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.     

Neurocognitive outcomes in children with unilateral basal ganglia arterial ischemic stroke and secondary hemidystonia

Dystonia is a movement disorder that involves excessive, involuntary muscle contractions resulting in repetitive movements and/or abnormal posturing. One common cause of unilateral dystonia in childhood is ischemic stroke involving the basal ganglia and/or thalamus. Virtually nothing is known about neuropsychological outcomes in children who have dystonia following basal ganglia stroke. The present study explored whether or not children with secondary dystonia experience additional cognitive challenges when compared to children with similar patterns of brain injury, but no dystonia. We examined intellectual function, academics, and several aspects of executive function in children with unilateral basal ganglia stroke during childhood, comparing those with dystonia and those without. Although groups did not differ in terms of lesion size, we found significantly lower performance on measures of verbal and nonverbal reasoning, inhibitory control, and academic ability in children with secondary dystonia compared to those without. In contrast, there were no significant group differences on parent ratings of their child’s executive function in daily life. These findings suggest that maladaptive reorganization following basal ganglia stroke may contribute to the development of secondary dystonia and also to poor intellectual and academic outcomes in this group.     

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.     

Analysis of five cases with neurogenic stuttering following brain injury in the basal ganglia

This study examined stuttering patterns in five patients with basal ganglia injury. None of the patients had a history of developmental stuttering. Four patients were right-handed; one patient was ambidextrous. Stuttering tests administered to patients assessed sentence repetition, reading aloud, explanations of a comic strip, and conversation. Accessory behaviors such as facial grimaces, associated movements of the limbs, and avoidance behaviors were observed. The results of this study differ from those of previous studies of neurogenic stuttering in several respects: (1) blocks were frequently observed. (2) Adaptation was observed. (3) Almost all stuttering occurred at the initiation of words. (4) Across patients, stuttering frequency did not vary in a consistent manner with speaking task. New speech characteristics for neurogenic stuttering without aphasia following injury to the basal ganglia are described.Educational objectives: After reading this text, the reader will be able to: (1) provide characteristics of neurogenic stuttering after the basal ganglia in patients without aphasia; (2) discuss the difference of the features and characteristics of stuttering between previously reported patients and present patients.     

Comparing the neural correlates of affective and cognitive theory of mind using fMRI: Involvement of the basal ganglia in affective theory of mind

Theory of Mind (ToM) is the ability to infer other people’s mental states like intentions or desires. ToM can be differentiated into affective (i.e., recognizing the feelings of another person) and cognitive (i.e., inferring the mental state of the counterpart) subcomponents. Recently, subcortical structures such as the basal ganglia (BG) have also been ascribed to the multifaceted concept ToM and most BG disorders have been reported to elicit ToM deficits. In order to assess both the correlates of affective and cognitive ToM as well as involvement of the basal ganglia, 30 healthy participants underwent event-related fMRI scanning, neuropsychological testing, and filled in questionnaires concerning different aspects of ToM and empathy. Directly contrasting affective (aff) as well as cognitive (cog) ToM to the control (phy) condition, activation was found in classical ToM regions, namely parts of the temporal lobe including the superior temporal sulcus, the supplementary motor area, and parietal structures in the right hemisphere. The contrast aff > phy yielded additional activation in the orbitofrontal cortex on the right and the cingulate cortex, the precentral and inferior frontal gyrus and the cerebellum on the left. The right BG were recruited in this contrast as well. The direct contrast aff > cog showed activation in the temporoparietal junction and the cingulate cortex on the right as well as in the left supplementary motor area. The reverse contrast cog > aff however did not yield any significant clusters. In summary, affective and cognitive ToM partly share neural correlates but can also be differentiated anatomically. Furthermore, the BG are involved in affective ToM and thus their contribution is discussed as possibly providing a motor component of simulation processes, particularly in affective ToM.     

Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.     

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.     

