Ms Window Research Articles

Methods for determining free-swimming positioning and echolocation beam patterns

Echolocation beam patterns were recorded using a 25-element autonomous, self-contained hydrophone array during free-swimming echoic match tasks. Two GoPro HERO2 cameras mounted at 45-degree angles to the plane of the 4.5 × 4.5 ft PVC array recorded the position of the dolphin during approach and investigation of the sample object presented in front of the array. Using a pre-session calibration file and MaxTRAQ3D software, analysis of video determined exact positioning of the head region during echolocation, including distance from the array and angle to the plane of the array. An LED and ITC-1042 transducer, operated by an Arduino Uno processor board and a Hafler amplifier, were mounted on the array. Simultaneously emitted visual pulses (LED) and acoustic pulse trains were used for synchronization of the acoustic recorders and video cameras. The distinct pulse train was used during post-recording analysis to synchronize the hydrophones using a custom-designed Matlab routine. The hydrophones are sampled at 400 kHz and analyzed in real-time. The maximum and minimum values and time stamps within a 0.32 ms window are stored continuously to reduce the amount of data that needs to be stored. Using the 3-D positioning of the animal, dynamic beam patterns can be reconstructed.

Looking Beyond The SRM to High-Resolution MS Paradigm Shift for DMPK Studies

Kean University, New Jersey Center for Science, Technology & Mathematics, 1000 Morris Avenue, Union, NJ 07033, USA Tel.: +1 908 737 7217 E-mail: ramanatd@kean.edu A 1900 statement from Lord Kelvin to British physicists stated the following: “There is nothing new to be discovered in physics now. All that remains is more and more precise measurement” [101]. In a nutshell the SRM to HRMS paradigm shift revolves around precise or accurate measurement of mass using highresolution MS (HRMS). Over the last few years, HRMS systems facilitated by new technological advances and userfriendly software have evolved from a specialist to a generalist analytical tool. The HRMS-based methods are now routinely used in most discovery DMPK bioanalytical and biotransformation laboratories and they are also slowly infiltrating some of the regulated bioanalytical laboratories. New additions to the HRMS workflow, such as MS (where e represents collision energy) and sequential window acquisition of all theoretical fragments (SWATH) technologies, have started to pave the way to improved selectivity, specificity and signal-to-noise ratio of DMPK assays and are poised to help the paradigm shift come to completion. Success in drug R&D is critical for meeting the needs of medicine and patient care with the demands of running a growing, profitable business. For new drugs to be beneficial to patients, they must show improved efficacy and safety over existing treatments. For a drug to enter clinical trials and to become a product for patients, four separate but somewhat interrelated processes influence a drug’s movement in the body: absorption (A), distribution (D), metabolism (M) and excretion (E). A drug’s ADME properties are studied and optimized by pre-clinical and clinical drug metabolism and DMPK scientists. Over the past 20 years, LC–MS-based techniques have grown to replace every other technique and become the gold standard analytical technique for DMPK studies. The crystallization of the LC–MS technique as the gold standard DMPK analytical tool happened with the introduction of atmospheric pressure ionization (API) techniques, specifically, ESI and atmospheric-pressure chemical ionization (APCI). API techniques facilitated efficient coupling of LC separation technologies, which simplifies complex biological samples, before MS analysis. Since routine DMPK assays involve measuring m/z ratios of drugs and/or their metabolites present in complex biological samples, adequate sample clean-up and chromatographic separation are essential for quantification and characterization of these components. Two major chromatographic separation techniques used in DMPK studies are HPLC and UHPLC. Over the last 3–5 years, major developments in columns based on sub-2 μm porous particles, monoliths, and wide pore core-shell particles (2–3 μm) combined with the introduction of rugged UHPLC systems have improved the speed and throughput of small-molecule separations. Along with the developments in sample separation and preparation technologies, the evolutions of MS technologies have streamlined how DMPK studies are conducted. If you had to pinpoint it, the last paradigm shift in the bioanalytical sciences in support of DMPK studies happened in the late 1980s and early 1990s. And it revolved around shifting from LC–UV to LC–MS/MS for PK and TK quantitation [1] and the combined use of benchtop quodrupole ion trap and triple quadrupole for metabolite detection and characterization [2]. These shifts allowed DMPK scientists to bring bioanalysis into drug metabolism laboratories rather than be dependent on centralized MS facilities operated by a specialist. Furthermore, during this shift the ability to couple LC with sensitive MS/MS-based SRM methods allowed bioanalysts to improve the detection

Exploratory MEG Study of the Illusory Contour Perception: Positive and Inverted Effects

