Regional brain activation associated with different performance patterns during learning of a complex motor skill

In understanding the brain's response to extensive practice and development of high-level, expert skill, a key question is whether the same brain structures remain involved throughout the different stages of learning and a form of adaptation occurs, or a new functional circuit is formed with some structures dropping off and others joining. After training subjects on a set of complex motor tasks (tying knots), we utilized fMRI to observe that in subjects who learned the task well new regional activity emerged in posterior medial structures, i.e. the posterior cingulate gyrus. Activation associated with weak learning of the knots involved areas that mediate visual spatial computations. Brain activity associated with no substantive learning indicated involvement of areas dedicated to the declarative aspects learning such as the anterior cingulate and prefrontal cortex. The new activation for the pattern of strong learning has alternate interpretations involving either retrieval during episodic memory or a shift toward non-executive cognitive control of the task. While these interpretations are not resolved, the study makes clear that single time-point images of motor skill can be misleading because the brain structures that implement action can change following practice.     

Acquired Equivalence in U.S. Veterans With Symptoms of Posttraumatic Stress: Reexperiencing Symptoms Are Associated With Greater Generalization

The severity and number of reexperiencing symptoms (e.g., flashbacks) show considerable variability across individuals with posttraumatic stress disorder (PTSD). One interpretation of reexperiencing symptoms invokes generalization: Specifically, the traumatic memory may be stored in such a way that neutral stimuli that only vaguely resemble some feature of the traumatic event are sufficient to trigger the memory. If this is the case, then individuals with higher levels of reexperiencing symptoms might show greater generalization, even in contexts unrelated to trauma. In the current study, an acquired equivalence test was used to assess associative learning and generalization in 114 U.S. veterans who were also given a test of declarative memory. PTSD symptoms were rated by the veteran. After adjusting for demographic variables, psychoactive medication use, and initial learning, regression analyses showed that the number of PTSD reexperiencing symptoms significantly improved the model for generalization (β = ?.23, R² = .34) but not associative learning or declarative memory. The results support the idea that generalization is linked to reexperiencing symptoms, is not limited to learning about traumatic events, and can emerge even in a relatively innocuous computer‐based learning task.     

The role of the dorsolateral prefrontal cortex during sequence learning is specific for spatial information.

Many studies have implicated the dorsolateral prefrontal cortex in the acquisition of skill, including procedural sequence learning. However, the specific role it performs in sequence learning has remained uncertain. This type of skill has been intensively studied using the serial reaction time task. We used three versions of this task: a standard task where the position of the stimulus cued the response; a non-standard task where the color of the stimulus was related to the correct response; and a combined task where both the color and position simultaneously cued the response. We refer to each of these tasks based upon the cues available for guiding learning as position, color and combined tasks. The combined task usually shows an enhancement of skill acquisition, a result of being driven by two simultaneous and congruent cues. Prior to the performance of each of these tasks the function of the dorsolateral prefrontal cortex was disrupted using repetitive transcranial magnetic stimulation. This completely prevented learning within the position task, while sequence learning occurred to a similar extent in both the color and combined tasks. So, following prefrontal stimulation the expected learning enhancement in the combined task was lost, consistent with only a color cue being available to guide sequence learning in the combined task. Neither of these effects was observed following stimulation at the parietal cortex. Hence the critical role played by the dorsolateral prefrontal cortex in sequence learning is related exclusively to spatial cues. We suggest that the dorsolateral prefrontal cortex operates over the short term to retain and manipulate spatial information to allow cortical and subcortical structures to learn a predictable sequence of actions. Such functions may emerge from the broader role the dorsolateral prefrontal cortex has in spatial working memory. These results argue against the dorsolateral prefrontal cortex constituting part of the neuronal substrate responsible for general aspects of implicit or explicit sequence learning.     

