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1.  [No title available] 
PMCID: PMC3844121  PMID: 23916406
2.  Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants 
Objective
Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation (TMS) protocol, capable of enhancing or suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after stimulation over the primary motor cortex. Continuous TBS (cTBS) produces a long-term depression (LTD)-like reduction of cortical excitability. The purpose of this study was to assess the test–retest reproducibility of the effects of cTBS and to investigate which neurophysiologic markers of cTBS-induced plasticity are most reproducible.
Methods
In ten healthy participants we evaluated in two different sessions the effects of cTBS (using AP–PA current direction, opposite to most commercial rTMS stimulators) on MEPs induced by single-pulse suprathreshold TMS (using AP–PA or PA current direction) over left motor cortex in the first dorsal inter-osseus (FDI) muscle.
Results
Results demonstrate that the marker of cTBS induced-plasticity with highest within-subject reproducibility is the modulation of corticospinal excitability measured 5 min after cTBS.
Conclusion
Overall the effects of cTBS modulation show limited test–retest reproducibility and some measures of the cTBS effects are more reproducible than others.
Significance
Studies comparing cTBS effects in healthy subjects and patients need to proceed with care. Further characterization of the effects of TBS and identification of the best metrics warrant future studies.
doi:10.1016/j.clinph.2013.07.004
PMCID: PMC4169192  PMID: 23932365
Transcranial magnetic stimulation; Primary motor cortex; Variability; Neurophysiological markers
3.  Theta and delta band activity explain N2 and P3 ERP component activity in a go/no-go task 
Objectives
Recent work indicates that the feedback negativity (FN) and P3 components from gambling feedback tasks can be understood as mixtures of functionally distinct processes occurring separately in theta and delta frequency bands. The current study was conducted to assess whether dissociable processes occurring in the theta and delta bands would similarly account for activity underlying N2 and P3 components in a go/no-go task.
Methods
The current study measured EEG signals from 66 participants during a go/nogo task, and a time-frequency (TF) principal components analysis (PCA) decomposition approach was used to extract theta and delta measures from condition averages.
Results
Theta and delta measures separately increased in relation to response inhibition, and were uniquely related to the N2 and P3 components, as predicted.
Conclusions
Findings support the view that the theta and delta measures indexed separable processes related to response inhibition, and better indexed the processes underlying N2 and P3 components in this go/no-go task
Significance
Theta and delta measures may index separable functional processes across other common ERP tasks, and may represent an improved target for research relative to standard time-domain components.
doi:10.1016/j.clinph.2013.06.025
PMCID: PMC4312493  PMID: 23891195
response inhibition; time-frequency; EEG; theta; delta
4.  Determination of motor threshold using visual observation overestimates transcranial magnetic stimulation dosage: Safety implications 
Objective
While the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT.
Methods
Left motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT.
Results
OM-MT was 11.3% higher than EMG-MT (p<0.001), ranging from 0-27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%.
Conclusions
These findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits.
Significance
For applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG-MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.
doi:10.1016/j.clinph.2013.06.187
PMCID: PMC3954153  PMID: 23993680
transcranial magnetic stimulation; TMS; motor threshold; electromyography; EMG; safety
5.  Graph theory findings in the pathophysiology of temporal lobe epilepsy 
Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE.
doi:10.1016/j.clinph.2014.04.004
PMCID: PMC4281254  PMID: 24831083
Graph theory; Temporal lobe epilepsy; Pathophysiology; Functional connectivity; Diffusion tensor imaging; Small-world networks
6.  Animal category-preferential gamma-band responses in the lower- and higher-order visual areas: intracranial recording in children 
Objective
We determined where and when category-preferential augmentation of gamma activity took place during naming of animal or non-animal pictures.
Methods
We studied 41 patients with focal epilepsy who underwent measurement of naming-related gamma-augmentation50–120 Hz during extraoperative electrocorticography. The assigned task consisted of naming of a visually-presented object classified as either ‘animal’ or ‘non-animal’.
