Timing Of Conditioned Responses Research Articles

Neurite density of the hippocampus is associated with trace eyeblink conditioning latency in 4- to 6-year-olds.

Limited options exist to evaluate the development of hippocampal function in young children. Research has established that trace eyeblink conditioning (EBC) relies on a functional hippocampus. Hence, we set out to investigate whether trace EBC is linked to hippocampal structure, potentially serving as a valuable indicator of hippocampal development. Our study explored potential associations between individual differences in hippocampal volume and neurite density with trace EBC performance in young children. We used onset latency of conditioned responses (CR) and percentage of conditioned responses (% CR) as measures of hippocampal-dependent associative learning. Using a sample of typically developing children aged 4 to 6years (N = 30; 14 girls; M = 5.70years), participants underwent T1- and diffusion-weighted MRI scans and completed a 15-min trace eyeblink conditioning task conducted outside the MRI. % CR and CR onset latency were calculated based on all trials involving tone-puff presentations and tone-alone trials. Findings revealed a connection between greater left hippocampal neurite density and delayed CR onset latency. Children with higher neurite density in the left hippocampus tended to blink closer to the onset of the unconditioned stimulus, indicating that structural variations in the hippocampus were associated with more precise timing of conditioned responses. No other relationships were observed between hippocampal volume, cerebellum volume or neurite density, hippocampal white matter connectivity and any EBC measures. Preliminary results suggest that trace EBC may serve as a straightforward yet innovative approach for studying hippocampal development in young children and populations with atypical development.

Relationship of Impairments in Associative Learning With Intellectual Disability and Cerebellar Hypoplasia in Autistic Children.

The severity of autism spectrum disorder (ASD) varies widely and is associated with intellectual disability (ID) and brain dysmorphology. We tested the hypothesis that the heterogeneity of ASD can be accounted for, in part, by altered associative learning measured by eye-blink conditioning (EBC) paradigms, used to test for forebrain and cerebellar dysfunction across the full range of ASD severity and intellectual ability. Children in this cohort study were diagnosed with ASD or typical development (TD); most children were recruited from a 10-year longitudinal study. Outcome measures were the percentage and timing of conditioned eye-blink responses (CRs) acquired to a tone, recorded photometrically and related to measures of ASD severity, IQ, and age 2 brain morphometry by MRI. A sequence of trace and delay EBC was used. Analysis of variance, t test, and logistic regression (LR) were used. Sixty-two children were studied at school age. Nine children with ASD with ID since age 2 (ASD + ID; IQ = 49 ± 6; 11.9 ± 0.2 years old [±SD]) learned more slowly than 30 children with TD (IQ = 120 ± 16; 10.5 ± 1.5 years old [±SD]) during trace EBC and showed atypically early-onset CRs (1.4 SD pre-TD) related to hypoplasia of the cerebellum at age 2 but not of the amygdala, hippocampus, or cerebral cortex. Conversely, 16 children with ASD with robust intellectual development since age 2 (IQ = 100 ± 3; 12.0 ± 0.4 years old [±SD]) learned typically but showed early-onset CRs only during long-delay EBC (0.8 SD pre-TD) unrelated to hypoplasia of any measured brain area. Using 16 EBC measures, binary LR classified ASD and TD with 80% accuracy (95% CI = 72-88%), 81% sensitivity (95% CI = 69-92%), and 79% specificity (95% CI = 68-91%); multinomial LR more accurately classified children based on ID (94% accuracy, 95% CI = 89-100%) than ASD severity (85% accuracy, 95% CI = 77-93%). Separate analyses of 39 children with MRI (2.1 ± 0.3 years old [±SD]) indicated that cerebellar hypoplasia did not predict ASD + ID over ages 2-4 (Cohen d = 0.3) compared with early-onset CRs during age 11 trace EBC (Cohen d = -1.3). Trace EBC reveals the relationship between cerebellar hypoplasia and ASD + ID likely by engaging cerebrocerebellar circuits involved in intellectual ability and implicit timing. Follow-up prospective studies using associative learning can determine whether ID can be predicted in children with early ASD diagnoses.

