC projections significantly decreased the Lent-dentate gyrus (DG) rsFC. Disruption of the PC-Lent or Lent-DG circuit effec­tively suppressed PC-stimulation-triggered seizures and brain-wide hyperactivation. Our findings demonstrate the dominant role of the PCVglut1-Lentglut-DG circuit in mediating piriform seizures and driving their resulting brain-wide functional reorganization, offering new insights for targeted epilepsy treatments.

Objective: Vagus nerve stimulation (VNS) is a commonly used treatment for drug‐resistant epilepsy. However, response to VNS is variable, while understanding of this response variability is limited. The vagus afferent network (VagAN), the neural circuits thought to be involved in response to vagal afferents, has been implicated in response prediction in modalities such as diffusion‐weighted imaging, functional imaging, and neurophysiology. Structural abnormality in the VagAN from T1w MRI has not yet been studied. Methods: We assessed if VagAN abnormalities, derived from pre‐implantation T1w MRI, were associated with VNS response in 92 individuals with epilepsy two years post‐implantation (42 responders, 50 non‐responders). We used the first principal component (PC1) from a robust principal component analysis for a variety of region sets trained using 100 healthy controls. We investigated two primary hypotheses. (i) If VagAN regions' PC1 differentiates response groups, (ii) if other region sets did not differentiate response groups. Results: Non‐responders had significantly higher VagAN PC1 abnormality scores than both responders (, ) and controls (, ). By contrast, non‐VagAN PC1 showed no discriminatory value (, ). VagAN outperformed all other region sets. Significance: Structural abnormality of VagAN was associated with non‐response to VNS. This suggests that volume abnormalities in key VNS regions correlate negatively with reduction of seizures. Abnormalities in other regions, such as the non‐VagAN region set, were not associated with VNS response. This metric, when combined with other modalities, may be a useful measure to improve the selection of individuals with drug‐resistant epilepsy for VNS therapy. Plain Language Summary: Vagus nerve stimulation (VNS) is a common treatment for drug‐resistant epilepsy; however, it is not always effective. We tested whether volumes of brain regions related to VNS efficacy and found that abnormality within a set of regions known to be affected by VNS related to non‐response. No other set of regions showed this effect implying that this set of regions is uniquely placed to determine if someone may respond to VNS. This work supports the idea that VNS efficacy is limited by an individual's brain abnormality and should be considered in further studies.

Stuttering is a neurodevelopmental disorder marked by impaired speech production and substantial interindividual variability in symptom severity. Although neuroimaging studies have identified abnormalities in the basal ganglia-thalamocortical circuitry, the specific white matter pathways that underpin dysfluent speech production remain poorly understood. Here, we focus on the frontal aslant tract (FAT), a dorsoventral intralobar tract connecting the superior and inferior frontal cortices and proposed to support both cognitive and motor functions. Using diffusion MRI, we first compared the quantitative anisotropy of the FAT and relevant control tracts in individuals who stutter (n = 30, mean age = 35.67, SD = 13.03) and fluent speakers (n = 22, mean age = 35.64, SD = 10.87) and observed no significant group-level differences in either hemisphere. To delineate the role of FAT subbundles in speech dysfluency, we then segmented the tract at its dorsal and ventral cortical terminations and assessed their relationships with stuttering severity (Stuttering Severity Instrument-Fourth Edition). We identified left FAT subbundles connecting the posteroventral frontal structures, particularly the rostroventral precentral gyrus and, to a lesser extent, the pars opercularis to a dorsal prefrontal region whose integrity predicts stuttering severity. The left-lateralized nature of these associations suggests that stuttering results, in part, from abnormal connectivity between prefrontal systems governing volitional control and the motor circuits engaged in speech production. Together, these findings refine current neurobiological models of stuttering by implicating frontofrontal white matter pathways underlying speech dysfluency and highlight a potential anatomical target for individualized therapeutic interventions.

Epilepsy is one of the most common chronic neurological disorders, and temporal lobe epilepsy (TLE) is its most prevalent form in adults. Although TLE is classified as a focal epilepsy, it has traditionally been defined by hippocampal and extra-hippocampal atrophy. However, several studies also report regions of increased cortical thickness, or cortical hypertrophy, in TLE, challenging the notion that structural change in epilepsy is unidirectional. In this narrative review, we synthesize evidence for cortical hypertrophy in TLE and place these findings in a broader neurobiological context. We provide an overview of cortical thickness and MRI approaches used to measure it, highlighting differences between surface-based, volume-based and voxel-based methods. We then review MRI studies reporting cortical hypertrophy in TLE, noting variability in affected regions, patient populations and analytical techniques. We discuss potential mechanisms that may underlie cortical hypertrophy, including seizure-related structural remodelling, glial or inflammatory processes, compensatory neuroplasticity, network effects and methodological limitations. Finally, we outline key gaps and controversies regarding the biological validity, temporal dynamics and clinical relevance of cortical hypertrophy in TLE. We conclude that consideration of both cortical atrophy and hypertrophy may improve broader understanding of TLE as a disorder involving brain remodelling rather than isolated regional atrophy.