Results
Within 80 ms following the onset of picture presentation, regardless of stimulus type, gamma-activity in bilateral occipital regions began to be augmented compared to the resting period. Initially in the occipital poles (at 140 ms and after) and subsequently in the lateral, inferior and medial occipital regions (at 320 ms and after), the degree of gamma-augmentation elicited by ‘animal naming’ became larger (by up to 52%) than that by ‘non-animal naming’. Immediately prior to the overt response, left inferior frontal gamma-augmentation became modestly larger during ‘animal naming’ compared to ‘non-animal naming’.
Conclusions
Animal category-preferential gamma-augmentation sequentially involved the lower- and higher-order visual areas. Relatively larger occipital gamma-augmentation during ‘animal naming’ can be attributed to the more attentive analysis of animal stimuli including the face. Animal-preferential gamma-augmentation in the left inferior frontal region could be attributed to a need for selective semantic retrieval during ‘animal naming’.
Significance
A specific program of cortical processing to distinguish an animal (or face) from other objects might be initiated in the lower-order visual cortex.
doi:10.1016/j.clinph.2013.05.030
PMCID: PMC3834016  PMID: 23910987
Epilepsy; Intracranial ECoG recording; Ripples; Gamma activity; High-frequency oscillations (HFOs)
8.  Forward and inverse electroencephalographic modeling in health and in acute traumatic brain injury 
Objective
EEG source localization is demonstrated in three cases of acute traumatic brain injury (TBI) with progressive lesion loads using anatomically faithful models of the head which account for pathology.
Methods
Multimodal magnetic resonance imaging (MRI) volumes were used to generate head models via the finite element method (FEM). A total of 25 tissue types—including 6 types accounting for pathology— were included. To determine the effects of TBI upon source localization accuracy, a minimum-norm operator was used to perform inverse localization and to determine the accuracy of the latter.
Results
The importance of using a more comprehensive number of tissue types is confirmed in both health and in TBI. Pathology omission is found to cause substantial inaccuracies in EEG forward matrix calculations, with lead field sensitivity being underestimated by as much as ~200% in (peri-) contusional regions when TBI-related changes are ignored. Failing to account for such conductivity changes is found to misestimate substantial localization error by up to 35 mm.
Conclusions
Changes in head conductivity profiles should be accounted for when performing EEG modeling in acute TBI.
Significance
Given the challenges of inverse localization in TBI, this framework can benefit neurotrauma patients by providing useful insights on pathophysiology.
doi:10.1016/j.clinph.2013.04.336
PMCID: PMC3805748  PMID: 23746499
Electroencephalography; Traumatic brain injury; finite element method; Magnetic resonance imaging
9.  Electrophysiological Intermediate Biomarkers for Oxidative Stress in Schizophrenia 
Objective
Diverse electrophysiological abnormalities have been associated with schizophrenia, but the underlying causes remain elusive. We tested whether the altered oxidative stress in schizophrenia contributes to the electrophysiological abnormalities.
Methods
We used an auditory oddball task to measure mistmatch negativity (MMN) and gamma band response on 29 schizophrenia patients and 25 normal controls. Oxidative stress was assessed by monomeric glutathione (GSH, reduced form) and glutathione disulfide (GSSG, oxidized form).
Results
Patients had reduced MMN (p=0.015) and reduced power of gamma band responses at 21-40 Hz and 41-85 Hz (all p<0.001). GSH was significantly lower (p<0.001) while %GSSG was higher (p=0.023) in patients compared with controls. MMN was correlated with GSH in controls; while 21-40 Hz responses were correlated with GSH in patients. Lower GSH and higher GSSG levels were associated with low community functioning (p=0.018). Multivariate mediation modeling showed that gamma band at 21-40 Hz was a significant mediator for GSH effect on community functions.
Conclusions
High beta/low gamma range (21-40 Hz) responses may be an intermediate biomarker indexing oxidative stress and its effect on clinical functions.
Significance
Electrophysiological abnormalities and associated clinical functional changes may in part be associated with heightened oxidative stress in schizophrenia.
doi:10.1016/j.clinph.2013.05.021
PMCID: PMC4030436  PMID: 23823132
schizophrenia; oxidation; oscillations; MMN; GSH; GSSG
10.  Display of consistent ictal networks in refractory mesial temporal lobe epilepsy 
Objective
Exploration of emergent ictal networks was performed in homogeneous subjects with refractory medial temporal lobe epilepsy.
