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Author's response to: Disparity of neural and behavioral handedness in evaluating candidates for POCD
Psychobiological mechanisms underlying cognitive decline in cardiac surgery patients
Technological advances over the past four decades have decreased the major complications or mortality in cardiac surgery. However, a significant number of patients suffer from adverse neurological and cognitive outcomes which, in turn, remain an important cause of postoperative morbidity and are responsible for an increasing proportion of perioperative deaths. Adverse neurological and cognitive outcomes after cardiac surgery are the result of multiple preoperative and/or intraoperative factors. While demographic, biomedical, and psychological disorders (e.g., anxiety and depression) represent preoperative variables associated with postoperative adverse outcomes, intraoperative cerebral hypoperfusion, microembolization and neuroinflammation that are related to cardiopulmonary bypass also represent a major cause of impairment after surgery. Despite a growing interest in adverse psychological outcomes after cardiac surgery, the psychobiological mechanisms underlying postoperative cognitive decline have to be investigated yet. In this dissertation, four studies are described, that were meant to examine cognitive decline and depression after cardiac surgery and some psychobiological mechanisms underlying the afore-mentioned phenomena. The main aim of Experiment I was to provide further evidence about the preoperative relationships among anxiety, depression, cognitive dysfunctions and risk-stratification scores, namely the Stroke Index and European System for Cardiac Operative Risk Evaluation, in patients undergoing cardiac surgery. It was found that both the risk-stratification scores showed significant correlations with cognitive performance, whereas only the European System for Cardiac Operative Risk Evaluation was significantly associated also with anxiety and depression. The main goal of Experiment II and III was to investigate the hemodynamic cerebral factors underlying cognitive decline after cardiac surgery. Experiment II was designed to examine whether cerebral hypoperfusion may represent a predictor of cognitive decline in patients undergone cardiac surgery after controlling for common demographic and biomedical risk factors. Experiment II showed that hypoperfusion in the left middle cerebral artery selectively predicted the incidence of cognitive decline after surgery, whereas blood flow velocity in the right middle cerebral artery was unrelated to postoperative cognitive decline. Hence, cardiac surgery patients with reduced left cerebral blood flow velocity preoperatively are at greater risk for postoperative cognitive decline. Left cerebral hypoperfusion may also represent an independent predictor of cognitive decline in cardiac surgery patients. Experiment III was designed to determine the effects of lateralization and type of microembolization on postoperative cognitive decline in patients who had undergone heart valve surgery. Experiment III showed that microembolization in the left middle cerebral artery significantly correlated with early and late (i.e., 3-month follow-up) postoperative cognitive decline, while microembolization in the right middle cerebral artery was unrelated to early and late cognitive decline. Moreover, an association between solid microemboli with early but not late postoperative cognitive decline was noted. In contrast, gaseous microembolization was related to both early and late cognitive decline. Given the relevant role played by depression as a risk factor for postoperative adverse clinical and cognitive outcomes, the main aim of the Experiment IV was to examine, postoperatively, whether electroencephalographic activity could reflect the influence of depression during an emotional imagery task requiring the subject being involved in a cognitive task (retrieval and imagery), which is emotionally laden. There was no difference between groups in resting electroencephalographic activity, whereas patients with depression showed a significant reduced frontal theta power during the emotional imagery task compared to those without depression. Also, a significant correlation was selectively found between frontal theta power and emotional reappraisal. Taken together these experiments provide a better understanding of the psychological and physiological mechanisms underlying postoperative cognitive decline and depression in cardiac surgery patients. In conclusion, the present thesis suggests the need for including preoperative and postoperative evaluation of cognitive and affective status as well as objective hemodynamic and/or electroencephalographic measures to accurately predict and/or treat patient’s dysfunctional psychological outcomes after cardiac surgeryLe innovazioni tecnologiche conseguite nella seconda metà del XX secolo hanno ridotto le complicazioni maggiori e la mortalità nei pazienti sottoposti a cardiochirurgia. Nonostante gli evidenti benefici clinici nella pratica medica, un numero significativo di pazienti presenta disfunzioni neurologiche e/o psicologiche nel periodo postoperatorio che, a loro volta, sono responsabili per l’incremento