Parametric manipulations of auditory stimuli differentially affect P3 amplitude in schizophrenics and controls

Schizophrenics show P3 amplitude reduction and topographic asymmetries. It is unclear whether the underlying cause of these deficits is primarily functional or structural. This study examined the effect of stimulus discrimi-nability and task instruction on behavioral performance and P3 in schizophrenics and normal control subjects. Stimulus discriminability was manipulated by varying the overall loudness and pitch disparity of the two tones in an auditory oddball paradigm. Instructions emphasized either speed or accuracy of response. Instructions had no significant effects on reaction time, perceptual sensitivity, response bias, or P3. With increased discriminability, however, both groups improved in mean reaction time to targets and perceptual sensitivity. In controls, P3 became earlier and larger with increased stimulus discriminability and was consistently larger over left temporal areas than over right temporal areas. In schizophrenics, P3 latency was related to stimulus discriminability, but amplitude was not; P3 amplitude did not increase with improvement of perceptual sensitivity and reaction time. Unlike normal controls, schizophrenics had a P3 asymmetry at temporal sites, with reduced left-sided voltages. The results are not consistent with a primarily functional cause of P3 aberrations in schizophrenia and are compatible with the hypothesis that P3 amplitude deficits in schizophrenia are related to underlying pathophysiology of temporal lobe generator sites.     

Evaluation of Cortical Connectivity During Real and Imagined Rhythmic Finger Tapping

Accumulating evidence suggests the existence of a shared neural substrate between imagined and executed movements. However, a better understanding of the mechanisms involved in the motor execution and motor imagery requires knowledge of the way the co-activated brain regions interact to each other during the particular (real or imagined) motor task. Within this general framework, the aim of the present study is to investigate the cortical activation and connectivity sub-serving real and imaginary rhythmic finger tapping, from the analysis of multi-channel electroencephalogram (EEG) scalp recordings. A sequence of 250 auditory pacing stimuli has been used for both the real and imagined right finger tapping task, with a constant inter-stimulus interval of 1.5 s length. During the motor execution, healthy subjects were asked to tap in synchrony with the regular sequence of stimulus events, whereas in the imagery condition subjects imagined themselves tapping in time with the auditory cue. To improve the spatial resolution of the scalp fields and suppress unwanted interferences, the EEG data have been spatially filtered. Further, event related synchronization and desynchronization phenomena and phase synchronization analysis have been employed for the study of functionally active brain areas and their connectivity during real and imagery finger tapping. Our results show a fronto-parietal co-activation during both real and imagined movements and similar connectivity patterns among contralateral brain areas. The results support the hypothesis that functional connectivity over the contralateral hemisphere during finger tapping is preserved in imagery. The approach and results can be regarded as indicative evidences of a new strategy for recognizing imagined movements in EEG-based brain computer interface research.     

Effects of discrepancy between imagined and perceived sounds on the N2 component of the event‐related potential

Two experiments were conducted to examine whether the N2 component of the event‐related potential (ERP), typically elicited in a S1‐S2 matching task and considered to reflect mismatch process, can still be elicited when the S1 was imagined instead of perceived and to investigate how N2 amplitude varied with the degree of S1‐S2 discrepancy. Three levels of discrepancy were defined by the degree of separation between the heard (S2) and imagined (S1) sounds. It was found that the N2 was reliably elicited when the perceived S2 differed from the imagined S1, but whether N2 amplitude increased with the degree of discrepancy depended in part on the S1‐S2 discriminability (as evidenced by reaction time). Specifically, the effect of increasing discrepancy was attenuated as discriminability increased from hard to easy. These results, together with the dynamic ERP topography observed within the N2 window, suggest that the N2 effect reflects two sequential but overlapping processes: automatic mismatch and controlled detection.     

Imagery Vividness Affects Habituation Rate

In order to investigate the effect of individual differences in imagery vividness on habituation rate, 14 subjects were threatened with receiving and then imagined receiving an electric shock. Subjects first habituated to a tone which was then used as an auditory signal for the shock threat and the imagined shock. The skin conductance response (SCR) was used to follow the course of habituation. Results demonstrated that subjects with non-vivid imagery habituated to the tone more rapidly than subjects with vivid imagery when the tone was associated with imagining an electric shock. Implications of this finding for therapeutic techniques using instructed imagery are discussed.     

