Neural Mechanisms of Learning and Memory in Audition

试听中学习和记忆的神经机制

• 批准号: 8556897
• 负责人: MORTIMER MISHKIN
• 金额: $ 146.1万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8556897
• 关键词: Acoustics; Affect; Amygdaloid structure; Appearance; Apraxias; Area; Attention; Auditory; Auditory Evoked Potentials; Auditory area; Auditory system; Behavioral; Brain; Broca' s area; Canis familiaris; Categories; Cerebrum; Child; Complex; Corpus striatum structure; Data; Discrimination; Discrimination Learning; Dorsal; Emotions; Evolution; Family; Family member; Frequencies; Generations; Goals; Head; Human; Impairment; Implant; Inherited; Injection of therapeutic agent; Investigation; Joints; Label; Laboratories; Language; Language Disorders; Lateral; Learning; Lesion; Macaca; Maps; Medial; Medial geniculate body; Mediating; Memory; Metabolic; Methods; Modality; Modeling; Monkeys; Motor output; Neurobiology; Noise; Nucleus Accumbens; Oral; Outcome; Pathway interactions; Perception; Performance; Phenotype; Physiological; Play; Process; Research; Resolution; Rest; Rewards; Sampling; Sensory; Sensory Process; Short-Term Memory; Site; Specificity; Speech; Speech Sound; Staging; Stimulus; Stream; Structure of medial part of pulvinar; Superior temporal gyrus; Surface; System; Tail; Techniques; Testing; Thalamic structure; Time; Training; Verbal Learning; Vision; Visual; Visuospatial; Wernicke Area; Work; auditory stimulus; base; caudate nucleus; cognitive function; design; extrastriate visual cortex; follow-up; injured; insight; long term memory; member; memory recognition; multidisciplinary; neuroimaging; neuromechanism; nonhuman primate; orofacial; phonology; putamen; relating to nervous system; research study; response; sensory cortex; sensory stimulus; sound; sound frequency; spatiotemporal; stimulus interval; stimulus processing; visual memory; vocalization

Our neurobiological findings in monkeys have raised the possibility that, like occipitotemporal visual areas, superior temporal auditory areas send highly processed stimulus quality information to downstream targets via a multisynaptic corticocortical pathway. Previous evidence indicated that the auditory core (areas A1, R, and RT) on the supratemporal plane (STP) constitutes the first stage of cortical processing, with a serial progression from core outward, first to the belt and then to the parabelt. Our new data suggest that there is also a stepwise serial projection from A1 to R to RT and from there to the rostrotemporal polar field RTp. We have also investigated the subcortical connections of these auditory cortical areas and found that whereas A1 receives a preponderance of thalamic input from the ventral division of the medial geniculate (MGv), R receives a mix of inputs from both the ventral and dorsal subdivisions (MGv and MGd, respectively), and inputs to RT skew more heavily towards MGd. RT and RTp also project to the MGd and MGv. Injections beyond the core in RTp, RPB, and STGr revealed thalamic inputs from outside the medial geniculate body, including the suprageniculate nucleus and medial pulvinar. Additional projections were found to the striatum, with RT and RTp projecting to the tail of the caudate nucleus and the adjacent ventral putamen. RTp also projects to the ventromedial region of the head of the caudate nucleus and nucleus accumbens. Finally, RT and RTp are strongly interconnected with the amygdala. In summary, auditory fields rostral to the core receive little input from the auditory thalamus, suggesting that their physiological responses to sound are mediated by the previously described corticocortical pathways. The subcortical connectivity establishes circuits by which auditory processing may interact with systems involved in learning, attention, reward, and emotion. One of the fundamental features of sensory cortex is that it topologically maps the physical attributes of sensory stimuli. In the macaque auditory cortex, the attribute mapped is sound frequency, yielding tonotopic maps in the core regions on the