Cerebellum,temporal predictability and the updating of a mental model

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form (‘what’) and stimulus occurrence (‘when’). Consequently, behaviour is optimal when we can anticipate both the ‘what’ and ‘when’ dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention.     

Task difficulty,probability, and inter-stimulus interval as determinants of P300 from auditory stimuli

The P300 event-related potential was elicited with auditory stimuli in 4 experiments which manipulated combinations of stimulus target probability (10% vs. 30%), task difficulty (easy vs. hard), and inter-stimulus interval (5 sec vs. 2 sec). P300 amplitude was smaller and peak latency longer for the more difficult relative to the easier tasks across experiments. Increases in stimulus target probability generally diminished P300 amplitude and shortened peak latency more for the easy relative to difficult task conditions. Increasing the number of non-target stimulus tones decreased P300 amplitude reliably, but increased latency only slightly. Task difficulty did not interact with variations in inter-stimulus interval which produced generally weak effects for both amplitude and latency. These findings suggests that P300 amplitude and latency obtained from auditory discrimination paradigms reflect processing difficulty independently of stimulus target probability unless differences in task requirements affect stimulus encoding.     

Functionally independent components of early event-related potentials in a visual spatial attention task.

Spatial visual attention modulates the first negative-going deflection in the human averaged event-related potential (ERP) in response to visual target and non-target stimuli (the N1 complex). Here we demonstrate a decomposition of N1 into functionally independent subcomponents with functionally distinct relations to task and stimulus conditions. ERPs were collected from 20 subjects in response to visual target and non-target stimuli presented at five attended and non-attended screen locations. Independent component analysis, a new method for blind source separation, was trained simultaneously on 500 ms grand average responses from all 25 stimulus-attention conditions and decomposed the non-target N1 complexes into five spatially fixed, temporally independent and physiologically plausible components. Activity of an early, laterally symmetrical component pair (N1aR and N1aL) was evoked by the left and right visual field stimuli, respectively. Component N1aR peaked ca. 9 ms earlier than N1aL. Central stimuli evoked both components with the same peak latency difference, producing a bilateral scalp distribution. The amplitudes of these components were no reliably augmented by spatial attention. Stimuli in the right visual field evoked activity in a spatio-temporally overlapping bilateral component (N1b) that peaked at ca. 180 ms and was strongly enhanced by attention. Stimuli presented at unattended locations evoked a fourth component (P2a) peaking near 240 ms. A fifth component (P3f) was evoked only by targets presented in either visual field. The distinct response patterns of these components across the array of stimulus and attention conditions suggest that they reflect activity in functionally independent brain systems involved in processing attended and unattended visuospatial events.     

P300 from a single auditory stimulus

The P3(00) event-related brain potential (ERP) was elicited with auditory stimuli to compare 2 different discrimination tasks. The oddball paradigm presented both target and standard tones; the single-stimulus paradigm presented at target but no standard tone stimulus. Experiment 1 manipulated target stimulus probability (0.20, 0.50, 0.80) and produced highly similar P3 amplitude and latency results across probability levels for each paradigm. Experiment 2 factorially varied inter-stimulus interval (2 sec, 6 sec) and target stimulus probability (0.20, 0.80). P3 amplitude and latency were highly similar for both the oddball and single-stimulus procedures across all conditions.     

ERPs to stimuli requiring response production and inhibition: effects of age,probability and visual noise

Sixty-six normal adults ranging in age from 20 to 85 years were presented with stimuli containing explicit instructions to initiate or to inhibit a motor response (the words ‘push’ or ‘wait’). In one task, the effect of stimulus probability was investigated by varying probability between 0.25 and 0.75 for both Go and No-go stimuli. In another task, the effect of visual noise was investigated by degrading the stimuli with ampersands on half of the trials. Regression analysis was used to examine the effects of age on P3 amplitude and latency for each stimulus type. The effects of stimulus variables on P3, independent of age, were examined by standardizing each subject's data to those expected for a 20 year old.P3 latency to all stimuli and RT to Go stimuli increased with age. The latency of P3s to No-go stimuli was less sensitive to age than Go stimuli. P3 amplitude at Cz and Pz (but not Fz) diminished with age. P3s to Go stimuli were maximal at Pz and earlier than P3s to No-go stimuli. P3s to No-go stimuli were maximal at Cz. These differences between Go and No-go stimuli remained true under visual noise and probability manipulations. Visual noise prolonged the latency of Go and No-go P3. Less probable Go and No-go stimuli elicited larger and later P3s than more probable stimuli. Decreasing the probability of the No-go stimulus enhanced its central distribution.     