Cerebellar transcranial direct current stimulation modulates timing but not acquisition of conditioned eyeblink responses in SCA3 patients

BackgroundDelay eyeblink conditioning is an extensively studied motor learning paradigm that critically depends on the integrity of the cerebellum. In healthy individuals, modulation of cerebellar excitability using transcranial direct current stimulation (tDCS) has been reported to alter the acquisition and/or timing of conditioned eyeblink responses (CRs). It remains unknown whether such effects can also be elicited in patients with cerebellar disorders. ObjectiveTo investigate if repeated sessions of cerebellar tDCS modify acquisition and/or timing of CRs in patients with spinocerebellar ataxia type 3 (SCA3) and to evaluate possible associations between disease severity measures and eyeblink conditioning parameters. MethodsDelay eyeblink conditioning was examined in 20 mildly to moderately affected individuals with SCA3 and 31 healthy controls. After the baseline assessment, patients were randomly assigned to receive ten sessions of cerebellar anodal tDCS or sham tDCS (i.e., five days per week for two consecutive weeks). Patients and investigators were blinded to treatment allocation. The same eyeblink conditioning protocol was administered directly after the last tDCS session. The Scale for the Assessment and Rating of Ataxia (SARA), cerebellar cognitive affective syndrome scale (CCAS-S), and disease duration were used as clinical measures of disease severity. ResultsAt baseline, SCA3 patients exhibited significantly fewer CRs than healthy controls. Acquisition was inversely associated with the number of failed CCAS-S test items but not with SARA score. Onset and peak latencies of CRs were longer in SCA3 patients and correlated with disease duration. Repeated sessions of cerebellar anodal tDCS did not affect CR acquisition, but had a significant treatment effect on both timing parameters. While a shift of CRs toward the conditioned stimulus was observed in the sham group (i.e., timing became more similar to that of healthy controls, presumably reflecting the effect of a second eyeblink conditioning session), anodal tDCS induced a shift of CRs in the opposite direction (i.e., toward the unconditioned stimulus). ConclusionOur findings provide evidence that cerebellar tDCS is capable of modifying cerebellar function in SCA3 patients. Future studies should assess whether this intervention similarly modulates temporal processing in other degenerative ataxias.

Do Our Hands See What Our Eyes See: Investigating the Relationships Between Spatial and Haptic Abilities

IntroductionSpatial abilities (SA) are the cognitive ability to manipulate mental images of objects to problem solve and are linked to comprehension of three‐dimensional (3D) spatial knowledge in gross anatomy and in learning clinical procedures. Similarly, haptic abilities (HA) refer to translating tactile information from the immediate environment into mental images and are involved in handling anatomical specimens and technical skill acquisition common to clinicians. Both abilities independently play an important role in learning anatomy, yet the relationships between SA and HA are unknown. The objective of this study is to explore SA‐HA interactions.MethodsThe Mental Rotations Test (MRT) and the newly developed haptic abilities test (HAT) respectively quantified SA and HA in undergraduate students. The HAT, modelled after the MRT, consisted of untimed, matching questions utilizing MRT‐styled 3D handheld wooden objects (~10cm3) under three sensory conditions using sight (S), haptics (H) and the combination of both sight and haptics (SH). While HAT condition scores and response times determined accuracy, video recorded subject gaze and haptic behaviours on a question‐by‐question basis. Scores for MRT are presented as mean ± SD and HAT scores as median (Q1‐Q3).ResultsSubjects (n=16, 10F, 20‐28yrs) completed the MRT and HAT and were categorized into high (n=9, 4F, MRT: 14.8±3) and low (n=7, 6F, MRT: 6.3±3) (H/LSA) groups (p<0.0001). Scores obtained in the H condition [14 (13‐15) vs14 (14‐14), p=0.0031] were significantly lower than in the S [15 (15‐15) vs14 (14‐15)] and SH conditions [15 (15‐15) vs14 (14‐15)] in H/LSA groups respectively. Spearman’s correlation coefficient illustrated MRT scores were moderately related in the S condition (r=0.506, p=0.038), but unrelated in the SH and H conditions (SH: r=0.325, p=0.203; H: r=0.162, p=0.534). The number of pupillary fixations per question was similar (S:6.0±3.0 vs5.9±1.4, p=0.910; SH: 4.5±2.0 vs6.7±2.0, p=0.099) for H/LSA groups respectively. Initial descriptive analyses of hand behaviours (n=4) suggest H/LSA objects differently.DiscussionDespite significant difference in SA, when individuals are presented identical environmental 3D objects to view, view and touch, or touch alone, it is difficult to differentiate SA. These data suggest that the addition of haptic sensory information may aid LSA individuals completing spatial tasks. Although visual attention and timing of haptic behaviours may be similar between H/LSA subjects, further kinematic analysis of haptic strategies may be more meaningful to isolate how somatosensory inputs aid problem solving behaviours in LSA persons. This is some of the first data to simultaneously measure hand and gaze behaviour during spatially challenging tasks in individuals with divergent SA. Given recent migrations to online anatomy teaching and learning environments due to COVID‐19, understanding learner behaviour when sensory inputs, like haptics, are removed is valuable evidence that can inform future anatomy curriculum and resource development.

