Mismatch negativity as a marker of auditory pattern separation.

To what extent does incidental encoding of auditory stimuli influence subsequent episodic memory for the same stimuli? We examined whether the mismatch negativity (MMN), an event-related potential generated by auditory change detection, is correlated with participants' ability to discriminate those stimuli (i.e. targets) from highly similar lures and from dissimilar foils. We measured the MMN in 30 young adults (18-32 years, 18 females) using a passive auditory oddball task with standard and deviant 5-tone sequences differing in pitch contour. After exposure, all participants completed an incidental memory test for old targets, lures, and foils. As expected, participants at test exhibited high sensitivity in recognizing target items relative to foils and lower sensitivity in recognizing target items relative to lures. Notably, we found a significant correlation between MMN amplitude and lure discrimination, but not foil discrimination. Our investigation shows that our capacity to discriminate sensory inputs at encoding, as measured by the MMN, translates into precision in memory for those inputs.

Time of Day Effects on Inhibitory Functioning: Cognitive and Neural Evidence of Sundowning in Amnestic Mild Cognitive Impairment.

BACKGROUND: Amnestic mild cognitive impairment (aMCI), a prodromal phase of Alzheimer's disease (AD), is characterized by episodic memory dysfunction, but inhibitory deficits have also been commonly reported. Time of day (TOD) effects have been confirmed in 1) healthy aging on cognitive processes such as inhibitory control, and 2) on behavior in AD (termed the sundowning effect), but no such research has addressed aMCI. OBJECTIVE: The present study examined the impact of TOD on the behavioral and electrophysiological correlates of inhibition in 54 individuals with aMCI and 52 healthy controls (HCs), all of morning chronotype. METHODS: Participants were randomly assigned to complete two inhibition tasks (Go-NoGo and Flanker) during their optimal (morning) or non-optimal (evening) TOD, while electroencephalography was recorded. RESULTS: Both tasks elicited changes in N2 and P3 event-related potential (ERP) components, which commonly index inhibitory functioning. Analyses showed that the Go-NoGo difference in P3 amplitude was reduced in individuals with aMCI relative to HCs. Compared to HCs, the Flanker difference in P3 amplitude was also reduced and coincided with more errors in the aMCI group. Notably, these behavioral and ERP differences were exaggerated in the non-optimal TOD relative to the optimal TOD. CONCLUSION: Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI.

Transcranial Direct Current Stimulation Combined With Listening to Preferred Music Alters Cortical Speech Processing in Older Adults.

Emerging evidence suggests transcranial direct current stimulation (tDCS) can improve cognitive performance in older adults. Similarly, music listening may improve arousal and stimulate subsequent performance on memory-related tasks. We examined the synergistic effects of tDCS paired with music listening on auditory neurobehavioral measures to investigate causal evidence of short-term plasticity in speech processing among older adults. In a randomized sham-controlled crossover study, we measured how combined anodal tDCS over dorsolateral prefrontal cortex (DLPFC) paired with listening to autobiographically salient music alters neural speech processing in older adults compared to either music listening (sham stimulation) or tDCS alone. EEG assays included both frequency-following responses (FFRs) and auditory event-related potentials (ERPs) to trace neuromodulation-related changes at brainstem and cortical levels. Relative to music without tDCS (sham), we found tDCS alone (without music) modulates the early cortical neural encoding of speech in the time frame of ∼100-150 ms. Whereas tDCS by itself appeared to largely produce suppressive effects (i.e., reducing ERP amplitude), concurrent music with tDCS restored responses to those of the music+sham levels. However, the interpretation of this effect is somewhat ambiguous as this neural modulation could be attributable to a true effect of tDCS or presence/absence music. Still, the combined benefit of tDCS+music (above tDCS alone) was correlated with listeners' education level suggesting the benefit of neurostimulation paired with music might depend on listener demographics. tDCS changes in speech-FFRs were not observed with DLPFC stimulation. Improvements in working memory pre to post session were also associated with better speech-in-noise listening skills. Our findings provide new causal evidence that combined tDCS+music relative to tDCS-alone (i) modulates the early (100-150 ms) cortical encoding of speech and (ii) improves working memory, a cognitive skill which may indirectly bolster noise-degraded speech perception in older listeners.

The Effects of Aging and Time of Day on Inhibitory Control: An Event-Related Potential Study.