STP. While neural responses in these areas have been studied in detail, the spatiotemporal activation of these maps by acoustic stimuli has not. We designed a micro-electrocorticographic (ECoG) array to record field potentials simultaneously from multiple areas of macaque auditory cortex. We chronically implanted four such arrays on the surface of the STP as well as the caudal superior temporal gyrus. The arrays allowed us to record auditory evoked potentials from a large expanse of auditory cortex simultaneously with high temporal resolution, while the monkeys passively listened to 180 different pure tone stimuli. First we examined the auditory frequency tuning of auditory evoked potentials at conventional field potential frequency ranges. This analysis revealed tonotopic maps that reversed frequency direction at putative areal boundaries. Although all field potential frequency bands produced similar areal boundaries, the smoothest tonotopic-reversal map was obtained from the high-gamma band of the evoked activity. Next, we estimated when each site showed significant discrimination among different stimulus frequencies by evaluating the high-gamma power in a 40 ms moving window. We found that the onset time of the discrimination increased along the caudal-to-rostral as well as the medial-to-lateral axes, consistent with the hypothesis that auditory information is serially processed in these two directions in parallel. As part of our investigation of auditory processing we trained monkeys on a task designed to assess auditory recognition memory. The task is comparable to those used regularly to test visual recognition. However, in contrast to the ease with which monkeys acquire the rule for delayed match-to-sample in vision, they strugggled for over a year to learn the same rule in audition. Further, once they learned the auditory task, their memory performance was (i) limited to short-term memory, and (ii) unaffected by lesions of the rhinal cortex; this is in sharp contrast to their memory performance in vision which (i) extends to long-term memory (ii) is severely disrupted by rhinal lesions. In a follow-up experiment to further determine the capacity, specificity, and duration of the maintained representation of an auditory stimulus, monkeys were trained on a serial delayed-match-to sample task analogous to one used previously to study these aspects of memory in vision. Performance was accurate in the absence of distracters, but degraded severely after the presentation of intervening nonmatch stimuli. Manipulation of the inter-stimulus interval confirmed that the performance degradation was attributable to the appearance of the intervening stimuli, not simply to the decay of memory over time. Analysis of performance by stimulus type showed a weak and counter-intuitive effect of sound category that favored simple stimuli (e.g., tones and noise) over species-specific vocalizations. These results suggest a strong effect of retroactive interference, such that the nonmatch stimulus disrupted the trace of the sample, effectively lowering the similarity criterion at which monkeys indicated a match. In short, we found that the auditory memory trace in nonhuman primates is limited to one or two items, is extremely fragile, and is highly vulnerable to overwriting by subsequent sounds. The impoverished auditory memory ability in monkeys contrasts not only with their excellent memory in vision but also with the human facility to encode auditory stimuli in LTM, thus raising the question of whether the human ability is supported in some way by speech and language. To test this possibility, we asked whether humans can store representations of speech sounds that can be neither repeated nor labeled (e.g., speech sounds played backwards). Our results indicate that the less that articulation and verbal labeling can be used to support storage of auditory information in LTM, the poorer the memory performance. This in turn has led us to propose that human speech and human auditory memory evolved