della mortalità perioperatoria e della morbidità postoperatoria. Tali disfunzioni neurologiche e cognitive in seguito a cardiochirurgia sono il risultato di diversi fattori preoperatori e/o intraoperatori. Mentre le variabili demografiche, biomediche e psicologiche (tra cui ansia e depressione) rappresentano importati fattori preoperatori associati allo stato di salute postoperatorio, l’ipoperfusione cerebrale, l’embolizzazione e/o i processi neuroinfiammatori associati al bypass cardiopolmonare durante la chirurgia rappresentano fattori di rischio intraoperatori per le disfunzioni neurologiche e cognitive postoperatorie. Sebbene vi sia un sempre crescente interesse nello studio delle disfunzioni psicologiche in seguito a cardiochirurgia, i meccanismi psicobiologici sottostanti il declino cognitivo postoperatorio devono ancora essere indagati. Perciò, nella presente tesi sono descritti quattro studi che, per prima cosa, avevano lo scopo di indagare l’entità del declino cognitivo e della depressione in seguito a cardiochirurgia e, in secondo luogo, miravano ad identificare alcuni fattori di stampo psicobiologico coinvolti nel declino cognitivo e depressione postoperatori. L’Esperimento I mirava, come scopo principale, a fornire nuove evidenze circa la relazione, nel periodo preoperatorio, tra ansia, depressione, disfunzioni cognitive e punteggi di rischio biomedico (lo Stroke Index e l’European System for Cardiac Operative Risk Evaluation) in pazienti in attesa di intervento cardiochirurgico. I risultati del presente studio hanno indicato che, mentre entrambi i punteggi di rischio biomedico erano associati allo stato cognitivo preoperatorio dei pazienti cardiochirurgici, solo l’European System for Cardiac Operative Risk Evaluation teneva in considerazione anche i fattori di rischio associati all’ansia e depressione. Lo scopo principale degli Esperimenti II e III era indagare l’associazione fra fattori emodinamici cerebrali perioperatori e disfunzioni cognitive in seguito a cardiochirurgia. L’Esperimento II è stato disegnato per indagare se l’ipoperfusione cerebrale preoperatoria potesse essere un predittore di declino cognitivo postoperatorio nei pazienti sottoposti a cardiochirurgia, anche dopo aver controllato per i più comuni fattori di rischio demografici e biomedici. L’Esperimento II ha mostrato che l’incidenza del declino cognitivo si associava selettivamente all’ipoperfusione nell’arteria cerebrale media sinistra, mentre la velocità di flusso ematico nell’arteria cerebrale media destra non correlava con il declino cognitivo postoperatorio. L’ipoperfusione cerebrale sinistra, quindi, sembra rappresentare un fattore di rischio indipendente per il declino cognitivo in pazienti sottoposti a cardiochirurgia. L’Esperimento III è stato disegnato per determinare il ruolo dell’asimmetria e della natura della microembolizzazione intraoperatoria sul declino cognitivo postoperatorio in pazienti sottoposti a chirurgia valvolare. L’Esperimento III ha mostrato che la microembolizzazione intraoperatoria nell’arteria cerebrale media sinistra correlava significativamente sia con il declino cognitivo nell’immediato postoperatorio (alle dimissioni) che a distanza nel tempo (a 3 mesi dall’intervento chirurgico), mentre gli eventi embolici nell’arteria cerebrale media destra non erano associati né al declino cognitivo immediato né a distanza nel tempo. Inoltre, i microemboli solidi correlavano significativamente con il declino cognitivo immediato ma non al follow-up di 3 mesi. Al contrario, è stata riscontrata un’associazione significativa tra gli eventi microembolici gassosi ed il declino cognitivo immediato e a 3 mesi di distanza dall’intervento chirurgico. Dato il ruolo rilevante giocato dalla depressione come fattore di rischio per le disfunzioni cognitive postoperatorie, lo scopo principale dell’Esperimento IV è stato quello di indagare, nel periodo postoperatorio, se e come la depressione potesse influenzare l’attività elettroencefalografica durante un compito di imagery emozionale, il quale, a sua volta, implica sia un’elaborazione di tipo cognitivo che emozionale. Sebbene nessuna differenza tra i gruppi sia stata riscontrata nell’attività elettroencefalografica a riposo, rispetto ai controlli non depressi, si osservava nei pazienti depressi una ridotta attività theta frontale durante il compito di imagery emozionale. Inoltre, una ridotta ampiezza della theta frontale si associava selettivamente a disregolazione emozionale (ridotta capacità di reappraisal). Questi esperimenti, considerati nel loro insieme, forniscono una migliore e più approfondita comprensione dei meccanismi psicologici e fisiologici sottostanti il fenomeno del declino cognitivo e depressione postoperatori in pazienti cardiochirurgici. In conclusione, la presente tesi suggerisce la possibilità di includere sia una valutazione cognitiva e affettiva pre e postoperatoria che misure emodinamiche e/o elettroencefalografiche oggettive in grado di predire e/o facilitare il trattamento delle disfunzioni psicologiche postoperatorie nei pazienti sottoposti a cardiochirurgi
Familial risk for depression is associated with reduced P300 and late positive potential to affective stimuli and prolonged cardiac deceleration to unpleasant stimuli