Developmental changes in mental arithmetic: evidence for increased functional specialization in the left inferior parietal cortex

Arithmetic reasoning is arguably one of the most important cognitive skills a child must master. Here we examine neurodevelopmental changes in mental arithmetic. Subjects (ages 8-19 years) viewed arithmetic equations and were asked to judge whether the results were correct or incorrect. During two-operand addition or subtraction trials, for which accuracy was comparable across age, older subjects showed greater activation in the left parietal cortex, along the supramarginal gyrus and adjoining anterior intra-parietal sulcus as well as the left lateral occipital temporal cortex. These age-related changes were not associated with alterations in gray matter density, and provide novel evidence for increased functional maturation with age. By contrast, younger subjects showed greater activation in the prefrontal cortex, including the dorsolateral and ventrolateral prefrontal cortex and the anterior cingulate cortex, suggesting that they require comparatively more working memory and attentional resources to achieve similar levels of mental arithmetic performance. Younger subjects also showed greater activation of the hippocampus and dorsal basal ganglia, reflecting the greater demands placed on both declarative and procedural memory systems. Our findings provide evidence for a process of increased functional specialization of the left inferior parietal cortex in mental arithmetic, a process that is accompanied by decreased dependence on memory and attentional resources with development.     

Dissociation between explicit memory and configural memory in the human medial temporal lobe

Using functional magnetic resonance imaging, the current study explored the differential mnemonic contributions of the hippocampus and surrounding medial temporal lobe (MTL) cortices to explicit recognition memory and configural learning. Using a task that required processing of repeated and novel visuospatial contexts across multiple trials, we examined MTL activation in relation to 3 forms of learning in a single paradigm: 1) context-independent procedural learning, 2) context-dependent configural learning, and 3) explicit recognition memory. Activations in hippocampus and parahippocampal cortex were associated with explicit memory, differentiating between subsequently remembered and forgotten repeated contexts, but were unrelated to context-dependent configural learning. Activations in regions of perirhinal and entorhinal cortex were associated with configural learning of repeated contexts independent from explicit memory for those contexts. Procedural learning was unrelated to activation in any MTL region. The time course of activation across learning further differed in MTL subregions with MTL cortex demonstrating repetition-related decreases and hippocampus repetition-related increases. These repetition effects were differentially sensitive to recognition with only activation in hippocampus and parahippocampal cortex tracking recognized items. These imaging findings converge with studies of amnesia and indicate dissociable roles for hippocampus in learning that supports explicit recognition and for anterior MTL cortex in configural learning.     

The effect of water maze spatial training on posterior parietal cortex transcallosal evoked field potentials in the rat

Long-term potentiation (LTP) is the principal model of synaptic plasticity often used to explain the changes that occur in the brain as a result of learning and memory. In this experiment the relationship between rat posterior parietal cortex (PPC) transcallosal evoked field potentials (TCEPs) and spatial training in the water maze was examined to determine if LTP-like changes (i.e. learning-induced LTP) in PPC TCEPs occur as a result of spatial training. Spatial training consisted of 10 trials per day for 10 consecutive days. The location of the hidden platform was changed over the course of spatial training to ensure the rats' acquisition of several different platform positions. TCEPs were taken 1 and 23 h after each training session. Upon completion of all water maze training, the animals were administered LTP-inducing trains to ensure that the recording arrangement and procedure was capable of detecting LTP. The results showed that the rats quickly acquired the water maze task and that the recording arrangement and procedure were capable of detecting LTP, even after the first session of induction. However, despite robust place learning, the TCEPs taken after water maze training did not differ from those taken before water maze training. Although the present results failed to provide any evidence for a role of neocortical LTP in learning and memory, further studies of this nature are required to determine if the present results generalize to different behavioural tasks and/or cortical areas.      

Effects of acute and chronic physical exercise and stress on different types of memory in rats

Here we study the effect of acute and chronic physical exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests employed were: habituation in an open field, object recognition and spatial learning in the Morris water maze. Daily foot-shock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task at 2 weeks but only STM after 8 weeks and had no effect on spatial learning after either 2 or 8 weeks. Acute but not chronic exercise also enhanced habituation in the open field and hindered STM and LTM in the recognition task. Chronic exercise enhanced one important measure of spatial learning (latency to escape) but not others. Our findings indicate that some care must be taken when interpreting effects of forced exercise on brain parameters since at least part of them may be due to the stress inherent to the training procedure.     

