Browsing by Author "Appelbaum, Lawrence G"
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Item Open Access Application of long-interval paired-pulse transcranial magnetic stimulation to motion-sensitive visual cortex does not lead to changes in motion discrimination.(Neuroscience letters, 2020-05-12) Gamboa, Olga Lucia; Brito, Alexandra; Abzug, Zachary; D'Arbeloff, Tracy; Beynel, Lysianne; Wing, Erik A; Dannhauer, Moritz; Palmer, Hannah; Hilbig, Susan A; Crowell, Courtney A; Liu, Sicong; Donaldson, Rachel; Cabeza, Roberto; Davis, Simon W; Peterchev, Angel V; Sommer, Marc A; Appelbaum, Lawrence GThe perception of visual motion is dependent on a set of occipitotemporal regions that are readily accessible to neuromodulation. The current study tested if paired-pulse Transcranial Magnetic Stimulation (ppTMS) could modulate motion perception by stimulating the occipital cortex as participants viewed near-threshold motion dot stimuli. In this sham-controlled study, fifteen subjects completed two sessions. On the first visit, resting motor threshold (RMT) was assessed, and participants performed an adaptive direction discrimination task to determine individual motion sensitivity. During the second visit, subjects performed the task with three difficulty levels as TMS pulses were delivered 150 and 50 ms prior to motion stimulus onset at 120% RMT, under the logic that the cumulative inhibitory effect of these pulses would alter motion sensitivity. ppTMS was delivered at one of two locations: 3 cm dorsal and 5 cm lateral to inion (scalp-based coordinate), or at the site of peak activation for "motion" according to the NeuroSynth fMRI database (meta-analytic coordinate). Sham stimulation was delivered on one-third of trials by tilting the coil 90°. Analyses showed no significant active-versus-sham effects of ppTMS when stimulation was delivered to the meta-analytic (p = 0.15) or scalp-based coordinates (p = 0.17), which were separated by 29 mm on average. Active-versus-sham stimulation differences did not interact with either stimulation location (p = 0.12) or difficulty (p = 0.33). These findings fail to support the hypothesis that long-interval ppTMS recruits inhibitory processes in motion-sensitive cortex but must be considered within the limited parameters used in this design.Item Open Access Cortical Brain Activity Reflecting Attentional Biasing Toward Reward-Predicting Cues Covaries with Economic Decision-Making Performance.(Cereb Cortex, 2016-01) San Martín, René; Appelbaum, Lawrence G; Huettel, Scott A; Woldorff, Marty GAdaptive choice behavior depends critically on identifying and learning from outcome-predicting cues. We hypothesized that attention may be preferentially directed toward certain outcome-predicting cues. We studied this possibility by analyzing event-related potential (ERP) responses in humans during a probabilistic decision-making task. Participants viewed pairs of outcome-predicting visual cues and then chose to wager either a small (i.e., loss-minimizing) or large (i.e., gain-maximizing) amount of money. The cues were bilaterally presented, which allowed us to extract the relative neural responses to each cue by using a contralateral-versus-ipsilateral ERP contrast. We found an early lateralized ERP response, whose features matched the attention-shift-related N2pc component and whose amplitude scaled with the learned reward-predicting value of the cues as predicted by an attention-for-reward model. Consistently, we found a double dissociation involving the N2pc. Across participants, gain-maximization positively correlated with the N2pc amplitude to the most reliable gain-predicting cue, suggesting an attentional bias toward such cues. Conversely, loss-minimization was negatively correlated with the N2pc amplitude to the most reliable loss-predicting cue, suggesting an attentional avoidance toward such stimuli. These results indicate that learned stimulus-reward associations can influence rapid attention allocation, and that differences in this process are associated with individual differences in economic decision-making performance.Item Open Access Cross-modal stimulus conflict: the behavioral effects of stimulus input timing in a visual-auditory Stroop task.