Methods
Maximal Synchrony Index (SI) values were calculated for all electrode pairs for each second during 25 seizures and displayed as connectivity animations. Consistent temporal patterns of SI value and spatial connectivity were observed across seizures and subjects, and used to define a sequence of network stages.
Results
Highest SI values were found in electrodes within the area of surgical resection. Analysis of these electrodes by network stage demonstrated lateral temporal cortex dominance at seizure initiation, giving way to hippocampal synchrony during the major portion of the seizure, with lateral temporal regions re-emerging as the seizure terminated. SI values also corresponded to behavioral severity of seizures, and lower SI values were associated with post-surgical seizure freedom.
Conclusion
SI based methods of network characterization consistently display the intrinsic MTLE ictal network and may be sensitive to clinical features.
Significance
Consistency of EEG-derived network patterns is an important step as network features are applied towards improvement of clinical management. These data confirm consistency of network patterns within and across subjects and support the potential for these methods to distinguish relevant clinical variables.
doi:10.1016/j.clinph.2013.03.019
PMCID: PMC4215559  PMID: 23639378
Epilepsy; Hippocampus; Synchrony; Temporal lobectomy; Seizure; EEG; Quantitative EEG
11.  Comparison of spherical and realistically shaped boundary element head models for transcranial magnetic stimulation navigation 
Objective
MRI-guided real-time transcranial magnetic stimulation (TMS) navigators that apply electromagnetic modeling have improved the utility of TMS. However, their accuracy and speed depends on the assumed volume conductor geometry. Spherical models found in present navigators are computationally fast but may be inaccurate in some areas. Realistically-shaped boundary-element models (BEMs) could increase accuracy at a moderate computational cost, but it is unknown which model features have the largest influence on accuracy. Thus, we compared different types of spherical models and BEMs.
Methods
Globally and locally fitted spherical models and different BEMs with either one or three compartments and with different skull-to-brain conductivity ratios (1/1 – 1/80) were compared against a reference BEM.
Results
The one-compartment BEM at inner skull surface was almost as accurate as the reference BEM. Skull/brain conductivity ratio in the range 1/10 – 1/80 had only a minor influence. BEMs were superior to spherical models especially in frontal and temporal areas (up to 20 mm localization and 40% intensity improvement); in motor cortex all models provided similar results.
Conclusions
One-compartment BEMs offer a good balance between accuracy and computational cost.
Significance
Realistically-shaped BEMs may increase TMS navigation accuracy in several brain areas, such as in prefrontal regions often targeted in clinical applications.
doi:10.1016/j.clinph.2013.04.019
PMCID: PMC3790855  PMID: 23890512
Transcranial magnetic stimulation; image guided navigation; electromagnetic modeling; boundary element method
12.  Effects of non-pharmacological pain treatments on brain states 
Objective
To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations.
Methods
30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], and neurofeedback) and a control sham tDCS procedure.
Results
Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain.
Conclusions
Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments.
Significance
The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity.
doi:10.1016/j.clinph.2013.04.009
PMCID: PMC3759647  PMID: 23706958
spinal cord injury; chronic pain; electroencephalography; brain states; non-pharmacological treatments
13.  Variability of magnetoencephalographic sensor sensitivity measures as a function of age, brain volume and cortical area 
Objective
To assess the feasibility and appropriateness of magnetoencephalography (MEG) for both adult and pediatric studies, as well as for the developmental comparison of these factors across a wide range of ages.
Methods
For 45 subjects with ages from 1 to 24 years (infants, toddlers, school-age children and young adults), lead fields (LFs) of MEG sensors are computed using anatomically realistic boundary element models (BEMs) and individually-reconstructed cortical surfaces. Novel metrics are introduced to quantify MEG sensor focality.
Results
The variability of MEG focality is graphed as a function of brain volume and cortical area. Statistically significant differences in total cerebral volume, cortical area, MEG global sensitivity and LF focality are found between age groups.
Conclusions
Because MEG focality and sensitivity differ substantially across the age groups studied, the cortical LF maps explored here can provide important insights for the examination and interpretation of MEG signals from early childhood to young adulthood.
