In agreement with iEEG findings (Kahana et al., 1999
; Caplan et al., 2001
; Ekstrom et al., 2005
), we observed increased power in the 4–8Hz θ band in the human hippocampus and surrounding parahippocampal structures in a similar behavioral context as animals, namely goal-directed navigation. Using a spatial filtering technique for source analysis, we measured the distribution of θ activity across the brain during navigation in a virtual Morris water maze (vMWM) and also during a sensorimotor control condition (i.e., aimless movements). Two early peaks of left hippocampal and parahippocampal θ activity were observed on trials in which participants navigated to the fixed location of the hidden platform relative to trials in which they moved aimlessly around the virtual pool (). An additional source of increased θ power was localized to left parahippocampal cortices later in the trial period (i.e., 3.75–4.75s relative to trial onset). These results suggest that hippocampal and parahippocampal θ oscillations increased specifically under conditions in which spatial information was being encoded and/or retrieved rather than being elicited solely by virtual movements in general. Although θ was the only frequency band showing significant increase in medial temporal cortices during goal-directed navigation relative to aimless movements, this power increase was not significantly greater than power increases in other bands at other time intervals. Hippocampal neuronal populations have been shown to exhibit –4Hz oscillations during virtual navigation and may serve a similar function as 4–8Hz oscillations in humans (de Araujo et al., 2002
; Jacobs et al., 2007
). That we could not demonstrate medial temporal sources displaying significant power changes in other bands during navigation, perhaps due to insufficient statistical power, necessitates further investigation to clarify potential roles of other oscillations in the vMWM.
We found compelling evidence of a linear relationship between hippocampal and parahippocampal θ responses and navigation performance on the vMWM, consistent with the interpretation that oscillatory activity is involved in spatial learning. Indeed, participants exhibiting greater differential activity in the left posterior hippocampus at the start of navigation (relative to moving aimlessly) were the best performers in terms of average path length taken to the platform (). In other words, early hippocampal activity predicted navigation performance, with the former accounting for a sizeable proportion of variance in the latter (i.e., 76%) Previous fMRI studies also found positive linear associations (i.e., r2
= .55 and .31) between posterior hippocampal activation and virtual navigation performance (Hartley et al., 2003
; Maguire et al., 1998
). That we obtained a larger correlation than these previous results could be due to the ability of MEG to capture neural dynamics more directly than fMRI and isolate oscillatory changes in the relevant frequency bands. On the other hand, we were unable to show this same correlation at the single-trial level in more than 1 participant. This is likely the result of significant noise in single-trial estimates of power made at the depth of the hippocampus and perhaps reflects limitations of noninvasive MEG recordings, but nevertheless may be observed with a greater number of trials.
The robust correlation between posterior hippocampal θ and average path length emerged in the first second of navigation and may be indicative of rapid engagement of the hippocampus and parahippocampal cortices in the best navigators. This relationship may reflect a direct connection between posterior hippocampal θ activity and cognitive aspects of navigation performance or could be mediated by motor-related variables (i.e., speed). Although the relationship was obtained by factoring out θ activity during the sensorimotor control condition (i.e., by correlating difference volumes with path length), motor-related processes may not have been sufficiently controlled across these two conditions to disambiguate the meaning of the observed relationship. This problem remains unresolved in the rodent literature with some studies that have controlled for motor activity reporting cognitive-related hippocampal θ oscillations (e.g., Olvera-Cortes et al., 2004
) and others not (e.g., Kelemen et al., 2005
). By demonstrating similarities in hippocampal oscillatory activity across species, the current results may offer novel approaches to addressing its cognitive significance in humans.
