Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice

We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning.     

Orientation of attention in the visual space]

The display was composed of four boxes, horizontally aligned above the fixation point. In Experiment I, each box was cued by a digit shown at fixation. In Experiment II there were only two numeric cues, signalling the inner or the outer boxes, depending on the experimental condition. The subject was instructed to orient attention to the cued box, and to respond to the imperative stimulus as fast as possible, wherever it appeared. By using four time interval (SOAs), we tried to determine the route covered by attention movements. In Experiment I, with the shortest SOA (100 msec), it was shown that attention does not reach the cued box through a direct path. Rather it moves first on the inner boxes, thereafter focusing on the cued location. The same results were obtained in Experiment II, where the cue directed attention to the inner boxes. When the external boxes were cued, however, this trend was not observed.     

Tactile-spatial and cross-modal attention effects in the second somatosensory and 7b cortical areas of rhesus monkeys

Abstract This study analyzed neuronal responses in the second somatosensory (SII) and 7b cortical areas during a selective attention task. Cues directed attention to one of three simultaneous stimuli: vibrotactile stimuli applied to mirror sites on both hands or to a similarly timed auditory tone. Two stimulus patterns appeared with equal probability for the cued stimulus: a constant amplitude sinewave or the latter with a superimposed brief amplitude pulse midway in the trial. Uncued stimuli always contained amplitude pulses. Monkeys demonstrated whether an amplitude pulse at the cued location was present or absent by making appropriately rewarded up and down foot pedal movements. Cue location and stimulus pattern varied trial-wise and pseudo-randomly. Average firing rates to vibrotactile stimuli in 82 of 181 SII cells and 13 of 22 area 7b cells differed significantly during at least one epoch for trials cued to the contralateral hand when compared to trials cued to the ipsilateral hand or auditory stimulus. Predominant were relatively suppressed firing rates during times prior to the epoch containing the amplitude pulses or enhanced activity during and after these pulses. Generally, different cells showed suppression early vs enhancement later in a trial. Analyses of the ratio between firing rates before and during the amplitude pulses suggested improved evoked signals to the amplitude pulses. The discussion considers attention as a mechanism for reducing distractions, early in the trial through suppressing these signals, or for selectively increasing response magnitudes in the cued channel, especially around times when amplitude pulses were present or absent.     

Effect of age on the orientation of attention: effect of changing the interval between signal and stimulus]

The purpose of the experiment was to examine the effect of aging on spatial attention. One of two possible locations, horizontally arranged, was cued. The subject had to respond to the onset of a visual stimulus, wherever it appeared. The task demand was to orient attention to the stimulated location before producing a response, or to reorient it if the position is not the cued one. Younger and older adults showed the same response pattern, despite the overall slowing down of response presented by the latter.     

Tactile-spatial and cross-modal attention effects in the primary somatosensory cortical areas 3b and 1-2 of rhesus monkeys

Neuronal responses in somatosensory cortical areas 3b and 1-2 (S1) were recorded during an attention task involving cue directed selection of one of three simultaneous stimuli: dual sinewave shaped vibrotactile stimuli applied to mirror sites on both hands or a similarly timed auditory tone. The cued stimulus occurred with one of two equally probable patterns: a constant amplitude vibration or the latter with a superimposed brief sinewave amplitude pulse midway during stimulation. Uncued stimuli always contained amplitude pulses. Two monkeys signaled the absence or presence of an amplitude pulse by appropriately moving a foot pedal up or down. Cues initiated trials by marking the location where the monkey had to discriminate the stimulus pattern. Cue location and stimulus pattern varied randomly per trial. Approximately 50% of cells (44/77 in 3b and 39/77 in 1-2) had significantly different firing rates to stimulation cued to the contralateral hand relative to spatially cuing the ipsilateral hand or cross-modally the auditory stimulus. Relatively suppressed firing rates during times prior to the epoch containing amplitude pulses improved signal-to-noise ratios for responses to amplitude pulses. Instances of significant enhanced activity during and after intervals with amplitude pulses were rare and relative to suppressed activity when cues directed attention to the ipsilateral hand or auditory stimulus. The present findings suggest that attention influences even the earliest stage somatosensory cortical processing. Findings were more modest in S1 than those previously seen in S2 (Burton et al., Somatosens Mot Res 14: 237-267, 1997), which supports the concept of multistage attention processes for touch.     

