Asymmetric Frequency-Specific Feedforward and Feedback Information Flow between Hippocampus and Prefrontal Cortex during Verbal Memory Encoding and Recall.

Hippocampus and prefrontal cortex (PFC) circuits are thought to play a prominent role in human episodic memory, but the precise nature, and electrophysiological basis, of directed information flow between these regions and their role in verbal memory formation has remained elusive. Here we investigate nonlinear causal interactions between hippocampus and lateral PFC using intracranial EEG recordings (26 participants, 16 females) during verbal memory encoding and recall tasks. Direction-specific information theoretic analysis revealed higher causal information flow from the hippocampus to PFC than in the reverse direction. Crucially, this pattern was observed during both memory encoding and recall, and the strength of causal interactions was significantly greater during memory task performance than resting baseline. Further analyses revealed frequency specificity of interactions with greater causal information flow from hippocampus to the PFC in the delta-theta frequency band (0.5-8 Hz); in contrast, PFC to hippocampus causal information flow were stronger in the beta band (12-30 Hz). Across all hippocampus-PFC electrode pairs, propagation delay between the source and target signals was estimated to be 17.7 ms, which is physiologically meaningful and corresponds to directional signal interactions on a timescale consistent with monosynaptic influence. Our findings identify distinct asymmetric feedforward and feedback signaling mechanisms between the hippocampus and PFC and their dissociable roles in memory recall, demonstrate that these regions preferentially use different frequency channels, and provide novel insights into the electrophysiological basis of directed information flow during episodic memory formation in the human brain.SIGNIFICANCE STATEMENT Hippocampal-PFC circuits play a critical role in episodic memory in rodents, nonhuman primates, and humans. Investigations using noninvasive fMRI techniques have provided insights into coactivation of the hippocampus and PFC during memory formation; however, the electrophysiological basis of dynamic causal hippocampal-PFC interactions in the human brain is poorly understood. Here, we use data from a large cohort of intracranial EEG recordings to investigate the neurophysiological underpinnings of asymmetric feedforward and feedback hippocampal-PFC interactions and their nonlinear causal dynamics during both episodic memory encoding and recall. Our findings provide novel insights into the electrophysiological basis of directed bottom-up and top-down information flow during episodic memory formation in the human brain.

Vocal music enhances memory and language recovery after stroke: pooled results from two RCTs.

OBJECTIVE: Previous studies suggest that daily music listening can aid stroke recovery, but little is known about the stimulus-dependent and neural mechanisms driving this effect. Building on neuroimaging evidence that vocal music engages extensive and bilateral networks in the brain, we sought to determine if it would be more effective for enhancing cognitive and language recovery and neuroplasticity than instrumental music or speech after stroke. METHODS: Using data pooled from two single-blind randomized controlled trials in stroke patients (N = 83), we compared the effects of daily listening to self-selected vocal music, instrumental music, and audiobooks during the first 3 poststroke months. Outcome measures comprised neuropsychological tests of verbal memory (primary outcome), language, and attention and a mood questionnaire performed at acute, 3-month, and 6-month stages and structural and functional MRI at acute and 6-month stages. RESULTS: Listening to vocal music enhanced verbal memory recovery more than instrumental music or audiobooks and language recovery more than audiobooks, especially in aphasic patients. Voxel-based morphometry and resting-state and task-based fMRI results showed that vocal music listening selectively increased gray matter volume in left temporal areas and functional connectivity in the default mode network. INTERPRETATION: Vocal music listening is an effective and easily applicable tool to support cognitive recovery after stroke as well as to enhance early language recovery in aphasia. The rehabilitative effects of vocal music are driven by both structural and functional plasticity changes in temporoparietal networks crucial for emotional processing, language, and memory.

Effect of postlearning meditation on memory consolidation: level of focused attention matters.

Recent studies demonstrate that eyes-closed rest benefits memory consolidation, perhaps due to reduced attention to environmental stimuli. Here, we asked whether focusing attention to internal thoughts and feelings after learning similarly blocks memory consolidation. Verbal memory was tested following an eyes-closed consolidation period filled with either focused attention to breath or quiet rest. Although breath-focus did not impair memory relative to quiet rest overall, participants who reported being more successful in maintaining breath-focus during this condition showed increased forgetting. We interpret these findings as incompatible with a simple sensory-interference-based account of rest's effect on memory.

