Evolution of motor memory during the seconds after observation of motor error

When a movement results in error, the nervous system amends the motor commands that generate the subsequent movement. Here we show that this adaptation depends not just on error, but also on passage of time between the two movements. We observed that subjects learned a reaching task faster, i.e., with fewer trials, when the intertrial time intervals (ITIs) were lengthened. We hypothesized two computational mechanisms that could have accounted for this. First, learning could have been driven by a Bayesian process where the learner assumed that errors are the result of perturbations that have multiple timescales. In theory, longer ITIs can produce faster learning because passage of time might increase uncertainty, which in turn increases sensitivity to error. Second, error in a trial may result in a trace that decays with time. If the learner continued to sample from the trace during the ITI, then adaptation would increase with increased ITIs. The two models made separate predictions: The Bayesian model predicted that when movements are separated by random ITIs, the learner would learn most from a trial that followed a long time interval. In contrast, the trace model predicted that the learner would learn most from a trial that preceded a long time interval. We performed two experiments to test for these predictions and in both experiments found evidence for the trace model. We suggest that motor error produces an error memory trace that decays with a time constant of about 4 s, continuously promoting adaptation until the next movement.     

A comparison of multiple-unit activity in the medial prefrontal and agranular insular cortices during Pavlovian heart rate conditioning in rabbits

Summary Multiple-unit activity (MUA) was recorded from chronically implanted electrodes in the medial prefrontal cortex (PFCm) and the agranular insular cortex (Iag) in separate groups of rabbits during habituation training, followed by aversive Pavlovian conditioning and subsequent extinction training. Control animals received explicitly unpaired presentations of the tone conditioned stimulus (CS) and eye-shock unconditioned stimulus (US). Both the cardiac orienting reflex and the conditioned heart rate response (HR CR) consisted of bradycardia, whereas tone-evoked tachycardia was observed in animals that received unpaired stimuli. Short-latency (<20–60 ms), tone-evoked increases in PFCm MUA were observed during the initial trials of habituation training, with their magnitude declining predictably across repeated tonealone presentations. Subsequent CS/US pairings, however, served systematically to reinstate and enhance this CS-evoked MUA, while both non-associative (unpaired CS/US) and extinction (CS alone) training resulted in significant attenuation of such activity. Unconditioned tone-evoked increases in MUA were also observed in the Iag during habituation; however, such unit responses appeared to be more variable than their PFCm counterparts and were of considerably lesser magnitude. Moreover, in striking contrast to the above PFCm findings, conditioning and non-associative training did not differentially affect overall mean evoked MUA in the Iag, although different post-tone patterns of activity were obtained with the two procedures. The contrasting training effects observed in animals with PFCm vs. Iag electrode placements did not appear to be attributable to differences in regional sensitivity to the US, since excitatory patterns of MUA were elicited by unsignalled presentations of eye-shock at most placements within each cortical field. Accordingly, the present findings are consistent with our previous lesion data in suggesting that, although training-induced changes in PFCm neuronal activity may contribute to the initial events in aversive Pavlovian conditioning, an involvement of the Iag in such processes, if any, remains to be demonstrated.     

Comparison of effector-specific signals in frontal and parietal cortices

We previously demonstrated that the activities of neurons in the lateral intraparietal area (LIP) and the parietal reach region (PRR) of the posterior parietal cortex (PPC) are modulated by nonspatial effector-specific information. We now report similar modulation in FEF, an area of frontal cortex that is reciprocally connected with LIP. Although it is possible that these effector-specific signals originate in LIP and are conveyed to FEF, it is also possible that these signals originate in FEF and are "fed back" to LIP. We found that signal magnitude was no larger, and onset time no earlier, in FEF compared with LIP. Moreover, effector-specific activity in FEF, but not in LIP, was largely driven by spatial prediction. These results suggest that the saccade-related effector-specific signals found in LIP do not originate in FEF. Conversely, LIP may contribute to the effector-specific signals found in FEF, but does not wholly account for them.     

Retest reliability of medial frontal negativities during performance monitoring

The error‐related negativity (ERN) and feedback‐related negativity (FRN) have been used as electrophysiological indices of performance monitoring produced in response to internally generated (errors) and externally generated (feedback) activations of the anterior cingulate cortex (ACC). No studies to date have systematically examined the measurement reliability of these components. In this article, we present the retest reliability of the ERN and FRN during response tasks designed to elicit errors or feedback responses on two occasions. Data from four experiments are presented in which participants performed tasks over various periods of time. Results indicate good retest reliability of the ERN and FRN amplitudes and source generation of these components. The present article provides important validation of the ERN and FRN as stable and trait‐like electrophysiological reflections of performance monitoring and ACC functional integrity.     

