Chang-Chia Liu's research while affiliated with Johns Hopkins University and other places

Transcranial direct current stimulation (tDCS) is an emerging method, used for non-invasively stimulating the brain in normal healthy subjects and in patients with neurological disorders. However, the pattern of the spatial distribution of the current intensity induced by tDCS is poorly understood. In this study, we directly measured the spatial characteristics of the current intensity induced by tDCS using an intracranial strip electrode array implanted over the motor cortex in patients with Parkinson's disease undergoing deep brain stimulation lead placement surgery. We used a bilateral stimulation configuration for the tDCS electrode placement and measured the amount of electric current passing through the contacts along the implanted strip electrode contacts. Our results showed significant changes of the current flow induced by the tDCS in some of the contacts during stimulation with respect to baseline activities. These results may provide vital information regarding the biophysical effects of tDCS stimulation and might be potentially useful for developing more effective stimulation strategies.

The use of motion tracking devices in healthcare is under investigation. Although many motion tracking applications have been proposed to monitor the progress of rehabilitation, using such technology to quantify the progression or improvement of therapies for movement disorders is still scarce. In this study, we introduce a touch-free reaching task which uses a motion sensing device. Our motion tracking system combines a motion tracking device and visual feedback to implement a movement task for the evaluation of the state of motor functions impairment symptoms in Parkinson's disease and other movement disorders.

We hypothesized that distinct acute right hemisphere lesions disrupt separate components of valuation and emotional response to winning and losing money and of emotional empathy in observing a partner win or lose money. We measured skin conductance response (SCR) and ratings of emotions when acute right hemisphere stroke patients or healthy controls won or lost money in roulette, or when they watched a partner win or lose. Our results showed that percentage of damage after stroke to right anterior insula and frontal operculum negatively correlated with both SCR to winning and losing and difference between rating wins versus losses.

Introduction: Emotional empathy includes emotional contagion (sharing another’s feelings) and perspective-taking (inferring another’s feelings). Earlier studies show that right hemisphere stroke (RHS) can cause impaired perspective-taking. However, studies have not identified stroke lesions associated with impaired emotional contagion. Hypothesis: Acute infarcts in specific frontal, temporal, or limbic regions disrupt emotional contagion, measured with skin conductance response (SCR; a sensitive measure of emotional response), as well as perspective-taking. Methods: Participants (9 acute RHS, 9 age-matched controls) played a “roulette” game and watched a partner play. We measured SCR to winning and losing. They rated the emotions (happy to sad) of themselves and their partner when they won and lost money. A neurologist blind to behavioral responses measured percent damage to 10 frontal, temporal, and limbic regions of interest (ROI) on DWI after registration to an atlas. We evaluated differences in group means with unpaired t-tests and differences between ratings of emotions for wins versus losses with paired t-tests. We evaluated associations between SCR magnitude and percent damage to ROI with Spearman correlations. Results: SCR magnitude was significantly lower in response to both wins and losses in patients with right anterior insula (AI) or inferior frontal gyrus opercularis (IFGop) lesions, compared to those without these lesions, when they played or watched partner play (p=0.0001 to 0.008). SCR to partner winning or losing negatively correlated percent damage to insula (rho=-.64;p=0.005) and IFGop (rho=-.47; p=0.045). Controls and patients without AI or IFGop lesions rated partners and themselves as significantly happier when they won versus lost (p<0.0001); but patients with AI or IFGop lesions showed no difference in ratings for wins vs. losses. The difference between ratings for wins vs. losses negatively correlated with percent damage to AI (rho=-.75; p=0.0005) and IFGop (rho=-.80; p=0.0001) but not total infarct volume (rho=-.46; ns). Conclusions: Acute right AI and IFGop infarcts are associated with impaired emotional contagion measured with SCR and perspective-taking.

Although the thalamus is an important module in 'pain networks', there are few studies of the effect of experimental pain upon thalamic oscillations. We have now examined the hypothesis that during a series of painful cutaneous laser stimuli thalamic signals will show stimulus-related gamma band spectral activity, which is modulated by attention to versus distraction from the painful stimulus. When the series of laser stimuli was presented, attention was focused by counting the laser stimuli (count laser task) while distraction was produced by counting backward (count back plus laser task). We have studied the effect of a cutaneous laser upon thalamic local field potentials (LFPs) and EEG activity during awake procedures (DBS implants) for the treatment of essential tremor. At different delays after the stimulus, three low gamma (30-50 Hz) and two high gamma band (70-90 Hz) activations were observed during the two tasks. Greater high gamma activation was found during the count laser task for the earlier Window, while greater high gamma activation was found during the count back plus laser task for the later Window. Thalamic signals were coherent with EEG signals in the beta band, which indicated significant synchrony. Thalamic cross frequency coupling analysis indicated that the phase of the lower frequency activity (theta to beta) modulated the amplitude of the higher frequency activity (low and high gamma) more strongly during the count laser task than during the count back plus laser task. This modulation might result in multiplexed signals each encoding a different aspect of pain. Copyright © 2014, Journal of Neurophysiology.