(PLoS One, 2013) Donohue, Sarah E; Appelbaum, Lawrence G; Park, Christina J; Roberts, Kenneth C; Woldorff, Marty GCross-modal processing depends strongly on the compatibility between different sensory inputs, the relative timing of their arrival to brain processing components, and on how attention is allocated. In this behavioral study, we employed a cross-modal audio-visual Stroop task in which we manipulated the within-trial stimulus-onset-asynchronies (SOAs) of the stimulus-component inputs, the grouping of the SOAs (blocked vs. random), the attended modality (auditory or visual), and the congruency of the Stroop color-word stimuli (congruent, incongruent, neutral) to assess how these factors interact within a multisensory context. One main result was that visual distractors produced larger incongruency effects on auditory targets than vice versa. Moreover, as revealed by both overall shorter response times (RTs) and relative shifts in the psychometric incongruency-effect functions, visual-information processing was faster and produced stronger and longer-lasting incongruency effects than did auditory. When attending to either modality, stimulus incongruency from the other modality interacted with SOA, yielding larger effects when the irrelevant distractor occurred prior to the attended target, but no interaction with SOA grouping. Finally, relative to neutral-stimuli, and across the wide range of the SOAs employed, congruency led to substantially more behavioral facilitation than did incongruency to interference, in contrast to findings that within-modality stimulus-compatibility effects tend to be more evenly split between facilitation and interference. In sum, the present findings reveal several key characteristics of how we process the stimulus compatibility of cross-modal sensory inputs, reflecting stimulus processing patterns that are critical for successfully navigating our complex multisensory world.Item Open Access Effects of online repetitive transcranial magnetic stimulation (rTMS) on cognitive processing: A meta-analysis and recommendations for future studies.(Neuroscience and biobehavioral reviews, 2019-12) Beynel, Lysianne; Appelbaum, Lawrence G; Luber, Bruce; Crowell, Courtney A; Hilbig, Susan A; Lim, Wesley; Nguyen, Duy; Chrapliwy, Nicolas A; Davis, Simon W; Cabeza, Roberto; Lisanby, Sarah H; Deng, Zhi-DeOnline repetitive transcranial magnetic stimulation (rTMS), applied while subjects are performing a task, is widely used to disrupt brain regions underlying cognition. However, online rTMS has also induced "paradoxical enhancement". Given the rapid proliferation of this approach, it is crucial to develop a better understanding of how online stimulation influences cognition, and the optimal parameters to achieve desired effects. To accomplish this goal, a quantitative meta-analysis was performed with random-effects models fitted to reaction time (RT) and accuracy data. The final dataset included 126 studies published between 1998 and 2016, with 244 total effects for reaction times, and 202 for accuracy. Meta-analytically, rTMS at 10 Hz and 20 Hz disrupted accuracy for attention, executive, language, memory, motor, and perception domains, while no effects were found with 1 Hz or 5 Hz. Stimulation applied at and 10 and 20 Hz slowed down RTs in attention and perception tasks. No performance enhancement was found. Meta-regression analysis showed that fMRI-guided targeting and short inter-trial intervals are associated with increased disruptive effects with rTMS.Item Open Access Evaluating Human Performance in Virtual Reality Based on Psychophysiological Signal Analysis(2018) Clements, JillianPhysiological signals measured from the body, such as brain activity and motor behavior, can be used to infer different physiological states or processes in humans. Signal processing and machine learning often play a fundamental role in this assessment, providing unique approaches to analyzing and interpreting physiological data for a variety of applications, such as medical diagnosis and human-computer interaction. In this work, these approaches were utilized and adapted for two separate applications: brain-computer interfaces (BCIs) and the assessment of visual-motor skill in virtual reality (VR).
