A method to analyze low signal-to-noise ratio functional magnetic resonance imaging data.

The current practice of using a single, representative hemodynamic response function (canonical HRF) to model functional magnetic resonance imaging (fMRI) data is questionable given the trial-to-trial variability of the brain's responses. In addition, the changes in blood-oxygenation level due to sensory stimulation may be small, especially when auditory stimuli are used. Here we introduce a correlation-based single trial analysis method for fMRI data analysis to deal with the low signal-to-noise (SNR) ratio and variability of the HRF in response to repeated, identical auditory stimuli. The correlation technique identifies the "active" trials, i.e., those showing a robust hemodynamic response among all single trials. Using data collected from 14 healthy subjects, it was found that the correlation method can find significant differences between brain areas and brain states in actual fMRI data. Also, the correlation-based method confirmed that the superior temporal gyrus (STG), inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC) and thalamus (THA) are involved in auditory information processing in general, and the involvement of the bilateral STG, right THA and left DLPFC in sensory gating. In contrast, conventional analysis failed to find any regions involved in sensory gating. The findings suggest that our single trial analysis method can increase the sensitivity of fMRI data analysis.

Dynamic multi-channel TMS with reconfigurable coil.

Investigations of the causal involvement of particular brain areas and interconnections in behavior require an external stimulation system with reasonable spatio-temporal resolution. Current transcranial magnetic stimulation (TMS) technology is limited to stimulating a single brain area once in a given trial. Here, we present a feasibility study for a novel TMS system based on multi-channel reconfigurable coils. With this hardware, researchers will be able to stimulate multiple brain sites in any temporal order in a trial. The system employs a wire-mesh coil, constructed using x- and y-directional wires. By varying the current direction and/or strength on each wire, we can configure the proposed mesh-wire coil into a standard loop coil and figure-eight coil of varying size. This provides maximum flexibility to the experimenter in that the location and extent of stimulation on the brain surface can be modified depending on experimental requirement. Moreover, one can dynamically and automatically modify the site(s) of stimulation several times within the span of seconds. By pre-storing various sequences of excitation patterns inside a control unit, one can explore the effect of dynamic TMS on behavior, in associative learning, and as rehabilitative therapy. Here, we present a computer simulation and bench experiments that show the feasibility of the dynamically-reconfigurable coil.

Image and emotion: from outcomes to brain behavior.

AIM: A systematic review of neuroscience articles on the emotional states of fear, anxiety, and pain to understand how emotional response is linked to the visual characteristics of an image at the level of brain behavior. BACKGROUND: A number of outcome studies link exposure to visual images (with nature content) to improvements in stress, anxiety, and pain perception. However, an understanding of the underlying perceptual mechanisms has been lacking. In this article, neuroscience studies that use visual images to induce fear, anxiety, or pain are reviewed to gain an understanding of how the brain processes visual images in this context and to explore whether this processing can be linked to specific visual characteristics. CONCLUSIONS: The amygdala was identified as one of the key regions of the brain involved in the processing of fear, anxiety, and pain (induced by visual images). Other key areas included the thalamus, insula, and hippocampus. Characteristics of visual images such as the emotional dimension (valence/arousal), subject matter (familiarity, ambiguity, novelty, realism, and facial expressions), and form (sharp and curved contours) were identified as key factors influencing emotional processing. The broad structural properties of an image and overall content were found to have a more pivotal role in the emotional response than the specific details of an image. Insights on specific visual properties were translated to recommendations for what should be incorporated-and avoided-in healthcare environments.

A computational model for generation of the P300 evoked potential component.

The P300 is an endogenously evoked potential with amplitude and latency depending on the amount of information carried by the stimulus rather than its physical characteristics. It has been suggested that P300 is a manifestation of the context updating mechanism in the human working memory. We present a neural network-based model that mimics the learning and forgetting mechanisms of external stimuli in the human working memory that are believed to be responsible for P300 generation. A modified version of the Hebbian learning rule has been devised to govern the weight dynamics of the network. The model was validated by comparing the characteristics of simulated P300 with actual experimental findings such as the relationship between P300 amplitude and stimulus probability, and task relevance. The results show that the proposed P300 model mimics many aspects of the nervous system responsible for P300 generation.