Visual and somatosensory event-related brain potentials in autistic children and three different control groups

Event-related potentials (ERPs) to visual and somatosensory stimuli, generated during an oddball task, were obtained in a group of autistic children and 3 control groups (normal, attention-deficit, and dyslectic children, respectively). The task included the presentation of standard, deviant, and novel stimuli and had a (between-group) passive vs. active (counting) condition. Research questions were whether (a) autistic children differ from other children with respect to the processing of visual and/or somatosensory stimuli, as measured in the amplitude of the N1, mismatch activity, and P3, (b) autistic children specifically have problems in the processing in distal (visual) stimuli, compared to the processing of proximal (somatosensory) stimuli, and (c) autistic children have an atypical lateralization pattern of ERP activity. Only in the autistic group a task effect on the visual P2N2 (mismatch activity) and larger P3s to novels than to deviants were found, in both the visual and the somatosensory modality. There also was a smaller occipital P3 to visual standard stimuli in the passive condition in the autistic group than in 2 control groups. We concluded that autistics (a) differ from several other groups of children with respect to the visual P2N2 and the visual and somatosensory P3, (b) show abnormalities in the processing of both proximal and distal stimuli, and (c) show no indication of abnormal lateralization of ERPs.     

Evoked potentials in the brain of adolescents in norm and those with attention deficit during recognition of short-term acoustic stimuli

The effect of stimulus duration on auditory event-related potentials and performance of oddball task was studied in normal children and those with attention-deficit symptoms. Mismatch negativity was absent on presentation of short-term (11 ms) stimuli and present with longer stimuli (50 ms). The adolescents with deficit of attention performed much worse (errors of omission) with the short stimuli. The RT was significantly larger in subjects with attention-deficit with all types of tested stimulus duration. They also manifested a smaller P3b amplitude in response to task-relevant deviant stimuli and larger N2b peaks in response to the standard stimuli. It was possible to differentiate between the MMN and the N2b components owing to the fact that the MMN was absent with shorter stimuli. The findings suggest that there is a deficit in processing of sensory information at the cortical level in subjects with the attention-deficit symptoms.     

Topographic analysis of auditory event-related potentials associated with acoustic and semantic processing

The topography of auditory event-related potentials (ERPs) was examined during 3 kinds of tasks: selection of a specified real word or nonsense syllable from a list; simple detection of each of the same stimuli without discrimination; and classification of a set of words according to a specified semantic category. The potentials that were associated with the additional processing required by the discriminative tasks were disclosed by subtracting the wave forms obtained in the detection condition from those obtained during discriminative performance. Difference wave forms were also derived between the semantic classification and verbal discriminative ERP to delineate the changes associated with the extraction of word meaning.The topography of the ERP associated with stimulus detection was comparable to that found in previous studies of evoked potentials to non-speech stimuli. This distribution was consistent with 2 cortical generators, one within the supratemporal plane and the other on the lateral surface of the superior temporal gyrus. When discriminative performance was required on the basis of acoustic stimulus properties, the topography of the difference wave form that reflected this discriminative processing extended more posteriorly over temporal cortex. Semantic processing elicited a further posterior extension of ERP components by 330 msec after stimulus onset, as well as longer latency potentials that were not present in the verbal selection task. These differences imply that a more extensive portion of language cortex is engaged in semantic classification than in verbal identification.     

Pain-related and cognitive components of somatosensory evoked potentials following CO2 laser stimulation in man

We recorded cortical potentials evoked by painful CO₂ laser stimulation (pain SEP), employing an oddball paradigm in an effort to demonstrate event-related potentials (ERP) associated with pain. In 12 healthy subjects, frequent (standard) pain stimuli (probability 0.8) were delivered to one side of the dorsum of the left hand while rare (target) pain stimuli (probability 0.2) were delivered to the other side of the same hand. Subjects were instructed to perform either a mental count or button press in response to the target stimuli. Two early components (N2 and P2) of the pain SEP demonstrated a Cz maximal distribution, and showed no difference in latency, amplitude or scalp topography between the oddball conditions or between response tasks. In addition, another positive component (P3) following the P2 was recorded maximally at Pz only in response to the target stimuli with a peak latency of 593 msec for the count task and 560 msec for the button press task. Its scalp topography was the same as that for electric and auditory P3. The longer latency of pain P3 can be explained not only by its slower impulse conduction but also by the effects of task difficulty in the oddball paradigm employing the pain stimulus compared with electric and auditory stimulus paradigms. It is concluded that the P3 for the pain modality is mainly related to a cognitive process and corresponds to the P3 of electric and auditory evoked responses, whereas both N2 and P2 are mainly pain-related components.     

