Temporal expectations modulate face image repetition suppression of early stimulus evoked event-related potentials

Repeated exposure to a stimulus leads to reduced responses of stimulus-selective sensory neurons, an effect known as repetition suppression or stimulus-specific adaptation. Several influential models have been proposed to explain repetition suppression within hierarchically-organised sensory systems, with each specifying different mechanisms underlying repetition effects. We manipulated temporal expectations within a face repetition experiment to test a critical prediction of the predictive coding model of repetition suppression: that repetition effects will be larger following stimuli that appear at expected times compared to stimuli that appear at unexpected times. We recorded event-related potentials from 18 participants and mapped the spatiotemporal progression of repetition effects using mass univariate analyses. We then assessed whether the magnitudes of observed face image repetition effects were influenced by temporal expectations. In each trial participants saw an adapter face, followed by a 500 ms or 1000 ms interstimulus interval (ISI), and then a test face, which was the same or a different face identity to the adapter. Participants' expectations for whether the test face would appear after a 500 ms ISI were cued by the sex of the adapter face. Our analyses revealed multiple repetition effects with distinct scalp topographies, extending until at least 800 ms from stimulus onset. An early (158-203 ms) repetition effect was larger for stimuli following surprising, rather than expected, 500 ms ISI durations, contrary to the model predictions of the predictive coding model of repetition suppression. During this time window temporal expectation effects were larger for alternating, compared to repeated, test stimuli. Statistically significant temporal expectation by stimulus repetition interactions were not found for later (230-609 ms) time windows. Our results provide further evidence that repetition suppression can reduce neural effects of expectation and surprise, indicating that there are multiple interactive mechanisms supporting sensory predictions within the visual hierarchy.Daniel Feuerriegel, Owen Churches, Scott Coussens, Hannah A.D. Keag

Combining perceptual regulation and exergaming for exercise prescription in low-active adults with and without cognitive impairment

Background:Exercise adherence in already low-active older adults with and without mild cognitive impairment (MCI) remains low. Perceptual regulation and exergaming may facilitate future exercise behaviour by improving the affective experience, however evidence that this population can perceptually regulate is lacking. To explore this, we investigated 1) perceptual regulation of exercise intensity during either exergaming or regular ergometer cycling and 2) explored affective responses. Methods:Thirty-two low active older adults (73.9 ± 7.3 years, n = 16, 8 females) with or without MCI (70.9 ± 5.5 years, n = 16, 11 females) participated in a sub-maximal fitness assessment to determine ventilatory threshold (VT) and two experimental sessions (counterbalanced: exergaming or regular ergometer cycling). Experimental sessions consisted 21-min of continuous cycling with 7-min at each: RPE 9, 11 and 13. Oxygen consumption (VO2), heart rate (HR), and affect (Feeling Scale) were obtained throughout the exercise. Results:VO2 (p < 0.01) and HR (p < 0.01) increased linearly with RPE, but were not significantly different between exercise modes or cognitive groups. At RPE 13, participants worked above VT in both modes (exergaming: 115.7 ± 27.3; non-exergaming 114.1 ± 24.3 VO2 (%VT)). Regardless of cognitive group, affect declined significantly as RPE increased (p < 0.01). However on average, affect remained pleasant throughout and did not differ between exercise modes or cognitive groups. Conclusions:These results suggest low-active older adults can perceptually regulate exercise intensity, regardless of cognition or mode. At RPE 13, participants regulated above VT, at an intensity that improves cardiorespiratory fitness long-term, and affect remained positive in the majority of participants, which may support long-term physical activity adherence.Liam McAuliffe, Gaynor C. Parfitt, Roger G. Eston, Caitlin Gray, Hannah A. D. Keage and Ashleigh E. Smit

Risk factors for delirium and cognitive decline following coronary artery bypass grafting surgery: a systematic review and meta-analysis

Background: Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results: We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1–6 months) post-CABG cognitive decline. Conclusions: This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable.Danielle Greaves, Peter J. Psaltis, Daniel H.J. Davis, Tyler J. Ross, Erica S. Ghezzi, Amit Lampit, Ashleigh E. Smith, Hannah A.D. Keag

DelIrium VULnerability in GEriatrics (DIVULGE) study: A protocol for a prospective observational study of electroencephalogram associations with incident postoperative delirium

Delirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools.Monique S Boord, Daniel H J Davis, Peter J Psaltis, Scott W Coussens, Daniel Feuerriegel, Marta I Garrido, Alice Bourke, Hannah A D Keag

Burden of mood symptoms and disorders in implantable cardioverter defibrillator patients: a systematic review and meta-analysis of 39 954 patients.