Activation of Human Prefrontal Cortex during Spatial and Nonspatial Working Memory Tasks Measured by Functional MRI

Separate working memory domains for spatial location, and forobjects, faces, and patterns, have been identified in the prefrontalcortex (PFC) of nonhuman primates. We have used functional magneticresonance imaging to examine whether spatial and nonspatialvisual working memory processes are similarly dissociable inhuman PFC. Subjects performed tasks which required them to remembereither the location or shape of successive visual stimuli. Wefound that the mnemonic component of the working memory tasksaffected the hemispheric pattern of PFC activation. The spatial(LOCATION) working memory task preferentially activated themiddle frontal gyrus (MFG) in the right hemisphere, while thenonspatial (SHAPE) working memory task activated the NIFG inboth hemispheres. Furthermore, the area of activation in theleft hemisphere extended into the inferior frontal gyrus forthe nonspatial SHAPE task. A perceptual target (DOT) detectiontask also activated the MFG bilaterally, but at a level approximatelyhalf that of the working memory tasks. The activation in theMFG occurred within 3–6 s of task onset and declined followingtask offset. Time-course analysis revealed a different patternfor the cingulate gyrus, in which activation occurred upon taskcompletion. Cingulate activation was greatest following theSHAPE task and was greater in the left hemisphere. The presentresults support the prominent role of the PFC and, specifically,the MFG in working memory, and indicate that the mnemonic contentof the task affects the relative weighting of hemispheric activation.     

A dynamic shift of neural network activity before and after learning-set formation

Learning-set (LS) is a property of insight and hypothesis testing characterized by the ability to solve novel problems based on previous experiences with problem solving. However, the neural organization and mechanisms underlying LS remain unclear. To further characterize this process, positron emission tomography (PET) studies with [15O]H2O were performed to measure regional cerebral blood flow (rCBF) during the learning phase of the two-choice visual discrimination task under the LS paradigm in rhesus monkeys. When comparing studies before and after LS formation, the orbitofrontal and lateral prefrontal cortices were differentially activated, and functional connections between these structures and the striatum, which contributes to habit learning, were altered. We conclude that changes in the lateral prefrontal cortex during problem solving may contribute to the executive function of working memory and also inhibit control of a primitive learning system, thereby promoting LS formation.     

Memory functions in prednisone-treated kidney transplant patients

The literature indicates that high daily doses of gluco-corticosteroids have a degenerating effect upon the hippocampus and thus result in reduced declarative memory capacities. In order to prevent rejection, renal transplant recipients are treated with moderate daily doses of gluco-corticosteroids and, if necessary, with high pulse-doses during a few days. The question, therefore, arises as to whether or not such standard treatments result in memory impairments. For this reason, declarative memory capacities were measured, by means of a Dutch version of Rey's 15 Words Test, in a group of 52 renal transplant recipients. Results clearly indicated severe reductions in declarative memory capacities in these patients.     

Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks

Single cells were recorded with 'tetrodes' in regions of the rat medial prefrontal cortex, including those which are targets of hippocampal afferents, while rats were performing three different behavioral tasks: (i) an eight-arm radial maze, spatial working memory task, (ii) a figure-eight track, delayed spatial alternation task, and (iii) a random food search task in a square chamber. Among 187 recorded units, very few exhibited any evidence of place-specific firing on any of the behavioral tasks, except to the extent that different spatial locations were related to distinct phases of the task. Furthermore, no prefrontal unit showed unambiguous spatially dependent delay activity that might mediate working memory for spatial locations. Rather, the cells exhibited diverse correlates that were generally associated with the behavioral requirements of performing the task. This included firing related to intertrial intervals, onset or end of trials, selection of specific arms on the eight-arm radial maze, delay periods, approach to or departure from goals, and selection of paths on the figure-eight track. Although a small number of cells showed similar behavioral correlates across tasks, the majority of cells showed no consistent correlate when recorded across multiple tasks. Furthermore, some units did not exhibit altered firing patterns in any of the three tasks, while others showed changes in firing that were not consistently related to specific behaviors or task components. These results are in agreement with previous lesion and behavioral studies in rats that suggest a prefrontal cortical role in encoding 'rules' (i.e. structural features) or behavioral sequences within a task but not in encoding allocentric spatial information. Given that the hippocampal projection to this cortical region is capable of undergoing LTP, our data lead to the hypothesis that the role of this projection is not to impose spatial representations upon prefrontal activity, but to provide a mechanism for learning the spatial context in which particular behaviors are appropriate.      