Time of day (TOD) influences on executive functions have been widely reported, with greater efficiency demonstrated at optimal relative to non-optimal TOD according to one's chronotype (i.e., synchrony effect). Older adults (OAs) show declines in inhibitory control and are more sensitive to the effects of circadian variation on executive functioning. To date, no studies have investigated the effects of TOD and aging on executive functioning using electrophysiological measures. The present study investigated the effects of aging and TOD on the neural correlates of inhibitory processing (N2 and P3) using event-related potentials (ERPs). Go-NoGo and Flanker tasks were administered to 52 OAs of morning chronotype and 51 younger adults (YAs) of afternoon-to-evening chronotype who were randomly assigned to morning or afternoon test sessions, with the optimal TOD for OAs in the morning and for YAs in the afternoon/evening. While behavioral results demonstrated no TOD effects, ERPs indicated synchrony effects. Both YAs and OAs showed greater modulation of Go-NoGo N2 and greater P3 amplitude during the non-optimal than optimal TOD, consistent with the synchrony effect. For the Flanker task, age differences in P3 amplitude were only apparent during the non-optimal TOD. These results suggest that processes associated with inhibitory control are differentially affected by TOD and aging, with age-related reductions in inhibitory efficiency during off-peak test times on measures of interference control. These findings highlight the sensitivity of ERPs to detect TOD effects in the absence of behavioral differences, confirm more pronounced TOD effects in OAs relative to YAs on ERP measures of interference control, and reinforce the need to assess and control for circadian typology in research studies.

Default Mode Network and Neural Phase Synchronization in Healthy Aging: A Resting State EEG Study.

Aging is associated with altered brain connectivity within the default mode network (DMN). Although research using functional magnetic resonance imaging has quantified age-related alterations in functional connectivity within this network during resting state, it is less clear how this may be reflected in electrophysiological measures, and how this relates to cognitive performance in older adults. The aim of this study was to quantify age differences in phase synchrony of the DMN during resting state, with particular focus on connectivity between the anterior node (i.e., medial prefrontal cortex, or mPFC) and other associated regions in this network. Electroencephalography was recorded from 55 younger adults (18-30 years, 28 females) and 34 older adults (64-88 years, 16 females) in two resting state conditions (eyes-open and -closed). Source-level functional connectivity was quantified using phase-locking value (PLV) with a spatial filter of six sources of interest, and were subjected to data-driven permutation testing between groups from 1 to 50 Hz. Older adults also completed tests of memory, language, executive functioning, and processing speed. Findings indicated decreased connectivity in the alpha2 range for older than younger adults between the mPFC and other DMN regions including the left angular gyrus and bilateral lateral temporal cortices, the latter of which were associated with lower performance in semantic fluency and executive functioning in older adults. Furthermore, greater PLV in theta and beta bands between the mPFC and posterior cingulate regions were found in older than younger adults. These results suggest age-related changes in DMN functional connectivity are non-uniform and frequency-dependent, and may reflect poorer performance in cognitive domains thought to decline with aging.

Reaction Time Intraindividual Variability Reveals Inhibitory Deficits in Single- and Multiple-Domain Amnestic Mild Cognitive Impairment.

OBJECTIVES: Amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease and other dementias, is characterized by episodic memory impairment. Recent evidence has shown inhibitory control deficits in aMCI, but the extent of these deficits across inhibitory domains (i.e., response inhibition and interference control) and aMCI subtypes (i.e., single vs multiple domain) remains unclear. Few studies have included reaction time intraindividual variability (RT IIV) in these efforts. The aim of this study was to compare response inhibition and interference control between aMCI subtypes using measures of accuracy, mean RT, and RT IIV. METHODS: We report data from 34 individuals with single-domain aMCI (sdaMCI, 66-86 years), 20 individuals with multiple-domain aMCI (mdaMCI, 68-88 years), and 52 healthy controls (HC, 64-88 years) who completed tasks of response inhibition (Go-NoGo) and interference control (Flanker). Group differences in accuracy, mean RT, and RT IIV were examined for both tasks. RESULTS: Individuals with mdaMCI had higher RT IIV than the other groups on both tasks. In RT IIV, we observed an interference control deficit in mdaMCI and sdaMCI relative to healthy controls, a finding not observed through accuracy or mean RT. DISCUSSION: RT IIV may detect subtle differences in inhibition deficits between aMCI subtypes that may not be evident with conventional behavioral measures. Findings support the supplementary use of RT IIV when assessing early executive function deficits.