Symmetric facilitation between motor cortices during contraction of ipsilateral hand muscles

Using transcranial magnetic stimulation (TMS) over the contralateral motor cortex, motor evoked potentials (MEPs) were recorded from resting abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles of eight subjects while they either rested or produced one of six levels of force with the APB ipsilateral to the TMS. F-waves were recorded from each APB at rest in response to median nerve stimulation while subjects either rested or produced one of two levels of force with their contralateral APB. Contraction of the APB ipsilateral to TMS produced facilitation of the MEPs recorded from resting APB and FDI muscles contralateral to TMS but did not modulate F-wave amplitude. Negligible asymmetries in MEP facilitation were observed between dominant and subdominant hands. These results suggest that facilitation arising from isometric contraction of ipsilateral hand muscles occurs primarily at supraspinal levels, and this occurs symmetrically between dominant and subdominant hemispheres. Electronic Publication     

Saccade preparation signals in the human frontal and parietal cortices

Our ability to prepare an action in advance allows us to respond to our environment quickly, accurately, and flexibly. Here, we used event-related functional MRI to measure human brain activity while subjects maintained an active state of preparedness. At the beginning of each trial, subjects were instructed to prepare a pro- or antisaccade to a visual cue that was continually present during a long and variable preparation interval, but to defer the saccade's execution until a go signal. The deferred saccade task eliminated the mnemonic component inherent in memory-guided saccade tasks and placed the emphasis entirely on advance motor preparation. During the delay while subjects were in an active state of motor preparedness, the blood oxygen level-dependent signal in the frontal cortex showed 1) a sustained elevation throughout the preparation interval; 2) a linear increase with increasing delay length; 3) a bias for contra- rather than ipsiversive movements; 4) greater activity when the specific metrics of the planned saccade were known compared with when they were not; and 5) increased activity when the saccade was directed toward an internal versus an external representation (i.e., anticue location). These findings support the hypothesis that both the human frontal and parietal cortices are involved in the spatial selection and preparation of saccades.     

Single-unit activity related to bimanual arm movements in the primary and supplementary motor cortices

Single units were recorded from the primary motor (MI) and supplementary motor (SMA) areas of Rhesus monkeys performing one-arm (unimanual) and two-arm (bimanual) proximal reaching tasks. During execution of the bimanual movements, the task related activity of about one-half the neurons in each area (MI: 129/232, SMA: 107/206) differed from the activity during similar displacements of one arm while the other was stationary. The bulk of this "bimanual-related" activity could not be explained by any linear combination of activities during unimanual reaching or by differences in kinematics or recorded EMG activity. The bimanual-related activity was relatively insensitive to trial-to-trial variations in muscular activity or arm kinematics. For example, trials where bimanual arm movements differed the most from their unimanual controls did not correspond to the ones where the largest bimanual neural effects were observed. Cortical localization established by using a mixture of surface landmarks, electromyographic recordings, microstimulation, and sensory testing suggests that the recorded neurons were not limited to areas specifically involved with postural muscles. By rejecting this range of alternative explanations, we conclude that neural activity in MI as well as SMA can reflect specialized cortical processing associated with bimanual movements.     

A comparison of stimulus synchronous activity in the primary motor cortices of athletes and non-athletes

In this study, we measured primary motor cortex (MI) activity during a reaction time task to examine the appearance of MI activity that synchronized with the stimulus presentation (stimulus synchronous MI activity, SSMA). Because brain activity was expected to be enhanced by the repetitive/extensive activation, we hypothesized that the SSMA would be more clearly observable in athletes who were trained to perform reactive movements than in non-athletes. MI activity was measured in ten athletes and ten non-athletes by magnetoencephalography. The tasks were a simple reaction task and a Go/Nogo reaction task in which the subjects were asked to abduct their right index fingers in response to a visual stimulus. The Go/Nogo reaction time task was adopted to confirm the presence of the SSMA, because the MI activity in response to a Nogo stimulus did not overlap with the MI activity that was synchronous with the execution of the movement. The results show that the SSMA was clearly apparent in the athlete group (9/10). In the non-athlete group, however, only three subjects showed the SSMA (3/10). Moreover, the MI activity of the athletes tended to be larger than that of the non-athletes, even though the athletes did not specifically practice these index finger movements during their daily training. We concluded that long-term physical training promotes MI activity and the effects of reactive task repetition were more clearly apparent in the MI activity of the athletes.     

