Fornix transection impairs visuospatial memory acquisition more than retrieval

It has been hypothesized that some fornical fibres may instantiate a neuromodulatory reinforcement signal supporting memory acquisition in medial temporal cortical regions. This suggests that fornix transection should impair postoperative new learning more severely than the recall of preoperatively acquired information. Here, postoperative recall of 288 concurrent visuo-spatial discrimination problems acquired preoperatively was unaffected after fornix transection in the macaque, whereas new postoperative learning of 72 problems was impaired. This and other recent evidence supports the idea that the main function of the fornix in macaque monkeys is to support new learning about spatio-temporal context.     

Neuronal activity in the monkey striatum during conditional visuomotor learning

The brainstem projection of the saccular nerve was investigated by transganglionic tracing with horseradish peroxidase in the cat. The labeled fibers were located most caudally and laterally (dorsolaterally) in the vestibular nerve root. This was unique when compared with the locations of the fibers from the nerves of the other vestibular-end organs that were studied by the present authors by the same approach previously. In addition, such a comparison revealed a specific location, from lateral to medial, for the fibers from each of the five divisions of the vestibular nerve. In the present study, labeled fibers from the sacculus, of fine caliber, were found close to the restiform body, both medially and laterally, some even penetrating through this structure. Labeled terminals were present in cell group "y". This was unique, compared with the nerves from the other end organs. Such terminals were also found in the four main vestibular nuclei, except for the medial vestibular nucleus, where no labeled terminals could be detected. No labeled terminals were found in the interstitial nucleus of the vestibular nerve. Together with the findings from our previous studies, this suggests that, in contrast to the ampullar nerves, the nerves from the maculae do not project to this structure. This study confirms, but also extends, findings reported from a previous investigation in the cat, using an experimental degeneration technique. This article is based on experimental material that was prepared before the untimely death of Dr. Siegborn in 1997. He took active part in the planning of this study, and he carried out all of the microsurgery     

Interaction of ventral and orbital prefrontal cortex with inferotemporal cortex in conditional visuomotor learning

Five rhesus monkeys (Macaca mulatta) were trained to learn novel conditional visuomotor associations, to perform this task with familiar stimuli, and to perform a visual matching-to-sample task with the same familiar stimuli. Removal of the orbital and ventral prefrontal cortex (PFv+o) in 1 hemisphere and inferotemporal cortex (IT) in the other, thus completing a surgical disconnection of these 2 regions, yielded an impairment on all 3 tasks. Addition of a premotor cortex lesion to the hemisphere containing the PFv+o lesion did not worsen the impairments. The results indicate that PFv+o interacts with IT in both the learning and retention of conditional visuomotor associations. In addition to those associations, which might be considered lower order rules for choosing a response, frontotemporal interaction also appears to be important for higher order rules, such as those involved in the matching task.     

Prefrontal lesions impair the implicit and explicit learning of sequences on visuomotor tasks

OBJECTIVE: (1) To verify whether the prefrontal cortex (PFC) is specifically involved in visuomotor sequence learning as opposed to other forms of motor learning and (2) to establish the role of executive functions in visuomotor sequence learning. BACKGROUND: Visuomotor skill learning depends on the integrity of the premotor and parietal cortex; the prefrontal cortex, however, is essential when the learning of a sequence is required. METHODS: We studied 25 patients with PFC lesions and 86 controls matched for age and educational level. Participants performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task (perceptual learning) and a pattern tracking task (explicit motor sequence learning with learning indicated by the decrease in mean root square error across trial blocks), (2) a 12-item sequence version of a serial reaction time task (SRTT) with specific implicit motor sequence learning indicated by the rebound increase in response time when comparing the last sequence block with the next random block, and (3) a neuropsychological battery that assessed executive functions. RESULTS: PFC patients were impaired in sequence learning on the pattern tracking task of the PTT and on the SRTT as compared to controls, but performed normally on the PTT random tracking task. Learning on the PTT did not correlate with learning on the SRTT. PTT performance correlated with planning functions while SRTT performance correlated with working memory capacity. CONCLUSIONS: The PFC is specifically involved in explicit and implicit motor sequence learning. Different PFC regions may be selectively involved in such learning depending on the cognitive demands of the sequential task.     