The illusory contour is one of the most often used models in studies of Gestalt perception. In our MEG study we observed the so-called illusory contour effect (IC-effect): the activity of nonprimary visual and associative cortical areas was increased during the 150-250 ms time window after a stimulus onset in response to illusory stimulus, compared with the control stimulus. In addition to the positive IC-effect, the inverted IC-effect was revealed for the first time in adults. In our study it was manifested during the 60-120 ms window after the onset of stimulus. The inverted IC-effect is an early decrease in the activity of the visual cortex in response to the illusory contour compared with the control stimulus. The mechanism of the inverted IC-effect is yet unclear. The “bottom-up” and “top-down” hypotheses of the origin of the inverted IC-effect are discussed.

Inducing Gamma Oscillations and Precise Spike Synchrony by Operant Conditioning via Brain-Machine Interface

Neural oscillations in the low-gamma range (30-50 Hz) have been implicated in neuronal synchrony, computation, behavior, and cognition. Abnormal low-gamma activity, hypothesized to reflect impaired synchronization, has been evidenced in several brain disorders. Thus, understanding the relations between gamma oscillations, neuronal synchrony and behavior is a major research challenge. We used a brain-machine interface (BMI) to train monkeys to specifically increase low-gamma power in selected sites of motor cortex to move a cursor and obtain a reward. The monkeys learned to robustly generate oscillatory gamma waves, which were accompanied by a dramatic increase of spiking synchrony of highly precise spatiotemporal patterns. The findings link volitional control of LFP oscillations, neuronal synchrony, and the behavioral outcome. Subjects' ability to directly modulate specific patterns of neuronal synchrony provides a powerful approach for understanding neuronal processing in relation to behavior and for the use of BMIs in a clinical setting.

Microstimulation Activates a Handful of Muscle Synergies

Muscle synergies have been proposed as a mechanism to simplify movement control. Whether these coactivation patterns have any physiological reality within the nervous system remains unknown. Here we applied electrical microstimulation to motor cortical areas of rhesus macaques to evoke hand movements. Movements tended to converge toward particular postures, driven by synchronous bursts of muscle activity. Across stimulation sites, the muscle activations were reducible to linear sums of a few basic patterns-each corresponding to a muscle synergy evident in voluntary reach, grasp, and transport movements made by the animal. These synergies were represented nonuniformly over the cortical surface. We argue that the brain exploits these properties of synergies-postural equivalence, low dimensionality, and topographical representation-to simplify motor planning, even for complex hand movements.

Abstract 19176: Mapping of Electrogram Morphology Recurrence Patterns during Atrial Fibrillation

Introduction: Electrograms during atrial fibrillation (AF) are complex and seemingly chaotic. It is still unknown how to best analyze and utilize AF electrograms. Hypothesis: We hypothesize that the frequency and patterns of AF electrogram morphology recurrence determined by a modified recurrence plot (RP) analysis will show differences based on region in this pilot study. Methods: AF electrograms (>16 s) recorded from documented left atrial (LA) and right atrial (RA) sites in 13 patients (10 male, 59±10 years old) prior to AF ablation were analyzed. A 100 ms window for each automatically detected activation was extracted and cross-correlated with every other activation in a 30-sec recording. The result was a set of NxN cross-correlation (CC) values, where N is the number of detected activations. These values were displayed in a two-dimensional RP. A recurrence index (RI), the percentage of the most common morphology, was also computed. A high RI likely indicates consistent activation directions at the site of bipolar electrogram recording. Results: Figure A is a RP example. The checker board pattern of alternating high and low CC values indicates periodic recurrences in morphologies (RI=70% for this example). The mean RI for all sites and all patients was 38±25%. The highest RI was found in the left superior LA in all 4 paroxysmal AF patients (85±18%, see Figure B). For 9 persistent AF patients, the highest RI was found in the RA (91±10%) in 5 patients and in the left superior LA (95±6%) in 4 patients. The persistent AF patients had higher maximum RIs in the RA than the paroxysmal AF patients (87±16 vs. 51±15%, p=0.01). Conclusion: Electrogram morphology with highest recurrence rates were most frequently found in the left superior LA, a common location for AF triggers. Further work is needed to determine whether high electrogram repeatability reflects AF driver activity and whether RPs could be used as part of an ablation strategy.

Psychophysiological prediction of choice: relevance to insight and drug addiction

An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400-1000 ms) and late (1000-2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice--and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)--when insight (and self-report) is compromised.

Sensitivity to temporal reward structure in amygdala neurons.