together, possibly as a result of the evolution of the arcuate fasciculus from a primitive connection between the auditory and oromotor sytems present in nonhuman primates to the dense and complex linkage in humans, resulting in the elaboration of a Wernickes area as part of the auditory system connected to a Brocas area as part of the oromotor system. We have also begun assessing auditory memory in the three-generation KE family, half of whose the members have an inherited speech-language disorder, characterized as a verbal and orofacial dyspraxia. The core phenotype of the affected KE members (aKE) is a deficit in repeating words, especially non-words, and in moving the orofacial musculature. It is not clear whether the speech deficit results from combined working memory (WM) and motor output problems, or from motor output difficulties alone. We assessed WM using a test battery based on the Baddeley and Hitch WM model. The model posits that the central executive (CE), important for planning and manipulating information, works in conjunction with two modality-specific components: The phonological loop (PL), and the visuospatial sketchpad (VSSP). Our preliminary results indicate that the aKE, who have both structural and functional abnormalities in Broca's and Wernicke's areas, have a selective impairment in phonological WM, with relatively preserved CE and VSSP functions. Given that basic auditory sensory processes in the affected family members were found to be normal, we now suspect that auditory their WM may be impaired because of their structural and functional abnormalities at both ends of the arcuate fascicul

我们在猴子中的神经生物学发现提出了这样的可能性，即像枕颞视觉区域一样，上级听觉区域通过多突触皮质皮层途径向下游靶标发送高度加工的刺激质量信息。先前的证据表明，上颞平面（STP）上的听觉核心（A1，RT和RT区域）构成了皮质加工的第一阶段，其序列从核心向外，首先到皮带，然后再到par旁边。我们的新数据表明，还有一个从A1到R到RT的逐步串行投影，以及从那里到Rostormporal Polar Fielt RTP。我们还研究了这些听觉皮质区域的皮质下连接，发现A1从内侧基因剖分（MGV）的腹侧分裂（MGV）中获得了多数的丘脑输入，但收到了来自腹侧和背部细分（MGV和MGD和MGD，分别为MGD）的输入的组合，以及更多的sekiely seky seking sekew tote sekew skew rout skew rout sckew rc ckew rout skew rif skew rif sckew rif skew。 RT和RTP还将投影到MGD和MGV。 RTP，RPB和STGR中核心以外的注射显示了内侧基因体外体外的丘脑输入，包括上型核和内侧脉冲。在纹状体上发现了其他预测，RT和RTP投射到尾状核和邻近腹膜壳的尾部。 RTP还投射到尾状核和伏隔核的头部的腹侧区域。最后，RT和RTP与杏仁核密切相互关联。总而言之，核心的听觉场很少收到听觉丘脑的输入，这表明它们对声音的生理反应是由先前描述的皮质皮层途径介导的。皮层连通性建立了电路，通过该电路，听觉处理可能与学习，注意力，奖励和情感的系统相互作用。 感觉皮质的基本特征之一是它在拓扑上绘制了感觉刺激的物理属性。在猕猴的听觉皮层中，属性映射为声音频率，在STP上的核心区域中产生了Tonotopic图。尽管已经详细研究了这些区域中的神经反应，但声刺激没有通过声刺激对这些地图的时空激活。我们设计了一个微皮质学（ECOG）阵列，以同时从猕猴听觉皮层的多个区域记录场电位。我们长期将四个这样的阵列植入了STP的表面以及尾部的颞回。这些阵列使我们能够记录听觉诱发的潜力，并以高时间分辨率同时从大量的听觉皮层中引起了电位，而猴子被动地听取了180种不同的纯音刺激。首先，我们检查了在常规场电位频率范围内听觉诱发电势的听觉频率调整。该分析揭示了TONOTOPIC图，这些图逆转了假定的面积边界的频率方向。尽管所有场电位频带都产生了类似的面积边界，但最平稳的吨位反转图是从诱发活性的高γ带中获得的。接下来，我们估计每个位点通过在40毫秒移动窗口中评估高γ功率来显示不同刺激频率之间的显着歧视。我们发现，歧视的开始时间沿着尾部到骨的轴以及内侧到外侧轴增加，这与假设在这两个方向上并行在这两个方向上串行处理听觉信息。 作为对听觉处理的调查的一部分，我们培训了猴子，旨在评估听觉识别记忆的任务。 该任务与定期用于测试视觉识别的任务相当。 但是，与猴子获得视力延迟匹配的规则相比，他们陷入了一年多的时间，以学习相同的试镜规则。 此外，一旦他们学会了听觉任务，他们的记忆性能（i）仅限于短期记忆，并且（ii）不受鼻皮层病变的影响；这与他们在视觉中的记忆力形成鲜明对比，后者（i）扩展到长期记忆（II）受到Rhinal病变的严重破坏。在一项后续实验中，以进一步确定听觉刺激的维持表示的能力，特异性和持续时间，对猴子进行了训练，以串行延迟匹配的样本任务进行了类似于以前用于研究视觉中记忆方面的样本任务。在没有干扰物的情况下，性能是准确的，但是在介绍了介入非匹配刺激后会严重退化。对刺激间隔的操纵证实，性能降解归因于中间刺激的外观，而不仅仅是随着时间的推移记忆的衰减。通过刺激类型对性能的分析表明，声音类别的弱且违反直觉的影响，有利于简单的刺激（例如音调和噪声），而不是物种特异性的发声。这些结果表明追溯干扰的强烈影响，使得非匹配刺激破坏了样品的痕迹，从而有效地降低了猴子表明匹配的相似性标准。简而言之，我们发现非人类灵长类动物中的听觉记忆跟踪仅限于一个或两个项目，非常脆弱，并且非常容易受到随后的声音的覆盖。 猴子中贫穷的听觉记忆能力不仅与它们在视觉中的出色记忆形成对比，而且与人类的设施编码LTM中的听觉刺激，从而提出了一个问题，即是否通过语音和语言以某种方式支持人类能力。为了测试这种可能性，我们询问人类是否可以存储无法重复或标记的语音声音表示（例如，语音播放的语音向后播放）。我们的结果表明，发音和言语标记可以用来支持LTM中听觉信息的存储越少，记忆性能就越差。反过来，这又导致我们提出，人类的言语和人类听觉记忆也会一起发展，这可能是由于弧形筋膜的进化而导致的，是从非人类灵长类动物中的听觉和非人类动物中存在的原始联系与人类密集和复杂联系的人类与沃特尼克群岛的一部分，因此是在人类的范围内，因此是在人类的范围内，因此是在人类的范围内，因此是伴侣的一部分或伴侣，这是一个与听众系统的派系相关联。 我们还开始评估三代KE家族中的听觉记忆，其中一半的成员患有遗传性语言障碍，其特征是言语和口头性障碍。受影响的KE成员（AKE）的核心表型是重复单词，尤其是非词的缺陷，以及移动口面肌肉的缺陷。目前尚不清楚语音赤字是由工作记忆（WM）和电动机输出问题组合而导致的，还是仅出于电动机输出困难而引起的。 我们使用基于Baddeley和Hitch WM型号的测试电池评估了WM。该模型认为，中央主管（CE）对于计划和操纵信息很重要，与两个特定于模式的组件结合使用：语音循环（PL）和Visuospatial Sketchpad（VSSP）。我们的初步结果表明，AKE在Broca和Wernicke地区具有结构和功能异常，在语音WM中具有选择性损害，具有相对保留的CE和VSSP功能。鉴于发现受影响家庭成员的基本听觉感官过程是正常的，我们现在怀疑听觉的WM可能会受到损害