Modulation of rhythmic motor activity by pyrokinin peptides

Pyrokinin (PK) peptides localize to the central and peripheral nervous systems of arthropods, but their actions in the CNS have yet to be studied in any species. Here, we identify PK peptide family members in the crab Cancer borealis and characterize their actions on the gastric mill (chewing) and pyloric (filtering) motor circuits in the stomatogastric ganglion (STG). We identified PK-like immunolabeling in the STG neuropil, in projection neuron inputs to this ganglion, and in the neuroendocrine pericardial organs. By combining MALDI mass spectrometry (MS) and ESI tandem MS techniques, we identified the amino acid sequences of two C. borealis pyrokinins (CabPK-I, CabPK-II). Both CabPKs contain the PK family-specific carboxy-terminal amino acid sequence (FXPRLamide). PK superfusion to the isolated STG had little influence on the pyloric rhythm but excited many gastric mill neurons and consistently activated the gastric mill rhythm. Both CabPKs had comparable actions in the STG and these actions were equivalent to those of Pevpyrokinin (shrimp) and Leucopyrokinin (cockroach). The PK-elicited gastric mill rhythm usually occurred without activation of the projection neuron MCN1. MCN1, which does not contain CabPKs, effectively drives the gastric mill rhythm and at such times is also a gastric mill central pattern generator (CPG) neuron. Because the PK-elicited gastric mill rhythm is independent of MCN1, the underlying core CPG of this rhythm is different from the one responsible for the MCN1-elicited rhythm. Thus neuromodulation, which commonly alters motor circuit output without changing the core CPG, can also change the composition of this core circuit.     

Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion

One of the most common, and disruptive, neurological symptoms following neonatal brain injury is a motor impairment. Neonatal medial frontal cortical lesions in rats produce enduring motor impairments, and it is thought that lesion-induced abnormal cortical morphology and connectivity may underlie the motor deficits. In order to investigate the functional consequences of the lesion-induced anatomical abnormalities in adulthood, we used intracortical microstimulation to determine the neurophysiologic organization of motor maps within the lesion hemisphere. In addition, groups of neonatal lesion rats were given reach training or complex housing rehabilitation in adulthood and then mapped with intracortical microstimulation. The results demonstrate that neonatal medial frontal cortex lesions produce motor deficits in adulthood that are associated with abnormal motor maps. Further, adult behavioral treatment promoted partial recovery that was supported by reorganization of the motor maps whereby there were increases in the size of the forelimb motor maps. The experience-induced expansion of the forelimb motor maps in adulthood provides a neural mechanism for the experience-dependent improvements in motor performance.     

Modulation of shifting receptive field activity in frontal eye field by visual salience

In the monkey frontal eye field (FEF), the sensitivity of some neurons to visual stimulation changes just before a saccade. Sensitivity shifts from the spatial location of its current receptive field (RF) to the location of that field after the saccade is completed (the future field, FF). These shifting RFs are thought to contribute to the stability of visual perception across saccades, and in this study we investigated whether the salience of the FF stimulus alters the magnitude of FF activity. We reduced the salience of the usually single flashed stimulus by adding other visual stimuli. We isolated 171 neurons in the FEF of 2 monkeys and did experiments on 50 that had FF activity. In 30% of these, that activity was higher before salience was reduced by adding stimuli. The mean magnitude reduction was 16%. We then determined whether the shifting RFs were more frequent in the central visual field, which would be expected if vision across saccades were only stabilized for the visual field near the fovea. We found no evidence of any skewing of the frequency of shifting receptive fields (or the effects of salience) toward the central visual field. We conclude that the salience of the FF stimulus makes a substantial contribution to the magnitude of FF activity in FEF. In so far as FF activity contributes to visual stability, the salience of the stimulus is probably more important than the region of the visual field in which it falls for determining which objects remain perceptually stable across saccades.     

Cytology of human dorsal midcingulate and supplementary motor cortices

Human dorsal midcingulate cortex (MCC) is activated during many cognitive tasks and its role in skeletomotor functions is reflected in the size, density, and neurofilament proteins (NFP) expressed by neurons in this region. The present study used antibodies for neuron-specific nuclear binding protein and NFP in three postmortem cases to assess the cytology of the dorsal midcingulate areas 24c′, 24d, and 32′ and supplementary motor cortex. Area 24c′ has a thin layer Va and a Vb with large and NFP+ neurons not present on the gyral surface. Area 24d has two divisions; area 24dv on the ventral bank has layer Vb neurons that form aggregates, while area 24dd on the dorsal bank has large and solitary layer Vb pyramids. Co-registration of each case to standardized coordinates showed that the rostral area 24d border is at the vertical plane of the anterior commissure and its caudal border with area 23c is −2±0.21 cm in the y-axis. The transition to supplementary motor areas is characterized by significant increases in the density of large, NFP expressing neurons in layer IIIc and a substantial reduction in the size and density of such neurons in layer V. Since many acute pain studies activate dorsal MCC, understanding the architecture of this region will help explain its selective vulnerability to chronic pain and stress syndromes.     

