Michael X Cohen

Dissociable correlates of recollection and familiarity within the medial temporal lobes

Regions in the medial temporal lobes (MTL) have long been implicated in the formation of new memories for events, however, it is unclear whether different MTL subregions support different memory processes. Here, we used event-related functional magnetic resonance imaging (fMRI) to examine the degree to which two recognition memory processes-recollection and familiarity-were supported by different MTL subregions. Results showed that encoding activity in the rhinal cortex selectively predicted familiarity-based recognition, whereas, activity in the hippocampus and posterior parahippocampal cortex selectively predicted recollection. Collectively, these results support the view that different subregions within the MTL memory system implement unique encoding processes that differentially support familiarity and recollection.

Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression

BACKGROUNDnWhile most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising.nnnMETHODSnTen patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3).nnnRESULTSnTwelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala.nnnCONCLUSIONSnWe demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Inferior Temporal, Prefrontal, and Hippocampal Contributions to Visual Working Memory Maintenance and Associative Memory Retrieval

Higher order cognition depends on the ability to recall information from memory and hold it in mind to guide future behavior. To specify the neural mechanisms underlying these processes, we used event-related functional magnetic resonance imaging to compare brain activity during the performance of a visual associative memory task and a visual working memory task. Activity within category-selective subregions of inferior temporal cortex reflected the type of information that was actively maintained during both the associative memory and working memory tasks. In addition, activity in the anterior prefrontal cortex and hippocampus was specifically enhanced during associative memory retrieval. These data are consistent with the view that the active maintenance of visual information is supported by activation of object representations in inferior temporal cortex, but that goal-directed associative memory retrieval additionally depends on top-down signals from the anterior prefrontal cortex and medial temporal lobes.

Working Memory Maintenance Contributes to Long-term Memory Formation: Neural and Behavioral Evidence

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.

Reinforcement learning signals predict future decisions

Optimal behavior in a competitive world requires the flexibility to adapt decision strategies based on recent outcomes. In the present study, we tested the hypothesis that this flexibility emerges through a reinforcement learning process, in which reward prediction errors are used dynamically to adjust representations of decision options. We recorded event-related brain potentials (ERPs) while subjects played a strategic economic game against a computer opponent to evaluate how neural responses to outcomes related to subsequent decision-making. Analyses of ERP data focused on the feedback-related negativity (FRN), an outcome-locked potential thought to reflect a neural prediction error signal. Consistent with predictions of a computational reinforcement learning model, we found that the magnitude of ERPs after losing to the computer opponent predicted whether subjects would change decision behavior on the subsequent trial. Furthermore, FRNs to decision outcomes were disproportionately larger over the motor cortex contralateral to the response hand that was used to make the decision. These findings provide novel evidence that humans engage a reinforcement learning process to adjust representations of competing decision options.

Neural Representations of Self versus Other: Visual-Spatial Perspective Taking and Agency in a Virtual Ball-tossing Game

Human self-consciousness relies on the ability to distinguish between oneself and others. We sought to explore the neural correlates involved in self-other representations by investigating two critical processes: perspective taking and agency. Although recent research has shed light on the neural processes underlying these phenomena, little is known about how they overlap or interact at the neural level. In a two-factorial functional magnetic resonance imaging (fMRI) experiment, participants played a ball-tossing game with two virtual characters (avatars). During an active/agency (ACT) task, subjects threw a ball to one of the avatars by pressing a button. During a passive/nonagency (PAS) task, they indicated which of the other avatars threw the ball. Both tasks were performed from a first-person perspective (1PP), in which subjects interacted from their own perspective, and a third-person perspective (3PP), in which subjects interacted from the perspective of an avatar with another location in space. fMRI analyses revealed overlapping activity in medial prefrontal regions associated with representations of ones own perspective and actions (1PP and ACT), and overlapping activity in temporal-occipital, premotor, and inferior frontal, as well as posterior parietal regions associated with representation of others perspectives and actions (3PP and PAS). These findings provide evidence for distinct neural substrates underlying representations of the self and others and provide support for the idea that the medial prefrontal cortex crucially contributes to a neural basis of the self. The lack of a statistically significant interaction suggests that perspective taking and agency represent independent constituents of self-consciousness.

