Anticipating social incentives recruits alpha-beta oscillations in the human substantia nigra and invigorates behavior across the life span.

Anticipating social and non-social incentives recruits shared brain structures and promotes behavior. However, little is known about possible age-related behavioral changes, and how the human substantia nigra (SN) signals positive and negative social information. Therefore, we recorded intracranial electroencephalography (iEEG) from the SN of Parkinson's Disease (PD) patients (n = 12, intraoperative, OFF medication) in combination with a social incentive delay task including photos of neutral, positive or negative human gestures and mimics as feedback. We also tested a group of non-operated PD patients (n = 24, ON and OFF medication), and a sample of healthy young (n = 51) and older (n = 52) adults with behavioral readouts only. Behaviorally, the anticipation of both positive and negative social feedback equally accelerated response times in contrast to neutral social feedback in healthy young and older adults. Although this effect was not significant in the group of operated PD patients - most likely due to the small sample size - iEEG recordings in their SN showed a significant increase in alpha-beta power (9-20 Hz) from 300 to 600 ms after cue onset again for both positive and negative cues. Finally, in non-operated PD patients, the behavioral effect was not modulated by medication status (ON vs OFF medication) suggesting that other processes than dopaminergic neuromodulation play a role in driving invigoration by social incentives. Together, our findings provide novel and direct evidence for a role of the SN in processing positive and negative social information via specific oscillatory mechanisms in the alpha-beta range, and they suggest that anticipating social value in simple cue-outcome associations is intact in healthy aging and PD.

Theta oscillations underlie retrieval success effects in the nucleus accumbens and anterior thalamus: Evidence from human intracranial recordings.

Previous imaging studies independently highlighted the role of the anterior thalamus (ANT) and nucleus accumbens (NAcc) in successful memory retrieval. While these findings accord with theoretical models, the precise temporal, oscillatory and network dynamics as well as the interplay between the NAcc and ANT in successfully retrieving information from long-term memory are largely unknown. We addressed this issue by recording intracranial electroencephalography in human epilepsy patients from the NAcc (n = 5) and ANT (n = 4) during an old/new recognition test. Our findings demonstrate that differences in event-related potentials between correctly classified old (i.e., studied) and new (i.e., unstudied) images emerged in the NAcc and ANT already between 200 and 600 ms after stimulus onset. Moreover, time-frequency analyses revealed theta (4-8 Hz) power decreases for old compared to new items in the NAcc and the opposite effect in the ANT. Importantly, Granger causality analyses revealed a directional communication from ANT to NAcc suggesting that entrainment from ANT drives successful memory retrieval. Together, our findings show evidence for the notion that the NAcc and ANT receive memory signals, and that theta oscillations may serve as a mechanism to bind these distributed neural assemblies.

Neural Habituation to Painful Stimuli Is Modulated by Dopamine: Evidence from a Pharmacological fMRI Study.

In constantly changing environments, it is crucial to adaptively respond to threatening events. In particular, painful stimuli are not only processed in terms of their absolute intensity, but also with respect to their context. While contextual pain processing can simply entail the repeated processing of information (i.e., habituation), it can, in a more complex form, be expressed through predictions of magnitude before the delivery of nociceptive information (i.e., adaptive coding). Here, we investigated the brain regions involved in the adaptation to nociceptive electrical stimulation as well as their link to dopaminergic neurotransmission (placebo/haloperidol). The main finding is that haloperidol changed the habituation to the absolute pain intensity over time. More precisely, in the placebo condition, activity in left postcentral gyrus and midcingulate cortex increased linearly with pain intensity only in the beginning of the experiment and subsequently habituated. In contrast, when the dopaminergic system was blocked by haloperidol, a linear increase with pain intensity was present throughout the entire experiment. Finally, there were no adaptive coding effects in any brain regions. Together, our findings provide novel insights into the nature of pain processing by suggesting that dopaminergic neurotransmission plays a specific role for the habituation to painful stimuli over time.

Anticipation of electric shocks modulates low beta power and event-related fields during memory encoding.

In humans, the temporal and oscillatory dynamics of pain anticipation and its effects on long-term memory are largely unknown. Here, we investigated this open question by using a previously established behavioral paradigm in combination with magnetoencephalography (MEG). Healthy human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5 or 0.8). After encoding, memory for the studied images was tested using a remember/know recognition task. Behaviorally, pain anticipation did not modulate recollection-based recognition memory per se, but interacted with the perceived unpleasantness of the electric shock [visual analogue scale rating from 1 (not unpleasant) to 10 (highly unpleasant)]. More precisely, the relationship between pain anticipation and recollection followed an inverted u-shaped function the more unpleasant the shocks were rated by a subject. At the physiological level, this quadratic effect was mimicked in the event-related magnetic fields associated with successful memory formation ('DM-effect') ∼450ms after image onset at left frontal sensors. Importantly, across all subjects, shock anticipation modulated oscillatory power in the low beta frequency range (13-20Hz) in a linear fashion at left temporal sensors. Taken together, our findings indicate that beta oscillations provide a generic mechanism underlying pain anticipation; the effect on subsequent long-term memory, on the other hand, is much more variable and depends on the level of individual pain perception. As such, our findings give new and important insights into how aversive motivational states can drive memory formation.