The goal of BCI technology is to allow people with severe motor impairments to control a device without the need for voluntary muscle control. Conventional BCIs operate by converting electrophysiological signals measured from the brain into meaningful control commands, eliminating the need for physical interaction with the system. However, despite encouraging improvements over the last decade, BCI use remains primarily in research laboratories. One of the biggest obstacles limiting their daily in-home use is the significant amount of time and expertise that is often required to set up the biosensors (electrodes) for recording brain activity. The most common modality for brain recording is electroencephalography (EEG), which typically employs gel-based “wet” electrodes for recording signals with high signal-to-noise ratios (SNRs). However, while wet electrodes record higher quality signals than dry electrodes, they often hinder frequent use because of the complex and time-consuming process of applying the electrodes to the scalp. Therefore, in this research, a signal processing solution was implemented to help mitigate noise in a dry electrode system to facilitate a more practical BCI device for everyday use in people with severe motor impairments. This solution utilized a Bayesian algorithm that automatically determined the amount of EEG data to collect online based on the quality of incoming data. The hypothesis for this research was that the algorithm would detect the need for additional data collection in low SNR scenarios, such as those in the dry electrode systems, and collect sufficient data to improve BCI performance. In addition to this solution, two anomaly detection techniques were implemented to characterize the differences between the wet and dry electrode recordings to determine if any additional types of signal processing would further improve BCI performance with dry electrodes. Taken as a whole, this research demonstrated the impact of noise in dry electrode recordings on BCI performance and showed the potential of a signal processing approach for noise mitigation. However, further signal processing efforts are likely necessary for full mitigation and adoption of dry electrodes for use in the home.
The second study presented in this work focused on signal processing and machine learning techniques for assessing visual-motor skill during a simulated marksmanship task in immersive VR. Immersive VR systems offer flexible control of an interactive environment, along with precise position and orientation tracking of realistic movements. These systems can also be used in conjunction with brain monitoring techniques, such as EEG, to record neural signals as individuals perform complex motor tasks. In this study, these elements were fused to investigate the psychophysiological mechanisms underlying visual-motor skill during a multi-day simulated marksmanship training regimen. On each of 3 days, twenty participants performed a task where they were instructed to shoot simulated clay pigeons that were launched from behind a trap house using a mock firearm controller. Through the practice of this protocol, participants significantly improved their shot accuracy and precision. Furthermore, systematic changes in the variables extracted from the EEG and kinematic signals were observed that accompanied these improvements in performance. Using a machine learning approach, two predictive classification models were developed to automatically determine the combinations of EEG and kinematic variables that best differentiated successful (target hit) from unsuccessful (target miss) trials and high-performing participants (top fourth) from low-performing participants (bottom fourth). Finally, in order to capture the more complex patterns of human motion in the spatiotemporal domain, time series methods for motion trajectory prediction were developed that utilized the raw tracking data to estimate the future motion of the firearm controller. The objective of this approach was to predict whether the controller’s virtually projected ray would intersect with the target before the trigger was pulled to shoot, with the eventual goal of alerting participants in real-time when shooting may be suboptimal.
Overall, the findings from this research project point towards a comprehensive psychophysiological signal processing approach that can be used to characterize and predict human performance in VR, which has the potential to revolutionize the design of current simulation-based training programs for realistic visual-motor tasks.