The non-phase locked EEG response to painful stimuli has usually been characterized as decreased oscillatory activity (event-related desynchronization, ERD) in the alpha band. Increased activity (event-related synchronization, ERS) in the gamma band has been reported more recently. We have now tested the hypothesis that the non-phase locked responses to non-painful electro-cutaneous stimuli are different from those to painful cutaneous laser stimuli when the baseline salience of the two stimuli is the same and the salience during the protocol is modulated by attention and distraction tasks. Both of these stimuli were presented in random order in a single train at intensities which produced the same baseline salience in the same somatic location. The response to the laser stimulus was characterized by five windows in the Time-frequency domain: early (200-400 ms) and late (600-1400 ms) delta/theta ERS, 500-900 ms alpha ERD, 1200-1600 ms beta ERS (rebound), and 800-1200 ms gamma ERS. Similar ERS/ERD windows of activity were found for the electric stimulus. Individual participants largely had activity in windows consistent with the overall analysis. Linear regression of ERS/ERD for parietal channels was most commonly found for sensory- (pain or unpleasantness) or attention- (salience) related measures. Overall, the main effect for modality was the result of activity in Windows I and V, and the modality with task interaction was found for all five windows. There was no significant interaction term which did not include modality. Therefore, the modality was the most common factor explaining of our results, which is consistent with our hypothesis.

During attention to a painful cutaneous laser stimulus, event-related causality (ERC) has been detected in recordings from subdural electrodes implanted directly over cortical modules for the treatment of epilepsy. However, these studies afforded limited sampling of modules, and did not examine interactions with a non-painful stimulus as a control. We now sample scalp EEG to test the hypothesis that attention to the laser stimulus is associated with post-stimulus ERC interactions which are different from those with attention to a non-painful stimulus. Subjects attended to (counted) either a painful laser stimulus (laser attention task), or a non-painful electrical cutaneous stimulus which produced distraction from the laser (laser distraction task). Both of these stimuli were presented in random order in a single train. The intensities of both stimuli were adjusted to produce the similar baseline salience, and sensations in the same cutaneous territory. The results demonstrated that EEG channels with post-stimulus ERC interactions were consistently different during the laser versus the electric stimulus. Post-stimulus ERC interactions were different for the laser attention than the laser distraction task. Furthermore, scalp EEG frontal channels play a driver role while parietal temporal channels play a receiver role during both tasks, although this does not prove that these channels are connected. Sites at which large numbers of ERC interactions were found for both laser attention and distraction tasks (critical sites) were located at Cz, Pz, and C3. Stimulation leading to disruption of sites of these pain-related interactions may produce analgesia for acute pain.

The human 'pain network' includes cortical areas that are activated during the response to painful stimuli (termed category 1) or during psychological processes that modulate pain, for example, distraction (termed category 2). These categories include parts of the parasylvian (PS), medial frontal (MF), and paracentral cortex (S1&M1). Here we test the hypothesis that causal interactions both within and between category 1 and category 2 modules occur during attention to a painful stimulus. Event-related causality (ERC) was calculated from local field potentials recorded directly from these cortical areas during the response to a painful cutaneous laser stimulus in patients being monitored for epilepsy. The number of electrodes involved in pairs with significant ERC in category 1 was greater for pre-stimulus vs post-stimulus and for attention vs distraction. This is consistent with our prior evidence that the category 1 'pain network' changes rapidly with time intervals and tasks. In contrast, the interaction between categories was often unchanged or stable across intervals and tasks, particularly in MF. The proportion of contacts involved in interactions with PS was greater during distraction vs attention while activation was less, which suggests that distraction involves an inhibitory process in PS. Functional interactions between categories were overwhelmingly in the direction from category 2>1, particularly for contacts in MF which often had a driver role. These results demonstrate that MF is densely interconnected throughout the 'pain network' so that stimulation of MF might be used to disrupt the 'pain network' as a therapy for pain.

The unified myoclonus rating scale (UMRS) has been utilized to assess the severity of myoclonus and the efficacy of antiepileptic drug (AED) treatment in patients with Unverricht–Lundborg disease (ULD). Electroencephalographic (EEG) recordings are normally used as a supplemental tool for the diagnosis of epilepsy disorders. In this study, mutual information and nonlinear interdependence measures were applied to the EEG recordings in an attempt to identify the effect of treatment on the coupling strength and directionality of mutual information and nonlinear interdependences between different brain cortical regions. Two 1-h EEG recordings were acquired from four ULD subjects; one prior and one after a minimum of 2 months treatment with an add-on AED. Subjects in this study were siblings of same parents and suffered from ULD for approximately 37 years. Our results indicated that the coupling strength was low between different brain cortical regions in the patients with disease of less severity. Adjunctive AED treatment was associated with significant decrease of the coupling strength in all subjects. The mutual information between different brain cortical regions was also reduced after treatment. These findings could provide a new insight for developing a novel surrogate outcome measure for patients with epilepsy when clinical tools or observations could potentially fail to detect a significant difference. keywordsNonlinear interdependence-Mutual information-Electroencephalogram-epilepsy-Unverricht–Lundborg disease-Progressive myoclonic epilepsy