Timothy W. Budd

Decrement of the N1 auditory event-related potential with stimulus repetition: Habituation vs. refractoriness

We examined whether the amplitude decrement traditionally found for the N1 peak of the event-related potential (ERP) with repetition of auditory stimuli results from the process of habituation or from the refractory period of the neural elements underlying the N1 response. These competing accounts of the process underlying the N1 decrement with repetition differ in terms of the predicted effects of variations in stimulus repetition and interstimulus interval (ISI). These predictions were examined using a short-term habituation design with a factorial combination of stimulus repetition and ISI. Forty-five subjects received 21 stimulus trains, each consisting of seven innocuous tones, all at 1 kHz except the sixth, which was a 1.5-kHz tone. Each subject was assigned to one of three ISI conditions (either 1, 3 or 10 s). The results provide little support for the view that N1 response decrement with stimulus repetition reflects a process of habituation. The present results provide greater support for the view that this decrement is based on the separate refractory periods or recovery cycle processes of at least two neural generators contributing to activity in the N1 peak latency range.

Duration and frequency mismatch negativity in schizophrenia

OBJECTIVES The aim of the present study was to elucidate the reasons for apparent inconsistencies in the schizophrenia literature with respect to the mismatch negativity (MMN) waveform of the event-related potential (ERP). While most previous research has shown that MMN is reduced in schizophrenia, there are a small number of studies reporting that frequency MMN is not reduced. METHODS We recorded ERPs to auditory stimuli with different frequencies and durations from patients with schizophrenia (N = 14) and control subjects (N = 17) of similar age and sex. MMNs to small but discriminable frequency deviants were contrasted with large frequency deviants and duration deviants. RESULTS Only the MMN to duration deviants was significantly reduced in patients, although there was evidence of a similar trend for large frequency deviants. CONCLUSIONS The results together with a review of the frequency MMN literature suggest that there are 3 variables which are important in determining whether patients exhibit a reduced MMN to frequency deviants: deviant probability, degree of deviance and interstimulus interval. The results also indicated that patients with schizophrenia may have particular deficits in processing the temporal properties of auditory stimuli. This finding has implications for the pathophysiology of the disorder as time-dependent processing is reliant on the integrity of an extensive network of brain areas consisting of auditory cortex, areas of pre-frontal cortex, the basal ganglia and cerebellum.

The attentional blink and P300.

The attentional blink (AB) is a brief impairment of visual processing occurring 200-500 ms after a target in a rapid stream of visual stimuli. At issue here is the relationship between AB and the P300 ERP component, as both are maximal at about 300 ms and have been hypothesised to reflect inhibitory processes. Two experiments revealed that AB and P300 follow a similar time course at the individual and group level, that reducing task difficulty has similar effects on AB and P300 magnitude at the group level, but that there is no relationship between the magnitude of AB and P300 within observers. These findings suggest a moderate association between the two phenomena, which may mirror transient inhibition of cortical networks to facilitate processing of target events.

Epidural Auditory Event-Related Potentials in the Rat to Frequency and duration Deviants: Evidence of Mismatch Negativity?

The capacity of the human brain to detect deviance in the acoustic environment pre-attentively is reflected in a brain event-related potential (ERP), mismatch negativity (MMN). MMN is observed in response to the presentation of rare oddball sounds that deviate from an otherwise regular pattern of frequent background standard sounds. While the primate and cat auditory cortex (AC) exhibit MMN-like activity, it is unclear whether the rodent AC produces a deviant response that reflects deviance detection in a background of regularities evident in recent auditory stimulus history or differential adaptation of neuronal responses due to rarity of the deviant sound. We examined whether MMN-like activity occurs in epidural AC potentials in awake and anesthetized rats to high and low frequency and long and short duration deviant sounds. ERPs to deviants were compared with ERPs to common standards and also with ERPs to deviants when interspersed with many different standards to control for background regularity effects. High frequency (HF) and long duration deviant ERPs in the awake rat showed evidence of deviance detection, consisting of negative displacements of the deviant ERP relative to ERPs to both common standards and deviants with many standards. The HF deviant MMN-like response was also sensitive to the extent of regularity in recent acoustic stimulation. Anesthesia in contrast resulted in positive displacements of deviant ERPs. Our results suggest that epidural MMN-like potentials to HF sounds in awake rats encode deviance in an analogous manner to the human MMN, laying the foundation for animal models of disorders characterized by disrupted MMN generation, such as schizophrenia.

Mismatch Negativity (MMN) in Freely-Moving Rats with Several Experimental Controls

Mismatch negativity (MMN) is a scalp-recorded electrical potential that occurs in humans in response to an auditory stimulus that defies previously established patterns of regularity. MMN amplitude is reduced in people with schizophrenia. In this study, we aimed to develop a robust and replicable rat model of MMN, as a platform for a more thorough understanding of the neurobiology underlying MMN. One of the major concerns for animal models of MMN is whether the rodent brain is capable of producing a human-like MMN, which is not a consequence of neural adaptation to repetitive stimuli. We therefore tested several methods that have been used to control for adaptation and differential exogenous responses to stimuli within the oddball paradigm. Epidural electroencephalographic electrodes were surgically implanted over different cortical locations in adult rats. Encephalographic data were recorded using wireless telemetry while the freely-moving rats were presented with auditory oddball stimuli to assess mismatch responses. Three control sequences were utilized: the flip-flop control was used to control for differential responses to the physical characteristics of standards and deviants; the many standards control was used to control for differential adaptation, as was the cascade control. Both adaptation and adaptation-independent deviance detection were observed for high frequency (pitch), but not low frequency deviants. In addition, the many standards control method was found to be the optimal method for observing both adaptation effects and adaptation-independent mismatch responses in rats. Inconclusive results arose from the cascade control design as it is not yet clear whether rats can encode the complex pattern present in the control sequence. These data contribute to a growing body of evidence supporting the hypothesis that rat brain is indeed capable of exhibiting human-like MMN, and that the rat model is a viable platform for the further investigation of the MMN and its associated neurobiology.

