What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called "conflict of paradigms." Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting "horizontal modulation" of cortico-cortical relation. Furthermore, alteration in "top-down modulation" reflecting "vertical modulation" of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered "bottom-up modulation" between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation--"vertical" and "horizontal" modulation, respectively.     

Hippocampus, cortex, and basal ganglia: insights from computational models of complementary learning systems

We present a framework for understanding how the hippocampus, neocortex, and basal ganglia work together to support cognitive and behavioral function in the mammalian brain. This framework is based on computational tradeoffs that arise in neural network models, where achieving one type of learning function requires very different parameters from those necessary to achieve another form of learning. For example, we dissociate the hippocampus from cortex with respect to general levels of activity, learning rate, and level of overlap between activation patterns. Similarly, the frontal cortex and associated basal ganglia system have important neural specializations not required of the posterior cortex system. Taken together, this overall cognitive architecture, which has been implemented in functioning computational models, provides a rich and often subtle means of explaining a wide range of behavioral and cognitive neuroscience data. Here, we summarize recent results in the domains of recognition memory, contextual fear conditioning, effects of basal ganglia lesions on stimulus-response and place learning, and flexible responding.     

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.     

Providing explicit information disrupts implicit motor learning after basal ganglia stroke

Despite their purported neuroanatomic and functional isolation, empirical evidence suggests that sometimes conscious explicit processes can influence implicit motor skill learning. Our goal was to determine if the provision of explicit information affected implicit motor-sequence learning after damage to the basal ganglia. Individuals with stroke affecting the basal ganglia (BG) and healthy controls (HC) practiced a continuous implicit motor-sequencing task; half were provided with explicit information (EI) and half were not (No-EI). The focus of brain damage for both BG groups was in the putamen. All of the EI participants were at least explicitly aware of the repeating sequence. Across three days of practice, explicit information had a differential effect on the groups. Explicit information disrupted acquisition performance in participants with basal ganglia stroke but not healthy controls. By retention (day 4), a dissociation was apparent--explicit information hindered implicit learning in participants with basal ganglia lesions but aided healthy controls. It appears that after basal ganglia stroke explicit information is less helpful in the development of the motor plan than is discovering a motor solution using the implicit system alone. This may be due to the increased demand placed on working memory by explicit information. Thus, basal ganglia integrity may be a crucial factor in determining the efficacy of explicit information for implicit motor-sequence learning.     

时间认知神经科学研究进展

当前对时间认知的脑机制探讨有三个模型：特异化计时模型、分布网络模型和定域计时模型。在这些模型的框架下,时间认知的神经心理学研究集中探讨了小脑、基底神经节、前额叶在时间信息加工中的作用和大脑两半球在时间认知中的不对称性。小脑作为内部计时系统对时间控制具有重要作用,在周期性动作任务中,小脑对不连续动作计时具有特异性。基底神经节在时间加工任务中与小脑存在明显的作用分离,其具体机制还有待深入研究。前额叶的计时功能可能与注意和工作记忆对时间信息的获得、维持和组织有关。此外,还发现大脑右半球与时问信息的加工关系密切。     

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 modular neural-network model of the basal ganglia’s role in learning and selecting motor behaviours

This work presents a modular neural-network model (based on reinforcement-learning actor–critic methods) that tries to capture some of the most relevant known aspects of the role that basal ganglia play in learning and selecting motor behavior related to different goals. The model uses a mixture of experts network for the critic and a hierarchical network with two levels for the actor. Some simulations with the model show that basal ganglia select ‘chunks’ of behavior whose ‘details’ are specified by direct sensory-motor pathways, and how emergent modularity can help to deal with tasks with asynchronous multiple goals. A ‘top-down’ approach is adopted that first analyses some adaptive non-trivial interaction of a whole (simulated) organism with the environment, and its capacity to learn, and then attempts to implement these functions with neural architectures and mechanisms that have an empirical neuroanatomical and neurophysiological foundation.     

标量计时模型中的神经机制

标量计时模型中各阶段的神经机制有重叠也有分离。从当今认知神经科学的研究结果看,与内部时钟有关的神经结构有小脑、基底神经节、前额皮质、前运动辅助皮质及顶叶下回皮质等;与记忆阶段有关的神经结构有基底神经节、背外侧前额皮质、右侧额下皮质及外侧前运动皮质等;与决策阶段有关的神经结构有背外侧前额皮质、前扣带回、高级颞叶皮质和基底神经节等。文章还从神经机制角度论证了计时的标量特性,讨论了今后研究值得注意的三个问题,即研究结果的确定性、研究手段的局限性以及该模型的适用性     

Cortical cell assemblies: a possible mechanism for motor programs

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.     