: Despite evidence of abnormal affective processing as a key correlate of depression, specific attentional mechanisms underlying processing of emotions in familial risk for depression have yet to be investigated in a single study. To this end, the amplitude of the P300 and late positive potential (LPP) complex and cardiac deceleration were assessed during the passive viewing of affective pictures in 32 individuals who had family history of depression (without depressive symptoms) and in 30 controls (without depressive symptoms and family history of depression). Individuals with familial risk for depression revealed reduced P300-LPP amplitudes in response to pleasant and unpleasant stimuli relative to controls, and comparable P300-LPP amplitudes in response to pleasant and neutral stimuli. Controls, but not individuals with familial risk for depression, reported cardiac deceleration during the viewing of pleasant vs. neutral and unpleasant stimuli in the 0-3 s time window. Also, only individuals with familial risk for depression showed a prolonged cardiac deceleration in response to unpleasant vs. neutral stimuli. Overall, the present study provides new insights into the characterization of emotion-related attentional processes in familial risk for depression as potential vulnerability factors for the development of the disorder
Early indicators of vulnerability to depression: The role of rumination and heart rate variability
Background: Despite the evidence of increased levels of rumination and reduced heart rate variability (HRV) in depression, whether these measures can be considered early indicators of vulnerability to depression has yet to be investigated. Therefore, the present study aimed to investigate both levels of rumination and resting HRV in individuals with familial risk for depression that is the most reliable risk factor for the disorder.
Methods: Rumination and vagally-mediated HRV were assessed using the Ruminative Response Scale and a smartphone-based photoelectric volumetric pulse wave assay, respectively, in 25 individuals who had family history of depression (but did not report current depressive symptoms), 15 individuals who reported depressive symptoms (but had no family history of depression), and 25 controls (without depressive symptoms and family
history of depression).
Results: Individuals with depressive symptoms and those with a family history of depression were characterized by higher levels of rumination and lower cardiac vagal control than controls.
Limitations: Given the small sample size, this study should be used to design larger confirmatory studies; the cross-sectional nature of the study does not allow discussing the results in terms of cause-effect relationships.
Conclusions: Our findings suggested that individuals at risk of developing depression, also in absence of depressive symptoms, are defined by defective self-regulation capacity that may lead to future depression episodes. Increased ruminative thoughts and reduced HRV may represent early indicators of vulnerability to depression. Effective prevention programs designed to reduce rumination and/or increase HRV may reduce the
risk of developing a full-blown depressive episode
Appetitive and aversive motivation in dysphoria: A time-domain and time-frequency study of response inhibition
The study of emotional response inhibition could provide novel insight into dysphoria-related deficits in appetitive and aversive motivational systems. Therefore, dysphoric (N = 21) and nondysphoric (N = 21) participants completed an emotional Go/Nogo paradigm, including the presentation of pleasant, neutral and unpleasant pictures. Behavioral measures [reaction times (RTs), accuracy to Go and Nogo stimuli] and neural correlates (Go/Nogo-N2 and Go/Nogo-P3) of response inhibition were compared between the two groups. Time-frequency analysis was also used as a novel approach to disentangle the multiple processes underlying time-domain ERP data. A reduced Go/Nogo effect for P3 and oscillatory delta activity was found in response to pleasant and neutral, but not unpleasant, stimuli in dysphoric relative to nondysphoric individuals. These findings showed that dysphoric individuals need a reduced and/or less effortful response inhibition to pleasant stimuli, suggesting that dysphoria is characterized by under-engagement of appetitive rather than over-engagement of aversive motivational system
Posture affects emotional responses: A Head Down Bed Rest and ERP study
Body posture, mainly represented by horizontal bed rest, has been found to be associated with cortical inhibition, altered perceptual and cognitive processing. In the present research, the influence of Head Down Bed Rest (HDBR) – a condition also termed simulated microgravity – on emotional responses has been studied. Twenty-two male subjects were randomly assigned to either Sitting Control or HDBR group. After 3-h, subjects attended to a passive viewing emotional task in which 75 IAPS slides, divided into 25 pleasant, 25 neutral and 25 unpleasant, were presented in random order for 6 s each, while EEG was recorded from F7, F8 and Pz locations. Results showed in Sitting Controls the expected greater P300 and Late Positive Potential (LPP) to pleasant and unpleasant compared with neutral slides, an effect which indicates greater processing of emotional arousing stimuli. The HDBR group showed smaller non-significant differences among all emotional conditions in both ERP components. Arousal and valence subjective evaluations, typically less sensitive to experimental manipulation, did not differentiate groups. The observed ability of HDBR to inhibit cortical emotional responses raises an important issue on the risk that astronauts underestimate a dangerous/threatening situation or that long-term bedridden inpatients develop depressive symptoms