Aims: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. Anxiety, depression, and post-traumatic stress disorder (PTSD) are underappreciated symptoms. We aimed to systematically synthesize prevalence estimates of mood disorders and symptom severities, pre- and post-ICD insertions. Comparisons were made with control groups, as well as within ICD patients by indication (primary vs. secondary), sex, shock status, and over time. Methods: Databases (Medline, PsycINFO, PubMed, and Embase) were searched without limits from inception to 31 August 2022; 4661 articles were identified, 109 (39 954 patients) of which met criteria. Results: Random-effects meta-analyses revealed clinically relevant anxiety in 22.58% (95%CI 18.26–26.91%) of ICD patients across all timepoints following insertion and depression in 15.42% (95%CI 11.90–18.94%). Post-traumatic stress disorder was seen in 12.43% (95%CI 6.90–17.96%). Rates did not vary relative to indication group. Clinically relevant anxiety and depression were more likely in ICD patients who experienced shocks [anxiety odds ratio (OR) = 3.92 (95%CI 1.67–9.19); depression OR = 1.87 (95%CI 1.34–2.59)]. Higher symptoms of anxiety were seen in females than males post-insertion [Hedges’ g = 0.39 (95%CI 0.15–0.62)]. Depression symptoms decreased in the first 5 months post-insertion [Hedges’ g = 0.13 (95%CI 0.03–0.23)] and anxiety symptoms after 6 months [Hedges’ g = 0.07 (95%CI 0–0.14)]. Conclusion: Depression and anxiety are highly prevalent in ICD patients, especially in those who experience shocks. Of particular concern is the prevalence of PTSD following ICD implantation. Psychological assessment, monitoring, and therapy should be offered to ICD patients and their partners as part of routine care.Erica S. Ghezzi, Rhianna L.S. Sharman, Joseph B. Selvanayagam, Peter J. Psaltis, Prashanthan Sanders, Jack M. Astley, Sara Knayfati, Vrinda Batra, and Hannah A.D. Keag

The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia

Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population. Methods: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies. Findings: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0–91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20–0·42]). Interpretation: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted. Funding: Gates Ventures

Association of delirium with cognitive decline in late life: A neuropathologic study of 3 population-based cohort studies

Importance Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (−2.8 points; 95% CI, −4.5 to −1.0; P < .001). Cognitive decline attributable to delirium was −0.37 MMSE points per year (95% CI, −0.60 to −0.13; P < .001). Decline attributable to the pathologic processes of dementia was −0.39 MMSE points per year (95% CI, −0.57 to −0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional −0.16 MMSE points per year (95% CI, −0.29 to −0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level–matched controls. Conclusions and Relevance Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia

Is neural adaptation of the N170 category-specific? Effects of adaptor stimulus duration and interstimulus interval

