Theta-Alpha Oscillations Bind the Hippocampus, Prefrontal Cortex, and Striatum during Recollection: Evidence from Simultaneous EEG-fMRI.

Recollection of contextual information represents the core of human recognition memory. It has been associated with theta (4-8 Hz) power in electrophysiological recordings and, independently, with BOLD effects in a network including the hippocampus and frontal cortex. Although the notion of the hippocampus coordinating neocortical activity by synchronization in the theta range is common among theoretical models of recollection, direct evidence supporting this hypothesis is scarce. To address this apparent gap in our understanding of memory processes, we combined EEG and fMRI during a remember/know recognition task. We can show that recollection-specific theta-alpha (4-13 Hz) effects are correlated with increases in hippocampal connectivity with the PFC and, importantly, the striatum, areas that have been linked repeatedly to retrieval success. Together, our results provide compelling evidence that low-frequency oscillations in the theta and alpha range provide a mechanism to functionally bind the hippocampus, PFC, and striatum during successful recollection. SIGNIFICANCE STATEMENT: Low-frequency oscillations are supposed to drive the binding of information across a large-scale network centered on the hippocampus, which supports mnemonic functions. The electrophysiological means to investigate this phenomenon in humans (EEG/MEG), however, are inherently limited by their spatial resolution and therefore do not allow a precise localization of the brain regions involved. By combining EEG with BOLD-derived estimates of hippocampal connectivity during recognition, we can identify the striatum and specific areas in the medial and lateral PFC as part of a circuit linked to low-frequency oscillations (4-13 Hz) that promotes hippocampus-dependent context retrieval. Therefore, the current study closes an apparent gap in our understanding of the network dynamics of memory retrieval.

Early effects of reward anticipation are modulated by dopaminergic stimulation.

The abilities to predict future rewards and assess the value of reward delivery are crucial aspects of adaptive behavior. While the mesolimbic system, including dopaminergic midbrain, ventral striatum and prefrontal cortex have long been associated with reward processing, recent studies also indicate a prominent role of early visual brain regions. However, the precise underlying neural mechanisms still remain unclear. To address this issue, we presented participants with visual cues predicting rewards of high and low magnitudes and probability (2 × 2 factorial design), while neural activity was scanned using magnetoencephalography. Importantly, one group of participants received 150 mg of the dopamine precursor levodopa prior to the experiment, while another group received a placebo. For the placebo group, neural signals of reward probability (but not magnitude) emerged at ∼ 100 ms after cue presentation at occipital sensors in the event-related magnetic fields. Importantly, these probability signals were absent in the levodopa group indicating a close link. Moreover, levodopa administration reduced oscillatory power in the high (20-30 Hz) and low (13-20 Hz) beta band during both reward anticipation and delivery. Taken together, our findings indicate that visual brain regions are involved in coding prospective reward probability but not magnitude and that these effects are modulated by dopamine.

Dopamine controls the neural dynamics of memory signals and retrieval accuracy.

The human brain is capable of differentiating between new and already stored information rapidly to allow optimal behavior and decision-making. Although the neural mechanisms of novelty discrimination were often described as temporally constant (ie, with specific latencies), recent electrophysiological studies have demonstrated that the onset of neural novelty signals (ie, differences in event-related responses to new and old items) can be accelerated by reward motivation. While the precise physiological mechanisms underlying this acceleration remain unclear, the involvement of the neurotransmitter dopamine in both novelty and reward processing suggests that enhanced dopamine levels in the context of reward prospect may have a role. To investigate this hypothesis, we used magnetoencephalography (MEG) in combination with an old/new recognition memory task in which correct discrimination between old and new items was rewarded. Importantly, before the task, human subjects received either 150 mg of the dopamine precursor levodopa or placebo. For the placebo group, old/new signals peaked at ∼100 ms after stimulus onset over left temporal/occipital sensors. In contrast, after levodopa administration earliest old/new effects only emerged after ∼400 ms and retrieval accuracy was reduced as expressed in lower d' values. As such, our results point towards a previously unreported role of dopamine in controlling the chronometry of neural processes underlying the distinction between old and new information. They also suggest that this relationship follows a nonlinear function whereby slightly enhanced dopamine levels accelerate neural/cognitive processes and excessive dopamine levels impair them.

Reward modulates the neural dynamics of early visual category processing.

Converging evidence suggests that visual brain regions are part of a widespread network that signals forthcoming reward. However, the precise temporal dynamics underlying the interaction between reward and visual information processing remain unclear. To further investigate this issue, we used magnetoencephalography (MEG) in combination with two versions of a face/scene discrimination task followed by a recognition memory test. In experiment 1, the distinction between faces and scenes was associated with monetary reward prospect, whereas in experiment 2 subjects distinguished between both categories in the absence of reward. In both experiments characteristic neural category effects (i.e., differences between faces and scenes) were observed in the event-related magnetic fields (ERF) at ~100 ms (M100) and ~170 ms (M170) after stimulus onset. Importantly, both ERF components (M100 and M170) were amplified in the context of reward (i.e., experiment 1) and this interaction could be source localized to the lateral occipital cortex (~100 ms) and fusiform gyrus (~170 ms). Furthermore, neural effects of reward prediction emerged over frontal sensors at ~300 ms after stimulus onset which reliably correlated with subsequent recognition memory performance. These results demonstrate that reward motivation can modulate early neural computations of complex visual information, possibly by tuning sensory neurons within the visual cortex.