Effects of simulated microgravity on brain plasticity: a startle reflex habituation study
There is limited but increasing evidence that space environment, namely weightless condition, may affect astronauts' cerebral neurotransmitters and cognitive performance. The present experiment hypothesized that learning and brain plasticity are affected by simulated microgravity condition. To this aim, 22 male subjects matching astronauts' characteristics were divided in two groups, Head-Down Bed Rest (HDBR) and Sitting Control. After 3-h bed rest (or sitting condition) subjects started a picture viewing task during which 30 acoustic startle probes (100 dBA loudness), divided into three consecutive blocks, were delivered through headphones while startle reflex amplitude was measured from the EMG of the orbicularis oculi muscle. Habituation analysis of the startle reflex showed a normal reflex inhibition across blocks in sitting controls and no habituation in HDBR subjects. Results point to a microgravity-induced lack of startle reflex plasticity in subjects matching astronauts, a learning deficit which may affect the success of long-term space missions
Preoperative biomedical risk and depressive symptoms are differently associated with reduced health-related quality of life in patients 1year after cardiac surgery
Objective: To examine whether preoperative biomedical risk and depressive symptoms were associated with
physical and mental components of health-related quality of life (HRQoL) in patients 1 year after cardiac surgery.
Method: Seventy-five patients completed a psychological evaluation, including the Center for Epidemiological
Study of Depression scale, the 12-item Short-Form Physical Component Scale (SF-12-PCS) and Mental Component Scale (SF-12-MCS), the Instrumental Activities of Daily Living questionnaire for depressive symptoms and HRQoL, respectively, before surgery and at 1-year follow-up.
Results: Preoperative depressive symptoms predicted the SF-12-PCS (beta=−.22, P<.05) and SF-12-MCS
(beta=−.30, P<.04) scores in patients 1 year after cardiac surgery, whereas the European System for Cardiac
Operative Risk Evaluation was associated with SF-12-PCS (beta=−.28, P<.02), but not SF-12-MCS (beta=.01,
P=.97) scores postoperatively.
Conclusions: The current findings showed that preoperative depressive symptoms are associated with poor
physical and mental components of HRQoL, whereas high biomedical risk predicts reduced physical, but not
mental, functioning in patients postoperatively. This study suggests that a preoperative assessment of depressive symptoms in addition to the evaluation of common biomedical risk factors is essential to anticipate which patients are likely to show poor HRQoL after cardiac surgery
Preoperative and perioperative predictors of reactive and persistent depression after cardiac surgery: A three-month follow-up study
Objective: Depression is commonly reported in patients after cardiac surgery and increases the risk of postoperative cardiac morbidity and/or mortality. Although preoperative depression has been implicated as the strongest predictor of depression after surgery, the characteristics thought to influence reactive or persistent depression have been poorly investigated in cardiac surgery patients. Therefore, the main aim of this study was to examine whether preexisting depression rather than perioperative variables may predict postoperative reactive or persistent depression.
Methods: Ninety-six patients completed a psychological evaluation, including the Center for Epidemiologic Studies of Depression (CES-D) scale and the State and Trait Anxiety Inventory (STAI Y1/Y2) for depression and anxiety, respectively, before surgery and at three-month follow-up.
Results: Twenty-seven (28%) and 24 (25%) patients had depression preoperatively and at three-month follow-up, respectively. Postoperative depression was predicted by preoperative scores in CES-D (beta= 0.29, P .75). Specifically, patients with reactive depression showed greater EuroSCORE than those without depression (P < .05), whereas patients with persistent depression had greater preoperative CES-D scores than those whose depression improved after surgery (P < .01).
Conclusions: The severity of preexisting depression and biomedical risk factors can be markers of depression-related risk three months after cardiac surgery in patients with persistent and reactive depression, respectively. An integrated psychological and biomedical evaluation is essential to anticipate which patients are likely to show depression after cardiac surgery
Are patient- or procedure-related factors relevant to middle-term cognitive decline after cardiac surgery? This is the question
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