SummaryThe time of reward and the temporal structure of reward occurrence fundamentally influence behavioral reinforcement and decision processes [1–11]. However, despite knowledge about timing in sensory and motor systems [12–17], we know little about temporal mechanisms of neuronal reward processing. In this experiment, visual stimuli predicted different instantaneous probabilities of reward occurrence that resulted in specific temporal reward structures. Licking behavior demonstrated that the animals had developed expectations for the time of reward that reflected the instantaneous reward probabilities. Neurons in the amygdala, a major component of the brain's reward system [18–29], showed two types of reward signal, both of which were sensitive to the expected time of reward. First, the time courses of anticipatory activity preceding reward delivery followed the specific instantaneous reward probabilities and thus paralleled the temporal reward structures. Second, the magnitudes of responses following reward delivery covaried with the instantaneous reward probabilities, reflecting the influence of temporal reward structures at the moment of reward delivery. In being sensitive to temporal reward structure, the reward signals of amygdala neurons reflected the temporally specific expectations of reward. The data demonstrate an active involvement of amygdala neurons in timing processes that are crucial for reward function.

Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo

Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.

Plasticity of spatial hearing: behavioural effects of cortical inactivation

The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex.

Aerodynamic measures of speech in unilateral vocal fold paralysis (UVFP) patients

This paper reports the recording and analysis of an aerodynamic database of 51 words produced by four patients with unilateral vocal fold paralysis. The vowel–fricative–vowel boundaries were manually annotated, and the mean absolute oral airflow amplitude (OA), fundamental frequency (f0), and first formant intensity (IF1) were extracted from a 20 ms window in the steady state of each phone. A case study approach to analysis of phonatory behaviour for the subjects is presented.Significant differences were found between the absolute OA and IF1 for different phones. Large between-subject variations in absolute measures for OA and f0 were found. Relative values calculated from the difference in these parameters between phones show consistency for subjects of the same gender.

Neural Synchrony during Response Production and Inhibition

Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300–600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

Feedforward Origins of Response Variability Underlying Contrast Invariant Orientation Tuning in Cat Visual Cortex

Contrast invariant orientation tuning in simple cells of the visual cortex depends critically on contrast dependent trial-to-trial variability in their membrane potential responses. This observation raises the question of whether this variability originates from within the cortical circuit or the feedforward inputs from the lateral geniculate nucleus (LGN). To distinguish between these two sources of variability, we first measured membrane potential responses while inactivating the surrounding cortex, and found that response variability was nearly unaffected. We then studied variability in the LGN, including contrast dependence, and the trial-to-trial correlation in responses between nearby neurons. Variability decreased significantly with contrast, whereas correlation changed little. When these experimentally measured parameters of variability were applied to a feedforward model of simple cells that included realistic mechanisms of synaptic integration, contrast-dependent, orientation independent variability emerged in the membrane potential responses. Analogous mechanisms might contribute to the stimulus dependence and propagation of variability throughout the neocortex.

Induced EEG Gamma Oscillation Alignment Improves Differentiation Between Autism and ADHD Group Responses in a Facial Categorization Task

INTRODUCTION: Children diagnosed with an autism spectrum disorder (ASD) often lack the ability to recognize and properly respond to emotional stimuli. Emotional deficits also characterize children with attention deficit/hyperactivity disorder (ADHD), in addition to exhibiting limited attention span. These abnormalities may effect a difference in the induced EEG gamma wave burst (35-45 Hz) peaked approximately 300-400 milliseconds following an emotional stimulus. Because induced gamma oscillations are not fixed at a definite point in time post-stimulus, analysis of averaged EEG data with traditional methods may result in an attenuated gamma burst power. METHODS: We used a data alignment technique to improve the averaged data, making it a better representation of the individual induced EEG gamma oscillations. A study was designed to test the response of a subject to emotional stimuli, presented in the form of emotional facial expression images. In a four part experiment, the subjects were instructed to identify gender in the first two blocks of the test, followed by differentiating between basic emotions in the final two blocks (i.e. anger vs. disgust). EEG data was collected from ASD (n=10), ADHD (n=9), and control (n=11) subjects via a 128 channel EGI system, and processed through a continuous wavelet transform and bandpass filter to isolate the gamma frequencies. A custom MATLAB code was used to align the data from individual trials between 200-600 ms post-stimulus, EEG site, and condition by maximizing the Pearson product-moment correlation coefficient between trials. The gamma power for the 400 ms window of maximum induced gamma burst was then calculated and compared between subject groups. RESULTS AND CONCLUSION: Condition (anger/disgust recognition, gender recognition) × Alignment × Group (ADHD, ASD, Controls) interaction was significant at most of parietal topographies (e.g., P3-P4, P7-P8). These interactions were better manifested in the aligned data set. Our results show that alignment of the induced gamma oscillations improves sensitivity of this measure in differentiation of EEG responses to emotional facial stimuli in ADHD and ASD.