Epilepsy is increasingly recognized as a disorder of brain networks rather than a solely focal disease. Beyond the seizure focus, connected brain networks can exert inhibitory control over seizure initiation and propagation resulting in antiseizure effects. Here, we present data from animal and human studies on antiseizure networks and integrate recent results from lesion-, stimulation- and neurophysiological-experiments. Consistent with these results, we present the Interictal Suppression Hypothesis that posits that strong inward connectivity to the seizure focus maintains seizure freedom between events, while collapse of this connectivity accompanies seizure spread and generalization. Workshop discussions highlighted future directions, including mechanistic stimulation studies to interrogate the role of antiseizure networks seizure control and design of therapeutic studies towards network–guided neuromodulation for epilepsy. A deeper mechanistic understanding of antiseizure networks may enable development of precision therapies that target endogenous seizure control rather than simply target the seizure focus.

Ictal eye closure is commonly associated with functional seizures but may also occur in epileptic seizures. We retrospectively reviewed 113 consecutive stereo‐EEG (SEEG) recordings from adults with drug‐resistant focal epilepsy (2015–2024) to identify prolonged bilateral eye closure during seizures. Nine individuals exhibited this through 17 seizures; eight seizures arose from sleep. Inter‐rater reliability was good (ICC = 0.72). The median age was 35 years, and the epilepsy duration was 25 years. Eye closure started mainly at EEG onset and persisted for approximately 50% of the seizure. Consciousness was impaired in seven seizures and preserved in three. Presumed epileptogenic zones were unilateral in eight people and uncertain in one, involving various cortical and subcortical areas. Seven of them were offered surgical resection or laser interstitial thermal therapy (LITT). Ictal eye closure showed no clear localizing or lateralizing value, likely due to widespread network involvement. It may reflect disruption of sensory, executive, or arousal systems. SEEG spatial sampling limitations could have affected the detection of involved areas. Further prospective studies are needed to clarify its clinical significance.

Idiopathic generalized epilepsy (IGE) is typically responsive to treatment, yet some people remain poorly controlled despite multiple antiseizure medication trials. Whether this subgroup shows progressive structural brain changes remains uncertain. We aimed to investigate whether people with poorly controlled chronic IGE exhibit progressive morphological brain alterations and how these differ from those in early-stage IGE. This longitudinal case-control neuroimaging study included 2 cohorts: an early-stage IGE group from West China Hospital (Chengdu, China) and a chronic IGE group from the National Hospital for Neurology and Neurosurgery (London, United Kingdom). Participants had a history of generalized seizures and no focal pathology. Matched healthy controls were drawn from 3 public imaging data sets. Participants underwent 2 high-resolution T1-weighted MRI scans at least 12 months apart. Cortical thickness and hippocampal and subcortical volumes were measured on paired scans. Longitudinal changes were assessed using linear mixed-effects models, correcting for age and interscan interval. Structural covariance analysis was conducted to examine inter-regional relationships over time, focusing on thalamo-cortical coupling. Forty-two people with early-stage IGE and 67 with chronic IGE were recruited from 2 separate epilepsy centers, and 109 matched controls were included. The early-stage IGE group showed progressive atrophy limited to the left putamen. Chronic IGE was associated with widespread cortical thinning, primarily in frontal and temporal regions, and thickening in posterior and occipital areas. Subcortical atrophy involves the putamen, thalamus, and pallidum. People with ongoing generalized tonic-clonic seizures showed thickening in the precentral gyrus and additional thinning in the frontal cortex and precuneus. Photosensitive IGE was associated with thickening in the lingual gyrus and occipital cortex. Valproate use was associated with attenuated structural changes in motor, visual, and subcortical regions. Increased structural covariance was observed between the left thalamus and left lingual gyrus in chronic IGE. Chronic IGE, particularly with persistent generalized tonic-clonic seizures or photosensitivity, is associated with more extensive progressive brain changes compared with matched controls. Valproate may have a protective association with these structural changes, although further validation is needed. Longitudinal MRI may help monitor disease progression and treatment effects in poorly controlled IGE.

Temporal lobe resection for focal, drug-resistant temporal lobe epilepsy (TLE) causes verbal memory deficits in 30% of left hemisphere-operated patients. Structural, functional and computational modelling have shown a widespread structural and functional memory network with hubs in critical brain regions including the hippocampus, subcortical and neocortical regions. We hypothesized that damage to white matter pathways forming a network involving cortical and subcortical regions may be responsible for postoperative memory problems. In this study, we measured verbal memory encoding (immediate recall) and retrieval (delayed recall) outcome at three timepoints (preoperative, 3- and 12-month postoperatively) in 146 left TLE patients who underwent temporal lobe surgery and evaluated the impact of white matter tract section on verbal memory. Outcome was measured by the change in scores from preoperative to 3- and 12-month postoperatively and via the reliable change index. Utilizing resection masks from pre- and postoperative T1 scans, an atlas-based analysis utilizing reconstructions of the ventral cingulum and fornix confirmed these tracts involvement in verbal encoding but not retrieval. Using preoperative diffusion MRI (dMRI) reconstructions with resection masks to estimate the percentage of fibre bundle transection, we found that the ventral cingulum was significantly related to verbal encoding change and the fornix was related to verbal retrieval across both 3- and 12-month timepoints. Investigating volumes of ventral cingulum and fornix from postoperative dMRI reconstruction revealed that greater volume remaining of the ventral cingulum and fornix was related to less decline in verbal encoding but not retrieval. Our results suggest that verbal encoding may be supported by direct and indirect connections between the medial temporal lobe and subcortical regions with memory deficits arising from their transection. Verbal retrieval may rely on a greater neocortical network. These findings may inform a revised surgical approach to minimize damage to the fornix and ventral cingulum to optimize memory outcome, but recognizing the potential for worse seizure outcome with less ventral cingulum resections.