Significance
This is the first study to (1) investigate the relationship between MEG cortical LFs and brain volume as well as cortical area across development, and (2) compare LFs between subjects with different head sizes using detailed cortical reconstructions.
doi:10.1016/j.clinph.2014.01.027
PMCID: PMC4133309  PMID: 24589347
magnetoencephalography; pediatrics; lead field; modeling; boundary element method
15.  Role of posterior parietal cortex in reaching movements in humans. Clinical implication for ‘optic ataxia’ 
Objective
To clarify the spatio-temporal profile of cortical activity related to reaching movement in the posterior parietal cortex (PPC) in humans.
Methods
Four patients with intractable partial epilepsy who underwent subdural electrode implantation were studied as a part of pre-surgical evaluation. We investigated the Bereitschaftspotential (BP) associated with reaching and correlated the findings with the effect of electrical stimulation of the same cortical area.
Results
BPs specific for reaching, as compared with BPs for simple movements by the hand or arm contralateral to the implanted hemisphere, were recognized in all patients, mainly around the intraparietal sulcus (IPS), the superior parietal lobule (SPL) and the precuneus. BPs near the IPS had the earlier onset than BPs in the SPL. Electrical stimulation of a part of the PPC, where the reach-specific BPs were recorded, selectively impaired reaching.
Conclusions
Intracranial BP recording and cortical electrical stimulation delineated human reach-related areas in the PPC.
Significance
The present study for the first time by direct cortical recording in humans demonstrates that parts of the cortices around the IPS and SPL play a crucial role in visually-guided reaching.
doi:10.1016/j.clinph.2013.05.011
PMCID: PMC4157053  PMID: 23831168
Bereitschaftspotential; cortical electrical stimulation; optic ataxia; posterior parietal cortex; reaching
16.  Exploration of Computational Methods for Classification of Movement Intention during Human Voluntary Movement from Single Trial EEG 
Objectives
To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG).
Methods
Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis (ICA), common spatial patterns analysis (CSP), and surface Laplacian derivation (SLD); temporal filtering using power spectral density estimation (PSD) and discrete wavelet transform (DWT); pattern classification using linear Mahalanobis distance classifier (LMD), quadratic Mahalanobis distance classifier (QMD), Bayesian classifier (BSC), multi-layer perceptron neural network (MLP), probabilistic neural network (PNN), and support vector machine (SVM). A robust multivariate feature selection strategy using a genetic algorithm was employed.
Results
The combinations of spatial filtering using ICA and SLD, temporal filtering using PSD and DWT, and classification methods using LMD, QMD, BSC and SVM provided higher performance than those of other combinations. Utilizing one of the better combinations of ICA, PSD and SVM, the discrimination accuracy was as high as 75%. Further feature analysis showed that beta band EEG activity of the channels over right sensorimotor cortex was most appropriate for discrimination of right and left hand movement intention.
Conclusions
Effective combinations of computational methods provide possible classification of human movement intention from single trial EEG. Such a method could be the basis for a potential brain-computer interface based on human natural movement, which might reduce the requirement of long-term training.
Significance
Effective combinations of computational methods can classify human movement intention from single trial EEG with reasonable accuracy.
doi:10.1016/j.clinph.2007.08.025
PMCID: PMC4154235  PMID: 17967559
Movement intention; Self-paced movement; Combination; Computational methods; Classification; Movement-related cortical potentials (MRCPs); Event-related desynchronization/synchronization (ERD/ERS); Genetic Algorithm; Brain-computer interface (BCI)
17.  AUTOMATING THE ANALYSIS OF EEG RECORDINGS FROM PREMATURELY-BORN INFANTS: A BAYESIAN APPROACH 
Ojective
To implement an automated analysis of EEG recordings from prematurely-born infants and thus provide objective, reproducible results.
Methods
Bayesian probability theory is employed to compute the posterior probability for developmental features of interest in EEG recordings. Currently, these features include smooth delta waves (0.5-1.5 Hz, >100 μV), delta brushes (delta portion: 0.5-1.5Hz, >100 μV; “brush” portion: 8-22 Hz, <75 μV), and interburst intervals (<10 μV), though the approach taken can be generalized to identify other EEG features of interest.