Modulation of frontal and parietal neuronal activity by visuomotor learning. An ERP analysis of implicit and explicit pursuit tracking tasks

The present study investigated changes in frontal and parietal activity related to visuomotor learning. Improvement in task performance should be achieved by a transition from feedback control to feedforward control. Event-related potential (ERP) activity related to visual feedback analysis of successful error corrections was expected to decrease at parietal scalp locations. (Pre-) motor activity related to the execution of directional changes should increase and begin earlier.     

The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta)

Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less, within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions. Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex, but rapid, within-session learning does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift, which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session, and reducing the working memory load did not improve within-session learning.     

Early-life malnutrition impairs the performance of both young and adult rats on visual discrimination learning tasks

Previously malnourished young (20-40-day-old) and mature (70-77-day-old) rats were compared on position, brightness, and pattern discrimination problems using an aquatic version of the Lashley jump stand. Malnutrition did not affect performance on the position discrimination. In contrast, previously malnourished 24-34-day-olds failed to solve the brightness discrimination, 40-day-olds were impaired on the brightness problem, and 40-77-day olds were impaired on the pattern problem. The impaired performance of the 40-day-olds on the brightness problem was eliminated by prior training on the pattern discriminations, and the impaired performance of the 70-day-olds on the pattern discrimination could be eliminated if they were first trained on the brightness problem. These impairments were attributed to the effects of early-life malnutrition on the maturation of attention processes that enable the rat to suppress responding to irrelevant cues. The relevance of a contextual-organismic perspective for understanding the effects of early-life malnutrition was discussed.     

Early learning failure impairs adult learning in rats

Early life experiences may affect adult learning ability. In two experiments we tested the effect of early learning failure on adult performance in Wistar rats. In the first experiment 17-day-old rats (PN17), but not 25-day-old rats (PN25), trained in a hidden platform water maze task showed deficits in tone-shock avoidance learning when they were 3-months-old. The second experiment, which included random-platform and non-platform control groups, confirmed the effect of early (PN18) spatial learning failure on adult avoidance learning. However, post-weaning training (PN25) without platform also tended to induce adult learning deficits as long as the adult task difficulty was increased. The older non-platform group did not differ from the impaired group which received early training in a fixed hidden platform task. The results are discussed in terms of the relevance of early learning outcome and developmental stage on adult general learning deficits which may be related to the learned helplessness phenomenon and developmental neural plasticity.     

Sex differentiated responses to intranasal trigeminal stimuli.

The aim of the study was to address sex-related hemispheric differences in trigeminal event-related potentials while controlling for the subjects' olfactory sensitivity. Event-related potentials to lateralized stimulation using the trigeminal stimulant CO(2) were recorded in 28 healthy young subjects (16 women). There was no sex-related difference in olfactory sensitivity. Results indicated a sex-differentiated response to trigeminally induced pain. Women were found to have generally higher amplitudes and shorter latencies of the late positive component than men. Moreover, men and women exhibited different hemispheric activations in that women expressed shorter latencies over the left hemisphere than men. The pronounced sex-related difference of the late positive component suggests a cognitive/emotional impact on the processing of intranasal pain as indicated by others.     

