Short Interstimulus Intervals Research Articles

A Method for Investigating Change Blindness in Pigeons (Columba Livia).

Change blindness is a phenomenon of visual attention, whereby changes to a visual display go unnoticed under certain specific circumstances. While many laboratory procedures have been developed that produce change blindness in humans, the flicker paradigm has emerged as a particularly effective method. In the flicker paradigm, two visual displays are presented in alternation with one another. If successive displays are separated by a short inter-stimulus interval (ISI), change detection is impaired. The simplicity of the procedure and the clear, performance-based operational definition of change blindness make the flicker paradigm well-suited to comparative research using nonhuman animals. Indeed, a variant has been developed that can be implemented in operant chambers to study change blindness in pigeons. Results indicate that pigeons, like humans, are worse at detecting the location of a change if two consecutive displays are separated in time by a blank ISI. Furthermore, pigeons' change detection is consistent with an active, location-by-location search process that requires selective attention. The flicker task thus has the potential to contribute to investigations of the dynamics of pigeons' selective spatial attention in comparison to humans. It also illustrates that the phenomenon of change blindness is not exclusive to humans' visual perception, but may instead be a general consequence of selective attention. Finally, while the useful aspects of attention are widely appreciated and understood, it is also important to acknowledge that they may be accompanied by specific imperfections such as change blindness, and that these imperfections have consequences across a wide range of contexts.

Selection for encoding: No evidence of better endogenous orienting following forget than following remember instructions.

In an item-method directedforgetting task, attentional resources are withdrawn from forget item processing (e.g., Taylor & Fawcett in Attention, Perception, & Psychophysics, 73, 1790-1814, 2011). Taylor and Hamm (Attention, Perception, & Psychophysics, 78, 168-186, 2016) demonstrated that there is no corresponding increase in the proclivity for exogenous attention to be captured following a forget instruction. This means either that the attentional resources withdrawn from the forget item are reallocated immediately (and therefore not especially vulnerable to capture) or that it is not exogenous attention thatis withdrawn. Given that endogenous attention is distinct from exogenous attention, we therefore extended the Taylor and Hamm study by using endogenous orientingrather than exogenous orienting. Words appeared individually in a peripheral location (Exp. 1) or ina central location (Exp. 2), followed by an instruction to either remember or forget. After a short (50-ms) or long (250-ms) interstimulus interval (ISI), a central cue (80% accurate) directed participants to allocate their attention to the left or right. This was followed by a discrimination target that appeared at a 1,000-ms cue-target stimulus onset asynchrony. A subsequent yes-no recognition test assessed memory for all study items. In both experiments, we observed better recognition of remember wordsthan forget words-a directedforgetting effect. We also found a cueing effect, revealed as faster reaction times to discriminate cued targetsthan to discriminate uncued targets. There was not, however, an effect of memory instruction (and/or instruction-cue ISI) on the magnitude of this cueing effect. Thus, neither exogenous attentionnor endogenous attention remains in an unengaged state following an instruction to forget.

GABAergic and cholinergic modulation of repetition suppression in inferior temporal cortex

Neurons in many brain areas of different species reduce their response when a stimulus is repeated. Such adaptation or repetition suppression is prevalent in inferior temporal (IT) cortex. The mechanisms underlying repetition suppression in IT are still poorly understood. Studies in rodents and in-vitro experiments suggest that acetylcholine and GABA can contribute to repetition suppression by interacting with fatigue-related or local adaptation mechanisms. Here, we examined the contribution of cholinergic and GABAergic mechanisms to repetition suppression in macaque IT, using an adaptation paradigm in which familiar images were presented successively with a short interstimulus interval. We found that intracortical local injections of acetylcholine and of the GABAA receptor antagonist Gabazine both increased repetition suppression in awake macaque IT. The increased repetition suppression was observed for both spiking activity and local field potential power. The latter was present mainly for frequencies below 50 Hz, spectral bands that typically do not show consistent repetition suppression in IT. Although increased with drug application, repetition suppression remained stimulus selective. These findings agree with the hypothesis that repetition suppression of IT neurons mainly results from suppressed input from upstream and other IT neurons but depend less on intrinsic neuronal fatigue.

