Event-related functional magnetic resonance imaging of a low dose of dexmedetomidine that impairs long-term memory.

BACKGROUND: Work suggests the amnesia from dexmedetomidine (an α2-adrenergic agonist) is caused by a failure of information to be encoded into long-term memory and that dexmedetomidine might differentially affect memory for emotionally arousing material. We investigated these issues in humans using event-related neuroimaging to reveal alterations in brain activity and subsequent memory effects associated with drug exposure. METHODS: Forty-eight healthy volunteers received a computer-controlled infusion of either placebo or low-dose dexmedetomidine (target = 0.15 ng/ml plasma) during neuroimaging while they viewed and rated 80 emotionally arousing (e.g., graphic war wound) and 80 nonarousing neutral (e.g., cup) pictures for emotional arousal content. Long-term picture memory was tested 4 days later without neuroimaging. Imaging data were analyzed for drug effects, emotional processing differences, and memory-related changes with statistical parametric mapping-8. RESULTS: Dexmedetomidine impaired overall (mean ± SEM) picture memory (placebo: 0.58 ± 0.03 vs. dexmedetomidine: 0.45 ± 0.03, P = 0.001), but did not differentially modulate memory as a function of item arousal. Arousing pictures were better remembered for both groups. Dexmedetomidine had regionally heterogeneous effects on brain activity, primarily decreasing it in the cortex and increasing it in thalamic and posterior hippocampal regions. Nevertheless, a single subsequent memory effect for item memory common to both groups was identified only in the left hippocampus/amygdala. Much of this effect was found to be larger for the placebo than dexmedetomidine group. CONCLUSION: Dexmedetomidine impaired long-term picture memory, but did not disproportionately block memory for emotionally arousing items. The memory impairment on dexmedetomidine corresponds with a weakened hippocampal subsequent memory effect.

Returning from oblivion: imaging the neural core of consciousness.

One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in brain activity using regional cerebral blood flow imaging with positron emission tomography. Study design and methodology were chosen to dissociate the state-related changes in consciousness from the effects of the anesthetic drugs. We found the emergence of consciousness, as assessed with a motor response to a spoken command, to be associated with the activation of a core network involving subcortical and limbic regions that become functionally coupled with parts of frontal and inferior parietal cortices upon awakening from unconsciousness. The neural core of consciousness thus involves forebrain arousal acting to link motor intentions originating in posterior sensory integration regions with motor action control arising in more anterior brain regions. These findings reveal the clearest picture yet of the minimal neural correlates required for a conscious state to emerge.

Overlap between the neural correlates of cued recall and source memory: evidence for a generic recollection network?

Recall of a studied item and retrieval of its encoding context (source memory) both depend on recollection of qualitative information about the study episode. This study investigated whether recall and source memory engage overlapping neural regions. Participants (n = 18) studied a series of words, which were presented either to the left or right of fixation. fMRI data were collected during a subsequent test phase in which three-letter word-stems were presented, two thirds of which could be completed by a study item. Instructions were to use each stem as a cue to recall a studied word and, when recall was successful, to indicate the word's study location. When recall failed, the stem was to be completed with the first word to come to mind. Relative to stems for which recall failed, word-stems eliciting successful recall were associated with enhanced activity in a variety of cortical regions, including bilateral parietal, posterior midline, and parahippocampal cortex. Activity in these regions was enhanced when recall was accompanied by successful rather than unsuccessful source retrieval. It is proposed that the regions form part of a "recollection network" in which activity is graded according to the amount of information retrieved about a study episode.

Right dorsolateral prefrontal cortex is engaged during post-retrieval processing of both episodic and semantic information.

Post-retrieval processes are engaged when the outcome of a retrieval attempt must be monitored or evaluated. Functional neuroimaging studies have implicated right dorsolateral prefrontal cortex (DLPFC) as playing a role in post-retrieval processing. The present study used fMRI to investigate whether retrieval-related neural activity in DLPFC is associated specifically with monitoring the episodic content of a retrieval attempt. During study, subjects were cued to make one of two semantic judgments on serially presented pictures. One study phase was followed by a source memory task, in which subjects responded 'new' to unstudied pictures, and signaled the semantic judgment made on each studied picture. A separate study phase was followed by a task in which the studied items were subjected to a judgment about their semantic attributes. Both tasks required that retrieved information be evaluated prior to response selection, but only the source memory task required evaluation of retrieved episodic information. In both tasks, activity in a common region of right DLPFC was greater for studied than for unstudied items, and the magnitude of this effect did not differ between the tasks. Together with the results of a parallel event-related potential study [Hayama, H. R., Johnson, J. D., & Rugg, M. D. (2008). The relationship between the right frontal old/new ERP effect and post-retrieval monitoring: Specific or non-specific? Neuropsychologia, 46(5), 1211-1223, doi:S0028-3932(07)00390-9], the present findings indicate that putative right DLPFC correlates of post-retrieval processing are not associated exclusively with monitoring or evaluating episodic content. Rather, the effects likely reflect processing associated with monitoring or decision-making in multiple cognitive domains.

The relationship between the right frontal old/new ERP effect and post-retrieval monitoring: specific or non-specific?

Post-retrieval processes are thought to be engaged when the outcome of an attempt to retrieve information from long-term memory must be monitored or evaluated. Previous research employing event-related potentials (ERPs) has implicated a specific ERP modulation - the 'right frontal old/new effect' - as a correlate of post-retrieval processing. In two experiments we examined whether the right frontal effect is specifically associated with processing of the products of an episodic retrieval attempt. During study, subjects in both experiments made one of two semantic judgments on serially presented pictures. In experiment 1, one study phase was followed by a source memory task, in which subjects responded 'new' to unstudied pictures and signaled the semantic judgment made on each studied picture. A separate study phase was followed by a task in which the studied items required a judgment about their semantic attributes. Robust right frontal effects were elicited by old items in both tasks, indicating that the effects are not selective for the monitoring of the content of information retrieved from episodic memory. In experiment 2, separate study phases were followed by test phases where semantic judgments were made either on old items (as in experiment 1), or on new items. Right frontal effects were elicited by whichever class of items, old or new, required the semantic judgment. Together, these findings indicate that the right frontal old/new effect reflects generic monitoring or decisional processes, rather than processing dedicated to the evaluation of the products of an episodic retrieval attempt.

Electrophysiological dissociation of the neural correlates of recollection and familiarity.

Event-related potentials (ERPs) were employed to investigate electrophysiological correlates of recognition memory in a task that allowed segregation of test items according to whether they were recollected (operationalized by introspective report) or, if recollection failed, their level of familiarity (operationalized by recognition confidence). The amplitude of a negative-going ERP deflection that onsets around 300 ms post-stimulus varied inversely with familiarity strength. This effect was maximal over the left frontal scalp. It did not differ between the ERPs elicited by highly familiar versus recollected items, indicating that the recollection is not merely a consequence of strong familiarity. By contrast, a later positive deflection (onset ca. 500 ms post-stimulus) was enhanced in ERPs elicited by recollected relative to highly familiar items. This effect was maximal over the left posterior scalp and was insensitive to familiarity, as indicated by its absence in the contrast between items judged highly familiar versus highly unfamiliar. The findings constitute a double dissociation between the neural correlates of recollection and familiarity. Together with the results of a parallel functional magnetic resonance imaging study (A.P. Yonelinas et al., J. Neurosci. (2005), 25, 3002-3008), they indicate that recollection and familiarity rely on qualitatively distinct neural systems and strongly support dual-process models of recognition memory.