Item Open Access Evaluating the effects of image persistence on dynamic target acquisition in low frame rate virtual environments(2016 IEEE Symposium on 3D User Interfaces, 3DUI 2016 - Proceedings, 2016-04-26) Zielinski, David J; Rao, Hrishikesh M; Potter, Nicholas D; Sommer, Marc A; Appelbaum, Lawrence G; Kopper, Regis© 2016 IEEE.User performance in virtual environments with degraded visual conditions due to low frame rates is an interesting area of inquiry. Visual content shown in a low frame rate simulation has the quality of the original image, but persists for an extended period until the next frame is displayed (so-called high persistence-HP). An alternative, called low persistence (LP), involves displaying the rendered frame for a single display frame and blanking the screen while waiting for the next frame to be generated. Previous research has evaluated the usefulness of the LP technique in low frame rate simulations during a static target acquisition task. To gain greater knowledge about the LP technique, we have conducted a user study to evaluate user performance and learning during a dynamic target acquisition task. The acquisition task was evaluated under a high frame rate, (60 fps) condition, a traditional low frame rate HP condition (10 fps), and the experimental low frame rate LP technique. The task involved the acquisition of targets moving along several different trajectories, modeled after a shotgun trap shooting task. The results of our study indicate the LP condition approaches high frame rate performance within certain classes of target trajectories. Interestingly we also see that learning is consistent across conditions, indicating that it may not always be necessary to train under a visually high frame rate system to learn a particular task. We discuss implications of using the LP technique to mitigate low frame rate issues as well as its potential usefulness for training in low frame rate virtual environments.Item Open Access Examining the Role of Lateral Parietal Cortex in Emotional Distancing Using TMS.(Cognitive, affective & behavioral neuroscience, 2020-10) Powers, John P; Davis, Simon W; Neacsiu, Andrada D; Beynel, Lysianne; Appelbaum, Lawrence G; LaBar, Kevin SWe recently proposed a neurocognitive model of distancing-an emotion regulation tactic-with a focus on the lateral parietal cortex. Although this brain area has been implicated in both cognitive control and self-projection processes during distancing, fMRI work suggests that these processes may be dissociable here. This preregistered (NCT03698591) study tested the contribution of left temporoparietal junction (TPJ) to distancing using repetitive transcranial magnetic stimulation. We hypothesized that inhibiting left TPJ would decrease the efficiency of distancing but not distraction, another regulation tactic with similar cognitive control requirements, thus implicating this region in the self-projection processes unique to distancing. Active and sham continuous theta burst stimulation (cTBS) were applied to 30 healthy adults in a single-session crossover design. Tactic efficiency was measured using online reports of valence and effort. The stimulation target was established from the group TPJ fMRI activation peak in an independent sample using the same distancing task, and anatomical MRI scans were used for individual targeting. Analyses employed both repeated-measures ANOVA and analytic procedures tailored to crossover designs. Irrespective of cTBS, distancing led to greater decreases in negative valence over time relative to distraction, and distancing effort decreased over time while distraction effort remained stable. Exploratory analyses also revealed that active cTBS made distancing more effortful, but not distraction. Thus, left TPJ seems to support self-projection processes in distancing, and these processes may be facilitated by repeated use. These findings help to clarify the role of lateral parietal cortex in distancing and inform applications of distancing and distraction.Item Open Access Intensity- and timing-dependent modulation of motion perception with transcranial magnetic stimulation of visual cortex.(Neuropsychologia, 2020-10) Gamboa Arana, Olga Lucia; Palmer, Hannah; Dannhauer, Moritz; Hile, Connor; Liu, Sicong; Hamdan, Rena; Brito, Alexandra; Cabeza, Roberto; Davis, Simon W; Peterchev, Angel V; Sommer, Marc A; Appelbaum, Lawrence GDespite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the dose-response relations and neurophysiological correlates of modulatory effects remain relatively unexplored. To fill this gap, we studied modulation of visual processing as a function of TMS parameters. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During each participants' first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered at one of two latencies, either 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at the N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions at the N2-Onset. TMS effects on the P3 VEP showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal the influence of TMS intensity and timing on visual perception and electrophysiological responses, with optimal facilitation at stimulation intensities below RMT.Item Unknown Is one enough? The case for non-additive influences of visual features on crossmodal Stroop interference.