Isolation and characterisation of glutamate receptor antagonists from venoms of orb-web spiders

Two distinct families of low-molecular-weight toxins (argiotoxins) have been isolated from the venom of the orb-web spider. Argiope trifasciata. The toxins have been purified to homogeneity and characterised by spectroscopic, mass spectrometric and microchemical analysis. The major biologically active member of the first family of toxins is 2,4-dihydroxyphenylacetyl-asparagine linked through a C11-tetra-amine to N-terminal arginine; other members of this family are methylene homologues. The second family of toxins possesses an indolic group in place of the 2,4-dihydroxyphenyl chromophore. The toxins act as non-competitive inhibitors at quisqualate-type glutamatergic receptors on a metathoracic retractor unguis nerve-muscle preparation of Schistocerca gregaria. The loss of the N-terminal arginine reduces biological activity of the first family of toxins, but not of the second. The nature of the polyamine appears to be less important, perhaps acting as a spacer between the cationic arginine and the more hydrophobic aromatic tail of the toxins.

Binaural specialisation in human auditory cortex: an fMRI investigation of interaural correlation sensitivity

A listeners sensitivity to the interaural correlation (IAC) of sound plays an important role in several phenomena in binaural hearing. Although IAC has been examined humans, little is known about the neural basis of sensitivity to IAC in humans. The present study employed functional magnetic resonance imaging to measure blood oxygen level-dependent (BOLD) activity in auditory brainstem and cortical structures in human listeners during presentation of band-pass noise stimuli between which IAC was varied systematically. The stimuli evoked significant bilateral activation in the inferior colliculus, medial geniculate body, and auditory cortex. There was a significant positive relationship between BOLD activity and IAC which was confined to a distinct subregion of primary auditory cortex located bilaterally at the lateral extent of Heschls gyrus. Comparison with published anatomical data indicated that this area may also be cytoarchitecturally distinct. Larger differences in activation were found between levels of IAC near unity than between levels near zero. This response pattern is qualitatively compatible with previous measures of psychophysical and neurophysiological sensitivity to IAC. extensively in neurophysiological studies in animals and in psychophysical studies in

Auditory lateralization in schizophrenia--mismatch negativity and behavioral evidence of a selective impairment in encoding interaural time cues.

OBJECTIVE Behavioural evidence suggests that individuals with schizophrenia may exhibit impairment in the encoding of cues to sound location. There are three primary cues used by the auditory system to locate the position of a sound in space: interaural differences in the arrival-time (ITD), phase (IPD), and the loudness (ILD) of the sound at the two ears. The goal in this study was to obtain an electrophysiological index of preattentive detection of change in sound lateralization created by these cues. METHODS The amplitude of mismatch negativity (MMN) was measured in 18 individuals with schizophrenia and 19 healthy comparison subjects to changes in sound lateralization produced by interaural temporal cues (ITD and IPD) and interaural loudness cues (ILD). Performance was also investigated on a target detection task, where targets were defined by ITD, IPD, or ILD cues. RESULTS Individuals with schizophrenia had reduced MMN amplitudes and decreased hit rates when deviants were created by interaural temporal cues, but not when loudness cues were used. CONCLUSIONS Results from both the MMN and behavioural task revealed a selective impairment in the use of temporal cues to sound lateralization in individuals with schizophrenia. SIGNIFICANCE This finding supports previous research that suggests impairment in the encoding of the temporal information in schizophrenia.

Sustained brain activation supporting stop-signal task performance

Stop‐signal paradigms operationalize a basic test of goal‐directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop‐signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop‐signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop‐signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop‐signal task.

A Randomized Controlled Trial of the Effect of Early Upper-Limb Training on Stroke Recovery and Brain Activation

Background. Upper-limb (UL) dysfunction is experienced by up to 75% of patients poststroke. The greatest potential for functional improvement is in the first month. Following reperfusion, evidence indicates that neuroplasticity is the mechanism that supports this recovery. Objective. This preliminary study hypothesized increased activation of putative motor areas in those receiving intensive, task-specific UL training in the first month poststroke compared with those receiving standard care. Methods. This was a single-blinded, longitudinal, randomized controlled trial in adult patients with an acute, first-ever ischemic stroke; 23 participants were randomized to standard care (n = 12) or an additional 30 hours of task-specific UL training in the first month poststroke beginning week 1. Patients were assessed at 1 week, 1 month, and 3 months poststroke. The primary outcome was change in brain activation as measured by functional magnetic resonance imaging. Results. When compared with the standard-care group, the intensive-training group had increased brain activation in the anterior cingulate and ipsilesional supplementary motor areas and a greater reduction in the extent of activation (P = .02) in the contralesional cerebellum. Intensive training was associated with a smaller deviation from mean recovery at 1 month (Pr>F0 = 0.017) and 3 months (Pr>F = 0.006), indicating more consistent and predictable improvement in motor outcomes. Conclusion. Early, more-intensive, UL training was associated with greater changes in activation in putative motor (supplementary motor area and cerebellum) and attention (anterior cingulate) regions, providing support for the role of these regions and functions in early recovery poststroke.