Sensory gating-out and gating-in in normal and schizophrenic participants.

In contrast to sensory gating, the brain's ability to re-respond to relevant stimuli and the potential differences between healthy and schizophrenic participants have not been studied in great detail. Here, we explore what auditory paradigms are useful to measure this re-responding ability. Evoked potentials (EPs) were obtained from the Cz channel using 3 paired stimulus paradigms (pairs with equal stimuli {PE}, the second stimulus being lower {PL} or higher {PH} in frequency) and 2 short-train paradigms in which 5 identical stimuli were followed by a lower frequency stimulus (train lower {TL}) or higher frequency stimulus (train higher {TH}). Data were collected from 17 healthy control participants (NC) and 17 age and gender-matched patients with schizophrenia (SZ). Up to 4 data sets obtained on 4 different days were available for each participant. Ensemble averages were computed for each session, from which the P50, N100, and P200 latencies and amplitudes were obtained. No significant differences in amplitude or latency of the various EP components were found between the responses to the second stimulus obtained with the 5 paradigms. Neither did the responses to the fifth and sixth stimuli differ for the TL and TH paradigm, with the exception of the N100 latency of the fifth stimulus, which was longer for TH than TL for NC. Healthy participants had larger amplitudes and shorter latencies than the patients with schizophrenia for the responses to the first stimuli, with the latency differences continuing for the fifth and sixth response. Also, the amplitude and latency of the first response was larger than for the second response in both populations. In conclusion, none of the paradigms studied here, with the employed parameters, are useful to measure the re-responding ability of the brain. Also, the shorter latencies for the repeated stimulus suggest that the neural mechanism underlying attenuation of repeated stimuli is of a facilitating nature.

Impact of visual art on patient behavior in the emergency department waiting room.

BACKGROUND: Wait times have been reported to be one of the most important concerns for people visiting emergency departments (EDs). Affective states significantly impact perception of wait time. There is substantial evidence that art depicting nature reduces stress levels and anxiety, thus potentially impacting the waiting experience. STUDY OBJECTIVES: To analyze the effect of visual art depicting nature (still and video) on patients' and visitors' behavior in the ED. METHODS: A pre-post research design was implemented using systematic behavioral observation of patients and visitors in the ED waiting rooms of two hospitals over a period of 4 months. Thirty hours of data were collected before and after new still and video art was installed at each site. RESULTS: Significant reduction in restlessness, noise level, and people staring at other people in the room was found at both sites. A significant decrease in the number of queries made at the front desk and a significant increase in social interaction were found at one of the sites. CONCLUSIONS: Visual art has positive effects on the ED waiting experience.

On the relationship between human sensorimotor adaptability and event-related potentials.

It was explored if the speed with which an individual learns to deal with new environments and challenges can be predicted on the basis of his/her brain's response to irrelevant (repeating) and novel auditory stimuli. In this study, 26 subjects threw 30 light-weight balls at a target with and without vision-distorting goggles. The horizontal displacement from a bull's-eye target was measured and the rate and degree of adaptation were computed. The adaptation parameters were correlated with evoked and event-related potential (EP/ERP) measures of the subject's ability to suppress irrelevant information and respond to novel stimuli. Only a weak (or a trend to) correlation was found between the behavioral adaptation and some of the EP/ERP measures. The correlations were limited to EP parameters in the 100 to 200 ms post-stimulus range reflecting the ability to suppress irrelevant information. Thus we conclude that the speed with which an individual adapts to a new environment is at best weakly correlated with brain activity associated with stimulus memory and classification.

The effect of stimulus expectancy on dishabituation of auditory evoked potentials.