Results
When compared with experienced electroencephalographers, the algorithm had a true positive rate between 72% and 79% for the identification of delta waves (smooth or “brush”) and interburst intervals, which is comparable to the inter-rater reliability. When distinguishing between smooth delta waves and delta brushes, the algorithm's true positive rate was between 53% and 88%, which is slightly less than the inter-rater reliability.
Conclusions
Bayesian probability theory can be employed to consistently identify features of EEG recordings from premature infants.
Significance
The identification of features in EEG recordings provides a first step towards the automated analysis of EEG recordings from premature infants.
doi:10.1016/j.clinph.2012.09.003
PMCID: PMC4151276  PMID: 23014143
EEG; Bayesian; Neonatal
18.  Fatigue modulates synchronous but not asynchronous soleus activation during stimulation of paralyzed muscle 
Objective
Electrical stimulation over a motor nerve yields muscle force via a combination of direct and reflex-mediated activation. We determined the influence of fatigue on reflex-mediated responses induced during supra-maximal electrical stimulation in humans with complete paralysis.
Methods
We analyzed soleus electromyographic (EMG) activity during repetitive stimulation (15 Hz, 125 contractions) in 22 individuals with complete paralysis. The bout of stimulation caused significant soleus muscle fatigue (53.1% torque decline).
Results
Before fatigue, EMG at all latencies after the M-wave was less than 1% of the maximal M-wave amplitude (% MaxM). After fatigue there was a fourfold (p < 0.05) increase in EMG at the H-reflex latency; however, the overall magnitude remained low (< 2% change in %MaxM). There was no increase in “asynchronous” EMG ~ 1 s after the stimulus train.
Conclusions
Fatigue enhanced the activation to the paralyzed soleus muscle, but primarily at the H-reflex latency. The overall influence of this reflex modulation was small. Soleus EMG was not elevated during fatigue at latencies consistent with asynchronous activation.
Significance
These findings support synchronous reflex responses increase while random asynchronous reflex activation does not change during repetitive supra-maximal stimulation, offering a clinical strategy to consistently dose stress to paralyzed tissues.
doi:10.1016/j.clinph.2013.03.027
PMCID: PMC3735624  PMID: 23673062
Spinal cord injury; soleus; asynchronous EMG; H-reflex
19.  Gamma activity modulated by picture and auditory naming tasks: intracranial recording in patients with focal epilepsy 
Objective
We measured the spatial, temporal and developmental patterns of gamma activity augmented by picture- and auditory-naming tasks and determined the clinical significance of naming-related gamma-augmentation.
Methods
We studied 56 epileptic patients (age: 4-56 years) who underwent extraoperative electrocorticography. The picture-naming task consisted of naming of a visually-presented object; the auditory-naming task consisted of answering an auditorily-presented sentence question.
Results
Naming-related gamma-augmentation at 50-120 Hz involved the modality-specific sensory cortices during stimulus presentation and inferior-Rolandic regions during responses. Gamma-augmentation in the bilateral occipital and inferior/medial-temporal regions was more intense in the picture-naming than auditory-naming task, whereas that in the bilateral superior-temporal, left middle-temporal, left inferior-parietal, and left frontal regions was more intense in the auditory-naming task. Patients above 10 years old, compared to those younger, showed more extensive gamma-augmentation in the left dorsolateral-premotor region. Resection of sites showing naming-related gamma-augmentation in the left hemisphere assumed to contain essential language function was associated with increased risk of post-operative language deficits requiring speech therapy (p < 0.05).
Conclusions
Measurement of gamma-augmentation elicited by either naming task was useful to predict postoperative language deficits.