(Front Psychol, 2013) Appelbaum, Lawrence G; Donohue, Sarah E; Park, Christina J; Woldorff, Marty GWhen different perceptual signals arising from the same physical entity are integrated, they form a more reliable sensory estimate. When such repetitive sensory signals are pitted against other competing stimuli, such as in a Stroop Task, this redundancy may lead to stronger processing that biases behavior toward reporting the redundant stimuli. This bias would therefore, be expected to evoke greater incongruency effects than if these stimuli did not contain redundant sensory features. In the present paper we report that this is not the case for a set of three crossmodal, auditory-visual Stroop tasks. In these tasks participants attended to, and reported, either the visual or the auditory stimulus (in separate blocks) while ignoring the other, unattended modality. The visual component of these stimuli could be purely semantic (words), purely perceptual (colors), or the combination of both. Based on previous work showing enhanced crossmodal integration and visual search gains for redundantly coded stimuli, we had expected that relative to the single features, redundant visual features would have induced both greater visual distracter incongruency effects for attended auditory targets, and been less influenced by auditory distracters for attended visual targets. Overall, reaction times were faster for visual targets and were dominated by behavioral facilitation for the cross-modal interactions (relative to interference), but showed surprisingly little influence of visual feature redundancy. Post-hoc analyses revealed modest and trending evidence for possible increases in behavioral interference for redundant visual distracters on auditory targets, however, these effects were substantially smaller than anticipated and were not accompanied by a redundancy effect for behavioral facilitation or for attended visual targets.Item Unknown Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.(J ECT, 2014-06) McClintock, Shawn M; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G; Krystal, Andrew D; Lisanby, Sarah HFor many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.Item Unknown Non-invasive brain stimulation modalities for the treatment and prevention of opioid use disorder: a systematic review of the literature(Journal of Addictive Diseases, 2020-01-01) Young, Jonathan R; Smani, Shayan A; Mischel, Nicholas A; Kritzer, Michael D; Appelbaum, Lawrence G; Patkar, Ashwin A© 2020, © 2020 Taylor & Francis Group, LLC. The U.S. is currently facing an unprecedented epidemic of opioid-related deaths. Despite the efficacy of the current treatments for opioid use disorder (OUD), including psychosocial interventions and medication-assisted therapy (MAT), many patients remain treatment-resistant and at high risk for overdose. A potential augmentation strategy includes the use of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and auricular vagus nerve stimulation (aVNS). These approaches may have therapeutic benefits by directly or indirectly modulating the neurocircuitry affected in OUD. In this review, we evaluate the available studies on NIBS in the context of OUD withdrawal and detoxification, maintenance, and cravings, while also considering analgesia and safety concerns. In the context of opioid withdrawal and detoxification, a percutaneous form of aVNS has positive results in open-label trials, but has not yet been tested against sham. No randomized studies have reported on the safety and efficacy of NIBS specifically for maintenance treatment in OUD. TMS and tDCS have demonstrated effects on cravings, although published studies were limited by small sample sizes. NIBS may play a role in reducing exposure to opioids and the risk of developing OUD, as demonstrated by studies using tDCS in an experimental pain condition and TMS in a post-operative setting. Overall, while the preliminary evidence and safety for NIBS in the prevention and treatment of OUD appears promising, further research is needed with larger sample sizes, placebo control, and objective biomarkers as outcome measures before strong conclusions can be drawn.Item Unknown Rapid brain responses independently predict gain maximization and loss minimization during economic decision making.