Dynamic modulation of subthalamic nucleus activity facilitates adaptive behavior.

Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or adapting actions depending on their outcome. However, the corresponding electrophysiological correlates in the basal ganglia and the extent to which these causally contribute to action adaptation in humans is unclear. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus, a core area of the basal ganglia, in 16 patients with Parkinson's disease (PD) on medication using temporarily externalized deep brain stimulation (DBS) electrodes. Patients as well as 16 age- and gender-matched healthy participants attempted to produce forces as close as possible to a target force to collect a maximum number of points. The target force changed over trials without being explicitly shown on the screen so that participants had to infer target force based on the feedback they received after each movement. Patients and healthy participants were able to adapt their force according to the feedback they received (P < 0.001). At the neural level, decreases in subthalamic beta (13 to 30 Hz) activity reflected poorer outcomes and stronger action adaptation in 2 distinct time windows (Pcluster-corrected < 0.05). Stimulation of the subthalamic nucleus reduced beta activity and led to stronger action adaptation if applied within the time windows when subthalamic activity reflected action outcomes and adaptation (Pcluster-corrected < 0.05). The more the stimulation volume was connected to motor cortex, the stronger was this behavioral effect (Pcorrected = 0.037). These results suggest that dynamic modulation of the subthalamic nucleus and interconnected cortical areas facilitates adaptive behavior.

Favorable combinations of antiseizure medication with vagus nerve stimulation to improve health-related quality of life in patients with epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) is a non-pharmacological treatment of refractory epilepsy, which also has an antidepressive effect. The favorable combinations of VNS with specific mechanisms of action of antiseizure medication (ASM) on mood and health-related quality of life (HrQol) have not yet been studied. The objective was to identify favourable combinations of specific ASMs with VNS for the HrQoL and depression in refractory epilepsy. METHODS: We performed an observational study including patients with refractory epilepsy and an implanted VNS (N = 151). In the first 24 months after VNS implantation, all patients were on stable ASM therapy. We used the standardized questionnaires QOLIE10, EQVAS and EQ5D to evaluate HrQoL as well as the Beck Depression Inventory (BDI). Multiple regression analysis was performed to evaluate the synergistic combinations of ASM with VNS for HrQoL. RESULTS: At the year-two follow-up (N = 151, age 45.2 ± 17.0 years), significant improvement (p < 0.05) in BDI scores was found for combination of VNS with SV2A modulators (58.4 %) or AMPA antagonists (44.4 %). A significant increase of HrQoL by at least 30 % (p < 0.05) was measured for a combination of VNS with SV2A modulators (brivaracetam, levetiracetam) or slow sodium channel inhibitors (eslicarbazepine, lacosamide). CONCLUSION: The results of our study suggests a favorable effect of the combination of SV2A modulators or slow sodium channel inhibitors with VNS on the HrQoL in comparison to other ASMs. Besides the possible synergistic effects on the seizure frequency, the amelioration of behavioral side effects of SV2A modulators by VNS is an important factor of HrQoL-improvement in these combinations.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Presurgical selection of the ideal aneurysm clip by the use of a three-dimensional planning system.

Aneurysm occlusion rate after clipping is higher than after endovascular treatment. However, a certain percentage of incompletely clipped aneurysms remains. Presurgical selection of the proper aneurysm clips could potentially reduce the rate of incomplete clippings caused by inadequate clip geometry. The aim of the present study was to assess whether preoperative 3D image-based simulation allows for preoperative selection of a proper aneurysm clip for complete occlusion in individual cases. Patients harboring ruptured or unruptured cerebral aneurysms prior to surgical clipping were analyzed. CT angiography images were transferred to a 3D surgical-planning station (Dextroscope®) with imported models of 58 aneurysm clips. Intracranial vessels and aneurysms were segmented and the virtual aneurysm clips were placed at the aneurysm neck. Operating surgeons had information about the selected aneurysm clip, and patients underwent clipping. Intraoperative clip selection was documented and aneurysm occlusion rate was assessed by postoperative digital subtraction angiography. Nineteen patients were available for final analysis. In all patients, the most proximal clip at the aneurysm neck was the preselected clip. All aneurysms except one were fully occluded, as assessed by catheter angiography. One aneurysm had a small neck remnant that did not require secondary surgery and was occluded 15 months after surgery. 3D image-based preselection of a proper aneurysm clip can be translated to the operating room and avoids intraoperative clip selection. The associated occlusion rate of aneurysms is high.

