Brain reserve affects the expression of cognitive reserve networks.

Cognitive reserve (CR) explains differential susceptibility of cognitive performance to neuropathology. However, as brain pathologies progress, cognitive decline occurs even in individuals with initially high CR. The interplay between the structural brain health (= level of brain reserve) and CR-related brain networks therefore requires further research. Our sample included 142 individuals aged 60-70 years. National Adult Reading Test intelligence quotient (NART-IQ) was our CR proxy. On an in-scanner Letter Sternberg task, we used ordinal trend (OrT) analysis to extract a task-related brain activation pattern (OrT slope) for each participant that captures increased expression with task load (one, three, and six letters). We assessed whether OrT slope represents a neural mechanism underlying CR by associating it with task performance and NART-IQ. Additionally, we investigated how the following brain reserve measures affect the association between NART-IQ and OrT slope: mean cortical thickness, total gray matter volume, and brain volumes proximal to the areas contained in the OrT patterns. We found that higher OrT slope was associated with better task performance and higher NART-IQ. Further, the brain reserve measures were not directly associated with OrT slope, but they affected the relationship between NART-IQ and OrT slope: NART-IQ was associated with OrT slope only in individuals with high brain reserve. The degree of brain reserve has an impact on how (and perhaps whether) CR can be implemented in brain networks in older individuals.

Assessing partial errors via analog gaming keyboards in response conflict tasks: A proof-of-concept study with the concealed information test.

The response time-based Concealed Information Test (RT-CIT) is an established memory detection paradigm. Slower RTs to critical information (called 'probes') compared to control items (called 'irrelevants') reveal recognition. Different lines of research indicate that response conflict is a strong contributor to this RT difference. Previous studies used electromyography (EMG) to measure response conflict, but this requires special equipment and trained examiners. The aim of this study was to explore if response conflict can also be measured with an analog gaming keyboard that is sensitive to minimal finger movements. In a preregistered study, participants completed an autobiographical RT-CIT (n = 35) as well as a cued recognition task (modified Sternberg task; n = 33) for validation purposes. Partial errors, partial button presses of the incorrect response key, were more frequent in trials with response conflict than in trials without conflict. Partial errors were rare (CIT: 2.9%; Sternberg: 1.7% of conflict trials), suggesting analogue keyboards have lower sensitivity than EMG. This is the first evidence that analog keyboards can measure partial errors. Although likely less sensitive than EMG measures, potential benefits of analog keyboards include their accessibility, their compatibility with all tasks that use a standard keyboard, that no physical contact with the participant is needed, and ease of data collection (e.g., allowing for group testing).

Does heart rate variability mediate the association between chronic stress, cardiorespiratory fitness, and working memory in young adults?

Young adulthood is a demanding development phase rendering individuals at risk for high levels of stress. While chronic stress may impair working memory maintenance, cardiorespiratory fitness is suggested to have a protective effect. Heart rate variability (HRV) contributes to this cognitive domain, but also retaliates to stress and aerobic exercise. Therefore, the present study investigated the mediating role of resting HRV on the association between chronic stress, cardiorespiratory fitness, and working memory maintenance in young healthy adults. Healthy participants (N = 115, 48% female) aged 18-35 years (M = 24.1, SD = 3.8) completed the Åstrand test on a bicycle ergometer to estimate maximal oxygen consumption [ V ̇ O 2 max (ml/min/kg)]. In addition, working memory maintenance was assessed using the modified Sternberg task with low (three items) and high cognitive load (six items). Using electrocardiography, HRV was recorded and the LF/HF ratio was extracted for mediation analyses. Path analysis revealed that cardiorespiratory fitness was significantly associated with accuracy on high cognitive load trials (ß = 0.19, p = 0.035), but not on trials with low cognitive load. Perceived levels of chronic stress failed to show a significant association with working memory maintenance, independently of cognitive load. The pattern of results remained unchanged after introduction of HRV as a mediator (ß = 0.18, p = 0.045). In conclusion, higher cardiorespiratory fitness is associated with better maintenance of verbal information in working memory. However, this association cannot be explained by vagal influences on memory processing driven by the autonomic nervous system.

Neural waves and short-term memory in a neural net model.