Spatial cueing,sensory gating and selective response preparation: an ERP study on visuo-spatial orienting

Event-related brain potentials (ERPs) were recorded in a visuo-spatial attention task where the position of an imperative stimulus was indicated either validly or invalidly by a central arrow (trial-by-trial cueing). Subjects had to perform choice RT tasks with the response being dependent either on the identity of the target stimulus or on its position. When target identity was relevant for response selection, validly cued stimuli elicited amplitude enhancements of the early, sensory-evoked P1 and N1 components at lateral posterior sites. The N1 validity effect was limited to scalp sites ipsilateral to the visual field of stimulus presentation. Although these effects were found only when the sensory discrimination task was considerably difficult, they are in line with models assuming that modulations of sensory-perceptual processing (“sensory gating”) are induced by spatial cueing. However, when target location was response-relevant, N1 amplitude enhancements were consistently elicited by invalidly cued letters.CNV and LRP measures indicated that the arrow elicited response-related processing in the cue-target interval. Such processes occurred even when the cue contained no information about an upcoming response. Two consecutive lateralization phases were distinguishable in the LRP, with experimentally induced response assignments becoming effective only during the second phase.     

Meeting report

Neuronal responses in somatosensory cortical areas 3b and 1- 2 (S1) were recorded during an attention task involving cue directed selection of one of three simultaneous stimuli: dual sinewave shaped vibrotactile stimuli applied to mirror sites on both hands or a similarly timed auditory tone. The cued stimulus occurred with one of two equally probable patterns: a constant amplitude vibration or the latter with a superimposed brief sinewave amplitude pulse midway during stimulation. Uncued stimuli always contained amplitude pulses. Two monkeys signaled the absence or presence of an amplitude pulse by appropriately moving a foot pedal up or down. Cues initiated trials by marking the location where the monkey had to discriminate the stimulus pattern. Cue location and stimulus pattern varied randomly per trial. Approximately 50% of cells (44/77 in 3b and 39/77 in 1- 2) had significantly different firing rates to stimulation cued to the contralateral hand relative to spatially cuing the ipsilateral hand or cross-modally the auditory stimulus. Relatively suppressed firing rates during times prior to the epoch containing amplitude pulses improved signal-to-noise ratios for responses to amplitude pulses. Instances of significant enhanced activity during and after intervals with amplitude pulses were rare and relative to suppressed activity when cues directed attention to the ipsilateral hand or auditory stimulus. The present findings suggest that attention influences even the earliest stage somatosensory cortical processing. Findings were more modest in S1 than those previously seen in S2 (Burton et al. , Somatosens Mot Res 14 : 237-267, 1997), which supports the concept of multistage attention processes for touch.     

The effects of cross-modal manipulations of attention on the detection of vibrotactile stimuli in humans

Although it is well known that attention to a visual or auditory stimulus can enhance its perception, less is known concerning the effects of attention on the perception of natural tactile stimuli. The present study was conducted to examine the magnitude of the effect of cross-modal manipulations of attention in human subjects on the detection of weak, low-frequency vibrotactile stimuli delivered to the glabrous skin of the finger pad of the right index finger via an Optacon. Three suprathreshold vibrotactile arrays (40 Hz), varying in the number of activated pegs and hence the area of skin stimulated, were used. Subjects were trained to detect the occurrence of vibrotactile or visual stimuli and to respond by pressing a foot pedal as quickly as possible thereafter. Two instructional lights were used to cue the subjects as to which stimulus modality they should attend, in three experimental conditions. In the first cue condition, the forthcoming stimulus modality was indicated by the illumination of its associated light. In the second cue condition, both instructional lights were illuminated, and the subjects were asked to divide their attention equally between the two modalities. In the third cue condition, the stimulus modality was falsely indicated by the illumination of the cue not associated with the stimulus to be presented. Reaction times (RTs) were calculated for each trial. For each modality, tactile and visual, the RTs varied significantly with the cue condition, with the mean RT changing in a graded manner across the experimental conditions (being shortest for the correctly cued condition, intermediate for the neutrally cued condition, and longest for the incorrectly cued condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Children and Older Adults Exhibit Distinct Sub-Optimal Cost-Benefit Functions when Preparing to Move Their Eyes and Hands

Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented ‘cued’ and ‘non-cued’ conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18–25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation).     

Effects on discrimination performance of selective attention to tactile features

This study examined selective attention to tactile dimensions by combining a selective cueing paradigm with a test of integrality. In Experiment 1, subjects selectively attended to changes in the frequency or duration of pairs of vibrotactile stimuli and identified the higher frequency or longer duration stimulus. In Experiment 2, using surface gratings in an identical experimental procedure, subjects identified the rougher or longer duration stimulus. In both experiments, greater performance accuracy was found on trials where the cue correctly (valid) predicted the changing dimension, vs incorrectly (invalid) cued or no-cue (neutral) trials. More errors on the invalidly vs neutrally cued trials show the cost of focal attention. Increases in performance on validly vs neutrally cued trials show a benefit of filtering irrelevant stimuli in the cued conditions. Results effectively demonstrate focal attention to tactile features. Tests of integrality, in terms of the effects of correlated change in both dimensions, showed no redundancy gain for either vibrotactile or grating tasks, suggesting that frequency and roughness are separable from stimulus duration. Interference of negative correlated change for frequency but not roughness discriminations may be explained by differences in task difficulty.     