The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex

Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1–2), 1–16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague–Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75 min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400 ms, 100 Hz, 400 μA [±16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n = 16) had a 1 s CS–BLAstm interval while Group BLA/1.6 (n = 5) has a 1.6 s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75 min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS–BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific, enduring, learning-related modifications of stimulus representation in the cerebral cortex. These findings suggest that the ability of the BLA to alter specific cortical representations may underlie, at least in part, the modulatory influence of BLA activity on strengthening long-term memory.     

Cerebellar contributions to the perception of temporal cues within the speech and nonspeech domain

A previous study (Ackermann, Gr?ber, Hertrich, & Daum, 1997) reported impaired phoneme identification in cerebellar disorders, provided that categorization depended on temporal cues. In order to further clarify the underlying mechanism of the observed deficit, the present study performed a discrimination and identification task in cerebellar patients using two-tone sequences of variable pause length. Cerebellar dysfunctions were found to compromise the discrimination of time intervals extending in duration from 10 to 150 ms, a range covering the length of acoustic speech segments. In contrast, categorization of the same stimuli as a "short" or "long pause" turned out to be unimpaired. These findings, along with the data of the previous investigation, indicate, first, that the cerebellum participates in the perceptual processing of speech and nonspeech stimuli and, second, that this organ might act as a back-up mechanism, extending the storage capacities of the "auditory analyzer" extracting temporal cues from acoustic signals.     

前额叶在老年阶段的可塑性及相关机制

大量研究表明, 前额叶的结构和功能更容易受年老化影响; 然而, 近年来的研究发现, 前额叶的结构和功能在老年阶段具有一定的可塑性。对老年人进行认知训练, 能够延缓前额叶皮层厚度的萎缩, 提高白质完整性, 改善神经网络的功能连接和分化, 并可能通过调节多巴胺系统的活动改变前额叶皮质和皮质下结构的功能激活模式。有氧锻炼能够改善心脑血管功能, 保护和促进神经元的存活和生长, 引起前额叶灰质、白质体积的增加及功能激活的变化。认知训练与有氧锻炼等相结合的整合性训练不仅引起前额叶及相关认知功能的改变, 而且具有更好的生态学效度, 使老年人日常认知能力和生活质量得到提高。未来研究应采用多种技术手段, 从多个层面理解老年阶段前额叶的可塑性及相关机制; 加强对与前额叶关系密切的多种认知功能可塑性神经机制的研究; 并重视与整合性训练有关的前额叶可塑性。     

The cognitive significance of resonating neurons in the cerebral cortex

Most neural fibers of the cerebral cortex engage in electric signaling, but one particular fiber, the apical dendrite of the pyramidal neuron, specializes in electric resonating. This dendrite extends upward from somas of pyramidal neurons, the most numerous neurons of the cortex. The apical dendrite is embedded in a recurrent corticothalamic circuit that induces surges of electric current to move repeatedly down the dendrite. Narrow bandwidths of surge frequency (resonating) enable cortical circuits to use specific carrier frequencies, which isolate the processing of those circuits from other circuits. Resonating greatly enhances the intensity and duration of electrical activity of a neuron over a narrow frequency range, which underlies attention in its various modes. Within the minicolumn, separation of the central resonating circuit from the surrounding signal processing network separates “having” subjective impressions from “thinking about” them. Resonating neurons in the insular cortex apparently underlie cognitive impressions of feelings.     

Dissociable contributions of the left and right posterior medial orbitofrontal cortex in motivational control of goal-directed behavior

Several findings from both human neuroimaging and nonhuman primate studies suggest that the posterior medial orbitofrontal cortex (OFC) may be critical for the motivational control of goal-directed behavior. The present study was conducted to clarify the role of the left and right posterior medial OFC in that function by examining the effects of focal unilateral lesions to this region on the performance on an incentive working memory task. The study covered patients who had undergone surgery for an ACoA aneurysm and normal control subjects (C). The patients were subdivided into three groups: those with resection of the left (LGR+) or right (RGR+) posterior part of the gyrus rectus, and without such a resection (GR−). Participants performed a 2-back working memory task under three motivational conditions (penalty, reward, and no-incentive). The C group performed worse in the penalty condition and better in the reward condition as compared to the no-incentive condition. Similar results were obtained for the GR− group. Performance of the LGR+ group did not depend on incentive manipulations, whereas the RGR+ group performed better in both the penalty and reward conditions than in the no-incentive condition. The results show that the posterior medial OFC is involved in the motivational modulation of working memory performance. Our findings also suggest that the left posterior medial OFC plays a crucial role in this function, whereas the right posterior medial OFC is particularly involved in the processing of the punishing aspect of salient events and it probably mediates in guiding behavior on the basis of negative outcomes of action.     