We show that recognizable neural waveforms are reproduced in the model described in previous work. In so doing, we reproduce close matches to certain observed, though filtered, EEG-like measurements in closed mathematical form, to good approximations. Such neural waves represent the responses of individual networks to external and endogenous inputs and are presumably the carriers of the information used to perform computations in actual brains, which are complexes of interconnected networks. Then, we apply these findings to a question arising in short-term memory processing in humans. Namely, we show how the anomalously small number of reliable retrievals from short-term memory found in certain trials of the Sternberg task is related to the relative frequencies of the neural waves involved. This finding justifies the hypothesis of phase-coding, which has been posited as an explanation of this effect.

Age differences in functional network reconfiguration with working memory training.

Demanding cognitive functions like working memory (WM) depend on functional brain networks being able to communicate efficiently while also maintaining some degree of modularity. Evidence suggests that aging can disrupt this balance between integration and modularity. In this study, we examined how cognitive training affects the integration and modularity of functional networks in older and younger adults. Twenty three younger and 23 older adults participated in 10 days of verbal WM training, leading to performance gains in both age groups. Older adults exhibited lower modularity overall and a greater decrement when switching from rest to task, compared to younger adults. Interestingly, younger but not older adults showed increased task-related modularity with training. Furthermore, whereas training increased efficiency within, and decreased participation of, the default-mode network for younger adults, it enhanced efficiency within a task-specific salience/sensorimotor network for older adults. Finally, training increased segregation of the default-mode from frontoparietal/salience and visual networks in younger adults, while it diffusely increased between-network connectivity in older adults. Thus, while younger adults increase network segregation with training, suggesting more automated processing, older adults persist in, and potentially amplify, a more integrated and costly global workspace, suggesting different age-related trajectories in functional network reorganization with WM training.

Mapping working memory retrieval in space and in time: A combined electroencephalography and electrocorticography approach.

In this study, we investigated the time course and neural correlates of the retrieval process underlying visual working memory. We made use of a rare dataset in which the same task was recorded using both scalp electroencephalography (EEG) and Electrocorticography (ECoG), respectively. This allowed us to examine with great spatial and temporal detail how the retrieval process works, and in particular how the medial temporal lobe (MTL) is involved. In each trial, participants judged whether a probe face had been among a set of recently studied faces. With a method that combines hidden semi-Markov models and multivariate pattern analysis, the neural signal was decomposed into a sequence of latent cognitive stages with information about their durations on a trial-by-trial basis. Analyzed separately, EEG and ECoG data yielded converging results on discovered stages and their interpretation, which reflected 1) a brief pre-attention stage, 2) encoding the stimulus, 3) retrieving the studied set, and 4) making a decision. Combining these stages with the high spatial resolution of ECoG suggested that activity in the temporal cortex reflected item familiarity in the retrieval stage; and that once retrieval is complete, there is active maintenance of the studied face set in the decision stage in the MTL. During this same period, the frontal cortex guides the decision by means of theta coupling with the MTL. These observations generalize previous findings on the role of MTL theta from long-term memory tasks to short-term memory tasks.

Measurement of dynamic task related functional networks using MEG.

The characterisation of dynamic electrophysiological brain networks, which form and dissolve in order to support ongoing cognitive function, is one of the most important goals in neuroscience. Here, we introduce a method for measuring such networks in the human brain using magnetoencephalography (MEG). Previous network analyses look for brain regions that share a common temporal profile of activity. Here distinctly, we exploit the high spatio-temporal resolution of MEG to measure the temporal evolution of connectivity between pairs of parcellated brain regions. We then use an ICA based procedure to identify networks of connections whose temporal dynamics covary. We validate our method using MEG data recorded during a finger movement task, identifying a transient network of connections linking somatosensory and primary motor regions, which modulates during the task. Next, we use our method to image the networks which support cognition during a Sternberg working memory task. We generate a novel neuroscientific picture of cognitive processing, showing the formation and dissolution of multiple networks which relate to semantic processing, pattern recognition and language as well as vision and movement. Our method tracks the dynamics of functional connectivity in the brain on a timescale commensurate to the task they are undertaking.

Sex differences in verbal working memory performance emerge at very high loads of common neuroimaging tasks.