Different neural systems adjust motor behavior in response to reward and punishment

Individuals use the outcomes of their actions to adjust future behavior. However, it remains unclear whether the same neural circuits are used to adjust behavior due to rewarding and punishing outcomes. Here we used functional magnetic resonance imaging (fMRI) and a reward-providing reaction time task to investigate the adaptation of a simple motor response following four different outcomes (delivery versus omission and monetary gain versus loss). We found that activation in the thalamus and insula predicted adjustments of motor responses due to outcomes that were cued and delivered, whereas activation in the ventral striatum predicted such adjustments when outcomes were cued but omitted. Further, activation of OFC predicted improvement after all punishing outcomes, independent of whether they were omitted rewards or delivered punishments. Finally, we found that activity in anterior cingulate predicted adjustment after delivered punishments and activity in dorsal striatum predicted adaptation after delivered rewards. Our results provide evidence that different but somewhat overlapping circuits mediate the same behavioral adaptation when it is driven by different incentive outcomes.

Good vibrations: Cross-frequency coupling in the human nucleus accumbens during reward processing

The nucleus accumbens is critical for reward-guided learning and decision-making. It is thought to “gate” the flow of a diverse range of information (e.g., rewarding, aversive, and novel events) from limbic afferents to basal ganglia outputs. Gating and information encoding may be achieved via cross-frequency coupling, in which bursts of high-frequency activity occur preferentially during specific phases of slower oscillations. We examined whether the human nucleus accumbens engages such a mechanism by recording electrophysiological activity directly from the accumbens of human patients undergoing deep brain stimulation surgery. Oscillatory activity in the gamma (40–80 Hz) frequency range was synchronized with the phase of simultaneous alpha (8–12 Hz) waves. Further, losing and winning small amounts of money elicited relatively increased gamma oscillation power prior to and following alpha troughs, respectively. Gamma–alpha synchronization may reflect an electrophysiological gating mechanism in the human nucleus accumbens, and the phase differences in gamma–alpha coupling may reflect a reward information coding scheme similar to phase coding.

Assessing transient cross-frequency coupling in EEG data

Synchronization of oscillatory EEG signals across different frequency bands is receiving waxing interest in cognitive neuroscience and neurophysiology, and cross-frequency coupling is being increasingly linked to cognitive and perceptual processes. Several methods exist to examine cross-frequency coupling, although each has its limitations, typically by being flexible only over time or over frequency. Here, a method for assessing transient cross-frequency coupling is presented, which allows one to test for the presence of multiple, dynamic, and flexible cross-frequency coupling structure over both time and frequency. The method is applied to intracranial EEG data, and strong coupling between gamma ( approximately 40-80 Hz) and upper theta ( approximately 7-9 Hz) was observed. This method might have useful applications in uncovering the electrophysiological correlates of cognitive processes.

The extrastriate cortex distinguishes between the consequences of one's own and others' behavior.

The extrastriate body area (EBA) is traditionally considered a category-selective region for the visual processing of static images of the human body. Recent evidence challenges this view by showing motor-related modulations of EBA activity during self-generated movements. Here, we used functional MRI to investigate whether the EBA distinguishes self- from other-generated movements, a prerequisite for the sense of agency. Subjects performed joystick movements while the visual feedback was manipulated on half of the trials. The EBA was more active when the visual feedback was incongruent to the subjects own executed movements. Furthermore, during correct feedback evaluation, the EBA showed enhanced functional connectivity to posterior parietal cortex, which has repeatedly been implicated in the detection of sensorimotor incongruence and the sense of agency. Our results suggest that the EBA represents the human body in a more integrative and dynamic manner, being able to detect an incongruence of internal body or action representations and external visual signals. In this way, the EBA might be able to support the disentangling of ones own behavior from anothers.