publications

2023

1. ACNP

   Neurocysticercosis: Isolated Lesion in the Left Middle Frontal Gyrus

   Abel S Mathew,  Carly Clark,  Peter M Lauro,  Zain Khalid,  and Nicole C R McLaughlin

   Archives of Clinical Neuropsychology Dec 2023

   Abstract DOI PDF

   Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. We present a case study of a 21-year-old African man with an isolated NCC lesion to the left middle frontal gyrus, which is also known as the dorsolateral prefrontal cortex (dlPFC).A neuropsychological evaluation was requested by the patient’s inpatient psychiatry team regarding worsening attention and depressive symptoms approximately 6 months after NCC diagnosis and treatment.Neuropsychological findings revealed deficits in the aspects of executive functioning, attention, working memory, and significant depressive symptoms.To our knowledge, this is the first case study of its kind demonstrating deficits in cognitive functioning consistent with the dlPFC lesion location. Sociocultural and linguistic considerations, clinical findings, and limitations are discussed.

2. eLife

   Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson’s disease

   Peter M Lauro,  Shane Lee,  Daniel E Amaya,  David D Liu,  Umer Akbar,  and Wael F Asaad

   eLife May 2023

   Abstract bioRxiv DOI PDF

   Parkinson’s disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of 31 subjects with PD during a quantitative motor task to decode tremor and bradykinesia – two cardinal motor signs of PD – and relatively asymptomatic periods of behavior. Support vector regression analysis of microelectrode and electrocorticography recordings revealed that tremor and bradykinesia had nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the signal type and location. Cortical decoding generally outperformed subcortical decoding. Within the subthalamic nucleus (STN), tremor and bradykinesia were better decoded from distinct subregions. These results demonstrate how to leverage neurophysiology to more precisely treat PD.

3. Epilepsy + Behavior

   Seizure and anatomical outcomes of repeat laser amygdalohippocampotomy for temporal lobe epilepsy: A single-institution case series

   Bryan Zheng,  Hael Abdulrazeq,  Belinda Shao,  David D. Liu,  Owen Leary,  Peter M. Lauro,  Luca Bartolini,  Andrew S. Blum,  and Wael F. Asaad

   Epilepsy & Behavior Sep 2023

   Abstract DOI PDF

   Objective In patients with treatment-refractory temporal lobe epilepsy (TLE), a single stereotactic laser interstitial thermotherapy (LITT) procedure is sometimes insufficient to ablate epileptogenic tissue, particularly the medial structures often implicated in TLE. In patients with seizure recurrence after initial ablation, the extent to which a second ablation may achieve improved seizure outcomes is uncertain. The objective of this study was to investigate the feasibility and potential efficacy of repeat LITT amygdalohippocampotomy as a worthwhile strategy for intractable temporal lobe epilepsy by quantifying changes to targeted mesial temporal lobe structures and seizure outcomes. Methods Patients who underwent two LITT procedures for drug-resistant mesial TLE at our institution were included in the study. Lesion volumes for both procedures were calculated by comparing post-ablation intraoperative sequences to preoperative anatomy. Clinical outcomes after the initial procedure and repeat procedure were classified according to Engel scores. Results Five consecutive patients were included in this retrospective case series: 3 with right- and 2 with left-sided TLE. The median interval between LITT procedures was 294 days (range: 227–1918). After the first LITT, 3 patients experienced class III outcomes, 1 experienced a class IV, and 1 experienced a class IB outcome. All patients achieved increased seizure freedom after a second procedure, with class I outcomes (3 IA, 2 IB). Conclusions Repeat LITT may be sufficient to achieve satisfactory seizure outcomes in some individuals who might otherwise be considered for more aggressive resection or palliative neuromodulation. A larger study to establish the potential value of repeat LITT amygdalohippocampotomy vs. other re-operation strategies for persistent, intractable temporal lobe epilepsy is worth pursuing.