Working memory (WM) supports a broad range of intelligent cognition and has been the subject of rich cognitive and neural characterization. However, the highest ranges of WM have not been fully characterized, especially for verbal information. Tasks developed to test multiple levels of WM demand (load) currently predominate brain-based WM research. These tasks are typically used at loads that allow most healthy participants to perform well, which facilitates neuroimaging data collection. Critically, however, high performance at lower loads may obscure differences that emerge at higher loads. A key question not yet addressed at high loads concerns the effect of sex. Thoroughgoing investigation of high-load verbal WM is thus timely to test for potential hidden effects, and to provide behavioral context for effects of sex observed in WM-related brain structure and function. We tested 111 young adults, matched on genotype for the WM-associated COMT-Val108/158Met polymorphism, on three classic WM tasks using verbal information. Each task was tested at four WM loads, including higher loads than those used in previous studies of sex differences. All tasks loaded on a single factor, enabling comparison of verbal WM ability at a construct level. Results indicated sex effects at high loads across tasks and within each task, such that males had higher accuracy, even among groups that were matched for performance at lower loads.

Low intensity magnetic field influences short-term memory: A study in a group of healthy students.

This study analyzes if an external magnetic stimulus (2 kHz and approximately 0.1 µT applied near frontal cortex) influences working memory, perception, binary decision, motor execution, and sustained attention in humans. A magnetic stimulus and a sham stimulus were applied to both sides of the head (frontal cortex close to temporal-parietal area) in young and healthy male test subjects (n = 65) while performing Sternberg's memory scanning task. There was a significant change in reaction time. Times recorded for perception, sustained attention, and motor execution were lower in exposed subjects (P < 0.01). However, time employed in binary decision increased for subjects exposed to magnetic fields. From results, it seems that a low intensity 2 kHz exposure modifies short-term working memory, as well as perception, binary decision, motor execution, and sustained attention.

Nonlinear Effects of Noxious Thermal Stimulation and Working Memory Demands on Subjective Pain Perception.

OBJECTIVE: A bidirectional relationship between working memory (WM) and acute pain has long been assumed, but equivocal evidence exists regarding this relationship. This study characterized the relationship between WM and acute pain processing in healthy individuals using an adapted Sternberg WM task. DESIGN: Participants completed a Sternberg task while receiving noxious thermal stimulation. Participants received a pseudorandom presentation of four different temperatures (baseline temperatures and individually determined low-, medium-, and high-temperature stimuli) and four levels of Sternberg task difficulty (0-, 3-, 6-, and 9-letter strings). SUBJECTS: Twenty-eight healthy participants were recruited from Stanford University and the surrounding community to complete this study. RESULTS: A nonlinear interaction between intensity of thermal stimulation and difficulty of the Sternberg task was noted. Increased cognitive load from the Sternberg task resulted in increased perception of pain in low-intensity thermal stimulation but suppressed pain perception in high-intensity thermal stimulation. Thermal stimulation had no significant effect on participants' response time or accuracy on the Sternberg task regardless of intensity level. CONCLUSIONS: Pain perception appears to decrease as a function of WM load only for sufficiently noxious stimuli. However, increasing noxious stimuli did not affect cognitive performance. These complex relationships may reflect a shared cognitive space that can become "overloaded" with input of multiple stimuli of sufficient intensity.

Voluntary self-initiation of the stimuli onset improves working memory and accelerates visual and attentional processing.

The ability of an organism to voluntarily control the stimuli onset modulates perceptual and attentional functions. Since stimulus encoding is an essential component of working memory (WM), we conjectured that controlling the initiation of the perceptual process would positively modulate WM. To corroborate this proposition, we tested twenty-five healthy subjects in a modified-Sternberg WM task under three stimuli presentation conditions: an automatic presentation of the stimuli, a self-initiated presentation of the stimuli (through a button press), and a self-initiated presentation with random-delay stimuli onset. Concurrently, we recorded the subjects' electroencephalographic signals during WM encoding. We found that the self-initiated condition was associated with better WM accuracy, and earlier latencies of N1, P2 and P3 evoked potential components representing visual, attentional and mental review of the stimuli processes, respectively. Our work demonstrates that self-initiated stimuli enhance WM performance and accelerate early visual and attentional processes deployed during WM encoding. We also found that self-initiated stimuli correlate with an increased attentional state compared to the other two conditions, suggesting a role for temporal stimuli predictability. Our study remarks on the relevance of self-control of the stimuli onset in sensory, attentional and memory updating processing for WM.

