Dorsal visual stream is preferentially engaged during externally guided action selection in Parkinson Disease.

OBJECTIVE: In patients with Parkinson Disease (PD), self-initiated or internally cued (IC) actions are thought to be compromised by the disease process, as exemplified by impairments in action initiation. In contrast, externally-cued (EC) actions which are made in response to sensory prompts can restore a remarkable degree of movement capability in PD, particularly alleviating freezing-of-gait. This study investigates the electrophysiological underpinnings of movement facilitation in PD through visuospatial cuing, with particular attention to the dynamics within the posterior parietal cortex (PPC) and lateral premotor cortex (LPMC) axis of the dorsal visual stream. METHODS: Invasive cortical recordings over the PPC and LPMC were obtained during deep brain stimulation lead implantation surgery. Thirteen PD subjects performed an action selection task, which was constituted by left or right joystick movement with directional visual cuing in the EC condition and internally generated direction selection in the IC condition. Time-resolved neural activities within and between the PPC and LPMC were compared between EC and IC conditions. RESULTS: Reaction times (RT) were significantly faster in the EC condition relative to the IC condition (paired t-test, p = 0.0015). PPC-LPMC inter-site phase synchrony within the ß-band (13-35 Hz) was significantly greater in the EC relative to the IC condition. Greater PPC-LPMC ß debiased phase lag index (dwPLI) prior to movement onset was correlated with faster reaction times only in the EC condition. Multivariate granger causality (GC) was greater in the EC condition relative to the IC condition, prior to and during movement. CONCLUSION: Relative to IC actions, we report relative increase in inter-site phase synchrony and directional PPC to LPMC connectivity in the ß-band during preparation and execution of EC actions. Furthermore, increased strength of connectivity is predictive of faster RT, which are pathologically slow in PD patients. Stronger engagement of the PPC-LPMC cortical network by an EC specifically through the channel of ß-modulation is implicated in correcting the pathological slowing of action initiation seen in Parkinson's patients. SIGNIFICANCE: These findings shed light on the electrophysiological mechanisms that underlie motor facilitation in PD patients through visuospatial cuing.

Linear accelerator-based radiosurgery for trigeminal neuralgia: comparative outcomes of frame-based and mask-based techniques.

OBJECTIVE: Precise and accurate targeting is critical to optimize outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The aim of this study was to compare the outcomes after SRS for TN in which two different techniques were used: mask-based 4-mm cone versus frame-based 5-mm cone. METHODS: The authors performed a retrospective review of patients who underwent SRS for TN at their institution between 1996 and 2019. The Barrow Neurological Institute (BNI) pain score and facial hypesthesia scale were used to evaluate pain relief and facial numbness. RESULTS: A total of 234 patients were included in this study; the mean age was 67 years. In 97 patients (41.5%) radiation was collimated by a mask-based 4-mm cone, whereas a frame-based 5-mm cone was used in the remaining 137 patients (58.5%). The initial adequate pain control rate (BNI I-III) was 93.4% in the frame-based 5-mm group, compared to 87.6% in the mask-based 4-mm group. This difference between groups lasted, with an adequate pain control rate at ≥ 24 months of 89.9% and 77.8%, respectively. Pain relief was significantly different between groups from initial response until the last follow-up (≥ 24 months, p = 0.02). A new, permanent facial hypesthesia occurred in 30.3% of patients (33.6% in the frame-based 5-mm group vs 25.8% in the mask-based 4-mm group). However, no significant association between the BNI facial hypesthesia score and groups was found. Pain recurrence occurred earlier (median time to recurrence 12 months vs 29 months, p = 0.016) and more frequently (38.1% vs 20.4%, p = 0.003) in the mask-based 4-mm than in the frame-based 5-mm group. CONCLUSIONS: Frame-based 5-mm collimator SRS for TN resulted in a better long-term pain relief with similar toxicity profiles to that seen with mask-based 4-mm collimator SRS.

Amygdala Structural Connectivity Is Associated With Impulsive Choice and Difficulty Quitting Smoking.

Introduction: The amygdala is known to play a role in mediating emotion and possibly addiction. We used probabilistic tractography (PT) to evaluate whether structural connectivity of the amygdala to the brain reward network is associated with impulsive choice and tobacco smoking. Methods: Diffusion and structural MRI scans were obtained from 197 healthy subjects (45 with a history of tobacco smoking) randomly sampled from the Human Connectome database. PT was performed to assess amygdala connectivity with several brain regions. Seed masks were generated, and statistical maps of amygdala connectivity were derived. Connectivity results were correlated with a subject performance both on a delayed discounting task and whether they met specified criteria for difficulty quitting smoking. Results: Amygdala connectivity was spatially segregated, with the strongest connectivity to the hippocampus, orbitofrontal cortex (OFC), and brainstem. Connectivity with the hippocampus was associated with preference for larger delayed rewards, whereas connectivity with the OFC, rostral anterior cingulate cortex (rACC), and insula were associated with preference for smaller immediate rewards. Greater nicotine dependence with difficulty quitting was associated with less hippocampal and greater brainstem connectivity. Scores on the Fagerstrom Test for Nicotine Dependence (FTND) correlated with rACC connectivity. Discussion: These findings highlight the importance of the amygdala-hippocampal-ACC network in the valuation of future rewards and substance dependence. These results will help to identify potential targets for neuromodulatory therapies for addiction and related disorders.

Synchrony Drives Motor Cortex Beta Bursting, Waveform Dynamics, and Phase-Amplitude Coupling in Parkinson's Disease.