Peter H. Venables (1923–2017)

Peter H. Venables (1923–2017)

Training-Induced Changes in Rapid Auditory Processing in Children With Specific Language Impairment: Electrophysiological Indicators.

The brain’s ability to recognize acoustic changes occurring in rapid temporal succession is important for speech and successful language development. Children with specific language impairment (SLI) are characterized by deficient dynamics of temporal information processing (TIP) in the millisecond time range accompanied by disordered language development. Furthermore, previous studies have found that intervention based on amelioration of TIP resulted in improvement of both language and other cognitive functions. This study aimed to explain the changes associated with TIP training from the perspective of event-related potentials (ERPs). Thirty-six children aged 5–8 years (26 boys, 10 girls) diagnosed with SLI underwent two types of intense audio-visual computer intervention: experimental TIP training targeted at the millisecond time range (n = 18) or control non-TIP training (n = 18). Paired 50 ms tones of 1000 Hz and 1200 Hz were presented with inter-stimulus intervals (ISIs) of either 50 ms (Short ISI Condition) or 200 ms (Long ISI Condition). Auditory ERPs were measured in a passive oddball paradigm before and after each type of training. The mismatch negativity (MMN) paradigm was applied as an electrophysiological indicator of the brain’s ability to automatically detect violations of regularity in paired tones presented in rapid succession. Moreover, the P3a component was also analyzed. After 24 sessions of temporal training (in the experimental group) MMN amplitude enhancement was observed in both ISI conditions, reflecting increased efficiency in perceiving changes in rapid auditory sequences. In both experimental and control groups, P3a amplitude was enhanced in both ISIs. This may be due to the improvement of involuntary attention shifting to the auditory events involved in each training type. To conclude, temporal training, compared to non-temporal control training, improved the ability to detect changes in a rapid auditory stream in children with SLI.

A reappraisal of pain-paired associative stimulation suggesting motor inhibition at spinal level

Paired associative stimulation (PAS) can modulate motor excitability and consists of delivering repeated pairs of peripheral sensory stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral motor cortex. Our objective was to evaluate the effect of a PAS protocol using a painful stimulation. Ten healthy volunteers underwent pain-PAS protocol consisting of 90 pairs of nociceptive stimulus over the right hand followed by an image-guided navigated TMS of the contralateral motor cortex, delivered at 0.1Hz over 15minutes. Four distinct inter-stimuli intervals (ISI) were assessed: -40ms, +10ms, +30ms and +50ms with respect to the individual pain-related evoked potential (N2 latency). The impact of pain-PAS was assessed by measuring motor evoked potentials (MEPs) amplitudes before and up to 30minutes after the pain-PAS procedure. For the "N2 latency -40ms" ISI condition, a significant decrease of MEP amplitude was observed in the immediate post-pain-PAS period. For longer ISIs, no significant changes were observed. A motor inhibition effect was produced by repetitive pairs of painful peripheral stimulation and TMS pulse delivered to the motor cortex before the afferent volley reaches the somatosensory cortex. This short ISI falls into a period of time corresponding to the cutaneous silent period, suggesting that the motor inhibition effect produced by pain-PAS could occur at spinal level. The repeated interaction of the nociceptive afferent input and the descending motor corticospinal volley could lead to reduced excitability of homonymous spinal motoneurons.

The impact of auditory white noise on semantic priming

It has been proposed that white noise can improve cognitive performance for some individuals, particularly those with lower attention, and that this effect may be mediated by dopaminergic circuitry. Given existing evidence that semantic priming is modulated by dopamine, this study investigated whether white noise can facilitate semantic priming. Seventy-eight adults completed an auditory semantic priming task with and without white noise, at either a short or long inter-stimulus interval (ISI). Measures of both direct and indirect semantic priming were examined. Analysis of the results revealed significant direct and indirect priming effects at each ISI in noise and silence, however noise significantly reduced the magnitude of indirect priming. Analyses of subgroups with higher versus lower attention revealed a reduction to indirect priming in noise relative to silence for participants with lower executive and orienting attention. These findings suggest that white noise focuses automatic spreading activation, which may be driven by modulation of dopaminergic circuitry.