Managing Increased Cognitive Load in a Guided Search.

In the Sternberg item recognition task and its variants, an individual's mean reaction time increases with the number of items to be retained in the memory set. An increase in reaction time has also been seen when a secondary task was added. The usual interpretation for this increased reaction time is that adding cognitive load makes tasks more difficult. In a series of three experiments, we manipulated cognitive load through increases in the memory set or through a second task. In each experiment, high cognitive load was associated with higher mean response times but a reduced slope, based on the target position in a series of probes. Thus, in a Sternberg task with multiple word targets and multiple word probes, participants searched more efficiently per probe under high load than under low load. This pattern was replicated with the addition of a working memory task requiring participants to calculate a cumulative price based on the price per target word item. By considering both initial response times and reaction time slopes in large memory sets, this study provides a challenge to the traditional interpretation of cognitive load effects on search performance.

Repeated Subconcussive Exposure Alters Low-Frequency Neural Oscillation in Memory Retrieval Processing.

Repeated subconcussive head impacts are frequently experienced by athletes involved in competitive sports, such as boxing. The objective of the present study was to investigate the changes in working memory performance and memory retrieval-related neural oscillations in boxing athletes who experienced repeated subconcussive head impacts. Twenty-one boxing athletes (boxing group) and 25 matched controls (control group) completed a modified visual working memory task, and their continuous scalp electroencephalography (EEG) data were collected simultaneously. The behavioral measures and retrieval-related low-frequency neural oscillations were analyzed at each working memory set size in both groups. Subjects in the boxing group showed a reduced mean accuracy, diminished capacity estimates, and slower reaction time at demanding set sizes, and a marginally increased intra-individual coefficient of variation (ICV) for overall set sizes. Additionally, decreased event-related frontal theta synchronization, parieto-occipital alpha desynchronization, and frontal low beta synchronization were observed in the boxing group, suggesting underlying working memory dysfunction for efficient neurocognitive resource employment, inhibition of distracting stimuli, and post-retrieval control in the boxing group. Moreover, a negative correlation was found between frontal beta synchronization and reaction time for most set sizes in both groups. The present study was the first to reveal the underlying working memory deficits caused by the cumulative effects of boxing-related subconcussive head impacts from the perspective of behavior and EEG time-frequency oscillations. Joint analysis of EEG low-frequency oscillations and the innovative task with multiple challenging load conditions may serve as a promising way to detect concealed deficiencies within working memory processing.

Higher Cognitive Reserve Is Associated with Better Working Memory Performance and Working-Memory-Related P300 Modulation.

This study aims to examine how two levels of cognitive reserve, as evidenced by reading syntactic skill, modify performance and neural activity in a two-load-level (high vs. low) working memory (WM) task. Two groups of participants with different reading skills, high and low, were obtained from clustering analysis. We collected the P300 event-related potential component during the performance of the WM Sternberg task. The high reading performance (HRP) group showed a higher percentage of correct answers than the low reading performance (LRP) group in the negative probes of the WM task, which were probe stimuli not included in the memory set presented immediately before. Both groups showed P300 amplitude modulations, that is, larger WM-related P300 amplitudes for low than for high WM loads. Following the behavioral results, the HRP group displayed smaller WM-related amplitude modulations than the LRP group in the negative probes. The findings together suggest that higher levels of reading skill are associated with improved neural efficiency, which reflects in a better working memory performance.

The Sternberg Paradigm: Correcting Encoding Latencies in Visual and Auditory Test Designs.

The Sternberg task is a widely used tool for assessing the working memory performance in vision and cognitive science. It is possible to apply a visual or auditory variant of the Sternberg task to query the memory load. However, previous studies have shown that the subjects' corresponding reaction times differ dependent on the used variant. In this work, we present an experimental approach that is intended to correct the reaction time differences observed between auditory and visual item presentation. We found that the subjects' reaction time offset is related to the encoding speed of a single probe item. After correcting for these individual encoding latencies, differences in the results of both the auditory and visual Sternberg task become non-significant, p=0.252. Thus, an equal task difficulty can be concluded for both variants of item presentation.

