Temporal Analysis of Tachycardia During Catheter Directed Thrombolysis for Acute Pulmonary Embolism.

PURPOSE: To evaluate the effect of catheter directed thrombolysis (CDT) on heart rate (HR) in patients with sinus tachycardia and acute pulmonary embolism (PE). METHODS: A retrospective chart review was performed for patients who underwent CDT with tPA for acute massive or submassive PE between 12/2009 and 2/2020. Included were patients who presented with tachycardia at the time of initiation of CDT. Patients with chronic PE, atrial fibrillation, beta blocker therapy, adjunctive endovascular therapy, systemic thrombolysis, or who expired before conclusion of CDT were excluded. HR was measured approximately every hour during CDT. Graphs were plotted of HR as a function of CDT duration. Two interventional radiologists identified the point of plateau (POP) on the graph where CDT had maximized its benefit in decreasing the patient's HR. Discrepancies were adjudicated by a third interventional radiologist and the median of the 3 measurements was selected. The primary endpoint was the duration of CDT from initiation until the POP. RESULTS: 48 patients were included (52.5 ± 14.7 years, 56.3% female). The POP occurred after 13.1 ± 6.1 hours, by which point HR had been reduced from 110 ± 9.2 bpm to 88 ± 10.6 bpm. Sinus tachycardia was not resolved in 10 patients even though they achieved maximal improvement in HR after 11.3 ± 6.7 hours. CONCLUSION: Patients presenting with sinus tachycardia related to acute PE achieved maximal, sustained reduction in heart rate from CDT, after approximately 13 hours of infusion. Patients who did not resolve their tachycardia by that point in time were unlikely to resolve it by the conclusion of CDT.

Online feedback enhances early consolidation of motor sequence learning and reverses recall deficit from transcranial stimulation of motor cortex.

Feedback and monetary reward can enhance motor skill learning, suggesting reward system involvement. Continuous theta burst (cTBS) transcranial magnetic stimulation (TMS) of the primary motor area (M1) disrupts processing, reduces excitability and impairs motor learning. To see whether feedback and reward can overcome the learning impairment associated with M1 cTBS, we delivered real or sham stimulation to two groups of participants before they performed a motor sequence learning task with and without feedback. Participants were trained on two intermixed sequences, one occurring 85% of the time (the "probable" sequence) and the other 15% of the time (the "improbable" sequence). We measured sequence learning as the difference in reaction time (RT) and error rate between probable and improbable trials (RT and error difference scores). Participants were also tested for sequence recall with the same indices of learning 60 min after cTBS. Real stimulation impaired initial sequence learning and sequence knowledge recall as measured by error difference scores and impaired sequence knowledge recall as measured by RT difference score. Relative to non-feedback learning, the introduction of feedback during sequence learning improved subsequent sequence knowledge recall indexed by RT difference score, in both real and sham stimulation groups and feedback reversed the RT difference score based sequence knowledge recall impairment from real cTBS that we observed in the non-feedback learning condition. Only the real cTBS group in the non-feedback condition showed no evidence of explicit sequence knowledge when tested at the end of the study. Feedback improves recall of implicit and explicit motor sequence knowledge and can protect sequence knowledge against the effect of M1 inhibition. Adding feedback and monetary reward/punishment to motor skill learning may help overcome retention impairments or accelerate training in clinical and other settings.

Modulation of corticospinal excitability by reward depends on task framing.

Findings from previous transcranial magnetic stimulation (TMS) experiments suggest that the primary motor cortex (M1) is sensitive to reward conditions in the environment. However, the nature of this influence on M1 activity is poorly understood. The dopamine neuron response to conditioned stimuli encodes reward probability and outcome uncertainty, or the extent to which the outcome of a situation is known. Reward uncertainty and probability are related: uncertainty is maximal when probability is 0.5 and minimal when probability is 0 or 1 (i.e., certain outcome). Previous TMS-reward studies did not examine these factors independently. Here, we used single-pulse TMS to measure corticospinal excitability in 40 individuals while they performed a simple computer task, making guesses to find or avoid a hidden target. The task stimuli implied three levels of reward probability and two levels of uncertainty. We found that reward probability level interacted with the trial search condition. That is, motor evoked potential (MEP) amplitude, a measure of corticospinal neuron excitability, increased with increasing reward probability when participants were instructed to "find" a target, but not when they were instructed to "avoid" a target. There was no effect of uncertainty on MEPs. Response times varied with the number of choices. A subset of participants also received paired-pulse stimulation to evaluate changes in short-intracortical inhibition (SICI). No effects of SICI were observed. Taken together, the results suggest that the reward-contingent modulation of M1 activity reflects reward probability or a related aspect of utility, not outcome uncertainty, and that this effect is sensitive to the conceptual framing of the task.

Normative database of judgment of complexity task with functional near infrared spectroscopy--application for TBI.

The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury.

Transcranial magnetic brain stimulation: therapeutic promises and scientific gaps.

Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists studying the human motor system, TMS now has a growing list of applications in clinical and basic neuroscience. Although we understand many of its effects at the system level, detailed knowledge of its actions, particularly as a modulator of neural activity, has lagged, due mainly to the lack of suitable non-human models. Nevertheless, these gaps have not blocked the therapeutic application of TMS in brain disorders. Moderate success has been achieved in treating disorders such as depression, where the U.S. Food and Drug Administration has cleared a TMS system for therapeutic use. In addition, there are small, but promising, bodies of data on the treatment of schizophrenic auditory hallucinations, tinnitus, anxiety disorders, neurodegenerative diseases, hemiparesis, and pain syndromes. Some other nascent areas of study also exist. While the fate of TMS as a therapeutic modality depends on continued innovation and experimentation, economic and other factors may be decisive.

A pilot study on effects of 4×1 high-definition tDCS on motor cortex excitability.

High-Definition transcranial Direct Current Stimulation (HD-tDCS) using specialized small electrodes has been proposed as a focal, non-invasive neuromodulatory technique. Here we provide the first evidence of a change in cortical excitability after HD-tDCS of the motor cortex, using TMS motor evoked potential (MEP) as the measure of excitability. Stimulation for 20 minutes at 1 mA with an anode centered over the hand area of the motor cortex and four surrounding return electrodes (anodal 4×1 montage) produced a significant increase in MEP amplitude and variability after stimulation, compared to sham stimulation. Stimulation was well tolerated by all subjects with adverse effects limited to transient sensation under the electrodes. A high-resolution computational model confirmed predictions of increased focality using the 4×1 HD tDCS montage compared to conventional tDCS. Simulations also indicated that variability in placement of the center electrode relative to the location of the target (central sulcus) could account for increasing variability. These results provide support for the careful use of this technique where focal tDCS is desired.

Reward processing abnormalities in Parkinson's disease.

The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid-A-mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk-taking behavior in patients on agonist treatment.