Biology subjects

Zrinzo, L.

Publications and source records attributed to Zrinzo, L..

10 recordsLinked to original sources

bioRxiv2026

Electrophysiological Correlates of Reinforcement Learning in the Human Ventral Tegmental Area

The ventral tegmental area (VTA) is the principal source of dopaminergic input to the human prefrontal cortex and is hypothesised to play a central role in reward-based learning. However, direct electrophysiological evidence in humans has been lacking. Here, using intracranial recordings obtained during an instrumental learning task in patients undergoing deep brain stimulation surgery for chronic cluster headache (n=13), we show that VTA local field potentials selectively encode rewarding outcomes compared with losses or neutral outcomes independently of whether behavioural learning occurred. In a subset of participants (n= 8) who learned to prefer a high-reward option, VTA responses to unexpected rewards were larger than to expected rewards. In two participants who sufficiently explored both options, VTA activity reflected the expected value of the chosen option during decision-making. These findings provide direct electrophysiological evidence that the human VTA encodes reward-related signals consistent with reinforcement learning mechanisms described in animal models.

neuroscience↗

bioRxiv2025

Beyond beta: Aperiodic broadband power reflects Parkinson's disease severity - a multicenter study

Parkinsons disease is linked to increased beta oscillations in the subthalamic nucleus, which correlate with motor symptoms. However, findings across studies have varied. Our standardized analysis of multicenter datasets shows that small sample sizes contributed to these discrepancies--a challenge we address by pooling datasets into one large cohort (n=119). Moving beyond beta power, we disentangled spectral components reflecting distinct neural processes. Combining aperiodic offset, low beta, and low gamma oscillations explained significantly more variance in symptom severity than beta alone. Moreover, interhemispheric within-patient analyses showed that, unlike beta oscillations, aperiodic broadband power-likely reflecting spiking activity-was increased in the more affected hemisphere. These findings identify aperiodic broadband power as a potential biomarker for adaptive deep brain stimulation and provide novel insights into the relationship between subthalamic hyperactivity and motor symptoms in human Parkinsons disease.

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bioRxiv2024

Prediction of pathological subthalamic nucleus beta burst occurrence in Parkinson's disease

The cortico-basal ganglia network in Parkinsons disease (PD) is characterized by the emergence of transient episodes of exaggerated beta frequency oscillatory synchrony known as bursts. Although it is well established that bursts of prolonged duration associate closely with motor impairments, the mechanisms leading to burst initiation remain poorly understood. Crucially, it is unclear whether there are features of basal ganglia activity which reliably predict burst onset. Current adaptive Deep Brain Stimulation (aDBS) approaches can only reactively deliver stimulation following burst detection and are unable to stimulate proactively to prevent burst onset. The discovery of predictive biomarkers could allow for such proactive stimulation, thereby offering potential for improvements in therapeutic efficacy. Here, using deep learning, we show that the timing of subthalamic nucleus (STN) beta bursts can be accurately predicted up to 60 ms prior to onset. Furthermore, we highlight that a dip in the beta amplitude - which is likely to be indicative of a phase reset of oscillatory populations occurring between 80-100 ms prior to burst onset - is a predictive biomarker for burst occurrence. These findings demonstrate proof-of-principle for the feasibility of beta burst prediction for DBS and provide insights into the mechanisms of burst initiation.

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bioRxiv2020

Basal ganglia high-frequency activity is co-modulated with the phase of motor cortical beta and shifted between the subthalamic nucleus and the internal pallidum during sustained motor control

Beta oscillations are readily observed in motor cortex and the basal ganglia, but to which extent they are functionally relevant is unclear. To understand how activity transfer between different nodes of the cortico-basal ganglia network is affected by cortical beta oscillations in different behavioural conditions, we recorded local field potentials and electroencephalography (EEG) activity in a low-force motor control task and during rest in Parkinsons patients undergoing deep brain stimulation (DBS) surgery. The patients received DBS of either the subthalamic nucleus (STN) or the internal globus pallidus (GPi), which allowed us to investigate if STN and GPi broad-band high-frequency activity (HFA; >150 Hz) is co-modulated with the phase of motor cortical beta activity. We found significant modulation patterns in the STN and the GPi, which were inverted while patients performed the task, showing that GPi activity fluctuations likely are crafted by other inputs than the direct excitatory STN afferents. We also found that consistent STN modulation disappeared during rest, showing disengagement in this condition, while GPi modulation was maintained, again evidencing that beta-band activity fluctuations in the GPi can be relatively independent of those in the STN. The difference between HFA modulation patterns in the task and rest recordings suggests a potential functional role of beta phase-locked HFA modulation in controlling sustained contractions. Examination of HFA co-modulation patterns at different sites of the cortico-basal ganglia-thalamo-cortical network under different behavioural conditions may provide a tool with which to define the impact of beta synchronization on network communication.