Relationship Between Stimulus Intensity and the P300

The effect of stimulus intensity on the P300 component of the averaged auditory evoked potential was examined in healthy young adults. Although no effect on P300 amplitude was present, increasing loudness was inversely related to P300 latency. These data demonstrate a partial dependence of P300 on stimulus parameters, and underscore the importance of determining the hearing ability of subjects and patients in studies employing P300 as an index of information processing speed.     

Sustained BOLD and theta activity in auditory cortex are related to slow stimulus fluctuations rather than to pitch

Human functional MRI (fMRI) and magnetoencephalography (MEG) studies indicate a pitch-specific area in lateral Heschl's gyrus. Single-cell recordings in monkey suggest that sustained-firing, pitch-specific neurons are located lateral to primary auditory cortex. We reevaluated whether pitch strength contrasts reveal sustained pitch-specific responses in human auditory cortex. Sustained BOLD activity in auditory cortex was found for iterated rippled noise (vs. noise or silence) but not for regular click trains (vs. jittered click trains or silence). In contrast, iterated rippled noise and click trains produced similar pitch responses in MEG. Subsequently performed time-frequency analysis of the MEG data suggested that the dissociation of cortical BOLD activity between iterated rippled noise and click trains is related to theta band activity. It appears that both sustained BOLD and theta activity are associated with slow non-pitch-specific stimulus fluctuations. BOLD activity in the inferior colliculus was sustained for both stimulus types and varied neither with pitch strength nor with the presence of slow stimulus fluctuations. These results suggest that BOLD activity in auditory cortex is much more sensitive to slow stimulus fluctuations than to constant pitch, compromising the accessibility of the latter. In contrast, pitch-related activity in MEG can easily be separated from theta band activity related to slow stimulus fluctuations.     

Oscillatory brain activity in the alpha range is modulated by the content of word‐prompted mental imagery

Mental imagery is a fundamental cognitive process of interest to basic scientists and clinical researchers. This study examined large‐scale oscillatory brain activity in the alpha band (8–12 Hz) during language‐driven mental imagery using dense‐array EEG. Three experiments demonstrated relative increases in alpha amplitude: (1) during imagery prompted by words compared to fixation without imagery instruction, (2) during imagery of word content compared to imagery of geometric shapes, and (3) during imagery of emotionally evocative words compared to imagery of less emotionally arousing content. Alpha increases for semantically loaded imagery were observed in parieto‐occipital regions, sustained throughout the imagery period. Findings imply that alpha oscillations index active memory and internal cognitive processing, reflecting neural communication in cortical networks representing motor, semantic, and perceptual aspects of the imagined scene.     

Effects of phase duration and pulse rate on loudness and pitch percepts in the first auditory midbrain implant patients: Comparison to cochlear implant and auditory brainstem implant results

The auditory midbrain implant (AMI), which is designed for stimulation of the inferior colliculus (IC), is now in clinical trials. The AMI consists of a single shank array (20 contacts) and uses a stimulation strategy originally designed for cochlear implants since it is already approved for human use and we do not yet know how to optimally activate the auditory midbrain. The goal of this study was to investigate the effects of different pulse rates and phase durations on loudness and pitch percepts because these parameters are required to implement the AMI stimulation strategy. Although each patient was implanted into a different region (i.e. lateral lemniscus, central nucleus of IC, dorsal cortex of IC), they generally exhibited similar threshold versus phase duration, threshold versus pulse rate, and pitch versus pulse rate curves. In particular, stimulation with 100 mus/phase, 250 pulse per second (pps) pulse trains achieved an optimal balance among safety, energy, and current threshold requirements while avoiding rate pitch effects. However, we observed large differences across patients in loudness adaptation to continuous pulse stimulation over long time scales. One patient (implanted in dorsal cortex of IC) even experienced complete loudness decay and elevation of thresholds with daily stimulation. Comparing these results with those of cochlear implant and auditory brainstem implant patients, it appears that stimulation of higher order neurons exhibits less and even no loudness summation for higher rate stimuli and greater current leakage for longer phase durations than that of cochlear neurons. The fact that all midbrain regions we stimulated, which includes three distinctly different nuclei, exhibited similar loudness summation effects (i.e. none for pulse rates above 250 pps) suggests a possible shift in some coding properties that is affected more by which stage along the auditory pathway rather than the types of neurons are being stimulated. However, loudness adaptation occurs at multiple stages from the cochlea up to the midbrain.     