Sensory augmentation to aid training with retinal prostheses

Objective. Retinal prosthesis recipients require rehabilitative training to learn the non-intuitive nature of prosthetic ‘phosphene vision’. This study investigated whether the addition of auditory cues, using The vOICe sensory substitution device (SSD), could improve functional performance with simulated phosphene vision. Approach. Forty normally sighted subjects completed two visual tasks under three conditions. The phosphene condition converted the image to simulated phosphenes displayed on a virtual reality headset. The SSD condition provided auditory information via stereo headphones, translating the image into sound. Horizontal information was encoded as stereo timing differences between ears, vertical information as pitch, and pixel intensity as audio intensity. The third condition combined phosphenes and SSD. Tasks comprised light localisation from the Basic Assessment of Light and Motion (BaLM) and the Tumbling-E from the Freiburg Acuity and Contrast Test (FrACT). To examine learning effects, twenty of the forty subjects received SSD training prior to assessment. Main results. Combining phosphenes with auditory SSD provided better light localisation accuracy than either phosphenes or SSD alone, suggesting a compound benefit of integrating modalities. Although response times for SSD-only were significantly longer than all other conditions, combined condition response times were as fast as phosphene-only, highlighting that audio-visual integration provided both response time and accuracy benefits. Prior SSD training provided a benefit to localisation accuracy and speed in SSD-only (as expected) and Combined conditions compared to untrained SSD-only. Integration of the two modalities did not improve spatial resolution task performance, with resolution limited to that of the higher resolution modality (SSD). Significance. Combining phosphene (visual) and SSD (auditory) modalities was effective even without SSD training and led to an improvement in light localisation accuracy and response times. Spatial resolution performance was dominated by auditory SSD. The results suggest there may be a benefit to including auditory cues when training vision prosthesis recipients.

Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study.

It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well.

Delay of reinforcement versus rate of reinforcement in Pavlovian conditioning.

Conditioned stimulus (CS) duration is a determinant of conditioned responding, with increases in duration leading to reductions in response rates. The CS duration effect has been proposed to reflect sensitivity to the reinforcement rate across cumulative exposure to the CS, suggesting that the delay of reinforcement from the onset of the cue is not crucial. Here, we compared the effects of delay and rate of reinforcement on Pavlovian appetitive conditioning in mice. In Experiment 1, the influence of reinforcement delay on the timing of responding was removed by making the duration of cues variable across trials. Mice trained with variable duration cues were sensitive to differences in the rate of reinforcement to a similar extent as mice trained with fixed duration cues. Experiments 2 and 3 tested the independent effects of delay and reinforcement rate. In Experiment 2, food was presented at either the termination of the CS or during the CS. In Experiment 3, food occurred during the CS for all cues. The latter experiment demonstrated an effect of delay, but not reinforcement rate. Experiment 4 ruled out the possibility that the lack of effect of reinforcement rate in Experiment 3 was due to mice failing to learn about the nonreinforced CS exposure after the presentation of food within a trial. These results demonstrate that although the CS duration effect is not simply a consequence of timing of conditioned responses, it is dependent on the delay of reinforcement. The results provide a challenge to current associative and nonassociative, time-accumulation models of learning.