Aging Enhances Neural Activity in Auditory, Visual, and Somatosensory Cortices: The Common Cause Revisited.

In humans, age-related declines in vision, hearing, and touch coincide with changes in amplitude and latency of sensory-evoked potentials. These age-related differences in neural activity may be related to a common deterioration of supra-modal brain areas (e.g., PFC) that mediate activity in sensory cortices or reflect specific sensorineural impairments that may differ between sensory modalities. To distinguish between these two possibilities, we measured neuroelectric brain activity while 37 young adults (18-30 years, 18 males) and 35 older adults (60-88 years, 20 males) were presented with a rapid randomized sequence of lateralized auditory, visual, and somatosensory stimuli. Within each sensory domain, we compared amplitudes and latencies of sensory-evoked responses, source activity, and functional connectivity (via phase-locking value) between groups. We found that older adults' early sensory-evoked responses were greater in amplitude than those of young adults in all three modalities, which coincided with enhanced source activity in auditory, visual, and somatosensory cortices. Older adults also showed stronger neural synchrony than young adults between superior prefrontal and sensory cortices; and in older adults, the degree of phase synchrony was positively correlated with the magnitude of source activity in sensory areas. Critically, older adults who showed enhanced neural activity in one sensory domain also showed enhanced activity in other modalities. Together, these findings support the common cause hypothesis of aging and highlight the role of prefrontal regions in exerting top-down control over sensory cortices.SIGNIFICANCE STATEMENT A prominent theory of aging posits that age-related declines in sensory processing across domains are related to a single common neurobiological mechanism. However, the neural evidence supporting this common cause hypothesis has remained elusive. Our study revealed robust age-related changes in three sensory domains across a range of neural metrics. Importantly, older adults who showed increased neural activity within one sensory domain also showed enhanced neural activity in the other two sensory modalities. No such relation among activity in sensory cortices was observed in young adults. Age-related increases in neural activity in sensory cortices coincided with enhanced neural synchrony between the PFC and sensory cortices, underlining the importance of the PFC in regulating sensory processing.

Effects of transcranial direct current stimulation combined with listening to preferred music on memory in older adults.

Listening to autobiographically-salient music (i.e., music evoking personal memories from the past), and transcranial direct current stimulation (tDCS) have each been suggested to temporarily improve older adults' subsequent performance on memory tasks. Limited research has investigated the effects of combining both tDCS and music listening together on cognition. The present study examined whether anodal tDCS stimulation over the left dorsolateral prefrontal cortex (2 mA, 20 min) with concurrent listening to autobiographically-salient music amplified subsequent changes in working memory and recognition memory in older adults than either tDCS or music listening alone. In a randomized sham-controlled crossover study, 14 healthy older adults (64-81 years) participated in three neurostimulation conditions: tDCS with music listening (tDCS + Music), tDCS in silence (tDCS-only), or sham-tDCS with music listening (Sham + Music), each separated by at least a week. Working memory was assessed pre- and post-stimulation using a digit span task, and recognition memory was assessed post-stimulation using an auditory word recognition task (WRT) during which electroencephalography (EEG) was recorded. Performance on the backwards digit span showed improvement in tDCS + Music, but not in tDCS-only or Sham + Music conditions. Although no differences in behavioural performance were observed in the auditory WRT, changes in neural correlates underlying recognition memory were observed following tDCS + Music compared to Sham + Music. Findings suggest listening to autobiographically-salient music may amplify the effects of tDCS for working memory, and highlight the potential utility of neurostimulation combined with personalized music to improve cognitive performance in the aging population.

Investigating the neural correlates of phonological encoding using a cluster-based analysis approach.