Influence of somatosensory input on corticospinal excitability during motor imagery

Our previous studies showed that corticospinal excitability during imagery of squeezing a foam ball was enhanced by somatosensory input generated by passively holding the ball. In the present study, using the same experimental model, we investigated whether corticospinal excitability was influenced by holding the object with the hand opposite to the imagined hand. Corticospinal excitability was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal interosseous muscle following transcranial magnetic stimulation over the motor cortex during motor imagery. Subjects were asked to imagine squeezing a foam ball with the right hand (experiment 1) or the left hand (experiment 2), while either holding nothing (Null condition), a ball in the right hand (Right condition) or a ball in the left hand (Left condition). The MEPs amplitude during motor imagery was increased, only when the holding hand and the imagined hand were on the same side. These results suggest that performance improvement and rehabilitation exercises will be more effective when somatosensory stimulation and motor imagery are done on the same side.     

Consistency of abnormal sensory gating in first‐admission and chronic schizophrenia across quantification methods

The auditory P50/M50 ERP/event‐related field is subject to sensory gating, with partial suppression of the amplitude of the second of two (S1 and S2) clicks presented 500 ms apart. Schizophrenia patients have less gating, although quantification methods and associated effect sizes vary across studies using first‐admission and/or using chronic patients. The present study evaluated the impact of several methods of quantifying gating in first‐admission (FA) and chronic (CHR) schizophrenia patients and in healthy controls (HC). Magnetoencephalogram was measured in 35 FA, 58 CHR, and 28 HC during a paired‐click protocol. Sensory gating was quantified on sensor and source levels as a ratio (S2/S1) and as a S1‐minus‐S2 difference, with M50 amplitude scored relative to baseline and relative to M100 and to M40. Independent of quantification method, patients showed less sensory gating than HC, with medium‐to‐large effect sizes, without differences between FA and CHR. Results indicate that the frequently reported sensory gating deficit in schizophrenia is robust to variations in quantification methods and stage of disorder.     

Cross-modal interactions in auditory and visual discrimination.

Three experiments examined auditory-visual interactions using two sensory discrimination paradigms. Experiments 1 and 2 used a one-interval confidence-rating procedure and found modest effects of concurrent visual stimulation on auditory pitch and loudness discrimination, but little effect of auditory stimulation on visual brightness discrimination. The cross-modal interactions could have either a sensory or decisional basis. Experiment 3 used a two-interval same-different procedure and found no effect of visual stimulation on auditory sensitivity in pitch discrimination, and very little effect of auditory stimulation on visual sensitivity in brightness discrimination. Although the ensemble of results could be explained by sensory facilitation and/or inhibition that varies with the behavioral task, the pattern of these and related findings suggests instead that the cross-modal interactions result primarily from relatively late decisional processes (e.g. shifts in response criterion or 'bias').     

Response properties of long-latency event-related potentials evoked during NREM sleep

The experiments reported here sought to investigate whether the K-complex evoked during sleep is comprised of activity from two separate physiological systems with different response properties. To that end, the parameters of stimulation in a two tone auditory 'odd-ball' task were varied systematically as stimuli were presented to subjects during NREM sleep. During experiment 1, the frequency (pitch) of the odd-ball stimulus varied systematically while intensity (loudness) was matched between tones. During experiment 2, pitch was matched between tones while the loudness of the odd-ball stimulus was varied. The long-latency event-related potentials (ERPs) N2 and P3 could be dissociated from the K-complex (N3 and P4) in response to these parametric manipulations. Information processing occurs during sleep, and is reflected in ERPs with a morphology largely analogous to those observed under similar conditions while subjects are awake. The second (K-complex) system is sleep specific. A model was constructed to explain the activity of these two hypothesized systems. As predicted by the model, K-complex latency was longer in Stage 2 when N2 and P3 were also active, than in Stage 4 where N2-P3 activity was lessened. These results support the two-system hypothesis; electrical brain activity evoked during sleep should not be considered a unitary sleep-specific response. Furthermore, the data indicate that the K-complex is sensitive to the physical characteristics of stimuli, that the sleeping brain processes information to a high degree, and that the 'endogenous' components of the ERP observed in awake humans reflect more automatic processes than previously suspected.     

