Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning

Fear conditioning is a form of associative learning in which subjects come to express defense responses to a neutral conditioned stimulus (CS) that is paired with an aversive unconditioned stimulus (US). Considerable evidence suggests that critical neural changes mediating the CS-US association occur in the lateral nucleus of the amygdala (LA). Further, recent studies show that associative long-term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that drugs that interfere with this LTP also disrupt behavioral fear conditioning when infused into the LA, suggesting that associative LTP in LA might be a mechanism for storing memories of the CS-US association. Here, we develop a detailed cellular hypothesis to explain how neural responses to the CS and US in LA could induce LTP-like changes that store memories during fear conditioning. Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons. This depolarization, in turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA neuron to fire action potentials. The action potentials then back-propagate into the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic changes that support short-term fear memory, calcium entry through both NMDARs and VGCCs is required to initiate the molecular processes that consolidate synaptic changes into a long-term memory.     

Bidirectional plasticity in striatonigral synapses: a switch to balance direct and indirect basal ganglia pathways

There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral (direct pathway) synapses are not known. Here, we used electrophysiological techniques to describe dopamine D(1)-receptor-mediated facilitation in striatonigral synapses in the context of its interaction with glutamatergic inputs, probably coming from the subthalamic nucleus (STN) (indirect pathway) and describe a striatonigral cannabinoid-dependent long-term synaptic depression (LTD). It is shown that striatonigral afferents exhibit D(1)-receptor-mediated facilitation of synaptic transmission when NMDA receptors are inactive, a phenomenon that changes to cannabinoid-dependent LTD when NMDA receptors are active. This interaction makes SNr neurons become coincidence-detector switching ports: When inactive, NMDA receptors lead to a dopamine-dependent enhancement of direct pathway output, theoretically facilitating movement. When active, NMDA receptors result in LTD of the same synapses, thus decreasing movement. We propose that SNr neurons, working as logical gates, tune the motor system to establish a balance between both BG pathways, enabling the system to choose appropriate synergies for movement learning and postural support.     

Interactions between frontal cortex and basal ganglia in working memory: a computational model

The frontal cortex and the basal ganglia interact via a relatively well understood and elaborate system of interconnections. In the context of motor function, these interconnections can be understood as disinhibiting, or “releasing the brakes,” on frontal motor action plans: The basal ganglia detect appropriate contexts for performing motor actions and enable the frontal cortex to execute such actions at the appropriate time. We build on this idea in the domain of working memory through the use of computational neural network models of this circuit. In our model, the frontal cortex exhibits robust active maintenance, whereas the basal ganglia contribute a selective, dynamic gating function that enables frontal memory representations to be rapidly updated in a task-relevant manner. We apply the model to a novel version of the continuous performance task that requires subroutine-like selective working memory updating and compare and contrast our model with other existing models and theories of frontal-cortex-basal-ganglia interactions.     

Predictive coding as a model of cognition

Previous work has shown that predictive coding can provide a detailed explanation of a very wide range of low-level perceptual processes. It is also widely believed that predictive coding can account for high-level, cognitive, abilities. This article provides support for this view by showing that predictive coding can simulate phenomena such as categorisation, the influence of abstract knowledge on perception, recall and reasoning about conceptual knowledge, context-dependent behavioural control, and naive physics. The particular implementation of predictive coding used here (PC/BC-DIM) has previously been used to simulate low-level perceptual behaviour and the neural mechanisms that underlie them. This algorithm thus provides a single framework for modelling both perceptual and cognitive brain function.     

Marmosets as a next-generation model of comparative cognition

Common marmosets have traditionally been used in fields such as comparative psychology, cognitive neuroscience, and ethology, and as animal models of human disease research because of their relatively small body size, high reproductive rate, similar breeding system characteristics to those of humans, high dependency on vocal communication, and behavioral effects from drug administration that resemble those of humans. Although the animal has proved to be quite advantageous in animal model research in comparison to rodents, and has specific ecological and evolutionary characteristics that are worthy of exploration, few attempts have been made until recently to combine both types of approach. Thus, supported by neuroscientific methodologies that have recently been developed using this species, the authors suggest that the evolutionary origins of cognitive and social functions common to or differentiated in primates, could be uncovered through research that explores the behavioral and neural bases of cognition in the marmosets.     