Glossopharyngeal nerve transection impairs unconditioned avoidance of diverse bitter stimuli in rats

There is growing evidence of heterogeneity among responses to bitter stimuli at the peripheral, central and behavioral levels. For instance, the glossopharyngeal (GL) nerve and neurons receiving its projections are more responsive to bitter stimuli than the chorda tympani (CT) nerve, and this is particularly true for some bitter stimuli like PROP & cycloheximide that stimulate the GL to a far greater extent. Given this information, we hypothesized that cutting the GL would have a greater effect on behavioral avoidance of cycloheximide and PROP than quinine and denatonium, which also stimulate the CT, albeit to a lesser degree than salts and acids. Forty male SD rats were divided into four surgery groups: bilateral GL transection (GLX), chorda tympani transection (CTX), SHAM surgery, and combined transection (CTX + GLX). Postsurgical avoidance functions were generated for the four bitter stimuli using a brief-access test. GLX significantly compromised avoidance compared to both CTX and SHAM groups for all stimuli (p < .02), while CTX and SHAM groups did not differ. Contrary to our hypothesis, GLX had a greater effect on quinine than cycloheximide (mean shift of 1.02 vs. 0.27 log10 units). Moreover, combined CTX + GLX transection shifted the concentration-response function further than GLX alone for every stimulus except cycloheximide (ps < .03), suggesting that the GSP nerve is capable of maintaining avoidance of this stimulus to a large degree. This hypothesis is supported by reports of cycloheximide-responsive cells with GSP-innervated receptive fields in the NST and PBN.     

Differences in trace and delay visuomotor associative learning in cerebellar patients

Recent studies revealed an impairment of patients with cerebellar lesions in cognitive associative learning paradigms, which could not be explained by motor deficits or increased attentional demands during performance of the motor part of the particular task. To further test the role of the cerebellum in cognitive associative learning a visuomotor associative learning paradigm was conducted, which showed some similarities to reflex conditioning. Subjects had to learn the association between a visual stimulus (i.e., a colored square) and a correct motor response (i.e., pressing a left or right target button on a specialized keyboard) in a stimulus-response paradigm. The correct side of the response was always indicated by a growing circle. The stimuli were presented in two forms: (1) the colored square ("conditioned stimulus", "CS") preceded the growing circle ("unconditioned stimulus", "US") and coterminated with the "US" (delay-condition) or (2) the offset of the colored square was separated from the onset of the circle by a short time interval (trace-condition). Eight patients with degenerative cerebellar disorders and eight age-, sex-, IQ-, and education level-matched controls participated. Both control subjects and cerebellar patients showed significant effects of learning based on reduction of decision times during performance of the task. The explicit knowledge of the correct motor response associated with each of the presented colors, however, was significantly better in control subjects. Furthermore, within-group comparisons revealed that control subjects performed significantly better in the trace-condition compared to the delay-condition, whereas no significant difference was obtained in the cerebellar group. Part of the findings in controls was explained by an age-related decline in the delay-condition. In addition, elderly control subjects appeared to benefit from cue-effects and timing-effects (i.e., fixed trace interval) in the trace-condition resulting in reduced decision times. Neither cue- nor timing-related effects fully accounted for differences between cerebellar patients and controls. The lack of a better performance in the trace-condition compared to the delay-condition in cerebellar patients suggests deficits in learning the stimulus-response association. Electronic Publication     

Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses.

The encapsulated yeast Cryptococcus neoformans is a significant cause of opportunistic infection in patients with impaired cell-mediated immunity. The major virulence determinant of the organism is an antiphagocytic polysaccharide capsule synthesized after entry into the host. Using both an encapsulated virulent strain and an acapsular avirulent mutant, we have demonstrated the reduced ability of the encapsulated strain to stimulate specific T-cell responses in vitro. This reduction was mediated by the antiphagocytic action of the capsule rather than by direct inhibition of antigen processing and presentation, since prior opsonization with complement enhanced the ingestion of encapsulated yeast cells by purified antigen-presenting cells and allowed significant T-cell activation. Once ingestion had occurred, cryptococci were efficiently processed by activated macrophages via a chloroquine-sensitive pathway. Cryptococcal antigens were available for T-cell recognition within 1 to 2 h of interaction with macrophages and presented in a major histocompatibility complex-restricted manner. Our results suggest that the antiphagocytic action of the polysaccharide capsule is an important determinant for the development of T-cell immunity to C. neoformans.     

