Contributions of Areas LIP and VIP to Numerical Behavior

描述(申请人提供)：目前的证据表明，在人类中有两种相互关联的表示和操作量的系统：1)一种符号中介的精确数字系统，用于精确的数学运算；2)一种进化上原始的、早期存在于人类个体发育中的非语言近似感的数字。神经生物学和行为数据有力地表明，符号中介的精确数字系统利用了近似的数字意义。对数字的敏感度，即对物体或事件数量的模糊感觉，预测着整个发展过程中的数字和数学表现。此外，人类的脑成像和损伤研究表明，在精确的数字处理和近似的数字意义上，顶叶皮质都有影响。灵长类动物腹侧顶内区(VIP)和前额叶皮质(DlPFC)中的单个神经元对视觉阵列中特定数量的元素有选择地做出反应。相比之下，外侧顶内区(LIP)的神经元对位于神经元感受野内的视觉阵列中的元素数量做出单调反应。这些观察结果表明，嘴唇神经元整合了视觉信息以形成累积数字的表示，VIP和dlPFC中的神经元读出该数字以发出特定数值的信号。这一假设与几种数值表示的计算模型是一致的，在这些计算模型中，代表特定基数值的数字单位，如3或5，从编码其接受场内元素数量的总和单位接收输入。尽管这一假设很有吸引力，但仍有几个重要的问题。首先，代表基数的神经元在被训练成做出明确相同/不同判断的猴子中被描述，而代表累积数值大小的神经元在未被训练做出任何明确数字判断的猴子中被描述。因此，用来代表数字的神经元编码方案可能反映了训练或任务需求，而不是数字敏感区域神经元固有的数字编码特性。由于数学成绩可以通过简单的数字和空间操作任务的训练来提高，因此了解外显训练对顶叶皮质神经元数字编码的影响尤为重要。第二，假设LIP(或dlPFC)中的求和单位为VIP(或dlPFC)中的数字单位提供输入，并且这些连接在功能上与数字辨别相关，这一假设仍有待检验。拟议项目的目标是使用行为、神经生理学、药理学和计算技术来解决这些问题。了解视觉空间信息处理与数字表征之间的神经机制可能会对儿童早期数学教育和补救提出重要的改进，这将使所有儿童受益，特别是那些数量能力受损的儿童。几种神经和遗传疾病，包括注意力缺陷多动障碍(约占美国人口的5%)、特纳综合征(每2500名女婴中有1名)、脆性X综合征(每1250名男性中有1名、每2500名女性中有1名)和发育性计算障碍(约占世界人口的5%)，在许多其他疾病中，其特征是视觉空间和数学功能严重受损。此外，Gerstmann综合征由顶叶皮质受损引起，表现为一系列症状，包括视觉空间和数学能力的缺陷。因此，理解视觉空间和数学处理之间的关系是一个重要的公共卫生挑战。

DESCRIPTION (provided by applicant): Current evidence identifies two inter-related systems for representing and manipulating quantities in humans: 1) a symbolically-mediated exact numerical system used in precise mathematical operations; 2) a nonverbal approximate sense of numerosity that is evolutionarily primitive and which is present early in human ontogeny. Neurobiological and behavioral data strongly suggest that the symbolically-mediated exact numerical system taps into the approximate numerosity sense. Sensitivity to numerosity, a fuzzy sense of the number of objects or events, predicts numerical and mathematical performance throughout development. Moreover, brain imaging and lesion studies in humans implicate parietal cortex in both exact numerical processing and the approximate numerosity sense. Single neurons in the primate ventral intraparietal area (VIP), as well as in prefrontal cortex (dlPFC), respond selectively to a specific number of elements in a visual array. By contrast, neurons in the lateral intraparietal area (LIP) respond in a monotonic fashion to the number of elements in a visual array located within the neuronal receptive field. These observations suggest the hypothesis that LIP neurons integrate visual information to form a representation of accumulated numerosity, which is read out by neurons in VIP and dlPFC to signal a specific numerical value. This hypothesis is consistent with several computational models of numerical representation, in which numerosity units representing a specific cardinal value, such as 3 or 5, receive input from summation units encoding the quantity of elements within their receptive fields. Despite the attractiveness of this hypothesis, several important questions remain. First, neurons representing cardinal numerosity were described in monkeys trained to make explicit same/different judgments, while neurons representing accumulated numerical magnitude were described in monkeys that were not trained to make any explicit numerosity judgments. Thus, the neuronal coding scheme used to represent number may reflect training or task demands, rather than the intrinsic numerical coding properties of neurons in number-sensitive areas. Since math performance can be improved by training on simple numerosity and spatial manipulation tasks, understanding the effects of explicit training on numerosity encoding by neurons in parietal cortex is particularly important. Second, the assumption that summation units in LIP provide inputs to numerosity units in VIP (or dlPFC), and that these connections are functionally relevant for numerosity discrimination, remains to be tested. The goal of the proposed project is to address these questions using behavioral, neurophysiological, pharmacological, and computational techniques. Understanding the neural mechanisms that relate visuospatial information-processing to representations of numerosity may suggest important improvements in early childhood mathematical education and remediation that will benefit all children, particularly those suffering from impaired quantitative abilities. PUBLIC HEALTH RELEVANCE Several neurological and genetic disorders, including attention-deficit hyperactivity disorder (about 5% of the US population), Turner's syndrome (1 in 2,500 female births), fragile X syndrome (1 in 1250 males; 1 in 2500 females), and developmental dyscalculia (about 5% of the world's population), are characterized by, among many other maladies, severe impairment in both visuospatial and mathematical function. In addition, Gerstmann's syndrome, caused by damage to the parietal cortex, manifests itself as a suite of symptoms, including deficits in both visuospatial and mathematical abilities. Understanding the relationships between visuospatial and mathematical processing is thus an important public health challenge.