SURGICAL HEURISTICS

Heuristics are rules of thumb. Rarely described in surgical or other publications, they are an essential part of safe and expert performance. This study translates such implicit or procedural knowledge into explicit or declarative knowledge, with a view to improving both training and retraining of surgeons in the steps of dissection. Tools used include ordinary observation accompanied by introspection, and study of operative videos. Validation of the value of such heuristics is yet to be achieved.     

Synaptic and spiking dynamics underlying reward reversal in the orbitofrontal cortex

Cognitive and emotional flexibility involve a coordinated interaction between working memory, attention, reward expectations, and the evaluation of rewards and punishers so that behaviour can be changed if necessary. We describe a model at the integrate-and-fire neuronal level of the synaptic and spiking mechanisms which can hold an expectation of a reward rule in working memory, and can reverse the reward rule if expected rewards are not obtained. An example of a reward rule is that stimulus 1 is currently associated with reward, and stimulus 2 with punishment. The attractor-based reward rule working memory incorporates a spike-frequency synaptic adaptation mechanism which supports the neural switching between rules by being shut down by a general inhibitory input produced by punishment, so that when the attractor starts up again is in the opposite state. The mechanism can implement one-trial reward reversal, which is a property of orbitofrontal cortex neurons. We show how this reward rule input can operate in a biased competition way to influence which one of two stimuli is currently associated with reward and which with punishment, and to map the stimuli correctly to the reward or punishment representations, providing a basis for action selection required to obtain the reinforcer.     

Spatial and Temporal Factors in the Role of Prefrontal and Parietal Cortex in Visuomotor Integration

The effects of reversible lesion—by cooling—of dorsolateralprefrontal and posterior parietal cortex were studied in rhesusmonkeys performing a cognitive visuomotor integration task.Correct performance required the use of a learned set of cue-responsecontingencies, some spatial andsome nonspatial; in some cases,the task required the short-term retention, through a delay,of the color of the cue or its implicit response direction.Prefrontal cooling impaired performance of the task regardlessof its spatial demands, an effect that increased with delay.Parietal cooling, on the other hand, only impaired performanceif the task demanded the processing and retention of spatialinformation (i.e., if spatial active memory was required). Parietaleffects were not related to delay. Both prefrontal and, evenmore, parietal cooling increased response time in all task contingencies.Thus, the results dissociate the respective contributions ofthe prefrontal and the posterior parietal cortex to the temporaland spatial aspects of information processing in visuomotorperformance. They indicate that posterior parietal areas participatein spatial processing and in active memory of spatial information,whereas prefrontal areas subserve a broader role of visuomotorprocessing and cross-temporal integration of both spatial andnonspatial information.     

Dynamics and plasticity of stimulus-selective persistent activity in cortical network models

Persistent neuronal activity is widespread in many areas of the cerebral cortex of monkeys performing cognitive tasks with a working memory component. Modeling studies have helped understanding of the conditions under which persistent activity can be sustained in cortical circuits. Here, we first review several basic models of persistent activity, including bistable models with excitation only and multistable models for working memory of a discrete set of pictures or objects with structured excitation and global inhibition. In many experiments, persistent activity has been shown to be subject to changes due to associative learning. In cortical network models, Hebbian learning shapes the synaptic structure and, in turn, the properties of persistent activity when pictures are associated together in the course of a task. It is shown how the theoretical models can reproduce basic experimental findings of neurophysiological recordings from inferior temporal and perirhinal cortices obtained using the following experimental protocols: (i) the pair-associate task; (ii) the pair-associate task with color switch; and (iii) the delay match to sample task with a fixed sequence of samples.     

Attention, Learning, and Memory in Posttraumatic Stress Disorder

This study compared attention and declarative memory in a sample of combat veterans with posttraumatic stress disorder (PTSD, n = 24) previously reported to have reduced concentrations of the hippocampal neuronal marker N-acetyl aspartate (NAA), but similar hippocampal volume compared to veteran normal comparison participants (n = 23). Healthy, well-educated males with combat-related PTSD without current depression or recent alcohol/drug abuse did not perform differently on tests of attention, learning, and memory compared to normal comparison participants. Further, hippocampal volume, NAA, or NAA/Creatine ratios did not significantly correlate with any of the cognitive measures when adjustments for multiple comparisons were made. In this study, reduced hippocampal NAA did not appear to be associated with impaired declarative memory.     

