The hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended time courses. In this experiment with human subjects of both sexes, we tested for immediate stimulation impact on encoding-related activity of the hippocampus and immediately adjacent medial-temporal cortex by delivering theta-burst transcranial magnetic stimulation (TBS) concurrent with fMRI, as an immediate impact of stimulation would suggest an influence on neural activity. We reasoned that TBS would be particularly effective for influencing the hippocampus because rhythmic neural activity in the theta band is associated with hippocampal memory processing. First, we demonstrated that it is possible to obtain robust fMRI correlates of task-related activity during concurrent TBS. We then identified immediate effects of TBS on encoding of visual scenes. Brief volleys of TBS targeting the hippocampal network increased activity of the targeted (left) hippocampus during scene encoding and increased subsequent recollection. Stimulation did not influence activity during an intermixed numerical task with no memory demand. Control conditions using beta band and out-of-network stimulation also did not influence hippocampal activity or recollection. TBS targeting the hippocampal network therefore immediately impacted hippocampal memory processing. This suggests direct, beneficial influence of stimulation on hippocampal neural activity related to memory and supports the role of theta-band activity in human episodic memory.

SIGNIFICANCE STATEMENT Can noninvasive stimulation directly impact function of indirect, deep-brain targets, such as the hippocampus? We tested this by targeting an accessible region of the hippocampal network via transcranial magnetic stimulation during concurrent fMRI. We reasoned that theta-burst stimulation would be particularly effective for impacting hippocampal function, as this stimulation rhythm should resonate with the endogenous theta-nested-gamma activity prominent in hippocampus. Indeed, theta-burst stimulation targeting the hippocampal network immediately impacted hippocampal activity during encoding, improving memory formation as indicated by enhanced later recollection. Rhythm- and location-control stimulation conditions had no such effects. These findings suggest a direct influence of noninvasive stimulation on hippocampal neural activity and highlight that the theta-burst rhythm is relatively privileged in its ability to influence hippocampal memory function.

海马通过与分布式脑网络的相互作用来支持情景记忆。以前使用以网络为目标的非侵入性脑刺激的实验已经确定了海马网络中的情景记忆增强和活动调节。但是，机械学的见解是有限的，因为这些作用是在刺激后很长时间才测量的，因此可能会随着时间的流逝而反映出各种神经塑性后遗症。在这项针对男女受试者的实验中，我们通过同时进行功能性磁共振成像的θ-爆破经颅磁刺激（TBS），测试了对海马和紧邻的颞内侧皮层编码相关活动的即时刺激影响刺激提示对神经活动有影响。我们认为TBS在影响海马方面特别有效，因为theta频段的节律性神经活动与海马记忆处理有关。首先，我们证明有可能在并发TBS期间获得与任务相关活动的强大功能磁共振成像相关性。然后，我们确定了TBS对视觉场景编码的即时影响。靶向海马网络的TBS短暂抽射增加了场景编码过程中目标（左）海马的活动，并增加了后续记忆。在没有记忆需求的混合数字任务中，刺激不会影响活动。使用β带和网络外刺激的对照条件也不会影响海马活动或记忆。因此，针对海马网络的TBS立即影响了海马的记忆加工。这表明刺激对与记忆有关的海马神经活动具有直接，有益的影响，并支持θ带活动在人类情节记忆中的作用。

重要性声明非侵入性刺激能否直接影响诸如海马之类的间接，深脑目标的功能？我们通过在同时进行的功能磁共振成像中经颅磁刺激靶向海马网络的可访问区域来对此进行测试。我们认为，theta-burst刺激对影响海马功能特别有效，因为这种刺激节奏应与海马中突出的内源性theta-nested-γ活动产生共鸣。确实，针对海马网络的theta-burst刺激立即在编码过程中影响了海马的活动，改善了记忆形成，如后期记忆增强所表明的。节律和位置控制刺激条件没有这种影响。