4. Expert Reviews

   Thalamic Neuromodulation in Epilepsy: A Primer for Emerging Circuit-Based Therapies

   Bryan Zheng,  David D. Liu,  Brian B Theyel,  Hael Abdulrazeq,  Anna R. Kimata,  Peter M Lauro,  and Wael F. Asaad

   Expert Review of Neurotherapeutics Feb 2023

   Abstract DOI PDF

   Introduction Epilepsy is a common, often debilitating disease of hyperexcitable neural networks. While medically intractable cases may benefit from surgery, there may be no single, well-localized focus for resection or ablation. In such cases, approaching the disease from a network-based perspective may be beneficial.Areas covered Herein, the authors provide a narrative review of normal thalamic anatomy and physiology and propose general strategies for preventing and/or aborting seizures by modulating this structure. Additionally, they make specific recommendations for targeting the thalamus within different contexts, motivated by a more detailed discussion of its distinct nuclei and their respective connectivity. By describing important principles governing thalamic function and its involvement in seizure networks, the authors aim to provide a primer for those now entering this fast-growing field of thalamic neuromodulation for epilepsy.Expert opinion The thalamus is critically involved with the function of many cortical and subcortical areas, suggesting it may serve as a compelling node for preventing or aborting seizures, and so it has increasingly been targeted for the surgical treatment of epilepsy. As various thalamic neuromodulation strategies for seizure control are developed, there is a need to ground such interventions in a mechanistic, circuit-based framework.

2022

1. HBM

   A hierarchical anatomical framework and workflow for organizing stereotactic encephalography in epilepsy

   Bryan Zheng,  Ben Hsieh,  Nathaniel Rex,  Peter M. Lauro,  Scott A. Collins,  Andrew S. Blum,  Julie L. Roth,  Neishay Ayub,  and Wael F. Asaad

   Human Brain Mapping Jul 2022

   Abstract DOI PDF

   Stereotactic electroencephalography (SEEG) is an increasingly utilized method for invasive monitoring in patients with medically intractable epilepsy. Yet, the lack of standardization for labeling electrodes hinders communication among clinicians. A rational clustering of contacts based on anatomy rather than arbitrary physical leads may help clinical neurophysiologists interpret seizure networks. We identified SEEG electrodes on post-implant CTs and registered them to preoperative MRIs segmented according to an anatomical atlas. Individual contacts were automatically assigned to anatomical areas independent of lead. These contacts were then organized using a hierarchical anatomical schema for display and interpretation. Bipolar-referenced signal cross-correlations were used to compare the similarity of grouped signals within a conventional montage versus this anatomical montage. As a result, we developed a hierarchical organization for SEEG contacts using well-accepted, free software that is based solely on their post-implant anatomical location. When applied to three example SEEG cases for epilepsy, clusters of contacts that were anatomically related collapsed into standardized groups. Qualitatively, seizure events organized using this framework were better visually clustered compared to conventional schemes. Quantitatively, signals grouped by anatomical region were more similar to each other than electrode-based groups as measured by Pearson correlation. Further, we uploaded visualizations of SEEG reconstructions into the electronic medical record, rendering them durably useful given the interpretable electrode labels. In conclusion, we demonstrate a standardized, anatomically grounded approach to the organization of SEEG neuroimaging and electrophysiology data that may enable improved communication among and across surgical epilepsy teams and promote a clearer view of individual seizure networks.

2. MDS

   Where Do Parkinson’s Disease Patients Look while Walking?

   Nora Vanegas-Arroyave,  Denise F. Chen,  Peter M. Lauro,  Gina Norato,  Codrin Lungu,  and Mark Hallett

   Movement Disorders Jan 2022

   Abstract DOI PDF

   Background Parkinson’s disease (PD) is associated with gait and visuomotor abnormalities, but it is not clear where PD patients look during ambulation. Objective We sought to characterize the visual areas of interest explored by PD patients, with and without freezing of gait (FOG), compared to healthy volunteers (HVs). Methods Using an eye-tracking device, we compared visual fixation patterns in 17 HVs and 18 PD patients, with and without FOG, during an ambulatory and a nonambulatory, computer-based task. Results During ambulation, PD patients with FOG fixated more on proximal areas of the ground and less on the target destination. PD patients without FOG displayed a fixation pattern more similar to that of HVs. Similar patterns were observed during the nonambulatory, computer-based task. Conclusions Our findings suggest increased dependence on visual feedback from nearby areas in the environment in PD patients with FOG, even in the absence of motor demands. © 2022 International Parkinson and Movement Disorder Society

2021

1. JNS

   Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder

   Nicole C.R. McLaughlin,  Peter M. Lauro,  Morgan T. Patrick,  Francesco G. Pucci,  Adriel Barrios-Anderson,  Benjamin D. Greenberg,  Steven A. Rasmussen,  and Wael F. Asaad

   Neurosurgery Mar 2021

   Abstract DOI PDF

   Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration.To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo.A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies.A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery.LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.