Increased neural efficiency with repeated performance of a working memory task is information-type dependent

Unlike tasks in which practice leads to an automatic stimulus-response association, it is thought working memory (WM) tasks continue to require cognitive control processes after repeated performance. Previous studies investigating WM task repetition are in accord with this. However, it is unclear whether changes in neural activity after repetition imply alterations in general control processes common to all WM tasks or are specific to the selection, encoding and maintenance of the relevant information. In the present study, functional magnetic resonance imaging (fMRI) was used to examine changes during sample, delay and test periods during repetition of both object and spatial delayed recognition tasks. We found decreases in fMRI activation in both spatial and object-selective areas after spatial WM task repetition, independent of behavioral performance. Few areas showed changed activity after object WM task repetition. These results indicate that spatial task repetition leads to increased efficiency of maintaining task-relevant information and improved ability to filter out task-irrelevant information. The specificity of this repetition effect to the spatial task suggests a difference exists in the nature of the representation of object and spatial information and that their maintenance in WM is likely subserved by different neural systems.     

Structural synaptic modifications associated with hippocampal LTP and behavioral learning

An important problem in the neurobiology of memory is whether cellular mechanisms of learning and memory include the formation of new synapses or the remodeling of existing ones. To elucidate this problem, numerous studies have examined alterations in the number and structure of synapses following behavioral learning and hippocampal long-term potentiation (LTP), which is viewed as a synaptic model of memory. The data reported in the literature and obtained in this laboratory are analyzed here to evaluate what kind of structural modification is likely to account for synaptic plasticity associated with learning and memory. It has been demonstrated that LTP induction elicits the formation of additional synapses between activated axon terminals and newly emerging dendritic spines. Similarly, some forms of learning have been shown to increase the number of synapses. Although many ultrastructural studies examining the effect of LTP or learning failed to find a change in total synapse number, this population measure might not detect an increase in a small proportion of synapses established by activated terminals. LTP and learning have also been shown to induce a remodeling of synapses. This process is proposed to involve the transformation of certain synaptic subtypes into more efficacious ones, including the conversion of 'silent' synapses into functional synapses. It appears, therefore, that cellular mechanisms of learning and memory are likely to include both synaptogenesis and synapse remodeling.     

Lesions affecting the parahippocampal cortex yield spatial memory deficits in humans

Anatomical studies in monkeys, and functional imaging and lesion studies in humans, suggest that, within the primate medial temporal neocortex, the parahippocampal cortex (PHC) is particularly involved in spatial tasks. However, evidence for a functional specialization of the PHC regarding its spatial memory functions has so far been lacking. Here, we investigated spatial memory functions of the human perirhinal cortex (PRC) and PHC. Patients with lesions affecting the PRC but sparing the PHC, and patients with lesions affecting both PRC and PHC, performed an oculomotor delayed response task with unpredictably varied memory delays of up to 30 s. Compared to controls, patients with PRC+PHC lesions showed a significant delay-dependent inaccuracy of memory-guided eye movements contralateral to the lesion side, whereas patients with PRC lesions showed no significant inaccuracy. Our results show that the PHC is a critical component for spatial memory in humans and suggest that (i) extrahippocampal spatial memory functions of the medial temporal lobe may not be equally distributed in the medial temporal neocortex, but may be largely confined to the PHC, and (ii) damage to connections between cortices involved in spatial cognition and rostral regions of the temporal lobe is unlikely to account for the observed spatial memory deficits with PHC lesions.     

Neural correlates of rule-based and information-integration visual category learning

An emerging theory of the neurobiology of category learning postulates that there are separate neural systems supporting the learning of categories based on verbalizeable rules (RB) or through implicit information integration (II). The medial temporal lobe (MTL) is thought to play a crucial role in successful RB categorization, whereas the posterior regions of the caudate are hypothesized to support II categorization. Functional neuroimaging was used to assess activity in these systems during category-learning tasks with category structures designed to afford either RB or II learning. Successful RB categorization was associated with relatively increased activity in the anterior MTL. Successful II categorization was associated with increased activity in the caudate body. The dissociation observed with neuroimaging is consistent with the roles of these systems in memory and dissociations reported in patient populations. Convergent evidence from these approaches consistently reinforces the idea of multiple neural systems supporting category learning.