Phonological encoding, a subprocess in speech production, proceeds incrementally from word onset to offset. However, the incremental nature of encoding for multisyllabic words is unclear, and limited research has examined neural activity underlying the seriality of the process. In the present study, we investigated the timing of encoding between and within syllables of bisyllabic words using a data-driven cluster-based analysis of electroencephalography (EEG) data. In a phoneme-monitoring task, young adults covertly named pictures of bisyllabic words with a prespecified target phoneme present or absent. Target phonemes in target-present trials were distributed among four serial positions of the word concept: first syllable (S1) onset or offset and second syllable (S2) onset or offset. Upon covert naming, participants responded to target presence via button press or withheld responses for target absence. Neuroelectric activity during task performance was recorded using EEG and analyzed using cluster-based permutation testing. Faster response times and differences in neural activity were observed for monitoring targets at S1 onset than S2 onset, and for monitoring targets at S1 onset than S1 offset. No differences were found between monitoring targets at S2 onset and S2 offset. Our study supports the incremental nature of phonological encoding in bisyllabic words. Furthermore, the neural findings confirm that the serial time course of encoding in bisyllabic words extends to phonemes within the first, but not the subsequent syllable. Findings may have implications for current models of speech production.

Differential effects of mind-wandering and visual distraction on age-related changes in neuro-electric brain activity and variability.

Optimal performance in many tasks requires minimizing the impact of both visual distractors in the environment and distracting internal thoughts (i.e., mind-wandering). Prior research has indicated that older adults are disproportionately affected by the presence of visual distractors compared to young adults, but are not excessively affected by distracting thoughts. Yet an explanation for these dissociable effects remains elusive. In the current study, we assessed age-related differences in event-related potentials and neural variability associated with internal distraction and visual distractors in a go/no-go task. Compared to young adults, older adults showed an increased visual distraction cost in mean reaction time (RT) and RT variability but a reduction in internal distraction frequency and a reduced internal distraction cost on go accuracy and RT variability. Visual distraction and internal distraction were associated with opposite patterns of behavioral and neural effects. Behaviorally, across age groups, internal distraction was associated with more no-go errors whereas visual distraction was associated with reduced no-go errors. Across groups, internal distraction was associated with decreased P3 amplitude, whereas visual distraction was associated with increased P3 amplitude. In addition, internal distraction was associated with an increase in neural variability (more so in young versus older adults), while visual distraction was associated with a reduction in variability in young adults only. We suggest that the opposing effects of the two distractor types on behavioral and neural measures occur because visual distraction is associated with increased attentional resources devoted to the task to overcome visual interference whereas internal distraction is associated with decreased attentional resources devoted to the task. Moreover, older adults exhibited reduced flexibility of neural variability as a function of both distractor types, which may correspond to a diminished ability to up-regulate attention in the face of visual distraction and a diminished shift in attention away from the task during internal distraction.

Orienting Attention to Auditory and Visual Short-term Memory: The Roles of Age, Hearing Loss, and Cognitive Status.

Background/Study Context: Attention can be reflectively oriented to a visual or auditory representation in short-term memory, but it is not clear how aging and hearing acuity affects reflective attention. The purpose of the present study was to examine whether performance in auditory and visual reflective attention tasks varies as a function of participants' age and hearing status.Methods: Young (19 to 33 years) and older adults with normal or mild to moderate hearing loss (62-90 years) completed a delayed match-to-sample task in which participants were first presented with a memory array of four different digits to hold in memory. Two digits were presented visually (left and right hemifield), and two were presented aurally (left and right ears simultaneously). During the retention interval, participants were presented with a cue (dubbed retro-cue), which could be either uninformative or indicated to the participants to retrospectively orient their attention to either auditory short-term memory (ASTM) or visual short-term memory (VSTM). The cue was followed by another delay, after which a single item was presented (i.e., test probe) for comparison (match or no match) with the items held in ASTM and/or VSTM.Results: Overall, informative retro-cue yielded faster response time than uninformative retro-cue. The retro-cue benefit in response time was comparable for auditory and visual-orienting retro-cue and similar in young and older adults. Regression analyses showed that only the auditory-orienting retro-cue benefit was predicted by hearing status rather than age per se.Conclusion: Both younger and older adults can benefit from visual and auditory-orienting retro-cues, but the auditory-orienting retro-cue benefit decreases with poorer hearing acuity. This finding highlights changes in cognitive processes that come with age even in those with just mild-to-moderate hearing loss, and suggest that older adults' performance in working memory tasks is sensitive to low level auditory scene analysis (i.e., concurrent sound segregation).

A Modified Method for Creating Elastase-Induced Aneurysms by Ligation of Common Carotid Arteries in Rabbits and Its Effect on Surrounding Arteries.