Spatial conditional discrimination learning in developing rats

The present study established an effective procedure for studying spatial conditional discrimination learning in juvenile rats using a T-maze. Wire mesh located on the floor of the maze as well as a second, identical T-maze apparatus served as conditional cues which signaled whether a left or a right response would be rewarded. In Experiment 1, conditional discrimination was evident on Postnatal Day (PND) 30 when mesh+maze or maze-alone were the conditional cues, but not when mesh-alone was the cue. Experiment 2 confirmed that mesh-alone was sufficiently salient to support learning of a simple (nonconditional) discrimination. Its failure to serve as a conditional cue in Experiment 1 does not reflect its general ineffectiveness as a stimulus. Experiment 3 confirmed that the learning shown in Experiment 1 was indeed conditional in nature by comparing performance on conditional versus nonconditional versions of the task. Experiment 4 showed that PND19 and PND23 pups also were capable of performing the task when maze+mesh was the cue; however, the findings indicate that PND19 subjects do not use a conditional strategy to learn this task. The findings suggest postnatal ontogeny of conditional discrimination learning and underscore the importance of conditional cue salience, and of identifying task strategies, in developmental studies of conditional discrimination learning.     

Preparatory activity in motor cortex reflects learning of local visuomotor skills

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.     

Effects of explicit knowledge of workspace rotation in visuomotor sequence learning

Previous experimental and theoretical studies have suggested that two separate neural networks contribute to visuomotor learning of spatial sequences, one to the accuracy of performance and the other to the speed of performance (Nakahara et al. in J Cogn Neurosci 13:626-647, 2001). This study examined the influence of explicit knowledge of stimulus configuration (workspace) in visuomotor sequence learning. Twenty-eight right-handed subjects learned the sequences of button presses by trial and error (Hikosaka et al. in J Neurophysiol 76:617-621, 1996) in the course of two sessions. In the first session, both the number of completion failures (accuracy measure) and the performance time to complete a sequence (speed measure) decreased. In the second session, the workspace was rotated without notifying the subjects. About half the subjects remained unaware of the workspace rotation, and no transfer of learning occurred (i.e., neither accuracy nor speed of performance was preserved in the second session). The remaining subjects spontaneously noticed the rotation and they were able to use this knowledge to perform the task with less completion failures in the second session. However, the knowledge of workspace rotation did not decrease the performance time in the second session. The lack of influence of explicit knowledge on the speed of performance is consistent with the two-loop model of visuomotor sequence learning (Nakahara et al. in J Cogn Neurosci 13:626-647, 2001).     

Neonatal alcohol exposure impairs acquisition of eyeblink conditioned responses during discrimination learning and reversal in weanling rats

Discrimination and reversal of the classically conditioned eyeblink response depends on cerebellar-brainstem interactions with the hippocampus. Neonatal "binge" exposure to alcohol at doses of 5 g/kg/day or more has been shown to impair single-cue eyeblink conditioning in both weanling and adult rats. The present study exposed neonatal rats to acute alcohol intubations across different developmental periods (postnatal day [PND] 4-9 or PND7-9) and tested them from PND26-31 on discriminative classical eyeblink conditioning and reversal. A high dose of alcohol (5 g/kg/day) dramatically impaired conditioning relative to controls when exposure occurred over PND4-9, but produced mild or no impairments when delivered over PND7-9. These findings support previous claims that developmental exposure period plays a critical role in determining the deleterious effects of alcohol on the developing brain. A lower dose of alcohol (4 g/kg/day) delivered from PND4-9--lower than has previously been shown to affect single-cue eyeblink conditioning--also produced deficits on the discrimination task, suggesting that discrimination learning and acquisition of responding to CS+ during reversal may be especially sensitive behavioral indicators of alcohol-induced brain damage in this rat model.     