Several lines of inquiry have separately identified beta oscillations, synchrony, waveform shape, and phase-amplitude coupling as important but sometimes inconsistent factors in the pathophysiology of Parkinson's disease. What has so far been lacking is a means by which these neurophysiological parameters are interrelated and how they relate to clinical symptomatology. To clarify the relationship among oscillatory power, bursting, synchrony, and phase-amplitude coupling, we recorded local field potentials/electrocorticography from hand motor and premotor cortical area in human subjects with c (N = 10) and Parkinson's disease (N = 22) during deep brain stimulator implantation surgery (14 females, 18 males). We show that motor cortical high beta oscillations in Parkinson's disease demonstrate increased burst durations relative to essential tremor patients. Notably, increased corticocortical synchrony between primary motor and premotor cortices precedes motor high beta bursts, suggesting a possible causal relationship between corticocortical synchrony and localized increases in beta power. We further show that high beta bursts are associated with significant changes in waveform shape and that beta-encoded phase-amplitude coupling is more evident during periods of high beta bursting. These findings reveal a deeper structure to the pathologic changes identified in the neurophysiology of Parkinson's disease, suggesting mechanisms by which the treatment may be enhanced using targeted network synchrony disruption approaches.SIGNIFICANCE STATEMENT Understanding Parkinson's disease pathophysiology is crucial for optimizing symptom management. Present inconsistencies in the literature may be explained by temporal transients in neural signals driven by transient fluctuations in network synchrony. Synchrony may also act as a unifying phenomenon for the pathophysiological observations reported in Parkinson's disease. Here, simultaneous recordings from motor cortices show that increases in network beta synchrony anticipate episodes of beta bursting. We furthermore identify beta bursting as being associated with changes in waveform shape and increases in phase-amplitude coupling. Our results identify network synchrony as a driver of various pathophysiological observations reported in the literature and account for inconsistencies in the literature by virtue of the temporally variable nature of the phenomenon.

Assessing the volume of large cerebral arteriovenous malformations: Can the ABC/2 formula reliably predict true volume?

BACKGROUND: Outcomes of stereotactic radiosurgery in the treatment of cerebral arteriovenous malformations (AVMs) are volume-dependent. The ability to estimate AVM volume has significant value in guiding AVM management. OBJECTIVE: To determine whether AVM volume measurement calculated from the ABC/2 formula is accurate compared to volume calculated by a computer-assisted planimetric method for large AVMs. METHODS: Retrospective review of 42 intracranial AVMs >3 cm in diameter that underwent treatment with dose-staged hypofractionated stereotactic radiotherapy (HSRT) from 2001 to 2018. Two raters independently measured pre- and post-HSRT volumes using both the ABC/2 formula and computer-assisted planimetry in a blinded fashion. Inter-rater reliability was assessed by calculation of intra-class correlation coefficient (ICC). Absolute volumes and percent volume change following HSRT as determined using the two methods were compared using paired t-tests, linear regression, and Bland-Altman plot analyses. RESULTS: The ICC between the 2 raters for planimetric and ABC/2 volumes was 0.859 and 0.799, respectively. ABC/2 volumes, 26.1 ±â€¯26.6 cm3, were statistically smaller than planimetric volumes, 28.6 ±â€¯27.1 cm3 (P = .008). Despite differences, the two methods were highly correlated (R2 = 0.904, linear regression). The percent volume change following HSRT was significantly greater with the ABC/2 method than compared to planimetry (P = .009). CONCLUSION: The ABC/2 and planimetric methods are reproducible for measuring cerebral AVM volumes. Although the ABC/2 method of volume estimation underestimates planimetric AVM volume, the high correlation between the two suggests utility of the ABC/2 method if one understands its limits, particularly with respect to estimating change in AVM volume after treatment.

Dose Hypofractionated Stereotactic Radiotherapy for Intracranial Arteriovenous Malformations: A Case Series and Review of the Literature.

BACKGROUND: Brain arteriovenous malformations (AVMs) are pathologic tangles of intracerebral vessels. The treatment of AVMs aims to reduce the risk of devastating intracranial hemorrhage (ICH). Hypofractionated stereotactic radiotherapy (HSRT) can be used to treat large lesions and reduce the risk of radiation toxicity to the surrounding structures. We analyzed the data from our institutional experience of the past 15 years in treating large AVMs with both 5- and 6-fraction HSRT and evaluated the pretreatment characteristics that are most predictive of the radiographic response. METHODS: We included 37 patients and 42 treatments of intracranial AVMs measuring >3 cm in their largest dimension. Data were collected retrospectively by reviewing the electronic health records. The AVM volume was measured before HSRT and at the most recent follow-up appointment. Symptomatic outcomes, including treatment-related inflammation, were measured and defined categorically. RESULTS: Complete obliteration was achieved in 11.9% of the patients. The mean AVM volume had decreased significantly after HSRT (P = 8.7e-8). The percentage of volume reduction differed significantly between patients receiving 30-Gy fractions, (∂V = -48.7%) and those receiving 25-Gy fractions (∂V = -29.1%; P = 0.035). Patients with partial or complete obliteration were more likely to have received a total dose of 30 Gy rather than 25 Gy (P = 0.056) and showed a trend toward being treatment naive (P = 0.053). CONCLUSION: HSRT can be used as a method to manage large AVMs, with obliteration in some cases and sufficient volume reduction in most others for adjuvant treatment with other modalities. The 30-Gy total dose was generally superior to 25 Gy in achieving obliteration or volume reduction. Further studies focused on longer follow-up periods are warranted.