Differential corticostriatal plasticity during fast and slow motor skill learning in mice

BACKGROUND: Motor skill learning usually comprises "fast" improvement in performance within the initial training session and "slow" improvement that develops across sessions. Previous studies have revealed changes in activity and connectivity in motor cortex and striatum during motor skill learning. However, the nature and dynamics of the plastic changes in each of these brain structures during the different phases of motor learning remain unclear. RESULTS: By using multielectrode arrays, we recorded the simultaneous activity of neuronal ensembles in motor cortex and dorsal striatum of mice during the different phases of skill learning on an accelerating rotarod. Mice exhibited fast improvement in the task during the initial session and also slow improvement across days. Throughout training, a high percentage of striatal (57%) and motor cortex (55%) neurons were task related; i.e., changed their firing rate while mice were running on the rotarod. Improvement in performance was accompanied by substantial plastic changes in both striatum and motor cortex. We observed parallel recruitment of task-related neurons in both structures specifically during the first session. Conversely, during slow learning across sessions we observed differential refinement of the firing patterns in each structure. At the neuronal ensemble level, we observed considerable changes in activity within the first session that became less evident during subsequent sessions. CONCLUSIONS: These data indicate that cortical and striatal circuits exhibit remarkable but dissociable plasticity during fast and slow motor skill learning and suggest that distinct neural processes mediate the different phases of motor skill learning.     

Comparative MRI analysis of T2 changes associated with single and repeated bouts of downhill running leading to eccentric-induced muscle damage.

Although the exact mechanisms are still unclear, it is commonly acknowledged that acute eccentric exercise alters muscle performance, whereas the repetition of successive bouts leads to the disappearance of the deleterious signs. To clarify this issue, we measured blood creatine kinase and lactate dehydrogenase activities and proton transverse relaxation time (T2) in various leg muscles 72 h after single and repeated bouts of exhausting downhill running sessions (-15 degrees , 1.5 km/h) with either 4 or 7 days elapsed between bouts. After a single exercise bout, T2 and enzyme activities initially increased and recovered rapidly. When exercise bouts were repeated over a short time period (4 days), initial changes did not recover and endurance time throughout additional exercise sessions was significantly reduced. On the contrary, with a longer resting time between exercises (7 days), the endurance time of additional running sessions was significantly longer and muscle changes (T2 increase, muscle edema, and enzyme activity changes) slowly and completely reversed. Significant correlations were found between T2 changes and enzyme activities. T2 changes in the soleus and gastrocnemius muscle heads were differently affected by lengthening contractions, suggesting a muscle specificity and indicating that muscle alterations might be linked to different anatomical properties, such as fiber pennation angles, typology, and/or the exhausting nature of the downhill running sessions. We documented a "less muscle injury" effect due to the repetition of exercise bouts at a low frequency (i.e., 1 session per week) in accordance with the delayed muscle inflammation. This effect was not observed when the between-exercise resting time was shorter.     

Persistence of improvements in postural strategies following motor control training in people with recurrent low back pain.

This study investigated long-term effects of training on postural control using the model of deficits in activation of transversus abdominis (TrA) in people with recurrent low back pain (LBP). Nine volunteers with LBP attended four sessions for assessment and/or training (initial, two weeks, four weeks and six months). Training of repeated isolated voluntary TrA contractions were performed at the initial and two-week session with feedback from real-time ultrasound imaging. Home program involved training twice daily for four weeks. Electromyographic activity (EMG) of trunk and deltoid muscles was recorded with surface and fine-wire electrodes. Rapid arm movement and walking were performed at each session, and immediately after training on the first two sessions. Onset of trunk muscle activation relative to prime mover deltoid during arm movements, and the coefficient of variation (CV) of EMG during averaged gait cycle were calculated. Over four weeks of training, onset of TrA EMG was earlier during arm movements and CV of TrA EMG was reduced (consistent with more sustained EMG activity). Changes were retained at six months follow-up (p<0.05). These results show persistence of motor control changes following training and demonstrate that this training approach leads to motor learning of automatic postural control strategies.     