Writer's cramp: cortical excitability in tasks involving proximo-distal coordination

Aim: The aim of this work was to analyse how writer’s cramp patients coordinate each element of the proximal to distal upper arm muscle chain during voluntary movement. Methods: Using transcranial magnetic stimulation, we have assessed motor cortex excitability properties in patients by recording motor‐evoked potentials and silent periods in both the extensor carpi radialis (ECR) and the first dorsal interosseus muscles (FDI), activated either in isolation, or in conjunction with voluntary medial deltoid (MD) co‐activation during performance of precise tasks. Ten dystonic patients and ten healthy controls were tested. Results: In both test groups, the ECR muscle displayed a similar active motor threshold, but the excitability curves reached higher plateau values, when the proximal MD muscle was co‐activated. In the dystonic group, the FDI muscle excitability curves reached higher plateau values when the MD was co‐activated, whereas co‐activation had no effect on the control group. In the control group, silent periods, in both the ECR and the FDI were longer when the MD was co‐activated. This effect was not observed in the dystonic group. Conclusion: In the dystonic group, facilitation of the FDI was observed during a task involving proximo‐distal coordination. No differences in silent periods were observed when the muscle was activated alone. Our results suggest that such abnormal facilitation is not only an impairment of the central inhibitory mechanisms reported for dystonic patients, but, in addition, represents true abnormality in cortical muscle activation strategies.     

Cross talk in implicit assignment of error information during bimanual visuomotor learning

When a neural movement controller, called an "internal model," is adapted to a novel environment, the movement error needs to be appropriately associated with the controller. However, their association is not necessarily guaranteed for bimanual movements in which two controllers--one for each hand--result in two movement errors. Considering the implicit nature of the adaptation process, the movement error of one hand can be erroneously associated with the controller of the other hand. Here, we investigated this credit-assignment problem in bimanual movement by having participants perform bimanual, symmetric back-and-forth movements while displaying the position of the right hand only with a cursor. In the training session, the cursor position was gradually rotated clockwise, such that the participants were unaware of the rotation. The movement of the right hand gradually rotated counterclockwise as a consequence of adaptation. Although the participants knew that the cursor reflected the movement of the right hand, such gradual adaptation was also observed for the invisible left hand, especially when the cursor was presented on the left side of the display. Thus the movement error of the right hand was implicitly assigned to the left-hand controller. Such cross talk in credit assignment might influence motor adaptation performance, even when two cursors are presented; the adaptation was impaired when the rotations imposed on the cursors were opposite compared with when they were in the same direction. These results indicate the inherent presence of cross talk in the process of associating action with consequence in bimanual movement.     

Classification of frontal cortex haemodynamic responses during cognitive tasks using wavelet transforms and machine learning algorithms

Recent advances in neuroimaging demonstrate the potential of functional near-infrared spectroscopy (fNIRS) for use in brain–computer interfaces (BCIs). fNIRS uses light in the near-infrared range to measure brain surface haemoglobin concentrations and thus determine human neural activity. Our primary goal in this study is to analyse brain haemodynamic responses for application in a BCI. Specifically, we develop an efficient signal processing algorithm to extract important mental-task-relevant neural features and obtain the best possible classification performance. We recorded brain haemodynamic responses due to frontal cortex brain activity from nine subjects using a 19-channel fNIRS system. Our algorithm is based on continuous wavelet transforms (CWTs) for multi-scale decomposition and a soft thresholding algorithm for de-noising. We adopted three machine learning algorithms and compared their performance. Good performance can be achieved by using the de-noised wavelet coefficients as input features for the classifier. Moreover, the classifier performance varied depending on the type of mother wavelet used for wavelet decomposition. Our quantitative results showed that CWTs can be used efficiently to extract important brain haemodynamic features at multiple frequencies if an appropriate mother wavelet function is chosen. The best classification results were obtained by a specific combination of input feature type and classifier.