(J Neurosci, 2013-04-17) San Martín, René; Appelbaum, Lawrence G; Pearson, John M; Huettel, Scott A; Woldorff, Marty GSuccess in many decision-making scenarios depends on the ability to maximize gains and minimize losses. Even if an agent knows which cues lead to gains and which lead to losses, that agent could still make choices yielding suboptimal rewards. Here, by analyzing event-related potentials (ERPs) recorded in humans during a probabilistic gambling task, we show that individuals' behavioral tendencies to maximize gains and to minimize losses are associated with their ERP responses to the receipt of those gains and losses, respectively. We focused our analyses on ERP signals that predict behavioral adjustment: the frontocentral feedback-related negativity (FRN) and two P300 (P3) subcomponents, the frontocentral P3a and the parietal P3b. We found that, across participants, gain maximization was predicted by differences in amplitude of the P3b for suboptimal versus optimal gains (i.e., P3b amplitude difference between the least good and the best gains). Conversely, loss minimization was predicted by differences in the P3b amplitude to suboptimal versus optimal losses (i.e., difference between the worst and the least bad losses). Finally, we observed that the P3a and P3b, but not the FRN, predicted behavioral adjustment on subsequent trials, suggesting a specific adaptive mechanism by which prior experience may alter ensuing behavior. These findings indicate that individual differences in gain maximization and loss minimization are linked to individual differences in rapid neural responses to monetary outcomes.Item Unknown Reward associations reduce behavioral interference by changing the temporal dynamics of conflict processing.(PLoS One, 2013) Krebs, Ruth M; Boehler, Carsten N; Appelbaum, Lawrence G; Woldorff, Marty GAssociating stimuli with the prospect of reward typically facilitates responses to those stimuli due to an enhancement of attentional and cognitive-control processes. Such reward-induced facilitation might be especially helpful when cognitive-control mechanisms are challenged, as when one must overcome interference from irrelevant inputs. Here, we investigated the neural dynamics of reward effects in a color-naming Stroop task by employing event-related potentials (ERPs). We found that behavioral facilitation in potential-reward trials, as compared to no-reward trials, was paralleled by early ERP modulations likely indexing increased attention to the reward-predictive stimulus. Moreover, reward changed the temporal dynamics of conflict-related ERP components, which may be a consequence of an early access to the various stimulus features and their relationships. Finally, although word meanings referring to potential-reward colors were always task-irrelevant, they caused greater interference compared to words referring to no-reward colors, an effect that was accompanied by a relatively early fronto-central ERP modulation. This latter observation suggests that task-irrelevant reward information can undermine goal-directed behavior at an early processing stage, presumably reflecting priming of a goal-incompatible response. Yet, these detrimental effects of incongruent reward-related words were absent in potential-reward trials, apparently due to the prioritized processing of task-relevant reward information. Taken together, the present data demonstrate that reward associations can influence conflict processing by changing the temporal dynamics of stimulus processing and subsequent cognitive-control mechanisms.Item Unknown Site-Specific Effects of Online rTMS during a Working Memory Task in Healthy Older Adults.(Brain sciences, 2020-04-27) Beynel, Lysianne; Davis, Simon W; Crowell, Courtney A; Dannhauer, Moritz; Lim, Wesley; Palmer, Hannah; Hilbig, Susan A; Brito, Alexandra; Hile, Connor; Luber, Bruce; Lisanby, Sarah H; Peterchev, Angel V; Cabeza, Roberto; Appelbaum, Lawrence GThe process of manipulating information within working memory is central to many cognitive functions, but also declines rapidly in old age. Improving this process could markedly enhance the health-span in older adults. The current pre-registered, randomized and placebo-controlled study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) applied at 5 Hz over the left lateral parietal cortex to enhance working memory manipulation in healthy elderly adults. rTMS was applied, while participants performed a delayed-response alphabetization task with two individually titrated levels of difficulty. Coil placement and stimulation amplitude were calculated from fMRI activation maps combined with electric field modeling on an individual-subject basis in order to standardize dosing at the targeted cortical location. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. When compared to the results from our previous study, in which rTMS was applied over the left prefrontal cortex, we found equivalent effect sizes but opposite directionality suggesting a site-specific effect of rTMS. These results demonstrate engagement of cortical working memory processing using a novel TMS targeting approach, while also providing prescriptions for future studies seeking to enhance memory through rTMS.Item Unknown Suitability of Automated Writing Measures for Clinical Trial Outcome in Writer's Cramp.(Movement disorders : official journal of the Movement Disorder Society, 2023-01) Bukhari-Parlakturk, Noreen; Lutz, Michael W; Al-Khalidi, Hussein R; Unnithan, Shakthi; Wang, Joyce En-Hua; Scott, Burton; Termsarasab, Pichet; Appelbaum, Lawrence G; Calakos, NicoleBackground