Using TD learning to simulate working memory performance in a model of the prefrontal cortex and basal ganglia

Delayed-response tasks (DRTs) have been used to assess working memory (WM) processes in human and nonhuman animals. Experiments have shown that the basal ganglia (BG) and dorsolateral prefrontal cortex (DLPFC) subserve DRT performance. Here, we report the results of simulation studies of a systems-level model of DRT performance. The model was trained using the temporal difference (TD) algorithm and uses an actor-critic architecture. The matrisomes of the BG represent the actor and the striosomes represent the critic. Unlike existing models, we hypothesize that the BG subserve the selection of both motor- and cognitive-related information in these tasks. We also assume that the learning of both processes is based on reward presentation. A novel feature of the model is the incorporation of delay-active neurons in the matrisomes, in addition to DLPFC. Another novel feature of the model is the subdivision of the matrisomal neurons into segregated winner-take-all (WTA) networks consisting of delay- versus transiently-active units.Our simulation model proposes a new neural mechanism to account for the occurrence of perseverative responses in WM tasks in striatal-, as well as in prefrontal damaged subjects. Simulation results also show that the model both accounts for the phenomenon of time shifting of dopamine phasic signals and the effects of partial reinforcement and reward magnitude on WM performance at both behavioral and neural levels. Our simulation results also found that the TD algorithm can subserve learning in delayed-reversal tasks.     

The differential role of premotor frontal cortex and basal ganglia in motor sequence learning: evidence from focal basal ganglia lesions

There has been a growing interest in the differential role of various neural structures in implicit learning processes. The goal of our study was to clarify how focal lesions restricted to the basal ganglia interfere with different aspects of implicit visuo-motor sequence learning. A version of the Serial Reaction Time Task (SRTT) of Nissen and Bullemer using a 12-trial sequence was administered. A total of 20 subjects with focal basal ganglia lesions caused by ischemic or hemorrhagic infarction and 20 matched control subjects participated in this study. The results indicate that subjects with focal basal ganglia lesions showed unimpaired implicit learning of a 12-item motor sequence. Subjects with basal ganglia lesions, however, had more difficulties improving their general proficiency with the reaction-time task independent of sequence-specific learning. We observed a tendency toward smaller regional volumes in the cerebellum and left pre-supplementary motor area (pre-SMA) of subjects with basal ganglia lesions. Smaller cerebellar and pre-SMA volumes were related to lower implicit learning performance in the lesion group. The size of lesions in the basal ganglia was not related to sequence-specific implicit learning but had a significant influence on subjects' general proficiency for execution of the reaction-time task. We propose that implicit learning is achieved by a distributed network of cortical and subcortical structures. The basal ganglia seem to be responsible for adjusting to the general requirements of a task rather than for learning specific associations between stimuli that might be accomplished by premotor frontal areas and the cerebellum instead.     

A computational model of Parkinsonian handwriting that highlights the role of the indirect pathway in the basal ganglia

Parkinsonian handwriting is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen velocity. In this paper we present a computational model of handwriting generation that highlights the role of the basal ganglia, particularly the indirect pathway. Whereas reduced dopamine levels resulted in reduced letter size, transition of STN–GPe dynamics from desynchronized (normal) to synchronized (PD) condition resulted in increased fluctuations in velocity in the model. We also present handwriting data from PD patients (n = 34) who are at various stages of disease and had taken medication various lengths of time before the handwriting sessions. The patient data are compared with those of age-matched controls. PD handwriting statistically exhibited smaller size and larger velocity fluctuation compared to normal handwriting.     

Age-related similarities and differences in monitoring spatial cognition

Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual–spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.     

Adult's failures on euclidean and projective spatial tasks: Implications for characterizing spatial cognition

In their initial study of the development of children's spatial concepts, Piaget and Inhelder (1956) designed the “water-level” and “plumb-line” tasks to assess children's Euclidean abilities to perceive and represent horizontals and verticals. Surprisingly, subsequent research has shown that many adults perform badly on these tasks designed for children. Here we studied whether adults (N=160) would also have difficulty on a shadow projection task developed to assess theoretically related projective spatial concepts. The data showed that some adults had difficulty on the shadow task, whether tested by a drawing or by a selection task, and whether scored with respect to qualitative shape or metric accuracy. Performance was significantly worse on complex than simple forms, and when sex differences emerged, they favored males. As hypothesized, the best predictor of shadow performance was performance on the Euclidean tasks. Scores on the Embedded Figures Test and participant sex accounted for small (but significant) additional variance on shadow performance. Implications for theories of spatial development and for modeling individual differences in spatial cognition are discussed.     