A neurophysiologic model for aggressive behavior in the cat

A neurophysiologic model for aggessive behavior in the cat is proposed. Stimulus-bound and seizure-bound aggression was evaluated in relation to limbic and basal ganglia induced seizures (after-discharges). Electrically induced limbic and basal ganglia afterdischarges were used because they are known to implicate septohypothalamic sites from which aggression can be elicited by direct stimulation. The occurrence of behavioral aggression is correlated with the discharge characteristics of a single discharging system and with two interacting discharging systems. Aggression is composed of autonomic and somato-motor components which poses relatively low and high thresholds, respectively, for their activation. Aggression occurring during a combined septum and amygdala discharge was more intense and prolonged than with a septum discharge alone. Participation of a slow frequency discharging basal ganglia system activated seizurebound aggression in an otherwise nonaggressive limbic seizure. The limbic and basal ganglia stimulations and after-discharges lowered the excitability threshold of the aggression system and made it more vulnerable to being activated by external stimuli, such as visual and auditory stimuli. These observations are reminiscent of patients with aggressive behavior associated with psychomotor seizures.     

Individual Differences in Reward-Based Learning Predict Fluid Reasoning Abilities

The ability to reason and problem-solve in novel situations, as measured by the Raven's Advanced Progressive Matrices (RAPM), is highly predictive of both cognitive task performance and real-world outcomes. Here we provide evidence that RAPM performance depends on the ability to reallocate attention in response to self-generated feedback about progress. We propose that such an ability is underpinned by the basal ganglia nuclei, which are critically tied to both reward processing and cognitive control. This hypothesis was implemented in a neurocomputational model of the RAPM task, which was used to derive novel predictions at the behavioral and neural levels. These predictions were then verified in one neuroimaging and two behavioral experiments. Furthermore, an effective connectivity analysis of the neuroimaging data confirmed a role for the basal ganglia in modulating attention. Taken together, these results suggest that individual differences in a neural circuit related to reward processing underpin human fluid reasoning abilities.     

Cortical Cell Assemblies: A Possible Mechanism for Motor Programs

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its explanatory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel, re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.     

"Scared stiff": catatonia as an evolutionary-based fear response

Catatonia, long viewed as a motor disorder, may be better understood as a fear response, akin to the animal defense strategy tonic immobility (after G. G. Gallup & J. D. Maser, 1977). This proposal, consistent with K. L. Kahlbaum's (1874/1973) original conception, is based on similarities between catatonia and tonic immobility ("death feint") as well as evidence that catatonia is associated with anxiety and agitated depression and responds dramatically to benzodiazepines. It is argued that catatonia originally derived from ancestral encounters with carnivores whose predatory instincts were triggered by movement but is now inappropriately expressed in very different modern threat situations. Found in a wide range of psychiatric and serious medical conditions, catatonia may represent a common "end state" response to feelings of imminent doom and can serve as a template to understand other psychiatric disorders.     

Stuttering: a dynamic motor control disorder

The purpose of this review is to determine what neural mechanisms may be dysfunctional in stuttering. Three sources of evidence are reviewed. First, studies of dynamic inter-relationships among brain regions during normal speech and in persons who stutter (PWS) suggest that the timing of neural activity in different regions may be abnormal in PWS. Second, the brain lesions associated with acquired stuttering are reviewed. These indicate that in a high percentage of cases, the primary speech and language regions are not affected but lesions involve other structures, such as the basal ganglia, which may modulate the primary speech and language regions. Third, to characterize the motor control disorder in stuttering, similarities and differences from focal dystonias such as spasmodic dysphonia (SD) and Tourette’s syndrome (TS) are reviewed. This review indicates that the central control abnormalities in stuttering are not due to disturbance in one particular brain region but rather a system dysfunction that interferes with rapid and dynamic speech processing for production.

Educational objectives: The reader will be able to describe: (1) the similarities and differences between stuttering and other speech motor control disorders, (2) which brain lesions are most likely to produce acquired stuttering in adults, and (3) what type of brain abnormality most likely underlies stuttering.     

Prism adaptation in schizophrenia

The prism adaptation test examines procedural learning (PL) in which performance facilitation occurs with practice on tasks without the need for conscious awareness. Dynamic interactions between frontostriatal cortices, basal ganglia, and the cerebellum have been shown to play key roles in PL. Disruptions within these neural networks have also been implicated in schizophrenia, and such disruptions may manifest as impairment in prism adaptation test performance in schizophrenia patients. This study examined prism adaptation in a sample of patients diagnosed with schizophrenia (N=91) and healthy normal controls (N=58). Quantitative indices of performance during prism adaptation conditions with and without visual feedback were studied. Schizophrenia patients were significantly more impaired in adapting to prism distortion and demonstrated poorer quality of PL. Patients did not differ from healthy controls on aftereffects when the prisms were removed, but they had significantly greater difficulties in reorientation. Deficits in prism adaptation among schizophrenia patients may be due to abnormalities in motor programming arising from the disruptions within the neural networks that subserve PL.     