Learning the same motor task twice impairs its retention in a time- and dose-dependent manner

Anterograde interference emerges when two differing tasks are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when the same motor task is being learned twice, that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period—independent of fatigue—also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.     

Repeated exercise paired with "imperceptible" dead space loading does not alter VE of subsequent exercise in humans.

We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a "conditioning" and a "nonconditioning" session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the "control" and "test" runs) were compared for each session. Steady-state exercise end-tidal PCO(2) was significantly lower (P = 0.003) during test than during control runs for both sessions (dropping by 1.8 +/- 2 and 1.4 +/- 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.     

Habituation of vasodilatation in the calf elicited by repeated sensory stimulation in man

In 28 subjects the cardiovascular response to repeated stimulation was monitored during six daily sessions. Calf blood flow was measured with mercury-in-silastic venous occlusion plethysmography, blood pressure with electronic sphygmomanometer. The stimuli used were: 1 kHz sound of 90 dB and 100 dB intensity and immersion of one foot for 60 s in water at 4 degrees C. Initially sounds induced large vasodilatation in the calf, immersion of one foot in the water induced in the contralateral calf vasodilatation in one group and vasoconstriction in another group of subjects. The blood pressure changes were less prominent and less consistent. After the first session of repeated stimulation the vascular response during the second session was significantly diminished. The reduction of the vasodilatation was the most rapid. During the remaining 5 days the responses were suppressed. It has been established that in the patients in the initial stage of hypertension the ability to habituate vascular response is impaired (Zbrozyna and Krebbel 1985). It is therefore suggested that the test of the ability for long-term vascular habituation could be used as a supplementary diagnostic test.     

Stages of motor skill learning

Successful learning of a motor skill requires repetitive training. Once the skill is mastered, it can be remembered for a long period of time. The durable memory makes motor skill learning an interesting paradigm for the study of learning and memory mechanisms. To gain better understanding, one scientific approach is to dissect the process into stages and to study these as well as their interactions. This article covers the growing evidence that motor skill learning advances through stages, in which different storage mechanisms predominate. The acquisition phase is characterized by fast (within session) and slow learning (between sessions). For a short period following the initial training sessions, the skill is labile to interference by other skills and by protein synthesis inhibition, indicating that consolidation processes occur during rest periods between training sessions. During training as well as rest periods, activation in different brain regions changes dynamically. Evidence for stages in motor skill learning is provided by experiments using behavioral, electrophysiological, functional imaging, and cellular/molecular methods.     

Retention of memory traces in rats subjected to 10-minute clinical death procedure

Retention of memory traces was tested on the 12th day after 10-min clinical death (CD) produced by the total cessation of blood circulation in Albino rats previously trained for operant food conditioning in a multiple alternative maze. It was found that the structure of memory trace (sequence of operant actions in the maze), motivation activity and habit organization after the resuscitation were completely preserved in all rats independently of the number of the memory traces formed. Short-term negative changes were revealed only in the character of habit realization: the efficiency and reproduction parameters such as "readiness", mobilization activity, and stability of habit realization had lower values during 2-3 sessions. The rate of their recovery after the CD depended on rat's initial motivation state: the higher was the initial motivation, the faster recovered all the reproduction parameters. It is suggested that the observed negative changes in habit realization were nonspecific and were provoked by the CD-induced hyperexcitability of rats.     