Effects of restraint and haloperidol on sensory gating in the midbrain of awake rats

Deficits in sensory processing have been reported to be associated with an array of neuropsychiatric disorders including schizophrenia. Auditory sensory gating paradigms have been routinely used to test the integrity of inhibitory circuits hypothesized to filter sensory information. Abnormal dopaminergic neurotransmission has been implicated in the expression of schizophrenic symptoms. The aim of this study was to determine if inhibitory gating in response to paired auditory stimuli would occur in putative dopaminergic and non-dopaminergic midbrain neurons. A further goal of this study was to determine if restraint, a classic model of stress known to increase extracellular dopamine levels, and systemic haloperidol injections affected inhibitory mechanisms involved in sensory gating. Neural activity in the rat midbrain was recorded across paired auditory stimuli (first auditory stimulus (S1) and second auditory stimulus (S2)) under resting conditions, during restraint and after systemic haloperidol injections. Under resting conditions, a subset of putative GABA neurons showed fast, gated, short latency responses while putative dopamine neurons showed long, slow responses that were inhibitory and ungated. During restraint, gated responses in putative GABAergic neurons were decreased (increased S2/S1 or ratio of test to conditioning (T/C)) by reducing the response amplitude to S1. Systemic haloperidol decreased the T/C ratio by preferentially increasing response amplitude to S1. The results from this study suggest that individual neurons encode discrete components of the auditory sensory gating paradigm, that phasic midbrain GABAergic responses to S1 may trigger subsequent inhibitory filtering processes, and that these GABAergic responses are sensitive to restraint and systemic haloperidol.     

Frequency‐specific disruptions of neuronal oscillations reveal aberrant auditory processing in schizophrenia

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience‐related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady‐state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1‐s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady‐state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady‐state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady‐state frequency, and reduced amplitude of both M100 and M300 event‐related field components. During the no‐stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.     

Distributed cortical networks for focused auditory attention and distraction

We used behavioral measures and functional magnetic resonance imaging (fMRI) to study the effects of parametrically varied task-irrelevant pitch changes in attended sounds on loudness-discrimination performance and brain activity in cortical surface maps. Ten subjects discriminated tone loudness in sequences that also included infrequent task-irrelevant pitch changes. Consistent with results of previous studies, the task-irrelevant pitch changes impaired performance in the loudness discrimination task. Auditory stimulation, attention-enhanced processing of sounds and motor responding during the loudness discrimination task activated supratemporal (auditory cortex) and inferior parietal areas bilaterally and left-hemisphere (contralateral to the hand used for responding) motor areas. Large pitch changes were associated with right hemisphere supratemporal activations as well as widespread bilateral activations in the frontal lobe and along the intraparietal sulcus. Loudness discrimination and distracting pitch changes activated common areas in the right supratemporal gyrus, left medial frontal cortex, left precentral gyrus, and left inferior parietal cortex.     

Dynamic changes in corticospinal excitability during motor imagery

 We investigated temporal changes in the amplitudes of motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation over the left motor cortex during motor imagery. Nine subjects were instructed to imagine repetitive wrist flexion and extension movements at 1 Hz, in which the flexion timing was cued by a tone signal. Electromyographs (EMGs) were recorded from the first dorsal interosseous, flexor carpi radialis and extensor carpi radialis muscles of the right hand, and magnetic stimulation was delivered at 0, 250, 500 and 750 ms after the auditory cue. On average, the evoked EMG responses were larger in the flexor muscle during the phase of imagined flexion than during extension, whilst the opposite was true for the extensor muscle. There were no consistent changes in the amplitudes of MEPs in the intrinsic hand muscle (first dorsal interosseous). The EMG remained relaxed in all muscles and did not show any significant temporal changes during the test. The H-reflex in the flexor muscle was obtained in four subjects. There was no change in its amplitude during motor imagery. These observations lead us to suggest that motor imagery can have dynamic effects on the excitability of motor cortex similar to those seen during actual motor performance. Received: 23 July 1998 / Accepted: 26 October 1998     

Role of auditory feedback in the control of successive keystrokes during piano playing

The purpose of this study was to elucidate the role of auditory feedback derived from one keystroke in the control of the rhythmicity and velocity of successive keystrokes during piano playing. We examined the effects of transient auditory perturbations with respect to the pitch, loudness, and timing of one tone on subsequent keystrokes while six pianists played short excerpts from three simple musical pieces having different tempi (“event rates”). Immediately after a delay in tone production, the inter-keystroke interval became shorter. This compensatory action depended on the tempo, being most prominent at the medium tempo. This indicates that temporal information provided by auditory feedback is utilized to regulate the timing of movement elements produced in a sequence. We also found that the keystroke velocity changed after the timing, pitch, or loudness of a tone was altered, although the response differed depending on the type of perturbation. While delaying the timing or altering the pitch led to an increase in the velocity, altering the loudness changed the velocity in an inconsistent manner. Furthermore, perturbing a tone elicited by the right hand also affected the rhythmicity and velocity of keystrokes with the left hand, indicating that bimanual coordination of tone production was maintained. Finally, altering the pitch sometimes resulted in striking an incorrect key, mostly in the slow piece, emphasizing the importance of pitch information for accurate planning and execution of sequential piano keystrokes.     