Effects on discrimination performance of selective attention to tactile features

This study examined selective attention to tactile dimensions by combining a selective cueing paradigm with a test of integrality. In Experiment 1, subjects selectively attended to changes in the frequency or duration of pairs of vibrotactile stimuli and identified the higher frequency or longer duration stimulus. In Experiment 2, using surface gratings in an identical experimental procedure, subjects identified the rougher or longer duration stimulus. In both experiments, greater performance accuracy was found on trials where the cue correctly (valid) predicted the changing dimension, vs incorrectly (invalid) cued or no-cue (neutral) trials. More errors on the invalidly vs neutrally cued trials show the cost of focal attention. Increases in performance on validly vs neutrally cued trials show a benefit of filtering irrelevant stimuli in the cued conditions. Results effectively demonstrate focal attention to tactile features. Tests of integrality, in terms of the effects of correlated change in both dimensions, showed no redundancy gain for either vibrotactile or grating tasks, suggesting that frequency and roughness are separable from stimulus duration. Interference of negative correlated change for frequency but not roughness discriminations may be explained by differences in task difficulty.     

Mere expectation to move causes attenuation of sensory signals

When a part of the body moves, the sensation evoked by a probe stimulus to that body part is attenuated. Two mechanisms have been proposed to explain this robust and general effect. First, feedforward motor signals may modulate activity evoked by incoming sensory signals. Second, reafferent sensation from body movements may mask the stimulus. Here we delivered probe stimuli to the right index finger just before a cue which instructed subjects to make left or right index finger movements. When left and right cues were equiprobable, we found attenuation for stimuli to the right index finger just before this finger was cued (and subsequently moved). However, there was no attenuation in the right finger just before the left finger was cued. This result suggests that the movement made in response to the cue caused 'postdictive' attenuation of a sensation occurring prior to the cue. In a second experiment, the right cue was more frequent than the left. We now found attenuation in the right index finger even when the left finger was cued and moved. This attenuation linked to a movement that was likely but did not in fact occur, suggests a new expectation-based mechanism, distinct from both feedforward motor signals and postdiction. Our results suggest a new mechanism in motor-sensory interactions in which the motor system tunes the sensory inputs based on expectations about future possible actions that may not, in fact, be implemented.     

The Role of the Caudal Superior Parietal Lobule in Updating Hand Location in Peripheral Vision: Further Evidence from Optic Ataxia

Patients with optic ataxia (OA), who are missing the caudal portion of their superior parietal lobule (SPL), have difficulty performing visually-guided reaches towards extra-foveal targets. Such gaze and hand decoupling also occurs in commonly performed non-standard visuomotor transformations such as the use of a computer mouse. In this study, we test two unilateral OA patients in conditions of 1) a change in the physical location of the visual stimulus relative to the plane of the limb movement, 2) a cue that signals a required limb movement 180° opposite to the cued visual target location, or 3) both of these situations combined. In these non-standard visuomotor transformations, the OA deficit is not observed as the well-documented field-dependent misreach. Instead, OA patients make additional eye movements to update hand and goal location during motor execution in order to complete these slow movements. Overall, the OA patients struggled when having to guide centrifugal movements in peripheral vision, even when they were instructed from visual stimuli that could be foveated. We propose that an intact caudal SPL is crucial for any visuomotor control that involves updating ongoing hand location in space without foveating it, i.e. from peripheral vision, proprioceptive or predictive information.     

Neural Correlates of the Preserved Inhibition of Return in Schizophrenia

Inhibition of return (IOR) is an attentional mechanism that previously has been reported to be either intact or blunted in subjects with schizophrenia (SCZ). In the present study, we explored the neural mechanism of IOR in SCZ by comparing the target-locked N1 and P1 activity evoked by valid-cued trials with that evoked by invalid-cued trials. Twenty-seven schizophrenia patients and nineteen healthy controls participated in a task involving covert orienting of attention with two stimulus onset asynchronies (SOAs: 700 ms and 1200 ms) during which 64-channel EEG data were recorded. Behavioral reaction times (RTs) were longer in response to valid-cued trials than to invalid-cued ones, suggesting an intact IOR in SCZ. However, reduced N1 amplitude elicited by valid-cued trials suggested a stronger inhibition of attention from being oriented to a previously cued location, and therefore a relative inhibition of perceptual processing at that location in SCZ. These results indicate that altered N1 activity is associated with the preservation of IOR in SCZ and could be a sensitive marker to track the IOR effect.     