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bioRxiv2020

Entraining stepping movements of Parkinson's patients to alternating subthalamic nucleus deep brain stimulation

Patients with advanced Parkinsons can be treated by deep brain stimulation of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinsons patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients stepping movements as evidence of the STNs involvement in stepping control. Group analyses of ten Parkinsons patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study provides evidence that the STN is causally involved in dynamic control of step timing, and motivates further exploration of this biomimetic stimulation pattern as a basis for the development of specific deep brain stimulation strategies to ameliorate gait impairments.

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bioRxiv2020

Ventralis intermedius nucleus anatomical variability assessment by MRI structural connectivity

The ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results. Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim) in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds. We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.9 mm (left) and 2.1 mm (right) of the average midpoint and 4.9 mm (left) and 5.4 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTCp reconstructed. The superior cerebellar peduncle was identified as a potential source of artificial variance. This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based approaches fail to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; These findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor. HighlightsO_LIConnectivity-based Vim position varied markedly between subjects and from atlas-defined coordinates. C_LIO_LIThis positional variability was not related to any methodological confound tested. C_LIO_LIHemispheric asymmetry was observed in connectivity-based Vim position. C_LIO_LIWe hypothesise lateralization of cerebellar functions, such as language, may contribute to asymmetry. C_LIO_LIKnowledge of Vim position variability could help inform neurosurgical planning in the management of tremor. C_LI

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bioRxiv2020

Intersection of structural and functional connectivity of the nucleus basalis of Meynert in Parkinson's disease dementia and Lewy body dementia

Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography (MEG) with the spatial resolution of MRI tractography in order to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing Deep Brain Stimulation (DBS) of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: 1) a beta band network to supplementary motor area (SMA), where activity in the SMA was found to drive activity in the NBM, 2) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus and 3) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.

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bioRxiv2020

Neural signatures of pathological hyperdirect pathway activity in Parkinson's disease

Parkinsons disease (PD) is characterised by the emergence of pathological patterns of oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between anatomical connectivity and oscillatory synchronisation within this system remains poorly understood. We address this by integrating evidence from invasive electrophysiology, magnetoencephalography, tractography and computational modelling in patients. Coupling between supplementary motor area (SMA) and subthalamic nucleus (STN) within the high beta frequency (21-30 Hz) range correlated with fibre tract densities between these two structures. Additionally within the STN, non-linear waveform features suggestive of cortical synchronisation correlated with cortico-STN fibre densities. Finally, computational modelling revealed that exaggerated hyperdirect cortical inputs to the STN in the upper beta frequency range can provoke the generation of widespread pathological synchrony at lower beta (13-20 Hz) frequencies. These observations reveal a spectral signature of the hyperdirect pathway at high beta frequencies and provide evidence for its pathophysiological role in oscillatory network dysfunction in PD. One sentence summarySignatures of the hyperdirect pathway and its likely role in pathological network disruption in Parkinsons disease are identified.

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bioRxiv2020

Conflict detection in a sequential decision task is associated with increased cortico-subthalamic coherence and prolonged subthalamic oscillatory response in the beta band.

Making accurate decisions often involves the integration of current and past evidence. Here we examine the neural correlates of conflict and evidence integration during sequential decision making. Patients implanted with deep-brain stimulation (DBS) electrodes and age-matched healthy controls performed an expanded judgement task, in which they were free to choose how many cues to sample. Behaviourally, we found that while patients sampled numerically more cues, they were less able to integrate evidence and showed suboptimal performance. Using recordings of Magnetoencephalography (MEG) and local field potentials (LFP, in patients) in the subthalamic nucleus (STN), we found that beta oscillations signalled conflict between cues within a sequence. Following cues that differed from previous cues, beta power in the STN and cortex first decreased and then increased. Importantly, the conflict signal in the STN outlasted the cortical one, carrying over to the next cue in the sequence. Furthermore, after a conflict, there was an increase in coherence between the dorsal premotor cortex and subthalamic nucleus in the beta band. These results extend our understanding of cortico-subcortical dynamics of conflict processing, and do so in a context where evidence must be accumulated in discrete steps, much like in real life. Thus, the present work leads to a more nuanced picture of conflict monitoring systems in the brain and potential changes due to disease.

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bioRxiv2016

Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinson’s disease

Deep brain stimulation (DBS) for Parkinsons disease is a highly effective treatment in controlling otherwise debilitating symptoms yet the underlying brain mechanisms are currently not well understood. We used whole-brain computational modeling to disclose the effects of DBS ON and OFF during collection of resting state fMRI in ten Parkinsons Disease patients. Specifically, we explored the local and global impact of DBS in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts the global brain dynamics of patients nearer to that of healthy people by significantly changing the bifurcation parameters in brain regions implicated in Parkinsons Disease. We also found higher communicability and coherence brain measures during DBS ON compared to DBS OFF. Finally, by modeling stimulation we identified possible novel DBS targets. These results offer important insights into the underlying effects of DBS, which may in time offer a route to more efficacious treatments.

neuroscience↗