2. Epilepsia

   Two-trajectory laser amygdalohippocampotomy: Anatomic modeling and initial seizure outcomes

   David D. Liu,  Peter M. Lauro,  Ronald K. Phillips,  Owen P. Leary,  Bryan Zheng,  Julie L. Roth,  Andrew S. Blum,  David J. Segar,  and Wael F. Asaad

   Epilepsia Aug 2021

   Abstract DOI PDF

   Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. Methods We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. Results The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p \textless .05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, whereas one-laser trajectories could not. Five patients with at least 1 year of follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year of follow-up (mean = 6.6 months) are on track for Engel class I outcomes. Significance Our anatomic analyses and initial clinical results suggest that LITT amygdalohippocampotomy performed via two-laser trajectories may promote excellent seizure outcomes. Future studies are required to validate the long-term clinical efficacy and safety of this approach.

3. J Neurosci

   Subthalamic-Cortical Network Reorganization during Parkinson’s Tremor

   Peter M. Lauro,  Shane Lee,  Umer Akbar,  and Wael F. Asaad

   Journal of Neuroscience Nov 2021

   Abstract bioRxiv DOI PDF

   Tremor, a common and often primary symptom of Parkinson’s disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from ten (9M, 1F) patients performing a naturalistic visual-motor task. From this task we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state. SIGNIFICANCE STATEMENT: Tremor is a common symptom of Parkinson’s disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this manuscript, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation (DBS) surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson’s tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.

4. Brain

   Lesion location and lesion creation affect outcomes after focused ultrasound thalamotomy

   David J. Segar,  Asad M. Lak,  Shane Lee,  Maya Harary,  Vamsidhar Chavakula,  Peter Lauro,  Nathan McDannold,  Jason White,  and G. Rees Cosgrove

   Brain Nov 2021

   Abstract DOI PDF

   MRI-guided focused ultrasound thalamotomy has been shown to be an effective treatment for medication refractory essential tremor. Here, we report a clinical-radiological analysis of 123 cases of MRI-guided focused ultrasound thalamotomy, and explore the relationships between treatment parameters, lesion characteristics and outcomes.All patients undergoing focused ultrasound thalamotomy by a single surgeon were included. The procedure was performed as previously described, and patients were followed for up to 1 year. MRI was performed 24 h post-treatment, and lesion locations and volumes were calculated.We retrospectively evaluated 118 essential tremor patients and five tremor-dominant Parkinson’s disease patients who underwent thalamotomy. At 24 h post-procedure, tremor abated completely in the treated hand in 81 essential tremor patients. Imbalance, sensory disturbances and dysarthria were the most frequent acute adverse events. Patients with any adverse event had significantly larger lesions, while inferolateral lesion margins were associated with a higher incidence of motor-related adverse events. Twenty-three lesions were identified with irregular tails, often extending into the internal capsule; 22 of these patients experienced at least one adverse event.Treatment parameters and lesion characteristics changed with increasing surgeon experience. In later cases, treatments used higher maximum power (normalized to skull density ratio), accelerated more quickly to high power, and delivered energy over fewer sonications.Larger lesions were correlated with a rapid rise in both power delivery and temperature, while increased oedema was associated with rapid rise in temperature and the maximum power delivered. Total energy and total power did not significantly affect lesion size. A support vector regression was trained to predict lesion size and confirmed the most valuable predictors of increased lesion size as higher maximum power, rapid rise to high-power delivery, and rapid rise to high tissue temperatures. These findings may relate to a decrease in the energy efficiency of the treatment, potentially due to changes in acoustic properties of skull and tissue at higher powers and temperatures.We report the largest single surgeon series of focused ultrasound thalamotomy to date, demonstrating tremor relief and adverse events consistent with reported literature. Lesion location and volume impacted adverse events, and an irregular lesion tail was strongly associated with adverse events. High-power delivery early in the treatment course, rapid temperature rise, and maximum power were dominant predictors of lesion volume, while total power, total energy, maximum energy and maximum temperature did not improve prediction of lesion volume. These findings have critical implications for treatment planning in future patients.