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.

The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease.

Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter. We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.SIGNIFICANCE STATEMENT Bursts of beta frequency band activity in the basal ganglia are associated with slowing of voluntary movement in patients with Parkinson's disease. We show that slow movements are those that follow multiple bursts close to each other and bursts that are coupled across regions. These results suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, impacts on motor performance in this condition. The manipulation of burst dynamics may be a means of selectively improving motor impairment.

An age-dependent outcome analysis of microvascular decompression and percutaneous thermocoagulation in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a severe pain condition and the most common facial neuralgia. While microvascular decompression (MVD) presents an excellent treatment in neurovascular compression cases, percutaneous thermocoagulation (PT) of the ganglion Gasseri is an alternative option. This study aimed to evaluate post-operative complication rate and outcome of both treatment strategies related to the patient's age. METHODS: The medical records of all patients with the diagnosis of trigeminal neuralgia undergoing an MVD or PT of the ganglion Gasseri (between January 2007 and September 2017) were reviewed to determine the efficacy and the complication rate of both methods in regard to the patient's age. RESULTS: Seventy-nine patients underwent MVD surgery and 39 a PT. The mean age of patients in the MVD group was 61 years and 73 years in the PT group. There were 59 (50%) female patients. Nerve-vessel conflict could be identified in 78 (98.7%) MVD and 17 (43.6%) PT patients on preoperative MRI. Charlson comorbidity index was significantly higher in PT group (2.4 (1.8) versus 3.8 (1.8) p < 0.001). The Barrow pain score (BPS) at the last follow-up demonstrated higher scores after PT (p = 0.007). The complication rate was markedly higher in PT group, mostly due to the facial hypesthesia (84.6% versus 27.8%; p < 0.001). Mean symptom-free survival was significantly shorter in the PT group (9 vs. 26 months, p < 0.001). It remained statistically significant when stratified into age groups: (65 years and older: 9 vs. 18 months, p = 0.001). Duration of symptoms (OR 1.005, 95% CI 1.000-1.010), primary procedure (OR 6.198, 95% CI 2.650-14.496), patient age (OR 1.033, 95% CI 1.002-1.066), and postoperative complication rate (OR 2.777, 95% CI 1.309-5.890) were associated with treatment failure. CONCLUSION: In this patient series, the MVD is confirmed to be an excellent treatment option independent of patient's age. However, while PT is an effective procedure, time to pain recurrence is shorter, and the favorable outcome (BPS 1 and 2) rate is lower compared to MVD. Hence MVD should be the preferred treatment and PT should remain an alternative in very selected cases when latter is not possible but not in the elderly patient per se.

Cross-frequency coupling between gamma oscillations and deep brain stimulation frequency in Parkinson's disease.

The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson's disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-frequency interactions with gamma oscillations in a cortico-subcortical network of interconnected regions and normalizes the balance between beta and gamma oscillations. To this end we acquired resting state high-density (256 channels) EEG from 31 patients with Parkinson's disease who underwent deep brain stimulation to compare spectral power and power-to-power cross-frequency coupling using a beamformer algorithm for coherent sources. To show that modulations exclusively relate to stimulation frequencies that alleviate motor symptoms, two clinically ineffective frequencies were tested as control conditions. We observed a robust reduction of beta and increase of gamma power, attested in the regions of a cortical (motor cortex, supplementary motor area, premotor cortex) and subcortical network (subthalamic nucleus and cerebellum). Additionally, we found a clear cross-frequency coupling of narrowband gamma frequencies to the stimulation frequency in all of these nodes, which negatively correlated with motor impairment. No such dynamics were revealed within the control posterior parietal cortex region. Furthermore, deep brain stimulation at clinically ineffective frequencies did not alter the source power spectra or cross-frequency coupling in any region. These findings demonstrate that clinically effective deep brain stimulation of the subthalamic nucleus differentially modifies different oscillatory activities in a widespread network of cortical and subcortical regions. Particularly the cross-frequency interactions between finely tuned gamma oscillations and the stimulation frequency may suggest an entrainment mechanism that could promote dynamic neural processing underlying motor symptom alleviation.