P50 potential-associated gamma band activity: modulation by distraction.

We aimed to evaluate the effect of changing attentional demands towards stimulation in healthy subjects on P50 potential-related high-frequency beta and gamma oscillatory responses, P50 and N100 peak amplitudes and their gating measures. There are no data showing effect of attention on P50 potential-related beta and gamma oscillatory responses and previous results of attention effects on P50 and N100 amplitudes and gating measures are inconclusive. Nevertheless the variation in the level of attention may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Nine healthy volunteers participated in the study. A standard paired stimuli auditory P50 potential paradigm was applied. Four stimulation conditions were selected: focused attention (stimuli pair counting), unfocused attention (sitting with open eyes), easy distraction (reading a magazine article), and difficult distraction (searching for Landolt rings with appropriate gap orientation). Time-frequency responses to both S1 and S2 were evaluated in slow beta (13-16 Hz, 45-175 ms window); fast beta (20-30 Hz, 45-105 ms window) and gamma (32-46 Hz, 45-65 ms window) ranges. P50 and N100 peak amplitudes in response to both S1 and S2 and their ratio were evaluated. The phase-locked P50 potential-associated gamma activity was attenuated during distraction tasks as compared to focused attention and an unfocused attention condition. The amplitudes and gating measures of P50 and N100 waves and beta activity were not sensitive to the competing distraction task performance. The use of a distraction task is not favorable when phase-locked gamma range activity is a key interest in auditory potential studies.

Contextual impairments in schizophrenia and the FN400

Contextual impairments in schizophrenia and the FN400

Social Calls Exhibit a Distributed Consensus Map in the Auditory Cortex of Mustached Bats

Social Calls Exhibit a Distributed Consensus Map in the Auditory Cortex of Mustached Bats

Neural Coding of Call Pitch and Syllable Type in the Auditory Cortex of Mustached Bats

Neural Coding of Call Pitch and Syllable Type in the Auditory Cortex of Mustached Bats

Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator

In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.

Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

It has recently been demonstrated that soleus motor-evoked potentials (MEPs) are facilitated prior to the onset of dorsiflexion. The purpose of this study was to examine if this could be explained by removal of spinal inhibition of the descending command to soleus motoneurons. To test this, we investigated how afferent inputs from the tibialis anterior muscle modulate the corticospinal activation of soleus spinal motoneurons at rest, during static contraction and prior to movement. MEPs activated by transcranial magnetic stimulation (TMS) and Hoffmann reflexes (H-reflexes), activated by electrical stimulation of the posterior tibial nerve (PTN), were conditioned by prior stimulation of the common peroneal nerve (CPN) at a variety of conditioning-test (CT) intervals. MEPs in the precontracted soleus muscle were inhibited when the TMS pulse was preceded by CPN stimulation with a CT interval of 35 ms, and they were facilitated for CT intervals of 50-55 ms. A similar inhibition of the soleus H-reflex was not observed. To investigate which descending pathways might be responsible for the afferent-evoked inhibition and facilitation, we examined the effect of CPN stimulation on short-latency facilitation (SLF) and long-latency facilitation (LLF) of the soleus H-reflex induced by a subthreshold TMS pulse at different CT intervals. SLF is known to reflect the excitability of the fastest conducting, corticomotoneuronal cells whereas LLF is believed to be caused by more indirect descending pathways. At CT intervals of 40-45 ms, the LLF was significantly more inhibited compared to the SLF when taking the effect on the H-reflex into account. Finally, we investigated how the CPN-induced inhibition and facilitation of the soleus MEP were modulated prior to dorsiflexion. Whereas the late facilitation (CT interval: 55 ms) was similar prior to dorsiflexion and at rest, no inhibition could be evoked at the earlier latency (CT interval: 35 ms) prior to onset of dorsiflexion. The observation that the CPN-induced inhibition of soleus MEPs disappears prior to onset of dorsiflexion may explain why soleus MEPs are facilitated prior to onset of dorsiflexion contraction. A possible mechanism involves the removal of inhibition of the descending command to the motoneurons at a spinal interneuronal level because the inhibition was seen in LLF and not in SLF, and the MEP inhibition was not observed in the H-reflex. The data illustrate that spinal interneuronal pathways modify descending commands to human spinal motoneurons and influence the size of MEPs elicited by TMS.