Verbal and Behavioral Expressions of Child Sexuality Among 1-6-Year-Olds as Observed by Daycare Professionals in Finland.

A safe childhood respecting sexual rights forms the foundation of an individual's sexual health. However, the understanding, support, and protection of early sexuality are seldom discussed. Children already express their sexuality verbally and behaviorally in daycare, often requiring a response from staff. These day-to-day situations may have an influence on children's later sexuality. The World Health Organization Regional Office for Europe and BZgA (2010) published a framework for professionals on age-appropriate, holistic sexuality education. Using this framework, we evaluated children's sexuality-related expressions in Finnish daycare. Our nationwide questionnaire among professionals in early childhood education and care (n = 507) focused on how 1-6-year-old children expressed their sexuality in their speech and behavior. All eight topics in the WHO framework emerged regularly. The two most prevalent topics were the body and emotions. Also, 71% of professionals had a child in their group who masturbated openly. Early sexual development manifested as curiosity about one's own body, exploring its functions, traits, and attributes, while on an emotional level it manifested as abundant feelings of infatuation and tenderness, shown openly toward those-peers and adults alike-whom the child cares for. Childhood sexuality is broadly and diversely present in children's verbal and behavioral expressions in daycare settings. Children need and have the right to receive explicit responses related to issues concerning their sexual development and to receive age-appropriate information, skills, and attitudes fostering healthy development.

Neural Patterns in Linguistic Cortices Discriminate the Content of Verbal Working Memory.

An influential theoretical account of working memory (WM) considers that WM is based on direct activation of long-term memory knowledge. While there is empirical support for this position in the visual WM domain, direct evidence is scarce in the verbal WM domain. This question is critical for models of verbal WM, as the question of whether short-term maintenance of verbal information relies on direct activation within the long-term linguistic knowledge base or not is still debated. In this study, we examined the extent to which short-term maintenance of lexico-semantic knowledge relies on neural activation patterns in linguistic cortices, and this by using a fast encoding running span task for word and nonword stimuli minimizing strategic encoding mechanisms. Multivariate analyses showed specific neural patterns for the encoding and maintenance of word versus nonword stimuli. These patterns were not detectable anymore when participants were instructed to stop maintaining the memoranda. The patterns involved specific regions within the dorsal and ventral pathways, which are considered to support phonological and semantic processing to various degrees. This study provides novel evidence for a role of linguistic cortices in the representation of long-term memory linguistic knowledge during WM processing.

Individual Differences in Distributional Learning for Speech: What's Ideal for Ideal Observers?

Purpose Speech perception is facilitated by listeners' ability to dynamically modify the mapping to speech sounds given systematic variation in speech input. For example, the degree to which listeners show categorical perception of speech input changes as a function of distributional variability in the input, with perception becoming less categorical as the input, becomes more variable. Here, we test the hypothesis that higher level receptive language ability is linked to the ability to adapt to low-level distributional cues in speech input. Method Listeners (n = 58) completed a distributional learning task consisting of 2 blocks of phonetic categorization for words beginning with /g/ and /k/. In 1 block, the distributions of voice onset time values specifying /g/ and /k/ had narrow variances (i.e., minimal variability). In the other block, the distributions of voice onset times specifying /g/ and /k/ had wider variances (i.e., increased variability). In addition, all listeners completed an assessment battery for receptive language, nonverbal intelligence, and reading fluency. Results As predicted by an ideal observer computational framework, the participants in aggregate showed identification responses that were more categorical for consistent compared to inconsistent input, indicative of distributional learning. However, the magnitude of learning across participants showed wide individual variability, which was predicted by receptive language ability but not by nonverbal intelligence or by reading fluency. Conclusion The results suggest that individual differences in distributional learning for speech are linked, at least in part, to receptive language ability, reflecting a decreased ability among those with weaker receptive language to capitalize on consistent input distributions.

Mindfulness improves verbal learning and memory through enhanced encoding.