Event-related Potential Study of Novelty Processing Abnormalities in Autism

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.     

Spike generating dynamics and the conditions for spike-time precision in cortical neurons

Temporal precision of spiking response in cortical neurons has been a subject of intense debate. Using a canonical model of spike generation, we explore the conditions for precise and reliable spike timing in the presence of Gaussian white noise. In agreement with previous results we find that constant stimuli lead to imprecise timing, while aperiodic stimuli yield precise spike timing. Under constant stimulus the neuron is a noise perturbed oscillator, the spike times follow renewal statistics and are imprecise. Under an aperiodic stimulus sequence, the neuron acts as a threshold element; the firing times are precisely determined by the dynamics of the stimulus. We further study the dependence of spike-time precision on the input stimulus frequency and find a non-linear tuning whose width can be related to the locking modes of the neuron. We conclude that viewing the neuron as a non-linear oscillator is the key for understanding spike-time precision.     

Electrophysiologic study of the reactions of the brain to regular and skipped acoustic stimuli in man

Human electrical cerebral reactions to acoustic stimuli and to their omission at fixed moments of a restricted rhythmic sequence repeatedly presented in conditions of distraction and attraction of attention to stimuli, were recorded on the vertex. By special methods of bioelectrical signals processing on a computer, the potentials are singled out in response to stimulus omission (SO) with each set ordinal number, which, as well as the potentials, evoked by the actual stimulus (AS), possessed a main negative-positive complex N1P2. In conditions of attention distraction, the negative component of this complex had a latency of 144 ms and the positive one--about 207 ms. In the situation of the attraction of attention to stimuli a decrease of N1 latency up to 125 ms, took place, as well as complication of SO configuration due to the appearance of a later positive oscillation with a latency of about 560 ms, and parametres stabilization of SO as a whole. The analogous dynamics of N1 latency was characteristic of AS in both situations. The mechanisms of SO formation are discussed in connection with trace processes in the central nervous system.     

P300 in young and elderly subjects: Auditory frequency and intensity effects

Auditory event-related potentials (ERPs) were assessed in young and elderly subjects when stimulus intensity (40 vs. 60 dB SL) and standard/target tone frequency (250/500 Hz and 1000/2000 Hz) were manipulated to study the effects of these variables on the P3(00) and N1, P2 and N2 components. Auditory thresholds for each stimulus type were obtained, and the stimulus intensity was adjusted to effect perceptually equal intensities across conditions for each subject. Younger subjects demonstrated larger P3 amplitudes and shorter latencies than elderly subjects. The low frequency stimuli produced larger P3 amplitude and shorter latencies than the high frequency stimuli. Low intensity stimuli yielded somewhat smaller P3 amplitudes and longer peak latencies than high intensity stimulus tones. Although additional stimulus intensity and frequency effects were obtained for the N1, P2 and N2 components, these generally differed relatively little with subject age. The findings suggest that auditory stimulus parameters contribute to P3 measures, which are different for young compared to elderly subjects.     

Introducing the Event Related Fixed Interval Area (ERFIA) Multilevel Technique: a Method to Analyze the Complete Epoch of Event-Related Potentials at Single Trial Level

In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on this assumption, we introduce a new concept which allows for flexible investigation of the whole epoch and does not primarily focus on peaks and their corresponding latencies. For each trial, the entire epoch is partitioned into event-related fixed-interval areas under the curve (ERFIAs). These ERFIAs, obtained at single trial level, act as dependent variables in a multilevel random regression analysis. The ERFIA multilevel method was tested in an existing ERP dataset of 85 healthy subjects, who underwent a rating paradigm of 150 painful and non-painful somatosensory electrical stimuli. We modeled the variability of each consecutive ERFIA with a set of predictor variables among which were stimulus intensity and stimulus number. Furthermore, we corrected for latency variations of the P2 (260 ms). With respect to known relationships between stimulus intensity, habituation, and pain-related somatosensory ERP, the ERFIA method generated highly comparable results to those of commonly used methods. Notably, effects on stimulus intensity and habituation were also observed in non-peak-related latency ranges. Further, cortical processing of actual stimulus intensity depended on the intensity of the previous stimulus, which may reflect pain-memory processing. In conclusion, the ERFIA multilevel method is a promising tool that can be used to study event-related cortical processing.     