Pain anticipation recruits the mesolimbic system and differentially modulates subsequent recognition memory.

The ability to encode information into long-term memory is not a passive process but can be influenced by motivational factors. While the mesolimbic system has long been associated with reward-driven memory enhancement, the precise neurobiology of processing aversive events and their effects on declarative learning remain unclear. To address this issue, human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5, 0.8). Subsequently, recognition memory for the scenes was tested using a remember/know procedure. In a behavioral experiment, shock probability had linear effects on familiarity and inverted u-shaped effects on recollection. While the behavioral effect was absent in experiment 2 (fMRI), at the neural level encoding-related activity in the hippocampus mimicked the recollection specific quadratic effect, whereas activity in the anterior parahippocampal gyrus mirrored the familiarity specific linear relationship that was evident in experiment 1. Importantly, the probability of upcoming shocks was linearly coded in the substantia nigra / ventral tegmental area, and pain associated brain regions, such as the insula, responded to shock delivery. Our results demonstrate that anticipating primary aversive events recruits the human mesolimbic system and differentially modulates declarative memory functions via medial temporal lobe structures.

Dopaminergic stimulation facilitates working memory and differentially affects prefrontal low theta oscillations.

We used electroencephalography (EEG) together with psychopharmacological stimulation to investigate the role of dopamine in neural oscillations during working memory (WM). Following a within-subjects design, healthy humans either received the dopamine precursor L-Dopa (150 mg) or a placebo before they performed a Sternberg WM paradigm. Here, sequences of sample images had to be memorized for a delay of 5 s in three different load conditions (two, four or six items). On the next day, long-term memory (LTM) for the images was tested. Behaviorally, L-Dopa improved WM and LTM performance as a function of WM load. More precisely, there was a specific drug effect in the four-load condition with faster reaction times to the probe in the WM task and higher corrected hit-rates in the LTM task. During the maintenance period, there was a linear and quadratic effect of WM load on power in the high theta (5-8 Hz) and alpha (9-14 Hz) frequency range at frontal sensors. Importantly, a drug by load interaction--mimicking the behavioral results--was found only in low theta power (2-4 Hz). As such, our results indicate a specific link between prefrontal low theta oscillations, dopaminergic neuromodulation during WM and subsequent LTM performance.

White noise improves learning by modulating activity in dopaminergic midbrain regions and right superior temporal sulcus.

In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise-but not control sounds, such as a sinus tone-slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS-a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.

Nucleus accumbens activity dissociates different forms of salience: evidence from human intracranial recordings.

Theoretical models and empirical work indicate a critical role of the NAcc in salience processing. For instance, the NAcc not only responds to appetitive and aversive information, but it also signals novelty, contextual deviance, and action monitoring. However, because most studies have investigated only one specific type of salience independently, it remains unclear how the NAcc concurrently differentiates between different forms of salience. To investigate this issue, we used intracranial electroencephalography in human epilepsy patients together with a previously established visual oddball paradigm. Here, three different oddball categories (novel, neutral, and target images) were infrequently presented among a standard scene image, and subjects responded to the target via button press. This task allowed us to differentiate "item novelty" (new vs neutral oddballs) from "contextual deviance" (neutral oddballs vs standard images) and "targetness" (target vs neutral oddballs). Time-frequency analysis revealed a dissociation between item novelty and contextual deviance on the basis of decreases in either θ (4-8 Hz) or ß power (20-30 Hz). Targetness, on the other hand, was signaled by positive deflections in the stimulus-locked local field potentials, which, importantly, correlated with subjects' reaction times. These findings indicate that, in an ongoing stream of information, the NAcc differentiates between types of salience by distinct neural mechanisms to guide goal-directed behavior.

Study-test congruency affects encoding-related brain activity for some but not all stimulus materials.

Memory improves when encoding and retrieval processes overlap. Here, we investigated how the neural bases of long-term memory encoding vary as a function of the degree to which functional processes engaged at study are engaged again at test. In an incidental learning paradigm, electrical brain activity was recorded from the scalps of healthy adults while they made size judgments on intermixed series of pictures and words. After a 1-hr delay, memory for the items was tested with a recognition task incorporating remember/know judgments. In different groups of participants, studied items were either probed in the same mode of presentation (word-word; picture-picture) or in the alternative mode of presentation (word-picture; picture-word). Activity over anterior scalp sites predicted later memory of words, irrespective of type of test probe. Encoding-related activity for pictures, by contrast, differed qualitatively depending on how an item was cued at test. When a picture was probed with a picture, activity over anterior scalp sites predicted encoding success. When a picture was probed with a word, encoding-related activity was instead maximal over posterior sites. Activity differed according to study-test congruency from around 100 msec after picture onset. These findings indicate that electrophysiological correlates of encoding are sensitive to the similarity between processes engaged at study and test. The time course supports a direct and not merely consequential role of encoding-retrieval overlap in encoding. However, because congruency only affected one type of stimulus material, encoding-retrieval overlap may not be a universal organizing principle of neural correlates of memory.