Recent research has begun to demonstrate the effectiveness of mindfulness in improving certain cognitive abilities, including verbal learning and memory. However, no research has investigated the potential mechanism by which mindfulness may improve verbal learning and memory. We examined encoding, consolidation, and retrieval as potential mechanisms by which learning and memory may be increased on a list learning test (Rey Auditory Verbal Learning Task; RAVLT). After dividing participants into either a mindfulness or a control condition, in which they listened to a 10-min audio tape, results found that the mindfulness condition significantly outperformed the control condition on every RAVLT trial. Using the Item-Specific Deficit Approach, we discovered that this enhanced verbal learning and memory was specifically due to a significantly enhanced encoding process for the mindfulness group, which fully mediated the relationship between the mindfulness condition and performance on the RAVLT. There were no differences between the conditions on consolidation or retrieval. Furthermore, these improvements were not accompanied by improvements in verbal fluency or attention. In a second study, we presented a mindfulness or control audio before the first RAVLT delayed free-recall trial and another one before the second RAVLT delayed free-recall trial in order to better determine the effect of mindfulness on consolidation and retrieval. The results replicated Study 1, in that neither consolidation nor retrieval were significantly affected by mindfulness. This research indicates that mindfulness may primarily improve verbal learning and memory through improved encoding processes.

Regional Shape Abnormalities in Thalamus and Verbal Memory Impairment After Subcortical Infarction.

Background. Subcortical infarcts can result in verbal memory impairment, but the potential underlying mechanisms remain unknown. Objective. We investigated the spatiotemporal deterioration patterns of brain structures in patients with subcortical infarction and identified the regions that contributed to verbal memory impairment. Methods. Cognitive assessment and structural magnetic resonance imaging were performed 1, 4, and 12 weeks after stroke onset in 28 left-hemisphere and 22 right-hemisphere stroke patients with subcortical infarction. Whole-brain volumetric analysis combined with a further-refined shape analysis was conducted to analyze longitudinal morphometric changes in brain structures and their relationship to verbal memory performance. Results. Between weeks 1 and 12, significant volume decreases in the ipsilesional basal ganglia, inferior white matter, and thalamus were found in the left-hemisphere stroke group. Among those 3 structures, only the change rate of the thalamus volume was significantly correlated with that in immediate recall. For the right-hemisphere stroke group, only the ipsilesional basal ganglia survived the week 1 to week 12 group comparison, but its change rate was not significantly correlated with the verbal memory change rate. Shape analysis of the thalamus revealed atrophies of the ipsilesional thalamic subregions connected to the prefrontal, temporal, and premotor cortices in the left-hemisphere stroke group and positive correlations between the rates of those atrophies and the change rate in immediate recall. Conclusions. Secondary damage to the thalamus, especially to the left subregions connected to specific cortices, may be associated with early verbal memory impairment following an acute subcortical infarct.

Musical meaning modulates word acquisition.

Musical excerpts have been shown to have the capacity to prime the processing of target words and vice versa, strongly suggesting that music can convey concepts. However, to date no study has investigated an influence of musical semantics on novel word acquisition, thus corroborating evidence for a similarity of underlying semantic processing of music and words behaviourally. The current study investigates whether semantic content of music can assist the acquisition of novel words. Forty novel words and their German translation were visually presented to 26 participants accompanied by either semantically congruent or incongruent music. Semantic congruence between music and words was expected to increase performance in the subsequent forced-choice recognition test. Participants performed significantly better on the retention of novel words presented with semantically congruent music compared to those presented with semantically incongruent music. This provides first evidence that semantic "enrichment" by music during novel word learning can augment novel word acquisition. This finding may lead to novel approaches in foreign language acquisition and language rehabilitation, and further strongly supports the concept that music has a strong capacity to iconically convey meaning.

The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.

BACKGROUND: Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. OBJECTIVE: In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory. METHODS: Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. RESULTS: After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus ( p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p < 0.002). CONCLUSION: Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

Listeners' processing of a given reduced word pronunciation variant directly reflects their exposure to this variant: Evidence from native listeners and learners of French.

