BACKGROUND:The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients.METHODS:We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences.RESULTS:In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = -0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = - 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives.CONCLUSIONS:N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis.

We conducted a study in San Antonio, Texas, in the weeks preceding the 2022 state Governor election to determine if implicit or explicit measures of political preference could predict voter behavior. We adapted an established event-related potential (ERP) paradigm showing political statements to participants one word at the time where the last word made the statement pro-Republican or pro-Democratic. Our sample of college students included decided and undecided voters, and was reflective of the demographic make-up of south-central Texas. Our implicit measures were an established authoritarianism scale and the N400 effect to the sentence-final word. The N400 is an ERP to any stimulus that engages semantic memory and has been shown to measure implicit disagreement with political statements. Explicit measures of political preference and authoritarianism were predictive of vote choice. The expected N400 effect was found for Democratic voters, with larger amplitude to pro-Republican than pro-Democratic statements. Surprisingly, decided Republican voters showed no difference in N400 responses to pro-Republican and pro-Democratic statements and there was no group difference in the N400 effect. In turn, the N400 was not predictive of voter behavior. We argue that the N400 effect reflected individual political preferences, but that ultimately voter behavior aligned with partisan identity.

Alcohol abuse has become a serious health issue worldwide. Ketamine can reduce addiction risk among patients with alcohol use disorders. This study aimed to determine the effects of alcohol on the pharmacokinetics of ketamine during long-term alcohol exposure.An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of ketamine and norketamine was developed and validated. A total of 15 rats were given 40% alcohol for 3 weeks. The pharmacokinetics of ketamine were measured at time zero, 1 week, 2 weeks, and 3 weeks after alcohol exposure. The metabolic capability of liver CYP450 was evaluated using three probe drugs: metoprolol, phenacetin, and tolbutamide.During drinking of 40% alcohol, the AUC(0-t), AUC(0-∞), and Cmax of ketamine and norketamine significantly increased, while V and CL significantly decreased with time (p < 0.001). The pharmacokinetic changes of norketamine were highly consistent with ketamine. Additionally, the concentration ratio of norketamine/ketamine in sample time also decreased over time. However, there were no pharmacokinetic changes of three probe drugs, which indicated there was no significant change of liver CYPs activities.Alcohol significantly increases plasma concentration of ketamine and norketamine. The effect of alcohol on pharmacokinetics of ketamine should be considered in clinical therapy.

Older individuals' difficulty in remembering events from a particular time and place may be explained by changes in retrieval-related control processes. We investigated how aging affects neural activity leading up to a retrieval probe and how such activity relates to later performance. Electrical brain activity was recorded while healthy younger and older humans memorized visual word pairs consisting of an object word (e.g., doll) preceded by a location word (e.g., garden). Only object words were presented during the memory test, the task being to decide whether an object had been presented earlier and, if so, what location had been paired with it. A warning signal before each test probe alerted to an upcoming object. A sustained negative-going event-related potential deflection preceded objects whose associated location could be remembered, especially in older individuals. The poorer an older individual's associative memory, the bigger was this deflection. Aging thus seems accompanied by changes in anticipatory brain states that relate to recollection. Such states may serve to mobilize control processes that aid the recovery of contextual details.

Reading times on words in a sentence depend on the amount of information the words convey, which can be estimated by probabilistic language models. We investigate whether event-related potentials (ERPs), too, are predicted by information measures. Three types of language models estimated four different information measures on each word of a sample of English sentences. Six different ERP deflections were extracted from the EEG signal of participants reading the same sentences. A comparison between the information measures and ERPs revealed a reliable correlation between N400 amplitude and word surprisal. Language models that make no use of syntactic structure fitted the data better than did a phrase-structure grammar, which did not account for unique variance in N400 amplitude. These findings suggest that different information measures quantify cognitively different processes and that readers do not make use of a sentence’s hierarchical structure for generating expectations about the upcoming word.

Oscillatory brain activity in the theta frequency range (4-8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory.

Relative to abstract words, concrete words typically elicit faster response times and larger N400 and N700 event-related potential (ERP) brain responses. These effects have been interpreted as reflecting the denser links to associated semantic information of concrete words and their recruitment of visual imagery processes. Here, we examined whether there are ERP differences between concrete and abstract stimuli controlled for a large number of factors including context availability (i.e., richness of semantic associations) and imageability. We found that abstract words elicited faster behavioral responses but that concrete words still elicited larger N400 and N700 responses. We propose that once all other factors, including imageability and context availability are controlled, abstract words may trigger a larger number of superficial linguistic associations that can be quickly used for response decisions. The ERP differences, however, would index the greater semantic processing (integration of multimodal information) for concrete than abstract words during meaning activation.

We investigated the effect of word surprisal on the EEG signal during sentence reading. On each word of 205 experimental sentences, surprisal was estimated by three types of language model: Markov models, probabilistic phrasestructure grammars, and recurrent neural networks. Four event-related potential components were extracted from the EEG of 24 readers of the same sentences. Surprisal estimates under each model type formed a significant predictor of the amplitude of the N400 component only, with more surprising words resulting in more negative N400s. This effect was mostly due to content words. These findings provide support for surprisal as a generally applicable measure of processing difficulty during language comprehension.