Aberrant connections between climbing fibres and Purkinje cells induce alterations in the timing of an instrumental response in the rat.

Cerebellar participation in timing and sensory-motor sequences has been supported by several experimental and clinical studies. A relevant role of the cerebellum in timing of conditioned responses in the range of milliseconds has been demonstrated, but less is known regarding the role of the cerebellum in supra-second timing of operant responses. A dissociated role of the cerebellum and striatum in timing in the millisecond and second range had been reported, respectively. The climbing fibre-Purkinje cell synapse is crucial in timing models; thus, the aberrant connection between these cellular elements is a suitable model for evaluating the contribution of the cerebellum in timing in the supra-second range. The aberrant connection between climbing fibres and Purkinje cells was induced by administration of the antagonist of NMDA receptors MK-801 to Sprague-Dawley rats at postnatal days 7-14. The timing of an operant response with two fixed intervals (5 and 8s) and egocentric sequential learning was evaluated in 60-day-old adult rats. The aberrant connections caused a reduced accuracy in the timing of the instrumental response that was more evident in the 8-s interval and a reduced number of successive correct responses (responses emitted in the correct second without any other response between them) in the 8-s interval. In addition, an inability to incorporate new information in a sequence previously learned in egocentric-based sequence learning was apparent in rats with aberrant CF-PC synapses. These results support a relevant role for the cerebellum in the fine-tuning of the timing of operant responses in the supra-second range.

Conditional Sojourn times and the volatility of payment schemes for bandwidth sharing in packet networks

Predictability of revenue and costs to both operators and users is critical for payment schemes. We study the issue of the design of payment schemes in networks with bandwidth sharing. The model we consider is a processor sharing system that is accessed by various classes of users with different processing requirements or file sizes. The users are charged according to a Vickrey–Clarke–Groves mechanism because of its efficiency and fairness when logarithmic utility functions are involved. Subject to a given mean revenue for the operator, we study whether it is preferable for a user to pay upon arrival, depending on the congestion level, or whether the user should opt to pay at the end. This leads to a study of the volatility of payment schemes and we show that opting for prepayment is preferable from a user point of view. The analysis yields new results on the asymptotic behavior of conditional response times for processor sharing systems and connections to associated orthogonal polynomials.

Conditional Sojourn times and the volatility of payment schemes for bandwidth sharing in packet networks

Predictability of revenue and costs to both operators and users is critical for payment schemes. We study the issue of the design of payment schemes in networks with bandwidth sharing. The model we consider is a processor sharing system that is accessed by various classes of users with different processing requirements or file sizes. The users are charged according to a Vickrey–Clarke–Groves mechanism because of its efficiency and fairness when logarithmic utility functions are involved. Subject to a given mean revenue for the operator, we study whether it is preferable for a user to pay upon arrival, depending on the congestion level, or whether the user should opt to pay at the end. This leads to a study of the volatility of payment schemes and we show that opting for prepayment is preferable from a user point of view. The analysis yields new results on the asymptotic behavior of conditional response times for processor sharing systems and connections to associated orthogonal polynomials.

Relating cerebellar purkinje cell activity to the timing and amplitude of conditioned eyelid responses.

