Contributions of Areas LIP and VIP to Numerical Behavior

描述（由申请人提供）：目前的证据确定了两种用于表示和操纵人类数量的相互关联的系统：1）用于精确数学运算的符号介导的精确数字系统; 2）非语言的近似数字感，其在进化上是原始的，并且存在于人类个体发育的早期。神经生物学和行为学数据强烈表明，象征性介导的精确数字系统利用近似数字感。对数字的敏感性，对物体或事件数量的模糊感觉，预测了整个发展过程中的数字和数学表现。此外，对人类大脑成像和病变的研究表明，顶叶皮层参与了精确的数字处理和近似的数字感。灵长类动物腹侧顶内区（VIP）和前额叶皮层（dlPFC）的单个神经元对视觉阵列中特定数量的元素有选择性地做出反应。相比之下，外侧顶内区（LIP）的神经元以单调的方式对位于神经元感受野内的视觉阵列中的元素数量做出反应。这些观察结果表明，假设LIP神经元整合视觉信息，形成一个代表的积累的数字，这是由VIP和dlPFC的神经元读出信号的一个特定的数值。这一假设与几种数值表示的计算模型一致，其中表示特定基数值（如3或5）的数度单位接收来自求和单位的输入，这些求和单位对它们的感受野内的元素数量进行编码。尽管这一假设很有吸引力，但仍存在几个重要问题。首先，代表基数的神经元被描述在猴子训练，使明确的相同/不同的判断，而神经元代表累积的数值大小被描述在猴子没有受过训练，使任何明确的数字判断。因此，用于表示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中神经元的固有数字编码特性。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层神经元数字编码的影响尤为重要。第二，假设LIP中的求和单元为VIP（或dlPFC）中的数值单元提供输入，并且这些连接在功能上与数值判别相关，仍有待检验。该项目的目标是利用行为学、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相关的神经机制可能会对幼儿数学教育和补救措施产生重要影响，这将使所有儿童受益，特别是那些患有定量能力受损的儿童。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2 500名女婴中有1名），脆性X综合征（1/1250男性; 1/2500女性）和发育性计算障碍（约占世界人口的5%），在许多其他疾病中，其特征在于视觉空间和数学功能的严重损害。此外，由顶叶皮层损伤引起的Gerstmann综合征表现为一系列症状，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.