Significance
A smaller degree of frontal engagement in the picture-naming task can be explained by no requirement of syntactic processing or less working memory load. More extensive gamma-augmentation in the left dorsolateral-premotor region in older individuals may suggest more proficient processing by the mature brain.
doi:10.1016/j.clinph.2013.01.030
PMCID: PMC3735713  PMID: 23688918
Epilepsy surgery; Intracranial ECoG recording; Ripples; High-frequency oscillations (HFOs); Language; Speech; Outcome
20.  Cortico-cortical evoked potentials and stimulation-elicited gamma activity preferentially propagate from lower- to higher-order visual areas 
OBJECTIVE
The lower-order visual cortex in the medial-occipital region is suggested to send feed-forward signals to the higher-order visual cortex including ventral-occipital-temporal and dorsal-occipital regions. We determined how stimulation-elicited cortical-signals propagate between lower- and higher-order visual cortices, and whether the magnitudes of stimulation-elicited cortical-signals recorded in the higher-order visual cortex differed from those recorded in the lower-order one.
METHODS
We studied 10 patients with focal epilepsy who underwent extraoperative electrocorticography recording. Trains of 1-Hz stimuli with an intensity of 3 mA were delivered to an electrode pair within the medial-occipital region; then, cortico-cortical evoked-potential (CCEP) and stimulation-elicited gamma-activity at 80–150 Hz were measured in the ventral-occipital-temporal and dorsal-occipital regions. Likewise, CCEP and stimulation-elicited gamma-activity, driven by stimuli within the higher-order visual cortex, were measured in the lower-order visual cortex.
RESULTS
CCEPs generated, via feed-forward propagations, in the higher-order visual cortex were significantly larger than those generated, via feed-back propagations, in the lower-order visual cortex. Stimulation of the lower-order visual cortex elicited augmentation of gamma-activity in the higher-order visual cortex after the preceding CCEP subsided.
CONCLUSIONS
The propagation manners of stimulation-elicited cortical-signals differ between feed-forward and feed-back directions in the human occipital lobe.
SIGNIFICANCE
Such difference may need to be taken into consideration for future clinical application of CCEPs and stimulation-elicited gamma-augmentation in presurgical evaluation for epilepsy surgery.
doi:10.1016/j.clinph.2013.02.007
PMCID: PMC3679317  PMID: 23523110
Epilepsy surgery; High-frequency oscillations (HFOs); Ripples; Functional connectivity; Intracranial recording
21.  Persons with Parkinson’s disease exhibit decreased neuromuscular complexity during gait 
Objective
Individual muscle activation patterns may be controlled by motor modules constructed by the central nervous system to simplify motor control. This study compared modular control of gait between persons with Parkinson’s disease (PD) and neurologically-healthy older adults (HOA) and investigated relationships between modular organization and gait parameters in persons with PD.
Methods
Fifteen persons with idiopathic PD and fourteen HOA participated. Electromyographic recordings were made from eight leg muscles bilaterally while participants walked at their preferred walking speed for ten minutes on an instrumented treadmill. Non-negative matrix factorization techniques decomposed the electromyographic signals, identifying the number and nature of modules accounting for 95% of variability in muscle activations during treadmill walking.
Results
Generally, fewer modules were required to reconstruct muscle activation patterns during treadmill walking in PD compared to HOA (p<.05). Control of knee flexor and ankle plantarflexor musculature was simplified in PD. Activation timing was altered in PD while muscle weightings were unaffected. Simplified neuromuscular control was related to decreased walking speed in PD.
Conclusions
Neuromuscular control of gait is simplified in PD and may contribute to gait deficits in this population.
Significance
Future studies of locomotor rehabilitation in PD should consider neuromuscular complexity to maximize intervention effectiveness.
doi:10.1016/j.clinph.2013.02.006
PMCID: PMC3679225  PMID: 23474055
Motor modules; motor control; gait; Parkinson’s disease; non-negative matrix factorization; electromyography
22.  Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation 
Objective
To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology.
Methods
Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120 μs using a custom-built cTMS device. Strength–duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data.
Results
All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength–duration curve time constant is estimated to be 196 μs, 95% CI [181 μs, 210 μs]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies.
Conclusions
Our strength–duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology.
Significance
Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.
doi:10.1016/j.clinph.2013.01.011
PMCID: PMC3664250  PMID: 23434439
transcranial magnetic stimulation; pulse width; motor threshold; strength–duration curve; time constant; rheobase; input–output curve; slope
23.  Characterizing multivariate decoding models based on correlated EEG spectral features 
Objective
Multivariate decoding methods are popular techniques for analysis of neurophysiological data. The present study explored potential interpretative problems with these techniques when predictors are correlated.