Differences in prefrontal cortex activity based on difficulty in a working memory task using near-infrared spectroscopy.

The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.

Individuals with depression display abnormal modulation of neural oscillatory activity during working memory encoding and maintenance.

PURPOSE: To investigate neural oscillatory activity supporting working memory (WM) processing in depressed individuals and healthy controls. METHODS: Forty-six participants with Major Depressive Disorder (MDD) and 41 healthy controls balanced on age, gender, and WM ability completed a Sternberg verbal WM task with concurrent electroencephalography recording. Oscillatory activity was calculated for upper alpha, theta, and gamma frequency bands during WM encoding and maintenance. RESULTS: WM performance did not differ between groups. When compared to healthy controls, depressed individuals displayed reduced frontal-midline theta power and increased occipital upper alpha power during WM encoding, and reductions in frontal-midline theta power and occipital gamma and upper alpha power during WM maintenance. Higher depression severity was associated with greater reductions upper alpha and gamma power during WM maintenance. CONCLUSIONS: Depressed individuals displayed prominent alterations in oscillatory activity during WM encoding and maintenance, indicating that the neural processes which support WM processing are altered in MDD even when no cognitive impairments are observed.

Verbal working memory-related neural network communication in schizophrenia.

Impaired working memory (WM) in schizophrenia is associated with reduced hemodynamic and electromagnetic activity and altered network connectivity within and between memory-associated neural networks. The present study sought to determine whether schizophrenia involves disruption of a frontal-parietal network normally supporting WM and/or involvement of another brain network. Nineteen schizophrenia patients (SZ) and 19 healthy comparison subjects (HC) participated in a cued visual-verbal Sternberg task while dense-array EEG was recorded. A pair of item arrays each consisting of 2-4 consonants was presented bilaterally for 200 ms with a prior cue signaling the hemifield of the task-relevant WM set. A central probe letter 2,000 ms later prompted a choice reaction time decision about match/mismatch with the target WM set. Group and WM load effects on time domain and time-frequency domain 11-15 Hz alpha power were assessed for the cue-to-probe time window, and posterior 11-15 Hz alpha power and frontal 4-8 Hz theta power were assessed during the retention period. Directional connectivity was estimated via Granger causality, evaluating group differences in communication. SZ showed slower responding, lower accuracy, smaller overall time-domain alpha power increase, and less load-dependent alpha power increase. Midline frontal theta power increases did not vary by group or load. Network communication in SZ was characterized by temporal-to-posterior information flow, in contrast to bidirectional temporal-posterior communication in HC. Results indicate aberrant WM network activity supporting WM in SZ that might facilitate normal load-dependent and only marginally less accurate task performance, despite generally slower responding.

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans.

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects-primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.

The effects of a school-based exercise program on neurophysiological indices of working memory operations in adolescents.

OBJECTIVES: To examine the effects of a structured exercise program implemented during school break-time on working memory maintenance and neurophysiological indices of task preparation processes in adolescents. DESIGN: Using class-wise random allocation, participants from four classes were divided into an exercise (n=20) and a wait-list control group (n=16). Over a period of eight weeks, the exercise group engaged in 20min of combined aerobic and coordinative exercise on each school day. METHODS: Prior to and after the intervention period, participants performed a computer-based Sternberg task for the assessment of working memory performance. Simultaneously, the contingent negative variation (CNV) of event-related potentials was measured. RESULTS: The exercise group demonstrated a larger decrease in reaction time from pre- to post-test relative to the control group, F(1, 31)=13.5, p<0.001. No changes were found for accuracy on the Sternberg task across groups. Using cluster-based permutation testing, the analysis of event-related potentials revealed a significant increase of the initial CNV from pre- to post-test in the exercise group, cluster value=-2376.2, p=0.006, which was most pronounced for the fronto-central region, with no such effect observed for the control group. CONCLUSIONS: Daily engagement in a short combined aerobic and coordinative exercise program following the school lunch time break elicits benefits for working memory in adolescents. These changes are accompanied by improvements of task preparation processes, which allow the selection of a more appropriate cognitive control strategy.