How Purkinje cell (PC) activity may be altered by learning is central to theories of the cerebellum. Pavlovian eyelid conditioning, because of how directly it engages the cerebellum, has helped reveal many aspects of cerebellar learning and the underlying mechanisms. Theories of cerebellar learning assert that climbing fiber inputs control plasticity at synapses onto PCs, and thus PCs control the expression of learned responses. We tested this assertion by recording 184 eyelid PCs and 240 non-eyelid PCs during the expression of conditioned eyelid responses (CRs) in well trained rabbits. By contrasting the responses of eyelid and non-eyelid PCs and by contrasting the responses of eyelid PCs under conditions that produce differently timed CRs, we test the hypothesis that learning-related changes in eyelid PCs contribute to the learning and adaptive timing of the CRs. We used a variety of analyses to test the quantitative relationships between eyelid PC responses and the kinematic properties of the eyelid CRs. We find that the timing of eyelid PC responses varies systematically with the timing of the behavioral CRs and that there are differences in the magnitude of eyelid PC responses between larger-CR, smaller-CR, and non-CR trials. However, eyelid PC activity does not encode any single kinematic property of the behavioral CRs at a fixed time lag, nor does it linearly encode CR amplitude. Even so, the results are consistent with the hypothesis that learning-dependent changes in PC activity contribute to the adaptively timed expression of conditioned eyelid responses.

Cerebellar-dependent associative learning is preserved in Duchenne muscular dystrophy: a study using delay eyeblink conditioning.

ObjectiveBesides progressive muscle weakness cognitive deficits have been reported in patients with Duchenne muscular dystrophy (DMD). Cerebellar dysfunction has been proposed to explain cognitive deficits at least in part. In animal models of DMD disturbed Purkinje cell function has been shown following loss of dystrophin. Furthermore there is increasing evidence that the lateral cerebellum contributes to cognitive processing. In the present study cerebellar-dependent delay eyeblink conditioning, a form of associative learning, was used to assess cerebellar function in DMD children.MethodsDelay eyeblink conditioning was examined in eight genetically defined male patients with DMD and in ten age-matched control subjects. Acquisition, timing and extinction of conditioned eyeblink responses (CR) were assessed during a single conditioning session.ResultsBoth groups showed a significant increase of CRs during the course of learning (block effect p < 0.001). CR acquisition was not impaired in DMD patients (mean total CR incidence 37.4 ± 17.6%) as compared to control subjects (36.2 ± 17.3%; group effect p = 0.89; group by block effect p = 0.38; ANOVA with repeated measures). In addition, CR timing and extinction was not different from controls.ConclusionsDelay eyeblink conditioning was preserved in the present DMD patients. Because eyeblink conditioning depends on the integrity of the intermediate cerebellum, this older part of the cerebellum may be relatively preserved in DMD. The present findings agree with animal model data showing that the newer, lateral cerebellum is primarily affected in DMD.

Changes in the distribution of response rates across the CS-US interval: Evidence that responding switches between two distinct states.

Two experiments used the peak procedure to examine timing of conditioned responses in a magazine approach paradigm with rats. A conditioned stimulus (CS) was reinforced with food on 50% of trials. Food was delivered at a fixed time, 20 s, 30 s, or 40 s into the CS presentation. Response rates were recorded during nonreinforced CS presentations that extended well beyond the scheduled time of food delivery. The mean response rate (averaged over many trials) increased during the CS, peaking at the expected time of reinforcement, and decreased again. Detailed analyses of the frequency distribution of response rates showed that responding was described by 2 distinct distributions, consistent with the rat being in a low response state on some trials and in a high response state on others. Modeling of frequency distributions showed that the systematic rise and fall in response rate across a trial was primarily explained by a change in the proportion of time that the rat spent in the low versus high response state. However, the change in responding was also explained in part by a continuous shift in the high response state, such that responding in that state increased and then decreased gradually across the trial. These results support accounts describing response timing as an abrupt change from low to high responding during the CS, but also provide evidence for a continuous change in conditioning strength across the duration of the CS. The implications of these findings for timing and associative theories of conditioning are discussed. (PsycINFO Database Record

Effects of dorsal hippocampal damage on conditioning and conditioned-response timing: A pooled analysis.