The Art of Designing DNA Nanostructures with CAD Software.

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

Cortical network fingerprints predict deep brain stimulation outcome in dystonia.

BACKGROUND: Deep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns. METHODS: From a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior-outcome group or moderate-outcome group, depending on whether they had above or below 70% motor improvement, respectively. Fifty-one patients met MRI-quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray-matter fingerprints. RESULTS: The moderate-outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88% of accuracy using individual gray-matter atrophy patterns to predict DBS outcomes. CONCLUSIONS: The analysis of cortical integrity, informed by group-level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The role of stickiness in the rheology of semiflexible polymers.

Semiflexible polymers form central structures in biological material. Modelling approaches usually neglect influences of polymer-specific molecular features aiming to describe semiflexible polymers universally. Here, we investigate the influence of molecular details on networks assembled from filamentous actin, intermediate filaments, and synthetic DNA nanotubes. In contrast to prevalent theoretical assumptions, we find that bulk properties are affected by various inter-filament interactions. We present evidence that these interactions can be merged into a single parameter in the frame of the glassy wormlike chain model. The interpretation of this parameter as a polymer specific stickiness is consistent with observations from macro-rheological measurements and reptation behaviour. Our findings demonstrate that stickiness should generally not be ignored in semiflexible polymer models.

Correction: The role of stickiness in the rheology of semiflexible polymers.

Correction for 'The role of stickiness in the rheology of semiflexible polymers' by Tom Golde et al., Soft Matter, 2019, 15, 4865-4872.

Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor.

The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood-brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.

Glassy dynamics in composite biopolymer networks.

The cytoskeleton is a highly interconnected meshwork of strongly coupled subsystems providing mechanical stability as well as dynamic functions to cells. To elucidate the underlying biophysical principles, it is central to investigate not only one distinct functional subsystem but rather their interplay as composite biopolymeric structures. Two of the key cytoskeletal elements are actin and vimentin filaments. Here, we show that composite networks reconstituted from actin and vimentin can be described by a superposition of two non-interacting scaffolds. Arising effects are demonstrated in a scale-spanning frame connecting single filament dynamics to macro-rheological network properties. The acquired results of the linear and non-linear bulk mechanics can be captured within an inelastic glassy wormlike chain model. In contrast to previous studies, we find no emergent effects in these composite networks. Thus, our study paves the way to predict the mechanics of the cytoskeleton based on the properties of its single structural components.

Frontal Lobe Connectivity and Network Community Characteristics are Associated with the Outcome of Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson's Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is nowadays an evidence-based state of the art therapy option for motor and non-motor symptoms in patients with Parkinson's disease (PD). However, the exact anatomical regions of the cerebral network that are targeted by STN-DBS have not been precisely described and no definitive pre-intervention predictors of the clinical response exist. In this study, we test the hypothesis that the clinical effectiveness of STN-DBS depends on the connectivity profile of the targeted brain networks. Therefore, we used diffusion-weighted imaging (DWI) and probabilistic tractography to reconstruct the anatomical networks and the graph theoretical framework to quantify the connectivity profile. DWI was obtained pre-operatively from 15 PD patients who underwent DBS (mean age = 67.87 ± 7.88, 11 males, H&Y score = 3.5 ± 0.8) using a 3T MRI scanner (Philips Achieva). The pre-operative connectivity properties of a network encompassing frontal, prefrontal cortex and cingulate gyrus were directly linked to the postoperative clinical outcome. Eccentricity as a topological-characteristic of the network defining how cerebral regions are embedded in relation to distant sites correlated inversely with the applied voltage at the active electrode for optimal clinical response. We found that network topology and pre-operative connectivity patterns have direct influence on the clinical response to DBS and may serve as important and independent predictors of the postoperative clinical outcome.

Heavy-Hole States in Germanium Hut Wires.

Hole spins have gained considerable interest in the past few years due to their potential for fast electrically controlled qubits. Here, we study holes confined in Ge hut wires, a so-far unexplored type of nanostructure. Low-temperature magnetotransport measurements reveal a large anisotropy between the in-plane and out-of-plane g-factors of up to 18. Numerical simulations verify that this large anisotropy originates from a confined wave function of heavy-hole character. A light-hole admixture of less than 1% is estimated for the states of lowest energy, leading to a surprisingly large reduction of the out-of-plane g-factors compared with those for pure heavy holes. Given this tiny light-hole contribution, the spin lifetimes are expected to be very long, even in isotopically nonpurified samples.