Differential role of the medial and lateral prefrontal cortices in fear and anxiety

In the rat, both the medial and lateral prefrontal cortices (PFC; mPFC and lPFC, respectively) have direct connections with limbic structures that are important in the expression of fear and anxiety. The present study investigated the behavioral effects of excitotoxic lesions of either the mPFC or the lPFC on conditioned and unconditioned fear paradigms. In both unconditioned fear paradigms (open field, elevated plus-maze), lesions of the mPFC decreased anxiety. In fear conditioning, lPFC lesions substantially increased freezing throughout the different phases of the experiment, whereas mPFC lesions increased freezing to contextual cues and showed reduced freezing to discrete cues. These results support the functional role of the PFC in mediating or modulating central states of fear and anxiety and suggest a functional dissociation between the lPFC and mPFC in their role in fear and anxiety.     

Modulation of EMG power spectrum frequency during motor imagery

To provide evidence that motor imagery (MI) is accompanied by improvement of intramuscular conduction velocity (CV), we investigated surface electromyographic (EMG) activity of 3 muscles during the elbow flexion/extension. Thirty right-handed participants were asked to lift or to imagine lifting a weighted dumbbell under 3 types of muscular contractions, i.e. concentric, isometric and eccentric, taken as independent variables. The EMG activity of the agonist (long and short heads of biceps brachii) and the antagonist (long portion of triceps brachii) muscles was recorded and processed to determine the median frequency (MF) of EMG power spectrum as dependant variable. The MF was significantly higher during the MI sessions than during the resting condition while the participants remained strictly motionless. Moreover, the MF during imagined concentric contraction was significantly higher than during the eccentric. Thus, the MF variation was correlated to the type of contraction the muscle produced. During MI, the EMG patterns corresponding to each type of muscle contraction remained comparable to those observed during actual movement. In conclusion, specific motor programming is hypothesized to be performed as a function of muscle contraction type during MI.     

Medial frontal negativities predict performance improvements during motor sequence but not motor adaptation learning

Alterations in our environment require us to learn or alter motor skills to remain efficient. Also, damage or injury may require the relearning of motor skills. Two types have been identified: movement adaptation and motor sequence learning. Doyon et al. (2003, Distinct contribution of the cortico‐striatal and cortico‐cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252‐262) proposed a model to explain the neural mechanisms related to adaptation (cortico‐cerebellar) and motor sequence learning (cortico‐striatum) tasks. We hypothesized that medial frontal negativities (MFNs), event‐related electrocortical responses including the error‐related negativity (ERN) and correct‐response‐related negativity (CRN), would be trait biomarkers for skill in motor sequence learning due to their relationship with striatal neural generators in a network involving the anterior cingulate and possibly the supplementary motor area. We examined 36 participants' improvement in a motor adaptation and a motor sequence learning task and measured MFNs elicited in a separate Spatial Stroop (conflict) task. We found both ERN and CRN strongly predicted performance improvement in the sequential motor task but not in the adaptation task, supporting this aspect of the Doyon model. Interestingly, the CRN accounted for additional unique variance over the variance shared with the ERN suggesting an expansion of the model.     

Effects of motor cortical stimulation on the excitability of contralateral motor and sensory cortices

Single pulses of transcranial magnetic stimulation (TMS) were applied to the right hemisphere over either the hand sensory area, the hand motor area (M1), ventral premotor area (vPM), dorsolateral prefrontal cortex, or 10 cm away from head (sham stimulation) in order to test the effect on motor evoked potentials (MEPs) elicited by single pulse TMS or transcranial electrical stimulus (TES) over the left M1 or the somatosensory evoked potential (SEP) elicited by an electrical stimulus to the right median nerve. The interstimulus intervals (ISIs) for MEP experiments were 50, 100, 150, 200, 300 and 400 ms, with those for SEP experiments being adjusted for the impulse conduction time from the wrist to the cortex. TMS over the right M1 reduced MEPs elicited by TMS of the left motor cortex at ISIs of 50–150 ms, whereas MEPs produced by TES were unaffected. TMS over M1 and vPM facilitated the contralateral cortical median nerve SEPs at an ISI of 100–200 ms, whereas it had no effect on tibial nerve SEPs or paired median nerve stimulation SEP. Based on these results, we conclude that at around 150-ms intervals, TMS over the motor areas (M1 and vPM) reduces the excitability of the contralateral motor area. This has a secondary effect of enhancing the responsiveness of the sensory cortex through cortico-cortical connections.