A neural model of hippocampal–striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients

Building on our previous neurocomputational models of basal ganglia and hippocampal region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson’s disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy. Simulation results show that damage to the hippocampal region—as in patients with hippocampal atrophy (HA), hypoxia, mild Alzheimer’s (AD), or schizophrenia—leads to intact associative learning but impaired transfer generalization performance. Moreover, the model demonstrates how PD and anterior communicating artery (ACoA) aneurysm—two very different brain disorders that affect different neural mechanisms—can have similar effects on acquired equivalence performance. In particular, the model shows that simulating a loss of dopamine function in the basal ganglia module (as in PD) leads to slow acquisition learning but intact transfer generalization. Similarly, the model shows that simulating the loss of acetylcholine in the hippocampal region (as in ACoA aneurysm) also results in slower acquisition learning. We argue from this that changes in associative learning of stimulus–action pathways (in the basal ganglia) or changes in the learning of stimulus representations (in the hippocampal region) can have similar functional effects.     

Conditional visuo-motor learning and dimension reduction

Conditional visuo-motor learning consists in learning by trial and error to associate visual cues with correct motor responses, that have no direct link. Converging evidence supports the role of a large brain network in this type of learning, including the prefrontal and the premotor cortex, the basal ganglia (BG) and the hippocampus. In this paper we focus on the role of a major structure of the BG, the striatum. We first present behavioral results and electrophysiological data recorded from this structure in monkeys engaged in learning new visuo-motor associations. Visual stimuli were presented on a video screen and the animals had to learn, by trial and error, to select the correct movement of a joystick, in order to receive a liquid reward. Behavioral results revealed that the monkeys used a sequential strategy, whereby they learned the associations one by one although they were presented randomly. Human subjects, tested on the same task, also used a sequential strategy. Neuronal recordings in monkeys revealed learning-related modulations of neural activity in the striatum. We then present a mathematical model inspired by viability theory developed to implement the use of strategies during learning. This model complements existing models of the BG based on reinforcement learning (RL), which do not take into account the use of strategies to reduce the dimension of the learning space.     

Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies

The traditional view that the basal ganglia are simply involved in the control of movement has been challenged in recent years. Three lines of evidence indicate that the basal ganglia also are involved in nonmotor operations. First, the results of anatomical studies clearly indicate that the basal ganglia participate in multiple circuits or 'loops' with cognitive areas of the cerebral cortex. Second, the activity of neurons within selected portions of the basal ganglia is more related to cognitive or sensory operations than to motor functions. Finally, in some instances basal ganglia lesions cause primarily cognitive or sensory disturbances without gross motor impairments. In this report, we briefly review some of these data and present a new anatomical framework for understanding the basal ganglia contributions to nonmotor function.     

Subjective experience is probably not limited to humans: the evidence from neurobiology and behavior

In humans, conscious perception and cognition depends upon the thalamocortical (T-C) complex, which supports perception, explicit cognition, memory, language, planning, and strategic control. When parts of the T-C system are damaged or stimulated, corresponding effects are found on conscious contents and state, as assessed by reliable reports. In contrast, large regions like cerebellum and basal ganglia can be damaged without affecting conscious cognition directly. Functional brain recordings also show robust activity differences in cortex between experimentally matched conscious and unconscious events. This basic anatomy and physiology is highly conserved in mammals and perhaps ancestral reptiles. While language is absent in other species, homologies in perception, memory, and motor cortex suggest that consciousness of one kind or another may be biologically fundamental and phylogenetically ancient. In humans we infer subjective experiences from behavioral and brain evidence. This evidence is quite similar in other mammals and perhaps some non-mammalian species. On the weight of the biological evidence, therefore, subjectivity may be conserved in species with human-like brains and behavior.     

Subcortical functions in language: A working model

The current paper explains a model of subcortical language functions that focuses on dynamic interactions between the cortex, the thalamus, and the basal ganglia in the production of spoken language. The model was derived from (a) studies of subcortical lesions and language, (b) studies of subcortical stimulation and language, (c) knowledge regarding neural pathways between various cortical and subcortical structures, and (d) indications that preverbal monitoring of language occurs. In the current model, the thalamus plays roles in cortical arousal and activation and in preverbal semantic monitoring. The basal ganglia function to regulate the degree of excitation conveyed from the thalamus to the cortex and to time the release of formulated language for motor programming. Consistency with classical syndromes of aphasia and potential applications to other areas in the neurosciences are discussed. The current theory, unlike previous formulations, is specific enough that testable hypotheses can be derived.