Event-related potential correlates of non-motor anticipation.

A slow negative shift called "stimulus-preceding negativity" (SPN) has been observed preceding feedback. The aim of the present study is to investigate whether the SPN is related to perceptual or conceptual anticipation. Event-related potentials (ERPs) were recorded in an S1-S2-S3 sequence with intervals of 3 s. S1 was an auditory warning signal; the task stimulus presented at S2 consisted of two digits on which subjects (n = 8) performed an arithmetic task. They had to match their solution with a probe stimulus presented at S3. Perceptual anticipation was manipulated by varying the discriminability of S2 (intact vs. degraded). Conceptual anticipation was manipulated by varying the amount of information processing required at S2 (easy vs. difficult arithmetic). Motor preparation was varied by requiring a speeded versus a delayed response. No negativity was found before the task stimulus (S2), whereas the probe stimulus (S3) was always preceded by a negative shift. The amplitude of this negative shift was larger under the speed than under the delayed instruction. Its amplitude showed a left-hemisphere preponderance and was larger for the difficult than for the easy condition. ERPs preceding task stimuli seem to reflect functionally different processes from ERPs preceding probe and feedback stimuli. The difference is explained in terms of motivational factors that come into play with feedback and probably play a role in the anticipation of the probe stimulus.     

Habituation and Dishabituation of the Orienting Reaction to Between and Within Trial Changes in Pitch and Loudness

We investigated the effect of between and within trial changes in pitch and loudness on the electrodermal orienting reaction (OR), perceptions of movement, and their interaction. First, following 20 habituation trials (6-s, 80dB, 1000 Hz), four groups of 10 subjects experienced either an increase or a between-trial decrease in pitch (2000 or 500 Hz) or loudness (90 or 70 dB) on the 21st trial. Second, four additional groups of 20 subjects heard 20 tones that, within each 6-s trial, either increased or decreased in pitch (500 to 2000 or 2000 to 500 Hz) or loudness (70 to 90 or 90 to 70 dB). During a dishabituation phase each group was split into halves having a nonchanging tone either increasing or decreasing relative to mean pitch or loudness. After each session subjects rated whether they perceived tones as approaching, retreating, or motionless. Compared with groups experiencing constant stimuli, groups presented tones changing within trials had greater skin conductance responses that habituated slower irrespective of direction of change or its perception. During dishabituation a similar number of subjects dishabituated to a stimulus increase as compared to a decrease irrespective of whether the change was in pitch or loudness. Perceptions of movement treated as an independent variable did not predict habituation or dishabituation of the OR. The results generally support Sokolov, and are discussed in relation to hypotheses presented by Sokolov, O'Gorman, and Bernstein.     

Attention‐dependent sound offset‐related brain potentials

When performing sensory tasks, knowing the potentially occurring goal‐relevant and irrelevant stimulus events allows the establishment of selective attention sets, which result in enhanced sensory processing of goal‐relevant events. In the auditory modality, such enhancements are reflected in the increased amplitude of the N1 ERP elicited by the onsets of task‐relevant sounds. It has been recently suggested that ERPs to task‐relevant sound offsets are similarly enhanced in a tone‐focused state in comparison to a distracted one. The goal of the present study was to explore the influence of attention on ERPs elicited by sound offsets. ERPs elicited by tones in a duration‐discrimination task were compared to ERPs elicited by the same tones in not‐tone‐focused attentional setting. Tone offsets elicited a consistent, attention‐dependent biphasic (positive‐negative—P1‐N1) ERP waveform for tone durations ranging from 150 to 450 ms. The evidence, however, did not support the notion that the offset‐related ERPs reflected an offset‐specific attention set: The offset‐related ERPs elicited in a duration‐discrimination condition (in which offsets were task relevant) did not significantly differ from those elicited in a pitch‐discrimination condition (in which the offsets were task irrelevant). Although an N2 reflecting the processing of offsets in task‐related terms contributed to the observed waveform, this contribution was separable from the offset‐related P1 and N1. The results demonstrate that when tones are attended, offset‐related ERPs may substantially overlap endogenous ERP activity in the postoffset interval irrespective of tone duration, and attention differences may cause ERP differences in such postoffset intervals.