Dissociable effects of inter-stimulus interval and presentation duration on rapid face categorization

Fast periodic visual stimulation combined with electroencephalography (FPVS-EEG) has unique sensitivity and objectivity in measuring rapid visual categorization processes. It constrains image processing time by presenting stimuli rapidly through brief stimulus presentation durations and short inter-stimulus intervals. However, the selective impact of these temporal parameters on visual categorization is largely unknown. Here, we presented natural images of objects at a rate of 10 or 20 per second (10 or 20 Hz), with faces appearing once per second (1 Hz), leading to two distinct frequency-tagged EEG responses. Twelve observers were tested with three squarewave image presentation conditions: 1) with an ISI, a traditional 50% duty cycle at 10 Hz (50-ms stimulus duration separated by a 50-ms ISI); 2) removing the ISI and matching the rate, a 100% duty cycle at 10 Hz (100-ms duration with 0-ms ISI); 3) removing the ISI and matching the stimulus presentation duration, a 100% duty cycle at 20 Hz (50-ms duration with 0-ms ISI). The face categorization response was significantly decreased in the 20 Hz 100% condition. The conditions at 10 Hz showed similar face-categorization responses, peaking maximally over the right occipito-temporal (ROT) cortex. However, the onset of the 10 Hz 100% response was delayed by about 20 ms over the ROT region relative to the 10 Hz 50% condition, likely due to immediate forward-masking by preceding images. Taken together, these results help to interpret how the FPVS-EEG paradigm sets temporal constraints on visual image categorization.

The Duration of Auditory Sensory Memory for Vowel Processing: Neurophysiological and Behavioral Measures.

Speech perception behavioral research suggests that rates of sensory memory decay are dependent on stimulus properties at more than one level (e.g., acoustic level, phonemic level). The neurophysiology of sensory memory decay rate has rarely been examined in the context of speech processing. In a lexical tone study, we showed that long-term memory representation of lexical tone slows the decay rate of sensory memory for these tones. Here, we tested the hypothesis that long-term memory representation of vowels slows the rate of auditory sensory memory decay in a similar way to that of lexical tone. Event-related potential (ERP) responses were recorded to Mandarin non-words contrasting the vowels /i/ vs. /u/ and /y/ vs. /u/ from first-language (L1) Mandarin and L1 American English participants under short and long interstimulus interval (ISI) conditions (short ISI: an average of 575 ms, long ISI: an average of 2675 ms). Results revealed poorer discrimination of the vowel contrasts for English listeners than Mandarin listeners, but with different patterns for behavioral perception and neural discrimination. As predicted, English listeners showed the poorest discrimination and identification for the vowel contrast /y/ vs. /u/, and poorer performance in the long ISI condition. In contrast to Yu et al. (2017), however, we found no effect of ISI reflected in the neural responses, specifically the mismatch negativity (MMN), P3a and late negativity ERP amplitudes. We did see a language group effect, with Mandarin listeners generally showing larger MMN and English listeners showing larger P3a. The behavioral results revealed that native language experience plays a role in echoic sensory memory trace maintenance, but the failure to find an effect of ISI on the ERP results suggests that vowel and lexical tone memory traces decay at different rates.Highlights:We examined the interaction between auditory sensory memory decay and language experience.We compared MMN, P3a, LN and behavioral responses in short vs. long interstimulus intervals.We found that different from lexical tone contrast, MMN, P3a, and LN changes to vowel contrasts are not influenced by lengthening the ISI to 2.6 s.We also found that the English listeners discriminated the non-native vowel contrast with lower accuracy under the long ISI condition.

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia.

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100–250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer’s dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (β = 0.38, p = 0.003; β = −0.27, p = 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (β = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia.