OBJECTIVES: Having foreknowledge of the type and timing of sensory stimulation modulates the electrophysiological response and can result in short-term habituation. Here we explore if dishabituation is similarly affected. METHODS: Seventeen healthy subjects were tested with five different auditory stimuli paradigms to see if knowledge of the stimulus train length and/or deviant stimulus affects the amount of dishabituation of auditory evoked potentials. Furthermore it was determined if the degree of difference between the repeating stimulus and deviant stimulus affected the amount of dishabituation. RESULTS: Stimulus complexity is the main determinant of the degree of dishabituation, followed by lack of knowledge about train length. Not knowing the deviant stimulus has little or no effect on dishabituation. Also, P200 is the most affected by expectancy and P50 not at all. CONCLUSIONS: Foreknowledge of the type and timing of sensory stimulation modulates the degree of dishabituation. SIGNIFICANCE: Previous reports have shown that expectancy does affect (certain) evoked potential components. Here we extend this knowledge to the effect of expectancy on dishabituation.

Auditory evoked potential variability in healthy and schizophrenia subjects.

OBJECTIVES: To investigate if the reduced P50, N100 and P200 auditory evoked potential (EP) components and gating deficits seen in schizophrenia can be explained in terms of response incompleteness. METHODS: Twenty-five healthy and schizophrenia participants were studied using pairs of 1000Hz tones (S1 and S2, 0.5s apart) separated by 8.0s. A correlation-based clustering method identified the responses containing P50, N100, and/or P200 related-activity. RESULTS: Schizophrenia participants produced fewer S1 and S2 responses containing all three EP components than healthy participants. Healthy participants, but not the patient population, produced fewer and smaller S2 than S1 responses containing all three EP components. However, the S2 responses following complete S1 responses were smaller than the complete S1 responses in both populations. CONCLUSIONS: The gating deficits observed in schizophrenia are due to two mechanisms. First, the S1 response consistency is less in schizophrenia than in health. Second, the S2 responses are attenuated less in schizophrenia. SIGNIFICANCE: This research contributes to the understanding of response variability and sensory gating in health and schizophrenia. It also extends previous reports that fewer and smaller P300 components are produced in schizophrenia than in health to the mid-latency component range.

Evoked potential variability.

An unsupervised correlation-based clustering method was developed to assess the trial-to-trial variability of auditory evoked potentials (AEPs). The method first decomposes single trials into three frequency bands, each containing activity primarily associated with one of the three major AEP components, i.e., P50, N100 and P200. Next, single-trial evoked potentials with similar post-stimulus characteristics are clustered and selectively averaged to determine the presence or absence of an AEP component. The method was evaluated on actual AEP and spontaneous EEG data collected from 25 healthy participants using a paradigm in which pairs of identical tones were presented, with the first stimulus (S1) presented 0.5s before the second stimulus (S2). Homogeneous, well-separated clusters were obtained and substantial AEP variability was found. Also, there was a trend for S2 to produce fewer 'complete' (and significantly smaller) responses than S1. Tests conducted on spontaneous EEG produced similar clusters as obtained from EP data, but significantly fewer stimuli produced responses containing all three EP components than seen in AEP data. These findings suggest that the clustering method presented here performs adequately to assess trial-to-trial EP variability. Also, the results suggest that the sensory gating observed in normal controls may be caused by the fact that the second stimulus generates fewer 'responsive' trials than the first stimulus, thus resulting in smaller ensemble averages.

Oscillatory neural network for pattern recognition: trajectory based classification and supervised learning.

Computer algorithms that match human performance in recognizing written text or spoken conversation remain elusive. The reasons why the human brain far exceeds any existing recognition scheme to date in the ability to generalize and to extract invariant characteristics relevant to category matching are not clear. However, it has been postulated that the dynamic distribution of brain activity (spatiotemporal activation patterns) is the mechanism by which stimuli are encoded and matched to categories. This research focuses on supervised learning using a trajectory based distance metric for category discrimination in an oscillatory neural network model. Classification is accomplished using a trajectory based distance metric. Since the distance metric is differentiable, a supervised learning algorithm based on gradient descent is demonstrated. Classification of spatiotemporal frequency transitions and their relation to a priori assessed categories is shown along with the improved classification results after supervised training. The results indicate that this spatiotemporal representation of stimuli and the associated distance metric is useful for simple pattern recognition tasks and that supervised learning improves classification results.

Target probability affects the likelihood that a P300 will be generated in response to a target stimulus, but not its amplitude.