Effective cognitive functioning not only relies on brain activity elicited by an event, but also on activity that precedes it. This has been demonstrated in a number of cognitive domains, including memory. Here, we show that brain activity that precedes the effective encoding of a word into long-term memory depends on the availability of sufficient processing resources. We recorded electrical brain activity from the scalps of healthy adult men and women while they memorized intermixed visual and auditory words for later recall. Each word was preceded by a cue that indicated the modality of the upcoming word. The degree to which processing resources were available before word onset was manipulated by asking participants to make an easy or difficult perceptual discrimination on the cue. Brain activity before word onset predicted later recall of the word, but only in the easy discrimination condition. These findings indicate that anticipatory influences on long-term memory are limited in capacity and sensitive to the degree to which attention is divided between tasks. Prestimulus activity that affects later encoding can only be engaged when the necessary cognitive resources can be allocated to the encoding process.

Brain activity immediately before an event can predict whether the event will later be remembered. This indicates that memory formation is influenced by anticipatory mechanisms engaged ahead of stimulus presentation. Here, we asked whether anticipatory processes affect the learning of short word lists, and whether such activity varies as a function of serial position. Participants memorized lists of intermixed visual and auditory words with either an elaborative or rote rehearsal strategy. At the end of each list, a distraction task was performed followed by free recall. Recall performance was better for words in initial list positions and following elaborative rehearsal. Electrical brain activity before auditory words predicted later recall in the elaborative rehearsal condition. Crucially, anticipatory activity only affected recall when words occurred in initial list positions. This indicates that anticipatory processes, possibly related to general semantic preparation, contribute to primacy effects.

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.

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.

Women and men differ in the way they experience emotional events. Previous work has indicated that the impact of an emotional event depends on how it is anticipated. Separately, it has been shown that anticipation affects memory formation. Here, we assessed whether anticipatory brain activity influences the encoding of emotional events into long-term memory and, in addition, how biological sex affects the use of such activity. Electrical brain activity was recorded from the scalps of healthy men and women while they performed an incidental encoding task (indoor/outdoor judgments) on pleasant, unpleasant, and neutral pictures. Pictures were preceded by a cue that indicated the valence of the upcoming item. Memory was tested after a 20 min delay with a recognition task incorporating the remember/know procedure. Brain activity before picture onset predicted later memory of an event. Crucially, the role of anticipatory activity depended entirely on the valence of a picture and the sex of an individual. Right-lateralized anticipatory activity selectively influenced the encoding of unpleasant pictures in women, but not in men. These findings indicate that anticipatory processes influence the way in which women encode negative events into memory. The selective use of such activity may indicate that anticipatory activity is one mechanism by which individuals regulate their emotions.

Human neuroimaging studies have implicated a number of brain regions in long-term memory formation. Foremost among these is ventrolateral prefrontal cortex. Here, we used double-pulse transcranial magnetic stimulation (TMS) to assess whether the contribution of this part of cortex is crucial for laying down new memories and, if so, to examine the time course of this process. Healthy adult volunteers performed an incidental encoding task (living/nonliving judgments) on sequences of words. In separate series, the task was performed either on its own or while TMS was applied to one of two sites of experimental interest (left/right anterior inferior frontal gyrus) or a control site (vertex). TMS pulses were delivered at 350, 750, or 1,150 ms following word onset. After a delay of 15 min, memory for the items was probed with a recognition memory test including confidence judgments. TMS to all three sites nonspecifically affected the speed and accuracy with which judgments were made during the encoding task. However, only TMS to prefrontal cortex affected later memory performance. Stimulation of left or right inferior frontal gyrus at all three time points reduced the likelihood that a word would later be recognized by a small, but significant, amount (∼4%). These findings indicate that bilateral ventrolateral prefrontal cortex plays an essential role in memory formation, exerting its influence between ≥350 and 1,150 ms after an event is encountered.

A new development in our understanding of human long-term memory is that effective memory formation relies on neural activity just before an event. It is unknown whether such prestimulus activity is under voluntary control or a reflection of random fluctuations over time. In the present study, we addressed two issues: (1) whether prestimulus activity is influenced by an individual's motivation to encode, and (2) at what point in time encoding-related activity emerges. Electrical brain activity was recorded while healthy male and female adults memorized series of words. Each word was preceded by a cue, which indicated the monetary reward that would be received if the following word was later remembered. Memory was tested after a short delay with a five-way recognition task to separate different sources of recognition. Electrical activity elicited by the reward cue predicted later memory of a word. Crucially, however, this was only observed when the incentive to memorize a word was high. Encoding-related activity preceded high-reward words that were later recollected. This activity started shortly after cue onset and persisted until word onset. Prestimulus activity thus not only signals cue-related processing but also an ensuing preparatory state. In contrast, reward-related activity was limited to the time period immediately after the reward cue. These findings indicate that engaging neural activity that benefits the encoding of an upcoming event is under voluntary control, reflecting a strategic preparatory state in anticipation of processing an event.