The Macintosh as a user-friendly laboratory for perception and cognition

We present a radically user-friendly Macintosh laboratory, MindLab, for instruction in perception and cognition. MindLab’s forte is its ability to display pictorial stimuli, including digitized photographs, transferred via the clipboard from Macintosh graphics applications. An experiment is programmed by specifying sequences of event primitives, represented by icons, to which stimuli, temporal parameters, and feedback options are assigned.     

Behavioural context and a distributed system: metabolic mapping studies of the basal ganglia.

Behavioural context is known to affect neural activity in the striatum. Responses of single cells increase to rewarding stimuli, or drop out as a bar press or saccade is learned. Networks that can accomplish a unique response to changing contexts are of particular interest to systems neuroscience and were a part of Hebb's interest in perception and learning. An overall map of the striatum that localizes changes related to this remarkable phenomenon of contextual responses contributes to our understanding of anatomical substrates of neural systems that integrate information, and may lead us to new striatal regions to study synaptic mechanisms of learning.     

Dimensional transformation in tests of spatial and environmental cognition

In previous research, it has been argued that spatial performance on psychometric tests might be accounted for, in part, by the need for test-takers to transform mentally two-dimensional (2-D) test items into a three-dimensional (3-D) representation. With this in mind, the Landscape Perception Test (LPT) was designed to isolate the 2-D to 3-D (and vice versa) transformational aspect of spatial cognition. Gender differences were used as an indirect means to examine the contribution of the 2-D to 3-D transformation to spatial performance. Since the LPT was designed by means of an image relevant to geospatial cognition, measures of environmental cognition, as well as experience in various activities, were also examined. One hundred thirty undergraduate students (66 females and 64 males) completed the Childhood Activities Questionnaire, the Santa Barbara Sense of Direction Test, the Visualization of Views (VV) Test, the Perspective Taking/Spatial Orientation Test, and the LPT. Results showed higher scores for men than for women on LPT items requiring 2-D to 3-D conversion (LPT23), but not on those requiring the reverse operation. In addition, only the LPT23 produced significant indirect effects of gender on VV Test performance. Performance on the tests was also correlated with environmental cognition and previous experience with spatial activities. The results suggest that dimensional transformation might be a factor significantly contributing to spatial performance. Psychometric aspects of the LPT are also discussed.     

Speech and gesture in spatial language and cognition among the Yucatec Mayas

In previous analyses of the influence of language on cognition, speech has been the main channel examined. In studies conducted among Yucatec Mayas, efforts to determine the preferred frame of reference in use in this community have failed to reach an agreement (Bohnemeyer & Stolz, 2006; Levinson, 2003 vs. Le Guen, 2006, 2009). This paper argues for a multimodal analysis of language that encompasses gesture as well as speech, and shows that the preferred frame of reference in Yucatec Maya is only detectable through the analysis of co-speech gesture and not through speech alone. A series of experiments compares knowledge of the semantics of spatial terms, performance on nonlinguistic tasks and gestures produced by men and women. The results show a striking gender difference in the knowledge of the semantics of spatial terms, but an equal preference for a geocentric frame of reference in nonverbal tasks. In a localization task, participants used a variety of strategies in their speech, but they all exhibited a systematic preference for a geocentric frame of reference in their gestures.     

Synaptic plasticity and the organization of behaviour after early and late brain injury.

Hebb proposed that synaptic change underlies behavioural and cognitive plasticity. When applied to recovery from brain injury, the general hypothesis is that if there is recovery following brain injury, then there ought to be a correlated synaptic change, which is presumed to be responsible for recovery. In contrast, if recovery fails to occur, or expected recovery is blocked in some manner, then the synaptic change will likely not be present. Systematic study of functional recovery and synaptic change following brain injury at different ages supports these predictions. Good recovery is always correlated with enhanced connectivity whereas poor recovery is always correlated with an absence of reorganized connectivity. Furthermore, factors that stimulate recovery, such as neurotrophins or experience, stimulate synaptic change and functional recovery. Factors that retard recovery, such as depletion of neuromodulators, also block synaptic change. These results thus support Hebb's general idea that synaptic plasticity is related to behavioural change.     

Autism as impairment in the formation and use of meaning: an attempt to integrate a functional and a neurological model

Neurological approaches and functional approaches to impairments in autism provide different perspectives on the disorder. This study attempted an integration of the two approaches, based specifically on the role of the mesolimbic/neostriatal system in imparting adaptive meaning to percepts and problems that autistic persons have in making adaptive use of meaning.