In casual conversations, words often lack segments. This study investigates whether listeners rely on their experience with reduced word pronunciation variants during the processing of single segment reduction. We tested three groups of listeners in a lexical decision experiment with French words produced either with or without word-medial schwa (e.g., /ʀvy/ and /ʀvy/ for revue). Participants also rated the relative frequencies of the two pronunciation variants of the words. If the recognition accuracy and reaction times (RTs) for a given listener group correlate best with the frequencies of occurrence holding for that given listener group, recognition is influenced by listeners' exposure to these variants. Native listeners' relative frequency ratings correlated well with their accuracy scores and RTs. Dutch advanced learners' accuracy scores and RTs were best predicted by their own ratings. In contrast, the accuracy and RTs from Dutch beginner learners of French could not be predicted by any relative frequency rating; the rating task was probably too difficult for them. The participant groups showed behaviour reflecting their difference in experience with the pronunciation variants. Our results strongly suggest that listeners store the frequencies of occurrence of pronunciation variants, and consequently the variants themselves.

Speech illusions and working memory performance in non-clinical psychosis.

Psychotic disorders are characterized by auditory verbal hallucinations (AVHs), and research has shown that AVHs are linked to deficits in working memory. Our understanding of AVHs across the psychosis continuum is limited. To date, little research has tested whether hallucination proneness (HP) is linked with abnormalities on experimental multispeaker babble tasks. Few investigations have been conducted to determine how task performance might be linked to cognitive functioning. The objective of the current study is to better understand this empirical gap. A total of 70 adults (30 healthy controls and 40 HP individuals) were administered an experimental task in which they listened to multispeaker babble and were instructed to report any words or chains of consecutive words (CCWs) perceived. Participants also were administered nonverbal and verbal working memory tasks. Findings revealed that relative to the control group, the HP individuals perceived more words and longer CCWs during the task. While there were no significant differences in working memory tasks between the HP and control groups, longer CCW's were associated with decreased verbal working memory scores in the HP group. AVH proneness may occur across a continuum of psychosis and may be linked with other theoretically relevant cognitive vulnerability factors.

Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial.

OBJECTIVES: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. METHODS: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. RESULTS: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen's d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. CONCLUSIONS: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).

Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning.

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword-object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary.SIGNIFICANCE STATEMENT Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity declines once the task is learnt. The present study demonstrated that a node within MDC, located in midline frontal cortex, becomes active during the early stage of learning a novel vocabulary. Importantly, noninvasive brain stimulation of this node improved performance during this stage of learning. This observation demonstrated that MDC activity is important for learning.

Mindfulness-Based Stress Reduction for Older Adults With Stress Disorders and Neurocognitive Difficulties: A Randomized Controlled Trial.

OBJECTIVE: To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. METHODS: 103 adults aged 65 years or older with an anxiety or depressive disorder (diagnosed according to DSM-IV criteria) and subjective neurocognitive difficulties were recruited in St. Louis, Missouri, or San Diego, California, from September 2012 through August 2013 and randomly assigned in groups of 5-8 to mindfulness-based stress reduction (MBSR) or a health education control condition matched for time, attention, and credibility. The primary outcomes were memory (assessed by immediate and delayed paragraph and list recall) and cognitive control (Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test). Other outcomes included clinical symptoms (worry, depression, anxiety, and global improvement). HPA axis activity was assessed using peak salivary cortisol. Outcomes were measured immediately post-intervention and (for clinical outcomes only) at 3- and 6-month follow up. RESULTS: On the basis of intent-to-treat principles using data from all 103 participants, the mindfulness group experienced greater improvement on a memory composite score (P = .046). Groups did not differ on change in cognitive control. Participants receiving MBSR also improved more on measures of worry (P = .042) and depression (P = .049) at posttreatment and on worry (P = .02), depression (P = .002), and anxiety (P = .002) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale (47% vs 27%, χ² = 4.5, P = .03). Cortisol level decreased to a greater extent in the mindfulness group, but only among those participants with high baseline cortisol. CONCLUSIONS: In this population of older adults with stress disorders and neurocognitive difficulties, a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01693874.

Iron Concentration in Deep Gray Matter Structures is Associated with Worse Visual Memory Performance in Healthy Young Adults.