Neural adaptation paradigms have been used in the electrophysiological and neuroimaging literature to characterise neural populations underlying face and object perception. It was recently reported by Nemrodov and Itier (2012) that adaptation of the N170 event-related potential (ERP) component is not stimulus category-specific over rapid adapting stimulus durations (S1 durations) and interstimulus intervals (ISIs). We therefore tested the category-specificity of adaptation over a range of S1 durations and ISIs. Faces and chairs were presented at S1 (for 200, 500 or 1000ms) and S2 (for 200ms), over a variable ISI (200 or 500ms). Mean amplitudes of the P1, N170 and P2 visual ERP components were measured following S1 and S2 stimuli. Faces at S1 led to the smallest (i.e., most adapted) N170 amplitudes to both faces and chairs at S2, more than chairs at S1. N170s at S2 were smallest after a 500ms S1 duration; but N170 amplitude did not vary over ISI. Effects were also seen for the two surrounding positive components, the P1 and P2. Presenting faces at S1 led to enhanced P1 amplitudes evoked by S2 chair stimuli. The P2 showed the smallest amplitudes following the shorter 200ms ISI. These results indicate that adaptation of the N170 is not actually category-specific but instead dependent on the S1 category (regardless of S2 category), and may also be influenced by earlier effects at the P1 (i.e., not specific to the N170). This challenges the assumption that N170 category adaptation indexes effects on distinct neural populations that differ between faces and non-face objects.Daniel Feuerriegel, Owen F. Churches, Hannah A.D. Keag

Cerebrovascular function during cognition in Parkinson's disease: a functional transcranial Doppler sonography study

Objective: Recent evidence has linked cerebrovascular abnormalities with Parkinson's Disease (PD), which may provide a new neurophysiological understanding of cognitive impairment in PD. The current study aimed to compare cerebrovascular functioning, during a cognitive task and at rest, in those with and without PD. Methods: Idiopathic PD patients (n = 30) and age- and gender-matched healthy controls (n = 30) undertook cognitive testing and completed a word generation task while blood flow velocity was monitored bilaterally with functional transcranial Doppler sonography (fTCD) of the middle cerebral arteries. The lateralisation index and its standard deviation and timing, along with the maximum peak velocity for the left and right hemispheres and their latencies and standard deviations, were calculated for each participant. Results: The PD patients showed significantly more variability of the lateralisation index compared to the control group; but there were no differences in the lateralisation index itself nor in the peak velocities. In the PD group, the variability in the peak velocities showed significant positive correlations with performance on executive function tests. Conclusion: Normal ageing has been associated with a reduction in the lateralisation index, but no alterations in the standard deviation, suggesting that cerebrovascular functional changes associated with PD differ from those of typical ageing. The within-subject variability observed in the PD group indicate abnormalities within the neurovascular coupling response. Further, the association between the within-subject variability and executive functioning in the PD group, suggests that cerebrovascular dysfunction plays an important role in cognitive impairment in PD.Daria S.Gutteridge, Dimitrios Saredakis, Nicholas A.Badcock, Lyndsey E.Collins-Praino, Hannah A.D.Keag

Meta-analysis of prevalence and risk factors for cognitive decline and improvement after transcatheter aortic valve implantation

Changes to cognition, both decline and improvement, are commonly reported after transcatheter aortic valve implantation (TAVI). However, previous systematic reviews and meta-analyses have missed these subgroups by assessing whole-group-averages for cognitive outcomes. We sought to pool estimates to identify the prevalence of cognitive decline and improvement after TAVI, as well as associated factors for these outcomes. A systematic review identified 15 articles appropriate for meta-analysis. When robust cognitive change definitions were employed, the pooled prevalence of incident cognitive impairment up to 1-, 1 to 6-, and ≥6-months post-TAVI was 7%, 14%, and 12%, respectively. For cognitive improvement, the prevalence from 1 to 6 months and ≥6 months after TAVI was estimated to be 19% and 11%, respectively. Two factors were associated with these cognitive outcomes: (1) using a cerebral embolic protection device was associated with decreased prevalence of cognitive decline up to 1-week post-TAVI; (2) baseline cognitive impairment had a large association with post-TAVI cognitive improvement. In conclusion, cognitive decline and cognitive improvement are experienced by approximately 7% to 19% of patients after TAVI, respectively. Those with the lowest cognitive performance pre-TAVI appear to have the most to gain in terms of cognitive improvement post-TAVI. Identifying further predictive factors for cognitive decline and improvement post-TAVI will facilitate a personalized-medicine approach for cognitive care and prognosis.Erica S.Ghezzi, Tyler J.Ross, Daniel Davis, Peter J.Psaltis, Tobias Loetscher, Hannah A.D.Keag