Methods
Data from sensorimotor rhythm-based cursor control experiments was analyzed offline with linear univariate and multivariate models. Features were derived from autoregressive (AR) spectral analysis of varying model order which produced predictors that varied in their degree of correlation (i.e., multicollinearity).
Results
The use of multivariate regression models resulted in much better prediction of target position as compared to univariate regression models. However, with lower order AR features interpretation of the spectral patterns of the weights was difficult. This is likely to be due to the high degree of multicollinearity present with lower order AR features.
Conclusions
Care should be exercised when interpreting the pattern of weights of multivariate models with correlated predictors. Comparison with univariate statistics is advisable.
Significance
While multivariate decoding algorithms are very useful for prediction their utility for interpretation may be limited when predictors are correlated.
doi:10.1016/j.clinph.2013.01.015
PMCID: PMC3676699  PMID: 23466267
sensorimotor rhythm; multivariate decoding; multicollinearity; brain-computer interface
24.  Bilateral impairments in task-dependent modulation of the long-latency stretch reflex following stroke 
Objective
Modulation of the long-latency reflex (LLR) is important for sensorimotor control during interaction with different mechanical loads. Transcortical pathways usually contribute to LLR modulation, but the integrity of pathways projecting to the paretic and non-paretic arms of stroke survivors is compromised. We hypothesize that disruption of transcortical reflex pathways reduces the capacity for stroke survivors to appropriately regulate the LLR bilaterally.
Methods
Elbow perturbations were applied to the paretic and non-paretic arms of persons with stroke, and the dominant arm of age-matched controls as subjects interacted with Stiff or Compliant environments rendered by a linear actuator. Reflexes were quantified using surface electromyograms, recorded from biceps.
Results
LLR amplitude was significantly larger during interaction with the Compliant load compared to the Stiff load in controls. However, there was no significant change in LLR amplitude for the paretic or non-paretic arm of stroke survivors.
Conclusions
Modulation of the LLR is altered in the paretic and non-paretic arms after stroke.
Significance
Our results are indicative of bilateral sensorimotor impairments following stroke. The inability to regulate the LLR may contribute to bilateral deficits in tasks that require precise control of limb mechanics and stability.
doi:10.1016/j.clinph.2013.01.013
PMCID: PMC3674210  PMID: 23453250
stretch reflex; modulation; stroke; brain; arm; long-latency
25.  Utility of Temporally-Extended Signal Space Separation Algorithm for Magnetic Noise from Vagal Nerve Stimulators 
Object
To evaluate the utility of a temporally-extended Signal Space Separation algorithm (tSSS) for patients with vagal nerve stimulator (VNS)
Methods
We evaluated median nerve somatosensory evoked responses (SER) of magnetoencephalography (MEG) in 27 VNS patients (48 sides) with/without tSSS processing. We classified SER dipoles as ‘acceptable’ if: A) the location of the dipole was in the expected location in the central sulcus, and B) the Goodness Of Fit value (GOF) was greater than 80%. We evaluated 1) the number of sides which produced acceptable dipoles in each dataset (i.e. with/without tSSS processing), and in cases where the both data produced reliable dipoles, 2) compared their GOFs and the 95% Confidence Volumes (CV) (mm3). Statistical differences in the GOF and CV between with/without tSSS conditions were determined by paired t test.
Results
Only 11 (23%) responses had reliable dipoles without tSSS processing, while all 48 (100%) had acceptable dipoles under tSSS processing. Additionally, the latter group had significantly higher GOF (increased by 7% on average) and lower CV (mean decrease of 200 mm3) than the former (p < 0.01).
Conclusion
Processing with tSSS quantitatively improves dipole fitting of known sources in VNS patients.
Significance
This algorithm permits satisfactory MEG testing in the relatively commonly encountered epilepsy patient with VNS.
doi:10.1016/j.clinph.2012.03.082
PMCID: PMC3980452  PMID: 22727713
a temporally-extended Signal Space Separation algorithm; vagal nerve stimulator; magnetoencephalography

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