The ensemble-averaged P300 amplitude is affected by global and local target probability and interstimulus interval. We hypothesize that the local target probability-induced amplitude changes arise from a failure to consistently produce a P300 rather than producing lower amplitude responses. Single-trial analysis was conducted on auditory P300 data from 13 healthy subjects to determine the absence or presence of a P300 component for each target response separately. Selective, normalized averages were computed for each local target probability. Target stimuli preceded by one or two nontargets led to significantly more trials lacking a P300 than the other local target probability categories. The amplitudes of the responsive trials did not differ between the local target probability categories. This suggests that local target probability affects the consistency with which a subject responds to target stimuli, but not the P300 amplitude.

Auditory evoked responses in a comparison between schizophrenia patients with and without premorbid history of drug abuse: report of pilot results.

Evidence for a role for drugs of abuse in the development of chronic psychotic syndromes is scattered throughout 40 years of literature. Electrophysiological studies examining groups believed to have chronic drug-induced psychotic symptoms yielded interesting findings. To our knowledge, no studies directly compared schizophrenia patients whose drug use preceded and those whose drug use followed the onset of psychotic symptoms. Twenty-six schizophrenia patients and 10 healthy control subjects were recruited for the study. Based on the SCID interview, schizophrenia subjects were classified into a Psychosis First (Psy 1st) group (N=11), Drugs First (Drugs 1st; N=8), and No Drug Use (No Drugs; N=7). Schizophrenia subjects were administered the Positive and Negative Symptoms Scale (PANSS). The P300 evoked response and sensory gating were measured for all subjects. Despite the small sample sizes significant differences were found between the groups. Most significantly, the P300 amplitude was smallest in the Drugs 1st as compared to the No Drugs groups, while sensory gating deficit was worst in the Psy 1st group. The data suggest that significant clinical and electrophysiological differences between these groups can be identified. Further research to better define these differences seems warranted.

Morphological and latency abnormalities of the mid-latency auditory evoked responses in schizophrenia: a preliminary report.

INTRODUCTION: Evoked potential (EP) amplitude and latency abnormalities have been extensively examined in schizophrenia. Morphological abnormalities of the mid-latency auditory evoked responses (MLAERs; P50, N100, P200), on the other hand, received very little attention. METHODS: Based on a priori defined set of morphological criteria, the morphology and latency of the MLAERs were blindly compared between stable outpatients with schizophrenia (N=27) and age- and gender-matched healthy control subjects (N=22). The morphology of the MLAERs was considered abnormal if one or more of the components fell outside the expected latency range, if one or more of the components were missing, or if a later occurring component was smaller in amplitude than an earlier occurring one. RESULTS: Of the 27 schizophrenia subjects, 20 had waveforms that were deemed atypical, while only 8 from the control group were classified as atypical (chi(2)=5.52, p<0.02). The latencies of the P50 and N100 components, identified based on morphology, were significantly prolonged in schizophrenia patients. CONCLUSIONS: These preliminary data suggest that morphological abnormalities of the MLAERs in schizophrenia patients are significant and should be taken into consideration when examining the MLAERs of this patient population.

An exploratory study of factors affecting single trial P300 detection.

A threshold detector for single-trial P300 detection has been evaluated. The detector operates on the 0-4 Hz band, isolated from the raw electroencephalogram using low-pass filtering, wavelet transforms, or the piecewise prony method (PPM). A detection rate around 70% was found, irregardless of stimulus type, interstimulus interval (ISI), probability of occurrence (Pr) of the target stimuli, intrasession and intersession effects, or filtering method. This suggests that P300-based brain-machine interfaces can use an ISI as short as 1 s and a Pr of 45%, to increase throughput.

Contribution of different EEG frequencies to auditory evoked potential abnormalities in schizophrenia.