Changes in striatal dopamine release associated with human motor-skill acquisition

The acquisition of new motor skills is essential throughout daily life and involves the processes of learning new motor sequence and encoding elementary aspects of new movement. Although previous animal studies have suggested a functional importance for striatal dopamine release in the learning of new motor sequence, its role in encoding elementary aspects of new movement has not yet been investigated. To elucidate this, we investigated changes in striatal dopamine levels during initial skill-training (Day 1) compared with acquired conditions (Day 2) using (11)C-raclopride positron-emission tomography. Ten volunteers learned to perform brisk contractions using their non-dominant left thumbs with the aid of visual feedback. On Day 1, the mean acceleration of each session was improved through repeated training sessions until performance neared asymptotic levels, while improved motor performance was retained from the beginning on Day 2. The (11)C-raclopride binding potential (BP) in the right putamen was reduced during initial skill-training compared with under acquired conditions. Moreover, voxel-wise analysis revealed that (11)C-raclopride BP was particularly reduced in the right antero-dorsal to the lateral part of the putamen. Based on findings from previous fMRI studies that show a gradual shift of activation within the striatum during the initial processing of motor learning, striatal dopamine may play a role in the dynamic cortico-striatal activation during encoding of new motor memory in skill acquisition.     

Cortisol Response to Repeated Psychosocial Stress

Psychosocial stress plays a major role in the etiology and the course of mental disorders that often show an altered activation of the hypothalamus–pituitary–adrenal (HPA) axis. The Trier Social Stress Test (TSST) reliably activates the HPA axis and reflects real life stress exposure. However, habituation may confound the results of clinical trials that apply TSST. The present study investigates the cortisol response after repeated psychosocial stress induction with short-term and long-term intervals between repeated testing sessions. Forty-one healthy subjects were exposed to the TSST four times with an interval of 24 h between the first and the second testing session (t1 and t2). The 3rd and the 4th testing session (t3 and t4) were also separated by a 24-hour interval whereas there were 10 weeks between t2 and t3. A significant decrease in the salivary cortisol responses was noticed from testing session t1 to t2 as well as from testing session t3 to t4. By contrast, there were no differences in the HPA axis reactivity between testing session t2 and t3. Our results demonstrated the habituation of the HPA axis to a standardized psychosocial stress test when testing was repeated after 24 h. By contrast, a renewed challenge with a ten-week-interval in-between activated the HPA axis in a similar manner as before. It is suggested that studies designed to investigate the HPA axis activity under repeated psychosocial stress conditions should apply the TSST three times in order to separate habituation from intervention effects.     

Sleep-Effects on Implicit and Explicit Memory in Repeated Visual Search

In repeated visual search tasks, facilitation of reaction times (RTs) due to repetition of the spatial arrangement of items occurs independently of RT facilitation due to improvements in general task performance. Whereas the latter represents typical procedural learning, the former is a kind of implicit memory that depends on the medial temporal lobe (MTL) memory system and is impaired in patients with amnesia. A third type of memory that develops during visual search is the observers’ explicit knowledge of repeated displays. Here, we used a visual search task to investigate whether procedural memory, implicit contextual cueing, and explicit knowledge of repeated configurations, which all arise independently from the same set of stimuli, are influenced by sleep. Observers participated in two experimental sessions, separated by either a nap or a controlled rest period. In each of the two sessions, they performed a visual search task in combination with an explicit recognition task. We found that (1) across sessions, MTL-independent procedural learning was more pronounced for the nap than rest group. This confirms earlier findings, albeit from different motor and perceptual tasks, showing that procedural memory can benefit from sleep. (2) Likewise, the sleep group compared with the rest group showed enhanced context-dependent configural learning in the second session. This is a novel finding, indicating that the MTL-dependent, implicit memory underlying contextual cueing is also sleep-dependent. (3) By contrast, sleep and wake groups displayed equivalent improvements in explicit recognition memory in the second session. Overall, the current study shows that sleep affects MTL-dependent as well as MTL-independent memory, but it affects different, albeit simultaneously acquired, forms of MTL-dependent memory differentially.     