2020

1. Springer

   The Design of Clinical Studies for Neuromodulation

   Wael F. Asaad,  Peter M. Lauro,  and Shane Lee

   In Stereotactic and Functional Neurosurgery: Principles and Applications Feb 2020

   Abstract DOI PDF

   Creating successful new neuromodulation therapies requires innovative trial design and the balancing of a wide variety of complex factors. The ultimate goal is to advance our ability to restore appropriate brain function through the targeted manipulation of neural circuits and, to this end, clinical trials should be just as informative in failure as they are in success. Some aspects of neuromodulation trials are common to all clinical studies, while other aspects are fairly specific to invasive neurosurgical interventions for complex neurological and psychiatric disease. This chapter examines the major factors to be considered in constructing clinical studies to investigate the various forms and applications of novel neuromodulation strategies.

2. JNE

   Rapid motor fluctuations reveal short-timescale neurophysiological biomarkers of Parkinson’s disease

   Minkyu Ahn,  Shane Lee,  Peter M. Lauro,  Erin L. Schaeffer,  Umer Akbar,  and Wael F. Asaad

   Journal of Neural Engineering Aug 2020

   Abstract medRxiv DOI PDF

   Objective: Identifying neural activity biomarkers of brain disease is essential to provide objective estimates of disease burden, obtain reliable feedback regarding therapeutic efficacy, and potentially to serve as a source of control for closed-loop neuromodulation. In Parkinson’s Disease (PD), microelectrode recordings (MER) are routinely performed in the basal ganglia to guide electrode implantation for deep brain stimulation (DBS). While pathologically-excessive oscillatory activity has been observed and linked to PD motor dysfunction broadly, the extent to which these signals provide quantitative information about disease expression and fluctuations, particularly at short timescales, is unknown. Furthermore, the degree to which informative signal features are similar or different across patients has not been rigorously investigated. We sought to determine the extent to which motor error in PD across patients can be decoded on a rapid timescale using spectral features of neural activity. Approach: Here, we recorded neural activity from the subthalamic nucleus (STN) of subjects with PD undergoing awake DBS surgery while they performed an objective, continuous behavioral assessment that synthesized heterogenous PD motor manifestations to generate a scalar measure of motor dysfunction at short timescales. We then leveraged natural motor performance variations as a “ground truth” to identify corresponding neurophysiological biomarkers. Main Results: Support vector machines using multi-spectral decoding of neural signals from the STN succeeded in tracking the degree of motor impairment at short timescales (as short as one second). Spectral power across a wide range of frequencies, beyond the classic “β” oscillations, contributed to this decoding, and multi-spectral models consistently outperformed those generated using more isolated frequency bands. While generalized decoding models derived across subjects were able to estimate motor impairment, patient-specific models typically performed better. Significance: These results demonstrate that quantitative information about short-timescale PD motor dysfunction is available in STN neural activity, distributed across various patient-specific spectral components, such that an individualized approach will be critical to fully harness this information for optimal disease tracking and closed-loop neuromodulation.

3. Frontiers in Neurology

   Multi-Dimensional, Short-Timescale Quantification of Parkinson’s Disease and Essential Tremor Motor Dysfunction

   John B. Sanderson,  James H. Yu,  David D. Liu,  Daniel Amaya,  Peter M. Lauro,  Anelyssa D’Abreu,  Umer Akbar,  Shane Lee,  and Wael F. Asaad

   Frontiers in Neurology Sep 2020

   Abstract DOI PDF

   INTRODUCTION: Parkinson’s disease (PD) is a progressive movement disorder characterized by heterogenous motor dysfunction with fluctuations in severity. Objective, short-timescale characterization of these symptoms is necessary as therapies become increasingly adaptive. OBJECTIVES: This study aims to characterize a novel, naturalistic, and goal-directed tablet-based task and complementary analysis protocol designed to characterize the features of PD. METHODS: A total of 26 patients with PD and without deep brain stimulation (DBS), 20 control subjects, and eight patients with PD and with deep brain stimulation (DBS) completed the task. Eight metrics, each designed to capture an aspect of motor dysfunction in PD, were calculated from 1-second, non-overlapping epochs of the raw positional and pressure data. These metrics were used to generate a classifier to produce a unifying, scalar ‘motor error score’ (MES). These data were compared to standard clinical assessments of these same patients. Additionally, these data were compared to analogous data generated from a group of 12 patients with essential tremor (ET) to assess the task’s specificity for PD. Finally, a classifier was generated to differentiate between motor dysfunction in patients with PD with DBS in different stimulation states. RESULTS: The eight metrics calculated from the raw positional and force data captured during task completion were non-redundant. MES generated by the SVM analysis protocol showed a strong correlation with MDS-UPDRS-III scores assigned by movement disorder specialists. Analysis of the relative contributions of each of the eight metrics showed a significant difference between the motor dysfunction of PD and ET. Much of this difference was attributable to the homogenous, tremor-dominant phenotype of ET motor dysfunction. Finally, in individual patients with PD with DBS, task performance and subsequent SVM classification effectively differentiated between the ‘DBSOn’ and ‘DBSOff’ stimulation states. CONCLUSION: The tablet-based task correlated strongly with the MDS-UPDRS-III. Additionally, the task showed specificity for PD when compared to ET, another common movement disorder. Finally, the task was able to distinguish between the ‘DBSOn’ and ‘DBSOff’ states within single patients with PD. This task provides temporally-precise and specific information about motor dysfunction in two movement disorders that could feasibly correlate to neural activity.