Anterior hippocampal and parahippocampal activity was greater, in general, during goal-directed navigation relative to aimless movements, an outcome that may appear inconsistent with human studies indicating that posterior medial temporal cortical regions are especially critical to spatial navigation (Ghaem et al., 1997
; Bohbot et al., 1998
; Maguire et al., 1998
). An important difference between previous human neuroimaging studies and the current study is that the former studies usually involved significant training outside the scanner before neural activity was measured and the latter did not. We measured neuromagnetic activity during a single session in which participants, in general, showed significant improvement in performance across trials (), suggesting that they were continually learning and encoding the spatial environment. That the left anterior hippocampal θ activity observed was related to early encoding is supported by subsequent analyses that demonstrated that activity in this structure was clearly evident during the first 10 trials, when most participants had not mastered the task, but not the last 10, when some were approaching ceiling level performance. Wolbers and Buchel (2005)
, using fMRI, made a similar observation of early involvement of the left anterior hippocampus in virtual navigation when training was distributed across multiple sessions. Moreover, based on the correlations we observed in posterior hippocampal and parahippocampal regions, it could be expected that had we trained participants to a specific criterion before measuring neuromagnetic activity, we would have observed, similar to other studies, a more uniform response in posterior regions across participants. Nevertheless, no consensual view on functional subdivisions of the human hippocampus has emerged (Squire et al., 2004
); thus anterior hippocampal and parahippocampal oscillations during spatial learning could be involved in early encoding and in generating novel paths (Hartley et al., 2003
), and/or could reflect greater attentional orienting to the pool environment containing the hidden platform (Vinogradova, 2001
). More extensive training on the vMWM across multiple sessions would be necessary to clarify the significance of anterior versus posterior hippocampal activity.
Previous results point to a more critical role for the right hippocampus over the left in spatial memory processes in general (cf. Burgess et al., 2002
), but this has not always been demonstrated (e.g., Astur et al., 2002
; Ohnishi et al., 2006
) and the left anterior hippocampus may nonetheless mediate specific component processes of spatial navigation such as binding an object, in this case the platform, to its spatial location (Kessels et al., 2004
; Mitchell et al., 2000
). Although the peak response in left medial temporal cortices observed here was not significantly greater in magnitude than that observed on the right during goal-directed navigation, the relative lack of evidence for right hippocampal and parahippocampal activity in the present study may be due to the strategies used by participants to locate the platform. That is, associative strategies that rely on only a subset of cues may have been used instead of allocentric representations (i.e., cognitive maps) of the environment that are thought to be mediated by the right hippocampus (Burgess et al., 2002
). The latter is the optimal strategy when navigating from variable starting positions in the vMWM; yet simpler associative strategies seem to be sufficient to perform adequately (e.g., knowing only that the platform is left of the window). Aspects of the current procedures may have influenced the strategies used, such as the interleaved presentation of navigation and control trials that may have hindered formation of cognitive maps. Future studies could address the question of lateralization of hippocampal activity on the vMWM by more systematic manipulation of training variables and detailed characterizations of the paths taken by participants to the hidden platform.
Based on animal studies, θ is thought to behave as an order parameter by integrating sequentially-activated cell assemblies into higher-order dynamical structures embodying temporal context (Buzsaki, 2005
). The formation of spatial memories, and perhaps more generally episodic memories, may therefore be critically dependent on hippocampal θ oscillations (Buzsaki, 2005
; Samsonovich & Ascoli, 2005
). Along these lines, there is ample evidence in healthy humans that θ recorded noninvasively at the scalp (EEG) or externally (MEG) is related to memory processes such as successful encoding of target items (Klimesch et al., 1996
; Sederberg et al., 2003
) and maintenance of items in working memory (Gevins et al., 1997
; Tesche & Karhu, 2000
; Jensen & Tesche, 2002
). However, few studies have specifically implicated the hippocampus or parahippocampal cortices as the primary sources of θ related to memory processes (for exceptions, see Tesche & Karhu, 2000
; de Araujo et al., 2002
). The current study bridges this gap between animal and human research by demonstrating that major sources of θ activity during human spatial learning are located in the hippocampus and parahippocampal cortices, and that spatial navigation performance is highly associated with θ activity in these structures. Further research may reveal the full extent to which hippocampal θ oscillations, and other oscillatory changes, are critical to human learning and memory, spatial as well as non-spatial kinds.