Writer's cramp (WC) dystonia is a rare disease that causes abnormal postures during the writing task. Successful research studies for WC and other forms of dystonia are contingent on identifying sensitive and specific measures that relate to the clinical syndrome and achieve a realistic sample size to power research studies for a rare disease. Although prior studies have used writing kinematics, their diagnostic performance remains unclear.Objective
This study aimed to evaluate the diagnostic performance of automated measures that distinguish subjects with WC from healthy volunteers.Methods
A total of 21 subjects with WC and 22 healthy volunteers performed a sentence-copying assessment on a digital tablet using kinematic and hand recognition softwares. The sensitivity and specificity of automated measures were calculated using a logistic regression model. Power analysis was performed for two clinical research designs using these measures. The test and retest reliability of select automated measures was compared across repeat sentence-copying assessments. Lastly, a correlational analysis with subject- and clinician-rated outcomes was performed to understand the clinical meaning of automated measures.Results
Of the 23 measures analyzed, the measures of word legibility and peak accelerations distinguished subjects with WC from healthy volunteers with high sensitivity and specificity and demonstrated smaller sample sizes suitable for rare disease studies, and the kinematic measures showed high reliability across repeat visits, while both word legibility and peak accelerations measures showed significant correlations with the subject- and clinician-rated outcomes.Conclusions
Novel automated measures that capture key aspects of the disease and are suitable for use in clinical research studies of WC dystonia were identified. © 2022 International Parkinson and Movement Disorder Society.Item Unknown The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands.(Neuropsychologia, 2016-04) Donohue, Sarah E; Appelbaum, Lawrence G; McKay, Cameron C; Woldorff, Marty GBoth stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options.Item Unknown The role of stimulus salience and attentional capture across the neural hierarchy in a stop-signal task.(PLoS One, 2011) Boehler, Carsten N; Appelbaum, Lawrence G; Krebs, Ruth M; Chen, Ling-Chia; Woldorff, Marty GInhibitory motor control is a core function of cognitive control. Evidence from diverse experimental approaches has linked this function to a mostly right-lateralized network of cortical and subcortical areas, wherein a signal from the frontal cortex to the basal ganglia is believed to trigger motor-response cancellation. Recently, however, it has been recognized that in the context of typical motor-control paradigms those processes related to actual response inhibition and those related to the attentional processing of the relevant stimuli are highly interrelated and thus difficult to distinguish. Here, we used fMRI and a modified Stop-signal task to specifically examine the role of perceptual and attentional processes triggered by the different stimuli in such tasks, thus seeking to further distinguish other cognitive processes that may precede or otherwise accompany the implementation of response inhibition. In order to establish which brain areas respond to sensory stimulation differences by rare Stop-stimuli, as well as to the associated attentional capture that these may trigger irrespective of their task-relevance, we compared brain activity evoked by Stop-trials to that evoked by Go-trials in task blocks where Stop-stimuli were to be ignored. In addition, region-of-interest analyses comparing the responses to these task-irrelevant Stop-trials, with those to typical relevant Stop-trials, identified separable activity profiles as a function of the task-relevance of the Stop-signal. While occipital areas were mostly blind to the task-relevance of Stop-stimuli, activity in temporo-parietal areas dissociated between task-irrelevant and task-relevant ones. Activity profiles in frontal areas, in turn, were activated mainly by task-relevant Stop-trials, presumably reflecting a combination of triggered top-down attentional influences and inhibitory motor-control processes.Item Unknown The temporal dynamics of implicit processing of non-letter, letter, and word-forms in the human visual cortex.(Frontiers in human neuroscience, 2009-01) Appelbaum, Lawrence G; Liotti, Mario; Perez, Ricardo; Fox, Sarabeth P; Woldorff, Marty GThe decoding of visually presented line segments into letters, and letters into words, is critical to fluent reading abilities. Here we investigate the temporal dynamics of visual orthographic processes, focusing specifically on right hemisphere contributions and interactions between the hemispheres involved in the implicit processing of visually presented words, consonants, false fonts, and symbolic strings. High-density EEG was recorded while participants detected infrequent, simple, perceptual targets (dot strings) embedded amongst a of character strings. Beginning at 130 ms, orthographic and non-orthographic stimuli were