Abnormally high deposition of iron can contribute to neurodegenerative disorders with cognitive impairment. Since previous studies investigating cognition-brain iron accumulation relationships focused on elderly people, our aim was to explore the association between iron concentration in subcortical nuclei and two types of memory performances in a healthy young population. Gender difference was found only in the globus pallidus. Our results showed that iron load characterized by R2* value on the MRI in the caudate and putamen was related to visual memory, while verbal memory was unrelated to iron concentration.

A perceptual advantage for onomatopoeia in early word learning: Evidence from eye-tracking.

A perceptual advantage for iconic forms in infant language learning has been widely reported in the literature, termed the "sound symbolism bootstrapping hypothesis" by Imai and Kita (2014). However, empirical research in this area is limited mainly to sound symbolic forms, which are very common in languages such as Japanese but less so in Indo-European languages such as English. In this study, we extended this body of research to onomatopoeia-words that are thought to be present across most of the world's languages and that are known to be dominant in infants' early lexicons. In a picture-mapping task, 10- and 11-month-old infants showed a processing advantage for onomatopoeia (e.g., woof woof) over their conventional counterparts (e.g., doggie). However, further analysis suggests that the input may play a key role in infants' experience and processing of these forms.

Selective verbal recognition memory impairments are associated with atrophy of the language network in non-semantic variants of primary progressive aphasia.

Primary progressive aphasia (PPA) is clinically defined by an initial loss of language function and preservation of other cognitive abilities, including episodic memory. While PPA primarily affects the left-lateralized perisylvian language network, some clinical neuropsychological tests suggest concurrent initial memory loss. The goal of this study was to test recognition memory of objects and words in the visual and auditory modality to separate language-processing impairments from retentive memory in PPA. Individuals with non-semantic PPA had longer reaction times and higher false alarms for auditory word stimuli compared to visual object stimuli. Moreover, false alarms for auditory word recognition memory were related to cortical thickness within the left inferior frontal gyrus and left temporal pole, while false alarms for visual object recognition memory was related to cortical thickness within the right-temporal pole. This pattern of results suggests that specific vulnerability in processing verbal stimuli can hinder episodic memory in PPA, and provides evidence for differential contributions of the left and right temporal poles in word and object recognition memory.

Enhanced verbal abilities in the congenitally blind.

Numerous studies have found that congenitally blind individuals have better verbal memory than their normally sighted counterparts. However, it is not known whether this reflects superiority of verbal or memory abilities. In order to distinguish between these possibilities, we tested congenitally blind participants and normally sighted control participants, matched for age and education, on a range of verbal and spatial tasks. Congenitally blind participants were significantly better than sighted controls on all the verbal tasks but the groups did not differ significantly on the spatial tasks. Thus, the congenitally blind appear to have superior verbal, but not spatial, abilities. This may reflect greater reliance on verbal information and the involvement of visual cortex in language processing in the congenitally blind.

Verbal Learning and Memory Enhancement Strategies in Schizophrenia: A Randomized, Controlled Investigation.

OBJECTIVES: Verbal episodic memory is a key domain of impairment in people with schizophrenia with close ties to a variety of aspects of functioning and therapeutic treatment response. A randomized, blinded trial of two mnemonic strategies for verbal episodic memory deficits for people with schizophrenia was conducted. METHODS: Sixty-one people with schizophrenia were assigned to one of three experimental conditions: training in a mnemonic strategy that included both visualization and narrative structure (Story Method), a condition in which participants were trained to visualize words interacting with one another (Imagery), or a non-trained control condition in which participants received equivalent exposure to training word lists and other verbal memory assessments administered in the other two conditions, but without provision of any compensatory mnemonic strategy. Participants were assessed on improvements in recall of the word list used as part of training, as well as two, standardized verbal memory assessments which included stimuli not used as part of strategy training. RESULTS: The Story Method produced improvements on a trained word list that generalized to a non-trained, prose memory task at a 1-week follow-up. In contrast, provision of a mnemonic strategy of simple visualization of words produced little improvement on word recall of trained words or on measures of generalization relative to the performance of participants in the control condition. CONCLUSIONS: These findings support the inclusion of enriched mnemonic strategies consisting of both visualization and narrative structure in sustained and comprehensive programs of CR for enhancement of verbal episodic memory in schizophrenia. (JINS, 2017, 23, 352-357).