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个相互关联的系统，用于表示和操纵人类的数量：1)用于精确数学运算的符号介导的精确数字系统；2)一种非语言的近似的数字感觉，这种感觉在进化上是原始的，在人类个体发生的早期就存在。神经生物学和行为学数据有力地表明，符号介导的精确数字系统利用了近似数字感。对数字的敏感性，对物体或事件数量的模糊感觉，预示着整个发展过程中的数值和数学表现。此外，人类的脑成像和病变研究表明，顶叶皮层在精确数值处理和近似数值感觉中都有作用。灵长类动物腹侧顶叶内区（VIP）和前额叶皮质（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接受野内的视觉阵列中的元素数量作出反应。这些观察结果提出了一个假设，即LIP神经元整合视觉信息，形成累积数值的表示，由VIP和dlPFC的神经元读出，以发出特定数值的信号。这一假设与数字表示的几个计算模型是一致的，在这些模型中，代表特定基数的数字单位，如3或5，从编码其接受域内元素数量的求和单位接收输入。尽管这一假设很有吸引力，但仍存在几个重要问题。首先，在训练有素的猴子中描述了代表基数数量的神经元，以做出明确的相同/不同判断，而在未训练有素的猴子中描述了代表累积数量的神经元。因此，用于表示数字的神经元编码方案可能反映训练或任务需求，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数和空间操作任务的训练来提高，因此了解显性训练对顶叶皮层神经元数数编码的影响尤为重要。其次，LIP中的求和单元为VIP（或dlPFC）中的数数单元提供输入，并且这些连接在功能上与数数辨别相关的假设仍有待检验。拟建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。了解将视觉空间信息处理与数字表征联系起来的神经机制，可能会对儿童早期数学教育和补救提出重要建议，这将有利于所有儿童，特别是那些数量能力受损的儿童。一些神经和遗传疾病，包括注意力缺陷多动障碍（约占美国人口的5%）、特纳综合征（2500名女性中有1名）、脆性X综合征（1250名男性中有1名；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，由顶叶皮层损伤引起的格斯特曼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项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.