Behavioral findings suggest that the dorsal hippocampus (DHPC) plays a role in timing of appetitive conditioned responding. The present article explored the relationship between the extent of DHPC damage and timing ability, in a pooled analysis of three published studies from our laboratory. Initial analyses of variance confirmed our previous reports that DHPC damage reduced peak time (a measure of timing accuracy). However, the spread (a measure of timing precision) was unchanged, such that the coefficient of variation (spread/peak time) was significantly larger in DHPC-lesioned animals. This implies that, in addition to the well-established effect of DHPC lesions on timing accuracy, DHPC damage produced a deficit in precision of timing. To complement this analysis, different generalized linear mixed-effects models (GLMMs) were performed on the combined dataset, to examine which combinations of the different behavioral measures of timing were the best predictors of the degree of hippocampal damage. The results from the GLMM analysis suggested that the greater the DHPC damage, the greater the absolute difference between the observed peak time and reinforced duration. Nevertheless, this systematic relationship between damage and performance was not specific to the temporal domain: paradoxically the greater the damage the greater the magnitude of peak responding. We discuss these lesion effects in terms of scalar timing theory.

Cerebellar Inhibitory Output Shapes the Temporal Dynamics of Its Somatosensory Inferior Olivary Input

The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus' onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO's response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts.

Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS.

Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex. The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS. A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality. CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset. Acquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.

Subclinical cerebellar dysfunction in patients with migraine: Evidence from eyeblink conditioning

Clinical findings suggest cerebellar dysfunction in patients with migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative learning which depends on the integrity of the cerebellum. The aim of this study was to assess whether EBCC is disturbed in patients with migraine. A delay conditioning paradigm was used in the headache-free interval in 32 female patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA), and in 32 age-matched female controls. As primary outcome measure acquisition and as secondary outcome measures timing and extinction of conditioned eyeblink responses (CR) were assessed. CR acquisition was significantly reduced in all migraine patients (mean total CR incidence 35.2 ± 22.1%) compared to controls (54.7 ± 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in MwA patients (19.9 ± 20.2%) compared to matched controls (58.2 ± 27.0%; p = 0.006) but not in MwoA patients (40.3 ± 20.6%) compared to matched controls (53.6 ± 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of CR incidences in MwA patients was not significantly different compared to MwoA patients (p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and extinction was not affected in migraine patients. Reduced acquisition of CRs in the cohort of female patients studied here supports findings of a cerebellar dysfunction in migraine.

Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes the subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from TD subjects with regard to the learning rate or the timing of the conditioned response. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of the cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals.

Dorsal hippocampal involvement in conditioned-response timing and maintenance of temporal information in the absence of the CS

Involvement of the dorsal hippocampus (DHPC) in conditioned-response timing and maintaining temporal information across time gaps was examined in an appetitive Pavlovian conditioning task, in which rats with sham and DHPC lesions were first conditioned to a 15-s visual cue. After acquisition, the subjects received a series of non-reinforced test trials, on which the visual cue was extended (45 s) and gaps of different duration, 0.5, 2.5, and 7.5 s, interrupted the early portion of the cue. Dorsal hippocampal-lesioned subjects underestimated the target duration of 15 s and showed broader response distributions than the control subjects on the no-gap trials in the first few blocks of test, but the accuracy and precision of their timing reached the level of that of the control subjects by the last block. On the gap trials, the DHPC-lesioned subjects showed greater rightward shifts in response distributions than the control subjects. We discussed these lesion effects in terms of temporal versus non-temporal processing (response inhibition, generalisation decrement, and inhibitory conditioning).

Consensus Paper: Current Views on the Role of Cerebellar Interpositus Nucleus in Movement Control and Emotion

In the present paper, we examine the role of the cerebellar interpositus nucleus (IN) in motor and non-motor domains. Recent findings are considered, and we share the following conclusions: IN as part of the olivo-cortico-nuclear microcircuit is involved in providing powerful timing signals important in coordinating limb movements; IN could participate in the timing and performance of ongoing conditioned responses rather than the generation and/or initiation of such responses; IN is involved in the control of reflexive and voluntary movements in a task- and effector system-dependent fashion, including hand movements and associated upper limb adjustments, for quick effective actions; IN develops internal models for dynamic interactions of the motor system with the external environment for anticipatory control of movement; and IN plays a significant role in the modulation of autonomic and emotional functions.