distinguished by a sequence of ERP effects over occipital recording sites. These early latency occipital effects were dominated by enhanced right-sided negative-polarity activation for non-orthographic stimuli that peaked at around 180 ms. This right-sided effect was followed by bilateral positive occipital activity for false-fonts, but not symbol strings. Moreover the size of components of this later positive occipital wave was inversely correlated with the right-sided ROcc180 wave, suggesting that subjects who had larger early right-sided activation for non-orthographic stimuli had less need for more extended bilateral (e.g., interhemispheric) processing of those stimuli shortly later. Additional early (130-150 ms) negative-polarity activity over left occipital cortex and longer-latency centrally distributed responses (>300 ms) were present, likely reflecting implicit activation of the previously reported 'visual-word-form' area and N400-related responses, respectively. Collectively, these results provide a close look at some relatively unexplored portions of the temporal flow of information processing in the brain related to the implicit processing of potentially linguistic information and provide valuable information about the interactions between hemispheres supporting visual orthographic processing.Item Open Access The time course of segmentation and cue-selectivity in the human visual cortex.(PLoS One, 2012) Appelbaum, Lawrence G; Ales, Justin M; Norcia, Anthony MTexture discontinuities are a fundamental cue by which the visual system segments objects from their background. The neural mechanisms supporting texture-based segmentation are therefore critical to visual perception and cognition. In the present experiment we employ an EEG source-imaging approach in order to study the time course of texture-based segmentation in the human brain. Visual Evoked Potentials were recorded to four types of stimuli in which periodic temporal modulation of a central 3° figure region could either support figure-ground segmentation, or have identical local texture modulations but not produce changes in global image segmentation. The image discontinuities were defined either by orientation or phase differences across image regions. Evoked responses to these four stimuli were analyzed both at the scalp and on the cortical surface in retinotopic and functional regions-of-interest (ROIs) defined separately using fMRI on a subject-by-subject basis. Texture segmentation (tsVEP: segmenting versus non-segmenting) and cue-specific (csVEP: orientation versus phase) responses exhibited distinctive patterns of activity. Alternations between uniform and segmented images produced highly asymmetric responses that were larger after transitions from the uniform to the segmented state. Texture modulations that signaled the appearance of a figure evoked a pattern of increased activity starting at ∼143 ms that was larger in V1 and LOC ROIs, relative to identical modulations that didn't signal figure-ground segmentation. This segmentation-related activity occurred after an initial response phase that did not depend on the global segmentation structure of the image. The two cue types evoked similar tsVEPs up to 230 ms when they differed in the V4 and LOC ROIs. The evolution of the response proceeded largely in the feed-forward direction, with only weak evidence for feedback-related activity.Item Open Access Transcranial Magnetic Stimulation enhances working memory(2016-04-22) Austin, Rebecca GarlandCognitive decline associated with aging affects a large proportion of America’s progressively older population. To remedy this decline, various working memory (WM) training protocols are emerging, the most novel of which utilize Transcranial Magnetic Stimulation (TMS) to excite neuronal activity, induce long-term potentiation, and enhance cognitive functioning. Ultimately aiming to remediate WM decline in aging adults by using TMS, this study first sought to establish ideal TMS parameters to induce WM improvements. Using a delayed match-to-sample (DMS) WM task with both maintenance and manipulation conditions, it was hypothesized that active TMS, relative to sham TMS, would differentially impact task performance depending on its timing of administration, either before encoding or at the end of the delay phases. Following screening and practice, subjects trained on the DMS task for 4 hours over 2 days, receiving 5s of either active 5Hz TMS at 100% of motor threshold to the dorsolateral prefrontal cortex (DLPFC) or sham TMS. The phase of active versus sham TMS stimulation was counterbalanced across participants. The results suggest that active TMS improved DMS reaction time and accuracy as compared to sham TMS. Specifically, maintenance task performance improved with TMS before encoding, while manipulation task performance was aided by TMS during the delay period. Although promising, these results should be bolstered by increased sample sizes and individualized fMRI-based DLPFC targeting before deciding on the optimal timing of TMS for each DMS task condition in aging adults.