Single Actin Bundle Rheology.

Bundled actin structures play an essential role in the mechanical response of the actin cytoskeleton in eukaryotic cells. Although responsible for crucial cellular processes, they are rarely investigated in comparison to single filaments and isotropic networks. Presenting a highly anisotropic structure, the determination of the mechanical properties of individual bundles was previously achieved through passive approaches observing bending deformations induced by thermal fluctuations. We present a new method to determine the bending stiffness of individual bundles, by measuring the decay of an actively induced oscillation. This approach allows us to systematically test anisotropic, bundled structures. Our experiments revealed that thin, depletion force-induced bundles behave as semiflexible polymers and obey the theoretical predictions determined by the wormlike chain model. Thickening an individual bundle by merging it with other bundles enabled us to study effects that are solely based on the number of involved filaments. These thicker bundles showed a frequency-dependent bending stiffness, a behavior that is inconsistent with the predictions of the wormlike chain model. We attribute this effect to internal processes and give a possible explanation with regard to the wormlike bundle theory.

Intracranial multiple myeloma may imitate subdural hemorrhage: How to overcome diagnostic limitations and avoid errors in treatment.

BACKGROUND: Although the diagnosis of subdural hematoma is usually straightforward, occasionally it may be erroneous, leading to mistakes in the treatment. For example, leptomeningeal malignancies, even in the absence of bleeding, may clinically and radiologically mimic subdural hemorrhage. OBJECTIVE: To stress the importance of not only intuitive thinking but also in analytic thinking in appropriate and accurate treatment strategies. METHODS AND ILLUSTRATIVE CASE: In this report, the clinical and radiological pitfalls in differentiating malignant leptomeningeal infiltration and subdural hematomas are discussed. A sample case of an intracranial extra-osseous manifestation of a multiple myeloma that is atypical with regard to its location and clinical presentation is presented for illustration. CONCLUSIONS: The variability of intracranial presentation and the wide spectrum of leptomeningeal malignancies necessitate careful preoperative evaluation of the patient's individual history as well as radiological images to avoid misdiagnosis. A clinician who has become familiar with the pitfalls in the differential diagnosis between leptomeningeal infiltrations and subdural hematoma will act more analytically to solve the patient's problems properly and avoid potential complications for the patient.

Tuning Synthetic Semiflexible Networks by Bending Stiffness.

The mechanics of complex soft matter often cannot be understood in the classical physical frame of flexible polymers or rigid rods. The underlying constituents are semiflexible polymers, whose finite bending stiffness (κ) leads to nontrivial mechanical responses. A natural model for such polymers is the protein actin. Experimental studies of actin networks, however, are limited since the persistence length (l_{p}∝κ) cannot be tuned. Here, we experimentally characterize this parameter for the first time in entangled networks formed by synthetically produced, structurally tunable DNA nanotubes. This material enabled the validation of characteristics inherent to semiflexible polymers and networks thereof, i.e., persistence length, inextensibility, reptation, and mesh size scaling. While the scaling of the elastic plateau modulus with concentration G_{0}∝c^{7/5} is consistent with previous measurements and established theories, the emerging persistence length scaling G_{0}∝l_{p} opposes predominant theoretical predictions.

Transition from a Linear to a Harmonic Potential in Collective Dynamics of a Multifilament Actin Bundle.

Attractive depletion forces between rodlike particles in highly crowded environments have been shown through recent modeling and experimental approaches to induce different structural and dynamic signatures depending on relative orientation between rods. For example, it has been demonstrated that the axial attraction between two parallel rods yields a linear energy potential corresponding to a constant contractile force of 0.1 pN. Here, we extend pairwise, depletion-induced interactions to a multifilament level with actin bundles, and find contractile forces up to 3 pN. Forces generated due to bundle relaxation were not constant, but displayed a harmonic potential and decayed exponentially with a mean decay time of 3.4 s. Through an analytical model, we explain these different fundamental dynamics as an emergent, collective phenomenon stemming from the additive, pairwise interactions of filaments within a bundle.