Computational study of depth completion consistent with human bi-stable perception for ambiguous figures

We propose a computational model that is consistent with human perception of depth in “ambiguous regions,” in which no binocular disparity exists. Results obtained from our model reveal a new characteristic of depth perception. Random dot stereograms (RDS) are often used as examples because RDS provides sufficient disparity for depth calculation. A simple question confronts us: “How can we estimate the depth of a no-texture image region, such as one on white paper?” In such ambiguous regions, mathematical solutions related to binocular disparities are not unique or indefinite. We examine a mathematical description of depth completion that is consistent with human perception of depth for ambiguous regions. Using computer simulation, we demonstrate that resultant depth-maps qualitatively reproduce human depth perception of two kinds. The resultant depth maps produced using our model depend on the initial depth in the ambiguous region. Considering this dependence from psychological viewpoints, we conjecture that humans perceive completed surfaces that are affected by prior-stimuli corresponding to the initial condition of depth. We conducted psychological experiments to verify the model prediction. An ambiguous stimulus was presented after a prior stimulus removed ambiguity. The inter-stimulus interval (ISI) was inserted between the prior stimulus and post-stimulus. Results show that correlation of perception between the prior stimulus and post-stimulus depends on the ISI duration. Correlation is positive, negative, and nearly zero in the respective cases of short (0–200 ms), medium (200–400 ms), and long ISI (>400 ms). Furthermore, based on our model, we propose a computational model that can explain the dependence.

Syringaresinol suppresses excitatory synaptic transmission and picrotoxin-induced epileptic activity in the hippocampus through presynaptic mechanisms

Many neuromodulating drugs acting on the nervous system originate from botanical sources. These plant-derived substances modulate the activity of receptors, ion channels, or transporters in neurons. Their properties make the substances useful for medicine and research. Here, we show that the plant lignan (+)-syringaresinol (SYR) suppresses excitatory synaptic transmission via presynaptic modulation. Bath application of SYR rapidly reduced the slopes of the field excitatory postsynaptic potentials (fEPSPs) at the hippocampal Schaffer collateral (SC)-CA1 synapse in a dose-dependent manner. SYR preferentially affected excitatory synapses, while inhibitory synaptic transmission remained unchanged. SYR had no effect on the conductance or the desensitization of AMPARs but increased the paired-pulse ratios of synaptic responses at short (20–200 ms) inter-stimulus intervals. These presynaptic changes were accompanied by a reduction of the readily releasable pool size. Pretreatment of hippocampal slices with the Gi/o protein inhibitor N-ethylmaleimide (NEM) abolished the effect of SYR on excitatory synaptic transmission, while the application of SYR significantly decreased Ca2+ currents and hyperpolarized the resting membrane potentials of hippocampal neurons. In addition, SYR suppressed picrotoxin-induced epileptiform activity in hippocampal slices. Overall, our study identifies SYR as a new neuromodulating agent and suggests that SYR suppresses excitatory synaptic transmission by modulating presynaptic transmitter release.

Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study.

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.

P 160 Temporal discrimination and temporal discrimination motor thresholds – association with age, proprioception, and polyneuropathy

Introduction Temporal discrimination threshold (TDT) and temporal motor discrimination threshold (TMDT) are measures of somatosensory processing indicating the shortest time interval at which two stimuli applied to skin or muscle, respectively, are detected to be asynchronous. TDT and/or TDMT have been shown to be increased in patients with movement disorders, like essential tremor, dystonia, or Parkinson”s disease. However, the meaning of these findings is still quite unclear. Here, we assessed the association of TDT and TDMT with age, proprioception, and polyneuropathy (PNP). Materials and methods 54 healthy subjects (age 29–75 years) and 15 patients with neurophysiologically confirmed PNP were included. TDT was tested with surface electrodes placed over thenar or dorsal foot region, respectively. TDMT was measured via an insulated tungsten needle microelectrode inserted at the motor point of flexor carpi radialis (FCR) or tibialis anterior (TA) muscle. Pairs of subsequent electric stimuli with varying interstimulus intervals (ISI) were provided, and discrimination thresholds were defined as the shortest ISI at which subjects were able to identify two separate stimuli. Proprioception of upper and lower limbs was assessed by custom-built devices, basically consisting of a goniometer without direct visual feedback of the respective extremity and its movements (flexion/extension). Subjects were instructed (i) to point to LED markers attached to the outside of the device, (ii) to move in proportion to arrows of different length shown on a computer screen, and (iii) to estimate their limb position after passive hand movements. Part of the assessment was conducted under dual task condition (tone-counting task). Pointing (or estimation) error (in degree) was taken as a measure of proprioceptive performance. Results In healthy subjects higher age was associated with higher TDT in every tested condition (right hand [ r = 0.358, p r = 0.359, p r = 0.591, p r = 0.505, p r = 0.317, p = 0.05]). In PNP patients, TDMT and TDT were significantly higher at all sites as compared to controls ( p Discussion Our results point to an association between higher age and poorer capacity of discriminating somatosensory stimuli. The correlation of performance in a particular pointing task of the hand with lower TDMT suggests this measure as a potential surrogate marker of proprioceptive function. Both TDT and TDMT were markedly increased in PNP patients, indicating their clinical meaning in diseases with affection of the proprioceptive system. This might also be the pathophysiological link to previous findings of elevated thresholds in movement disorders.