The ceruloplasmin-transferrin antioxidant system during hyperbaric oxygenation in rats

Antioxidant system ceruloplasmin-transferrin (Cp-Tr) and malonic dialdehyde (MDA) concentration changes were studied in the rat serum after the exposure to hyperbaric oxygenation (HBO) at 4 atm for 25 min. 5 sessions of HBO led to an increase in serum MDA concentration. 5 HBO sessions were followed by the activation of Cp-Tr system. Afterwards MDA concentration began to decrease and by the 9th session even reached the initial levels. It is suggested that antioxidant system Cp-Tr takes part in the protection of the organism from toxic oxygen action.     

Post Learning Sleep Improves Cognitive-Emotional Decision-Making: Evidence for a ‘Deck B Sleep Effect’ in the Iowa Gambling Task

The Iowa Gambling Task (IGT) is widely used to assess real life decision-making impairment in a wide variety of clinical populations. Our study evaluated how IGT learning occurs across two sessions, and whether a period of intervening sleep between sessions can enhance learning. Furthermore, we investigate whether pre-sleep learning is necessary for this improvement. A 200-trial version of the IGT was administered at two sessions separated by wake, sleep or sleep and wake (time-of-day control). Participants were categorized as learners and non-learners based on initial performance in session one. In session one, participants initially preferred the high-frequency reward decks B and D, however, a subset of learners decreased choice from negative expected value ‘bad’ deck B and increased choices towards with a positive expected value ‘good’ decks (decks C and D). The learners who had a period of sleep (sleep and sleep/wake control conditions) between sessions showed significantly larger reduction in choices from deck B and increase in choices from good decks compared to learners that had intervening wake. Our results are the first to show that post-learning sleep can improve performance on a complex decision-making task such as the IGT. These results provide new insights into IGT learning and have important implications for understanding the neural mechanisms of “sleeping on” a decision.     

Further evidence of joint time-place control of rats' behavior: results from an 'open hopper' test

Rats were trained on an interval time-place task. Food was intermittently available on each of four levers for 4 min in a 16-min session. After baseline training the rats received 'open hopper' sessions in which food was available on all levers for all of the 16-min sessions. Despite the absence of any contingencies for doing so, the rats continued to press the levers in the 'correct' sequence, for roughly the 'correct' amount of time. This confirms that the rat behavior was controlled, in part, by a representation of an elapsed interval of time. The rats responding was more variable in 'open hopper' sessions and error increased (in an exponential fashion) as the session proceeded. This finding suggests that the rats may have used shifts in the location of food availability to minimize the accumulation of error throughout baseline sessions.     

Sleep quality and high intensity interval training at two different times of day: A crossover study on the influence of the chronotype in male collegiate soccer players

The influence of the chronotype on the sleep quality in male collegiate soccer players in response to acute high intensity interval training (HIIT) performed at two different times of day was evaluated. The sleep quality was poorer in the morning-type than in the evening-type players after the evening HIIT session, whereas no significant changes in the sleep quality of the two chronotypes after the morning HIIT session was observed. The results suggest that an athlete’s chronotype should be taken into account when scheduling training sessions and to promote faster recovery processes.     

Dominant-subordinate relationships in hamsters: sex differences in reactions to familiar opponents

In the majority of mammalian species, males are dominant over and more aggressive than females. In contrast, some reports suggest that female golden hamsters are more aggressive than males but systematic comparisons using the same methods for both sexes are rare. We observed same-sexed pairs of hamsters over repeated trials to assess whether sex differences existed in the level of agonistic behavior and in the development and maintenance of dominant-subordinate relationships with familiar partners. There were no sex differences in measures of agonistic behavior or fear responses (fleeing) during the initial series of three trials on the first day of testing. Following a four-day interval, males that had lost in session 1 showed fearful responses to a familiar dominant male and were not likely to engage in a fight with him. In contrast, females that lost the initial fights were not fearful and fought vigorously with the familiar winner in subsequent encounters. Although the amount of agonistic behavior engaged in by females did decrease over the course of the three sessions, females that lost did not demonstrate an increase in fear, as measured by the latency to flee. Males that lost fights did show increased fear during later trials and sessions. These results suggest that female hamsters are less affected by losing fights than males are and thus that females are less likely than males to develop highly polarized dominant-subordinate relationships. Further work is needed to understand the mechanisms underlying these sex differences.     

Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus

Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.     

Awareness modifies the skill-learning benefits of sleep

Behind every skilled movement lies months of practice. However, practice alone is not responsible for the acquisition of all skill; performance can improve between, not just within, practice sessions. An important principle shaping these offline improvements may be an individual's awareness of learning a new skill. New skills, such as a sequence of finger movements, can be learned unintentionally (with little awareness for the sequence, implicit learning) or intentionally (explicit learning). We measured skill in an implicit and explicit sequence-learning task before and after a 12 hr interval. This interval either did (8 p.m. to 8 a.m.) or did not (8 a.m. to 8 p.m.) include a period of sleep. Following explicit sequence learning, offline skill improvements were only observed when the 12 hr interval included sleep. This overnight improvement was correlated with the amount of NREM sleep. The same improvement could also be observed in the evening (with an interval from 8 p.m. to 8 p.m.), so it was not coupled to retesting at a particular time of day and cannot therefore be attributed to circadian factors. In contrast, in the implicit learning task, offline learning was observed regardless of whether the 12 hr interval did or did not contain a period of sleep. However, these improvements were not observed with only a 15 min interval between sessions. Therefore, the practice available within each session cannot account for these skill improvements. Instead, sufficient time is necessary for offline learning to occur. These results show a behavioral dissociation, based upon an individual's awareness for having learned a sequence of finger movements. Offline learning is sleep dependent for explicit skills but time dependent for implicit skills.     

Facial Expression Training Optimises Viewing Strategy in Children and Adults

This study investigated whether training-related improvements in facial expression categorization are facilitated by spontaneous changes in gaze behaviour in adults and nine-year old children. Four sessions of a self-paced, free-viewing training task required participants to categorize happy, sad and fear expressions with varying intensities. No instructions about eye movements were given. Eye-movements were recorded in the first and fourth training session. New faces were introduced in session four to establish transfer-effects of learning. Adults focused most on the eyes in all sessions and increased expression categorization accuracy after training coincided with a strengthening of this eye-bias in gaze allocation. In children, training-related behavioural improvements coincided with an overall shift in gaze-focus towards the eyes (resulting in more adult-like gaze-distributions) and towards the mouth for happy faces in the second fixation. Gaze-distributions were not influenced by the expression intensity or by the introduction of new faces. It was proposed that training enhanced the use of a uniform, predominantly eyes-biased, gaze strategy in children in order to optimise extraction of relevant cues for discrimination between subtle facial expressions.     

A pilot study investigating motor adaptations when learning to walk with a whole-body powered exoskeleton

Evidence is emerging on how whole-body powered exoskeleton (EXO) use impacts users in basic occupational work scenarios, yet our understanding of how users learn to use this complex technology is limited. We explored how novice users adapted to using an EXO during gait. Six novices and five experienced users completed the study. Novices completed an initial training/familiarization gait session, followed by three subsequent gait sessions using the EXO, while experienced users completed one gait session with the EXO. Spatiotemporal gait measures, pelvis and lower limb joint kinematics, muscle activities, EXO torques, and human-EXO interaction forces were measured. Adaptations among novices were most pronounced in spatiotemporal gait measures, followed by joint kinematics, with smaller changes evident in muscle activity and EXO joint torques. Compared to the experienced users, novices exhibited a shorter step length and walked with significantly greater anterior pelvic tilt and less hip extension. Novices also used lower joint torques from the EXO at the hip and knee, and they had greater biceps femoris activity. Overall, our results may suggest that novices exhibited clear progress in learning, but they had not yet adopted motor strategies similar to those of experienced users after the three sessions. We suggest potential future directions to enhance motor adaptations to powered EXO in terms of both training protocols and human-EXO interfaces.