BACKGROUND AND PURPOSE: Rabbit models of intracranial aneurysms are frequently used in pre-clinical settings. This study aimed to demonstrate an alternative, extravascular method for creating elastase-induced aneurysms, and how ligation of the right common carotid arteries (RCCA) can impact flow redistribution into left CCA (LCCA). METHODS: Elastase-induced aneurysms in 18 New Zealand rabbits (4.14 ± 0.314 kg) were created by applying 3-5 U of concentrated elastase solution to the exterior of the right and left CCA roots (RCCA and LCCA). After the induction of the aneurysm, the aneurysm was either kept intact to the rest of the corresponding CCA, severed from the rest of the CCA to allow for a free standing aneurysm, or was anchored to nearby tissue to influence the angle and orientation of the aneurysm with respect to the parent vessel. Ultrasound studies were performed before and after creation of aneurysms to collect blood flow measurements inside the aneurysm pouch and surrounding arteries. Prior to sacrificing the animals, computed tomography angiography studies were performed. Harvested aneurysmal tissues were used for histological analysis. RESULTS: Elastase-induced aneurysms were successfully created by the extravascular approach. Histological studies showed that the biological response was similar to human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Ultrasound measurements indicated that after the RCCA was ligated, blood flow significantly increased in the LCCA at one-month follow-up. CONCLUSION: An alternate method for creating elastase-induced aneurysms has been demonstrated. The novel aspects of our method allow for ligation of one or both common carotid arteries to create a single or bilateral aneurysm with an ability to control the orientation of the induced aneurysm.

Focal middle cerebral artery ischemia in rats via a transfemoral approach using a custom designed microwire.

OBJECTIVES: The aim of this study was to develop a reliable and repeatable method of inducing focal middle cerebral artery occlusion (MCAo) in rats without ligation of the external carotid artery (ECA), while reducing the risk of subarachnoid hemorrhage. METHODS: We prototyped microwires with different diameters (0.0120 inch, 0.0115 inch, 0.0110 inch), materials, and construction methods (coil-on-core, extruded polymer jacket-on-core). Under fluoroscopic guidance and using femoral artery access, the microwires were navigated into the internal carotid artery of male Wistar rats (n=50, weight 376±64 g) to induce MCAo for 1 or 2 h. We performed neurological assessments at baseline, and at 3, 24, 72, and 168 h after MCAo. MRI measurements were performed on a 9.4 T scanner at 1 and 7 days post-injury. RESULTS: The 0.0115 inch microwire with polymer jacket-on-core provided the most successful outcome. At 1 and 7 days post-injury, we observed similar infarction volumes for 1 and 2 h MCAo in the MRI study. Infarcted lesion volumes in both MCAo groups were significantly reduced at 7 days compared with 1 day post-injury. The trend in longitudinal changes for the scores of different neurological assessments was confirmed to be significant after the injury, but both groups showed a similar trend of neurological deficits over the course of the study. CONCLUSIONS: We have developed a reliable and repeatable MCAo method in rats, allowing for precise occlusion of the MCA under direct fluoroscopic visualization without alteration of the cerebral hemodynamics associated with ECA ligation. The custom designed microwire can also be sized for targeted focal ischemia in larger animals.

Intracranial aneurysms: review of current treatment options and outcomes.

Intracranial aneurysms are present in roughly 5% of the population, yet most are often asymptomatic and never detected. Development of an aneurysm typically occurs during adulthood, while formation and growth are associated with risk factors such as age, hypertension, pre-existing familial conditions, and smoking. Subarachnoid hemorrhage, the most common presentation due to aneurysm rupture, represents a serious medical condition often leading to severe neurological deficit or death. Recent technological advances in imaging modalities, along with increased understanding of natural history and prevalence of aneurysms, have increased detection of asymptomatic unruptured intracranial aneurysms (UIA). Studies reporting on the risk of rupture and outcomes have provided much insight, but the debate remains of how and when unruptured aneurysms should be managed. Treatment methods include two major intervention options: clipping of the aneurysm and endovascular methods such as coiling, stent-assisted coiling, and flow diversion stents. The studies reviewed here support the generalized notion that endovascular treatment of UIA provides a safe and effective alternative to surgical treatment. The risks associated with endovascular repair are lower and incur shorter hospital stays for appropriately selected patients. The endovascular treatment option should be considered based on factors such as aneurysm size, location, patient medical history, and operator experience.