Short inter-stimulus intervals can be used for olfactory electroencephalography in patients of varying olfactory function

Use of chemosensory event-related potentials (ERPs) is limited by relatively poor signal-to-noise ratios (SNRs). We hypothesized that by reducing the standard inter-stimulus interval (ISI), the increased number of trial repetitions possible may increase SNR. In order to further investigate this, we performed the largest study to date assessing chemosensory ERP using short and long ISIs in 101 participants of varying olfactory function. Using rose odor (phenylethylalcohol, PEA) as a relatively selective olfactory stimulant, we found no significant difference in the proportion of individuals in whom ERPs were recorded using short or long ISIs. This was true in normosmic, hyposmic and functionally anosmic individuals. We also demonstrated significantly increased SNR using short PEA-ISIs, in the normosmic and functionally anosmic groups. Comparing between groups of different olfactory function, hyposmic patients achieved faster onsets and greater amplitudes than normosmics under the PEA-10s protocol. This could be due to increased stimulus attendance, but requires confirmation with further research.

P252 Prepulse inhibition of blink reflex after different types of somatosensory stimuli

Objective Prepulse inhibition (PPI) is a neurophysiological method in which inhibition of a reflex response occurs when a preceding stimulus is applied. It is generally created by digital somatosensory stimulation. R2 magnitude gets reduced using certain interstimulus intervals (ISIs) whereas short ISI leads to facilitation of R1. We aimed to analyze the changes of BR-PPI using digital somatosensory stimulation and mixed nerve stimulation at wrist. Patients and method We included 18 healthy subjects (38.8 ± 10.9 years, 12 women) and performed BR investigations after unconditioned and conditioned supraorbital electrical stimuli. For conditioned stimuli, we applied two different preceding subthreshold somatosensory stimuli: i. stimulation of second finger, ii. stimulation of median nerve at wrist. Three different ISIs (50, 100, 300 ms) were used for each type of stimulation. Presence and extent of alteration after each conditioning stimulus were compared. Results R2 area significantly reduced after each conditioning stimulus at each ISI. R2 latency was longer at ISIs of 100 and 300 ms whereas R1 magnitude was higher at all ISIs. However, the increase in R1 magnitude was more pronounced at ISIs of 50 and 100 ms. Conclusions Our results clearly show that both digital somatosensory and mixed nerve stimulations lead to inhibition of R2 area and facilitation of R1 magnitude. Therefore, both stimulations and both techniques are comparable.

Decoding fMRI activity in the time domain improves classification performance

Most current functional Magnetic Resonance Imaging (fMRI) decoding analyses rely on statistical summaries of the data resulting from a deconvolution approach: each stimulation event is associated with a brain response. This standard approach leads to simple learning procedures, yet it is ill-suited for decoding events with short inter-stimulus intervals. In order to overcome this issue, we propose a novel framework that separates the spatial and temporal components of the prediction by decoding the fMRI time-series continuously, i.e. scan-by-scan. The stimulation events can then be identified through a deconvolution of the reconstructed time series. We show that this model performs as well as or better than standard approaches across several datasets, most notably in regimes with small inter-stimuli intervals (3–5s), while also offering predictions that are highly interpretable in the time domain. This opens the way toward analyzing datasets not normally thought of as suitable for decoding and makes it possible to run decoding on studies with reduced scan time.