2019

1. Thieme

   Intraoperative Research during Deep Brain Stimulation Surgery

   Shane Lee,  Meghal Shah,  Peter M. Lauro,  and Wael F. Asaad

   In Deep Brain Stimulation: Techniques and Practices May 2019

   HTML PDF

2018

1. SFN

   DBStar: An Open-Source Tool Kit for Imaging Analysis with Patient-Customized Deep Brain Stimulation Platforms

   Peter M. Lauro,  Shane Lee,  Minkyu Ahn,  Andrei Barborica,  and Wael F. Asaad

   Stereotactic and Functional Neurosurgery Feb 2018

   Abstract DOI PDF

   \textbf\textitBackground/Objectives: To create an open-source method for reconstructing microelectrode recording (MER) and deep brain stimulation (DBS) electrode coordinates along multiple parallel trajectories with patient-specific DBS implantation platforms to facilitate DBS research. \textbf\textitMethods: We combined the surgical geometry (extracted from WayPoint Planner), pre-/intra-/postoperative computed tomography (CT) and/or magnetic resonance (MR) images, and integrated them into the Analysis of Functional NeuroImages (AFNI) neuroimaging analysis environment using functions written in Python. Electrode coordinates were calculated from image-based electrode surfaces and recording trajectory depth values. Coordinates were translated into appropriate trajectories, and were tested for proximity to patient-specific or atlas-based anatomical structures. Final DBS electrode coordinates for 3 patient populations (ventral intermediate nucleus [VIM], subthalamic nucleus [STN], and globus pallidus pars interna [GPi]) were calculated. For STN cases, MER site coordinates were then analyzed to see whether they were inside or outside the STN. \textbf\textitResults: Final DBS electrode coordinates were described for VIM, STN, and GPi patient populations. 115/169 (68%) STN MER sites were within 1 mm of the STN in AFNI’s Talairach and Tournoux (TT) atlas. \textbf\textitConclusions: DBStar is a robust tool kit for understanding the anatomical location and context of electrode locations, and can easily be used for imaging, behavioral, or electrophysiological analyses.

2017

1. Neuroimage Clin.

   Changes in functional organization and white matter integrity in the connectome in Parkinson’s disease

   Sule Tinaz,  Peter M. Lauro,  Pritha Ghosh,  Codrin Lungu,  and Silvina G. Horovitz

   NeuroImage: Clinical Jan 2017

   Abstract DOI PDF

   Parkinson’s disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional “disconnection” in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