A few thoughts about the mind,the brain,and a child with early deprivation

Infant brain research is having an increasing impact on child psychotherapy and our understanding of the neurobiological effects of trauma and neglect. This paper outlines the 'experience-dependent' nature of brain development in infancy and the concept of critical periods in such development. The effects of deprivation on child development are illustrated and case material from a child who was institutionalized during his second year is used as a basis for posing questions about the nature of the mind and the brain. In spite of his deprivation, he was able to communicate imaginatively. Schore's proposal for the use of early interventions is put forward to counter discouragement that can be engendered by work with severely deprived children.     

Developmental stuttering and the role of the supplementary motor cortex

Developmental stuttering is a frequent neurodevelopmental disorder with a complex neurobiological basis. Robust neural markers of stuttering include imbalanced activity of speech and motor related brain regions, and their impaired structural connectivity. The dynamic interaction of cortical regions is regulated by the cortico-basal ganglia-thalamo-cortical system with the supplementary motor area constituting a crucial cortical site. The SMA integrates information from different neural circuits, and manages information about motor programs such as self-initiated movements, motor sequences, and motor learning. Abnormal functioning of SMA is increasingly reported in stuttering, and has been recently indicated as an additional “neural marker” of DS: anatomical and functional data have documented abnormal structure and activity of the SMA, especially in motor and speech networks. Its connectivity is often impaired, especially when considering networks of the left hemisphere. Compatibly, recent data suggest that, in DS, SMA is part of a poorly synchronized neural network, thus resulting in a likely substrate for the appearance of DS symptoms. However, as evident when considering neural models of stuttering, the role of SMA has not been fully clarified. Herein, the available evidence is reviewed, which highlights the role of the SMA in DS as a neural “hub”, receiving and conveying altered information, thus “gating” the release of correct or abnormal motor plans.     

Functional recovery of skilled forelimb use in rats obliged to use the impaired limb after grafting of the frontal cortex lesion with homotopic fetal cortex

The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the forelimb motor area of the hemisphere contralateral to the preferred paw in the paw-reaching-for-food task, while the other 5 animals were sham-operated. On retesting, the lesion animals changed the preferred paw. A solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed in the lesion cavity in 11 of the lesion rats. Three months later neither lesion alone nor lesion plus transplantation affected open field behavior and muscular strength, but the lesion permanently affected performance in the paw-reaching-for-food task, as shown by a change of preferred paw and a functional deficit in the paw contralateral to the lesion. Transplantation ameliorated the deficits caused by the lesion, but this was only evident when animals were forced to reach with the paw contralateral to the lesion plus transplant. The behavioral results were independent of the size of the lesion and graft. Connections between graft and host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled fibers was found in the host cortex adjacent to the transplant. The results suggest that functional recovery depends on grafting but is only evident when the animal is obliged to use the affected limb.     

双侧前额皮层的语言功能--用近红外技术研究语言功能的初步实验

本文报告一个用近红外技术进行的语言认知脑成像实验.实验通过脑f血流的变化情况考察了双侧前额皮层对由不同通道输入的,不同语言的各个层次的认知反应.实验结果表明,双侧前额皮层对高层语义加工,包括对篇章的归纳与抽象,具有特殊的功能,这种功能的神经学分布是对称的,这种功能及其对称性不随语言和输入通道的变化而变化.相比之下,前额皮层对读、听语言材料以及听音乐却显得不敏感.局部血流的变化只显示其对上述任务的一般性的注意力控制.