Implicit Versus Explicit Local Contextual Processing

We investigated the effects of implicit local contextual processing using behavioral and electrophysiological measures. EEG recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a predictive sequence signaling the occurrence of a target event. Subjects performed two sessions: in the first the regularity of the predictive sequence was implicit, while in the second this regularity was made explicit. Subjects pressed a button in response to targets. Both the implicit and explicit sessions showed shorter reaction times and peak P3b latencies for predicted versus random targets, although to a greater extent in the explicit session. In both sessions the middle and last most-informative stimuli of the three-standard predictive sequence induced a significant larger P3b compared with randomized standards. The findings show that local contextual information is processed implicitly, but that this modulation was significantly greater when subjects were explicitly instructed to attend to target-predictive contextual information. The findings suggest that top-down attentional networks have a role in modulating the extent to which contextual information is utilized.     

Neural Mechanisms of Selective Attention in Children with Amblyopia

Previous studies have indicated that amblyopia might affect children''s attention. We recruited amblyopic children and normal children aged 9–11 years as study subjects and compared selective attention between the two groups of children. Chinese characters denoting colors were used in the Stroop task, and the event-related potential (ERP) was analyzed. The results show that the accuracy of both groups in the congruent condition was higher than the incongruent condition, and the reaction time (RT) of amblyopic children was longer. The latency of the occipital P1 in the incongruent condition was shorter than the neutral condition for both groups; the peak of the occipital P1 elicited by the incongruent stimuli in amblyopic children was higher. In both groups, the N1 peak was higher in the occipital region than frontal and central regions. The N1 latency of normal children was shorter in the congruent and neutral conditions and longer in the incongruent condition; the N1 peak of normal children was higher. The N270 latencies of normal children in the congruent and neutral conditions were shorter; the N270 peak was higher in parietal and occipital regions than frontal and central regions for both groups. The N450 latency of normal children was shorter; in both groups, the N450 average amplitude was significantly higher in the parietal region than central and frontal regions. The accuracy was the same for both groups, but the response of amblyopic children was significantly slower. The two groups showed differences in both stages of the Stroop task. Normal children showed advantages in processing speed on both stimulus and response conflict stages.Brain regions activated during the Stroop task were consistent between groups, in line with their age characteristics.     

Timing Rhythms: Perceived Duration Increases with a Predictable Temporal Structure of Short Interval Fillers

Variations in the temporal structure of an interval can lead to remarkable differences in perceived duration. For example, it has previously been shown that isochronous intervals, that is, intervals filled with temporally regular stimuli, are perceived to last longer than intervals left empty or filled with randomly timed stimuli. Characterizing the extent of such distortions is crucial to understanding how duration perception works. One account to explain effects of temporal structure is a non-linear accumulator-counter mechanism reset at the beginning of every subinterval. An alternative explanation based on entrainment to regular stimulation posits that the neural response to each filler stimulus in an isochronous sequence is amplified and a higher neural response may lead to an overestimation of duration. If entrainment is the key that generates response amplification and the distortions in perceived duration, then any form of predictability in the temporal structure of interval fillers should lead to the perception of an interval that lasts longer than a randomly filled one. The present experiments confirm that intervals filled with fully predictable rhythmically grouped stimuli lead to longer perceived duration than anisochronous intervals. No general over- or underestimation is registered for rhythmically grouped compared to isochronous intervals. However, we find that the number of stimuli in each group composing the rhythm also influences perceived duration. Implications of these findings for a non-linear clock model as well as a neural response magnitude account of perceived duration are discussed.     

Mismatch field to tone pairs: neuromagnetic evidence for temporal integration at the sensory level

The mismatch field (MMF) to minor pitch changes in two experimental conditions was studied. Standard tones of 1000 Hz and deviant tones of 1050 Hz both of 50 ms duration were delivered in single tone condition. Paired tones of the same duration were used in the paired tone condition. The standard tone pair consisted of two 1000 Hz tones, whereas the deviant tone pair was composed of a 1000 Hz tone in the first position and a 1050 Hz tone in the second position with a silent interval of 15 ms between the two. Standards of 90% and deviants of 10% probability were presented in random order and with a randomized interstimulus interval between 600 and 900 ms. The source analysis showed a more lateral location for the MMF obtained in the paired tone condition (MMF.P) compared to the MMF elicited by the single deviants (MMF.S). The source location of both the MMF.P and MMF.S turned out to be significantly anterior relative to the sources of the M100. The increased stimulus repetition in the paired tone condition (two times more stimuli than in the single tone condition) lead to a strong suppression of the field amplitude and of the dipole moment of the M100, while this effect could not be seen for the MMF. The data demonstrate a fundamental difference between the processes reflected by the M100 and the MMF: while the M100 represents the processing of every individual tone, the MMF reflects the change detection of the paired stimuli as unitary events, forming a perceptual group. The different sources of the MMF.P and MMF.S also support an integrated processing of the paired stimuli.     

Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37–51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.