Allocentric or craniocentric representation of acoustic space: an electrotomography study using mismatch negativity

The world around us appears stable in spite of our constantly moving head, eyes, and body. How this is achieved by our brain is hardly understood and even less so in the auditory domain. Using electroencephalography and the so-called mismatch negativity, we investigated whether auditory space is encoded in an allocentric (referenced to the environment) or craniocentric representation (referenced to the head). Fourteen subjects were presented with noise bursts from loudspeakers in an anechoic environment. Occasionally, subjects were cued to rotate their heads and a deviant sound burst occurred, that deviated from the preceding standard stimulus either in terms of an allocentric or craniocentric frame of reference. We observed a significant mismatch negativity, i.e., a more negative response to deviants with reference to standard stimuli from about 136 to 188 ms after stimulus onset in the craniocentric deviant condition only. Distributed source modeling with sLORETA revealed an involvement of lateral superior temporal gyrus and inferior parietal lobule in the underlying neural processes. These findings suggested a craniocentric, rather than allocentric, representation of auditory space at the level of the mismatch negativity.     

Perceptual organization at attended and unattended locations

This study examined the effects of attention on forming perceptual units by proximity grouping and by uniform connectedness (UC). In Experiment 1 a row of three global letters defined by either proximity or UC was presented at the center of the visual field. Participants were asked to identify the letter in the middle of stimulus arrays while ignoring the flankers. The stimulus onset asynchrony (SOA) between stimulus arrays and masks varied between 180 and 500 ms. We found that responses to targets defined by proximity grouping were slower than to those defined by UC at median SOAs but there were no differences at short or long SOAs. Incongruent flankers slowed responses to targets and this flanker compatibility effect was larger for UC than for proximity-defined flankers. Experiment 2 examined the effects of spatial precueing on discrimination responses to proximity- and UC-defined targets. The advantage for targets defined by UC over targets defined by proximity grouping was greater at uncued relative to cued locations. The results suggest that the advantage for UC over proximity grouping in forming perceptual units is contingent on the stimuli not being fully attended, and that paying attention to the stimuli differentially benefits proximity grouping.     

Perceptual organization at attended and unattended locations

In order to perceive complex visual scenes, the human perceptual system has to organize discrete enti-ties in the visual field into chunks or perceptual units for higher-level processing. Perceptual organization is governed by Gestalt principles such as proximity, similarity, and continuity[1]. Thus spatially close ob-jects tend to be grouped together, as do elements that are similar to one another. Grouping based on the Ge-stalt laws (particularly proximity) is critical for the perception of…     

Preparatory effects of distractor suppression: evidence from visual cortex

Spatial selective attention is the mechanism that facilitates the selection of relevant information over irrelevant information in the visual field. The current study investigated whether foreknowledge of the presence or absence of distractors surrounding an impending target stimulus results in preparatory changes in visual cortex. We cued the location of the target and the presence or absence of distractors surrounding the target while changes in blood oxygen level dependent (BOLD) signals were measured. In line with prior work, we found that top-down spatial attention resulted in an increased contralateral BOLD response, evoked by the cue throughout early visual cortex (areas V1, V2 and V3). In addition, cues indicating distractor presence evoked a substantial increase in the magnitude of the BOLD signal in visual area V3, but not in V2 or V1. This study shows that prior knowledge concerning the presence of a distractor results in enhanced attentional modulation of visual cortex, in visual areas where neuronal receptive fields are large enough to encompass both targets and distractors. We interpret these findings as evidence that top-down attentional control processes include active preparatory suppression mechanisms for irrelevant, distracting information in the visual scene.     

Behavioral,Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.     

Temporal synchrony and integration of sub-threshold taste and smell signals

The importance of stimulus timing and location on the perceptual integration of taste and odour was studied based on a sub-threshold methodology. From a panel of 16 people, 12 showed the integration effect previously reported while 4 showed no effect. The experiment was repeated using retronasal and orthonasal delivery of the odour and with tastant present or absent in the mouth. Integration of taste and odour only occurred when both stimuli were present at the same time. Retro- or orthonasal presentation both produced integration providing that tastant delivery was synchronous but the threshold values for the two presentation methods were different. The relevance of these findings to flavour perception under realistic conditions is considered.