Biphasic attentional orienting triggered by invisible social signals

Biological motion (BM) is one of the most important social cues for detecting conspecifics, prey, and predators. We show that unconscious BM processing can reflexively direct spatial attention, and that this effect has a biphasic temporal profile. Participants responded to probes that were preceded by intact or scrambled BM cues rendered invisible through continuous flash suppression. With a short inter-stimulus interval (ISI, 100ms) between the invisible BM cues and the probe, responses to probes at the same location as the invisible, nonpredictive BM cue were faster than to probes at the location of the scrambled BM cue. With a longer ISI (800ms) this effect reversed, with slower responses to probes at the location of the invisible, nonpredictive BM. These effects were absent when BM and its scrambled control were made visible with both short and long cue durations across variable length of ISIs, indicating that the saliency of BM itself cannot account for the dynamic orienting effects from invisible social cues. Moreover, this dynamic attentional shifts were specific to upright BM cues and not obtained for inverted stimuli. Thus, this reflexive and dynamic attentional modulation triggered by invisible BM, with initial facilitation followed by inhibition, demonstrates that in the complete absence of conscious awareness, cue predictiveness, and saliency differences, attentional systems promote exploration of our visual environment for social signals.

Physiological profiles of cortical responses to mechanical stimulation of the tooth in the rat: An optical imaging study

The periodontal ligament (PDL) includes several types of nerve endings, such as Aβ-, Aδ-, and C-fibers, which play critical roles in detecting the strength and direction of occlusal force. Previous studies have demonstrated that electrical stimulation of the PDL activates the somatosensory and insular cortices. However, the profile of cortical excitation in response to mechanical PDL stimulation mostly remains unknown. To investigate the differences in cortical responses to electrical and mechanical stimulation of the maxillary first molar, we performed optical imaging to determine the responding cortical regions in combination with a pharmacological approach. The molar was mechanically stimulated by pulling in the rostral direction, and electrical stimulation was applied via bipolar electrodes inserted into the mesial PDL. Mechanical stimulation initially excited the primary somatosensory cortex (S1), whereas electrical stimulation evoked an initial response between the secondary somatosensory cortex (S2) and insular oral region (IOR). The characteristic feature responding to mechanical stimulation was the rebound response evoked at the end of mechanical stimulation. A longer mechanical stimulation evoked a larger amplitude of the rebound response. A paired-pulse protocol of mechanical stimulation revealed that the amplitude of the second response was smaller than the first response, in accordance with the shorter interstimulus interval. Systemic application of morphine, a potent blocker of nociception, reduced the amplitude of the maximum excitation, particularly in S2/IOR compared to S1. These results suggest that S1 and S2/IOR are principally excited by mechanical and electrical stimulation, respectively, and that S2/IOR is involved in nociception processing.

Learned response sequences in cerebellar Purkinje cells

Associative learning in the cerebellum has previously focused on single movements. In eyeblink conditioning, for instance, a subject learns to blink at the right time in response to a conditional stimulus (CS), such as a tone that is repeatedly followed by an unconditional corneal stimulus (US). During conditioning, the CS and US are transmitted by mossy/parallel fibers and climbing fibers to cerebellar Purkinje cells that acquire a precisely timed pause response that drives the overt blink response. The timing of this conditional Purkinje cell response is determined by the CS-US interval and is independent of temporal patterns in the input signal. In addition to single movements, the cerebellum is also believed to be important for learning complex motor programs that require multiple precisely timed muscle contractions, such as, for example, playing the piano. In the present work, we studied Purkinje cells in decerebrate ferrets that were conditioned using electrical stimulation of mossy fiber and climbing fiber afferents as CS and US, while alternating between short and long interstimulus intervals. We found that Purkinje cells can learn double pause responses, separated by an intermediate excitation, where each pause corresponds to one interstimulus interval. The results show that individual cells can not only learn to time a single response but that they also learn an accurately timed sequential response pattern.