2. J Neurosci

   Prefrontal Neurons Encode a Solution to the Credit-Assignment Problem

   Wael F. Asaad,  Peter M. Lauro,  János A. Perge,  and Emad N. Eskandar

   Journal of Neuroscience Jul 2017

   Abstract DOI PDF

   To adapt successfully to our environments, we must use the outcomes of our choices to guide future behavior. Critically, we must be able to correctly assign credit for any particular outcome to the causal features which preceded it. In some cases, the causal features may be immediately evident, whereas in others they may be separated in time or intermingled with irrelevant environmental stimuli, creating a potentially nontrivial credit-assignment problem. We examined the neuronal representation of information relevant for credit assignment in the dorsolateral prefrontal cortex (dlPFC) of two male rhesus macaques performing a task that elicited key aspects of this problem. We found that neurons conveyed the information necessary for credit assignment. Specifically, neuronal activity reflected both the relevant cues and outcomes at the time of feedback and did so in a manner that was stable over time, in contrast to prior reports of representational instability in the dlPFC. Furthermore, these representations were most stable early in learning, when credit assignment was most needed. When the same features were not needed for credit assignment, these neuronal representations were much weaker or absent. These results demonstrate that the activity of dlPFC neurons conforms to the basic requirements of a system that performs credit assignment, and that spiking activity can serve as a stable mechanism that links causes and effects. SIGNIFICANCE STATEMENT Credit assignment is the process by which we infer the causes of our successes and failures. We found that neuronal activity in the dorsolateral prefrontal cortex conveyed the necessary information for performing credit assignment. Importantly, while there are various potential mechanisms to retain a “trace” of the causal events over time, we observed that spiking activity was sufficiently stable to act as the link between causes and effects, in contrast to prior reports that suggested spiking representations were unstable over time. In addition, we observed that this stability varied as a function of learning, such that the neural code was more reliable over time during early learning, when it was most needed.

2016

1. Brain

   Tractography patterns of subthalamic nucleus deep brain stimulation

   Nora Vanegas-Arroyave,  Peter M. Lauro,  Ling Huang,  Mark Hallett,  Silvina G. Horovitz,  Kareem A. Zaghloul,  and Codrin Lungu

   Brain Apr 2016

   Abstract DOI PDF

   White matter structures near the subthalamic nucleus (STN) have been implicated in the therapeutic benefits of DBS in Parkinson’s disease. Vanegas-Arroyave et a

2. Brain Struct. + Funct.

   Deficits in task-set maintenance and execution networks in Parkinson’s disease

   Sule Tinaz,  Peter Lauro,  Mark Hallett,  and Silvina G. Horovitz

   Brain Structure and Function Apr 2016

   Abstract DOI PDF

   Patients with Parkinson’s disease have difficulties with self-initiating a task and maintaining a steady task performance. We hypothesized that these difficulties relate to reorganization in the sensorimotor execution, cingulo-opercular task-set maintenance, and frontoparietal adaptive control networks. We tested this hypothesis using graph theory-based network analysis of a composite network including a total of 86 nodes, derived from the three networks of interest. Resting-state functional magnetic resonance images were collected from 30 patients with Parkinson’s disease (age 42–75 years, 11 females; Hoehn and Yahr score 2–3, average 2.4 ± 0.4) in their off-medication state and 30 matched control subjects (age 44–75 years, 10 females). For each node, we calculated strength as a general measure of connectivity, global efficiency and betweenness centrality as measures of functional integration, and clustering coefficient and local efficiency as measures of functional segregation. We found reduced node strength, clustering, and local efficiency in sensorimotor and posterior temporal nodes. There was also reduced node strength and betweenness centrality in the dorsal anterior insula and temporoparietal junction nodes of the cingulo-opercular network. These nodes are involved in integrating multimodal information, specifically related to self-awareness, sense of agency, and ultimately to intact perception of self-in-action. Moreover, we observed significant correlations between global disease severity and averaged graph metrics of the whole network. In addition to the well-known task-related frontostriatal mechanisms, we propose that the resting-state reorganization in the composite network can contribute to problems with self-initiation and task-set maintenance in Parkinson’s disease.

2015

1. HBM

   DBSproc: An open source process for DBS electrode localization and tractographic analysis

   Peter M. Lauro,  Nora Vanegas‐Arroyave,  Ling Huang,  Paul A. Taylor,  Kareem A. Zaghloul,  Codrin Lungu,  Ziad S. Saad,  and Silvina G. Horovitz

   Human Brain Mapping Dec 2015

   Abstract DOI PDF

   Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders. Although stimulation sites for movement disorders such as Parkinson’s disease are established, the therapeutic mechanisms of DBS remain controversial. Recent research suggests that specific white-matter tract and circuit activation mediates symptom relief. To investigate these questions, we have developed a patient-specific open-source software pipeline called ‘DBSproc’ for (1) localizing DBS electrodes and contacts from postoperative CT images, (2) processing structural and diffusion MRI data, (3) registering all images to a common space, (4) estimating DBS activation volume from patient-specific voltage and impedance, and (5) understanding the DBS contact-brain connectivity through probabilistic tractography. In this paper, we explain our methodology and provide validation with anatomical and tractographic data. This method can be used to help investigate mechanisms of action of DBS, inform surgical and clinical assessments, and define new therapeutic targets. Hum Brain Mapp 37:422–433, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.