OBJECTIVE: We have shown previously [Clin Neurophysiol 2003;114:79] that phase reorganization of the ongoing electroencephalogram (EEG) plays an important role in the generation of auditory evoked potential (EP) components with a latency between 50 and 200 ms. In the present study, we investigate whether schizophrenia patients suffer from phase synchronization deficits as compared to normal subjects. METHODS: The auditory EPs from 20 normal subjects and 19 schizophrenia patients were analyzed. EPs were obtained using a double stimulus paradigm, in which two identical tone bursts (S1 and S2) were delivered with an average inter-stimulus interval of 500 ms and an inter-pair interval of 8 s. The Piecewise Prony Method (PPM) was used to decompose single trial auditory evoked potentials into different frequency bands. Pre- and post-stimulus phase histograms were compared for each frequency band to determine the degree of phase synchronization produced by auditory stimulation in the two populations. RESULTS: The S1 stimulus produced significantly less (P < 0.05) phase synchronization in schizophrenia patients than in normal subjects in the 2-12 Hz frequency range. Far fewer and smaller inter-population phase synchronization differences were seen for the S2 stimulus. Both populations showed more phase synchronization for S1 than S2. A significant correlation (P < 0.01) between N100 amplitude and phase synchronization 100 ms post S1 was observed for the normal population but not for the schizophrenia group. The correlation between P200 amplitude and phase synchronization 200 ms post S1 was significant for the normal group (P < 0.01) and the schizophrenia group (P < 0.03). CONCLUSIONS: Schizophrenia patients have a phase synchronization deficiency, as compared to a normal control group, especially for the first stimulus, in the 2-12 Hz frequency range. This deficiency explains the lower EP amplitudes and may be a significant factor contributing to reduced sensory gating reported in schizophrenic subjects. SIGNIFICANCE: The research presented here contributes to the understanding of the mechanism underlying sensory gating in health and gating deficiencies in schizophrenia.

Multidimensional EMG-based assessment of walking dynamics.

The electromyogram (EMG) provides a measure of a muscle's involvement in the execution of a motor task. Successful completion of an activity, such as walking, depends on the efficient motor control of a group of muscles. In this paper, we present a method to quantify the intricate phasing and activation levels of a group of muscles during gait. At the core of our method is a multidimensional representation of the EMG activity observed during a single stride. This representation is referred to as a "trajectory." A hierarchical clustering procedure is used to identify representative classes of muscle activity patterns. The relative frequencies with which these motor patterns occur during a session (i.e., a series of consecutive strides) are expressed as histograms. Changes in walking strategy will be reflected as changes in the relative frequency with which specific gait patterns occur. This method was evaluated using EMG data obtained during walking on a level and a moderately-inclined treadmill. It was found that the histogram changes due to artificially altered gait are significantly larger than the changes due to normal day-to-day variability.

Phase synchronization of the ongoing EEG and auditory EP generation.

OBJECTIVE: We investigated the role of phase synchronization of the spontaneous electroencephalogram (EEG) in auditory evoked potential (EP) generation in a sample of healthy individuals. METHODS: Auditory responses were obtained from 20 healthy subjects following a double stimulus paradigm, using two identical tone bursts (S1 and S2) separated by 0.5s. Single-trial auditory evoked potentials were decomposed into sinusoidal, exponentially decaying/increasing components using the piecewise Prony method (PPM). Pre- and post-stimulus phase histograms were compared to determine the degree of phase synchronization produced by auditory stimulation. RESULTS: Analysis of single responses revealed that the S1 stimuli produced phase synchronization in the 2-8Hz frequency range, with little or no concomitant amplitude increase. A significantly reduced phase effect was seen in response to S2 stimuli. CONCLUSIONS: Stimulus-induced phase synchronization of the ongoing EEG is a major mechanism for the generation of auditory EP components with a latency in the 50-250ms range. SIGNIFICANCE: The fact that the EP components accessed here are generated through phase synchronization implies that the ensemble-averaged EP will not resemble the single trial response, and it would certainly be misleading to consider the single trial response as an amplitude-scaled version of the ensemble average.

Measuring the similarity between trajectories using clustering techniques.

A clustering method has been developed to group signals that display similar dynamic behavior. The procedure involves using the method of time delay embedding to construct a trajectory in state space from a time series. Certain features that characterize the geometry of the trajectory have been defined. These features were subjected to a series of statistical tests to determine their usefulness in a hierarchical clustering analysis. The latter is aimed at finding groups of similar trajectories. The trajectory-based clustering algorithm has been applied to simulated data, which included both stochastic data generated by a linear AR model, and nonlinear data generated by a Duffing oscillator. The results show that the algorithm works reliably in both cases.