Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls

AbstractAlterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.

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Spatial working memory performance in people with obsessive–compulsive disorder, their unaffected first-degree relatives and healthy controls

BJPsych Open ◽

10.1192/bjo.2021.1052 ◽

2021 ◽

Vol 7 (6) ◽

Author(s):

Stephan Heinzel ◽

Katharina Bey ◽

Rosa Grützmann ◽

Julia Klawohn ◽

Christian Kaufmann ◽

...

Keyword(s):

Working Memory ◽

Obsessive Compulsive Disorder ◽

Spatial Working Memory ◽

Memory Performance ◽

Age Effects ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

First Degree Relatives ◽

Healthy Control

Summary Studies have shown that people with obsessive–compulsive disorder (OCD) have impairments in spatial working memory (SWM) performance. However, it remains unclear whether this deficit represents a cognitive endophenotype preceding symptoms or a correlate of OCD. We investigated SWM in 69 people with OCD, 77 unaffected first-degree relatives of people with OCD and 106 healthy control participants. Taking age effects into account, SWM performance was best in healthy controls, intermediate in relatives and worst in OCD participants. However, since performance did not differ significantly between healthy controls and relatives, our study does not fully support SWM performance as a core cognitive endophenotype of OCD.

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Modelling a Multi-Dimensional Model of Memory Performance in Obsessive-Compulsive Disorder: A Multi-Level Meta-Analytic Review.

10.31234/osf.io/u4tqa ◽

2020 ◽

Author(s):

Sofia Persson ◽

Alan Yates ◽

Klaus Kessler ◽

Ben Harkin

Keyword(s):

Executive Function ◽

Obsessive Compulsive Disorder ◽

Memory Load ◽

Memory Performance ◽

Effect Sizes ◽

Driving Mechanism ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Analytic Review ◽

Multi Level

Even though memory performance is a commonly researched aspect of Obsessive-Compulsive Disorder (OCD), a coherent and unified explanation of the role of specific cognitive factors has remained elusive. To address this, the present meta-analysis examined the predictive validity of Harkin and Kessler’s (2011) Executive Function (E), Binding Complexity (B) and Memory Load (L) Classification System with regards to affected vs. unaffected memory performance in OCD. We employed a multi-level meta-analytic approach (Viechtbauer, 2010) to accommodate the interdependent nature of the EBL model and interdependency of effect sizes (305 effect sizes from 144 studies, including 4424 OCD patients). Results revealed that the EBL model predicted memory performance, i.e., as EBL demand increases, those with OCD performed progressively worse on memory tasks. Executive function was the driving mechanism behind the EBL’s impact on OCD memory performance and negated effect size differences between visual and verbal tasks in those with OCD. Comparisons of sub-task effect sizes were also generally in accord with the cognitive parameters of the EBL taxonomy. We conclude that standardised coding of tasks along individual cognitive dimensions and multi-level meta-analyses provides a new approach to examine multi-dimensional models of memory and cognitive performance in OCD and other disorders.

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Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01233 ◽

2018 ◽

Vol 30 (9) ◽

pp. 1229-1240 ◽

Cited By ~ 32

Author(s):

Kirsten C. S. Adam ◽

Matthew K. Robison ◽

Edward K. Vogel

Keyword(s):

Working Memory ◽

Individual Differences ◽

Memory Load ◽

Memory Performance ◽

Memory Task ◽

Memory Storage ◽

Alpha Power ◽

Working Memory Load ◽

Contralateral Delay Activity ◽

Trial Performance

Neural measures of working memory storage, such as the contralateral delay activity (CDA), are powerful tools in working memory research. CDA amplitude is sensitive to working memory load, reaches an asymptote at known behavioral limits, and predicts individual differences in capacity. An open question, however, is whether neural measures of load also track trial-by-trial fluctuations in performance. Here, we used a whole-report working memory task to test the relationship between CDA amplitude and working memory performance. If working memory failures are due to decision-based errors and retrieval failures, CDA amplitude would not differentiate good and poor performance trials when load is held constant. If failures arise during storage, then CDA amplitude should track both working memory load and trial-by-trial performance. As expected, CDA amplitude tracked load (Experiment 1), reaching an asymptote at three items. In Experiment 2, we tracked fluctuations in trial-by-trial performance. CDA amplitude was larger (more negative) for high-performance trials compared with low-performance trials, suggesting that fluctuations in performance were related to the successful storage of items. During working memory failures, participants oriented their attention to the correct side of the screen (lateralized P1) and maintained covert attention to the correct side during the delay period (lateralized alpha power suppression). Despite the preservation of attentional orienting, we found impairments consistent with an executive attention theory of individual differences in working memory capacity; fluctuations in executive control (indexed by pretrial frontal theta power) may be to blame for storage failures.

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Performance Dissociation during Verbal and Spatial Working Memory Tasks

Perceptual and Motor Skills ◽

10.2466/pms.105.1.243-250 ◽

2007 ◽

Vol 105 (1) ◽

pp. 243-250 ◽

Cited By ~ 12

Author(s):

Bonnie J. Nagel ◽

Arthur Ohannessian ◽

Kevin Cummins

Keyword(s):

Working Memory ◽

Spatial Working Memory ◽

Memory Load ◽

Memory Task ◽

Past Research ◽

Neural Substrates ◽

Individual Performance ◽

Task Design ◽

Brain Response ◽

Working Memory Load

Past research has inconsistently distinguished the neural substrates of various types of working memory. Task design and individual performance differences are known to alter patterns of brain response during working-memory tasks. These task and individual differences may have produced discrepancies in imaging findings. This study of 50 healthy adults ( Mage = 19.6 yr., SD = .8) examined performance during various parametric manipulations of a verbal and spatial n-back working-memory task. Performance systematically dissociated on the basis of working-memory load, working memory type, and stimulus difficulty, with participants having greater accuracy but slower response time during conditions requiring verbal versus spatial working memory. These findings hold implications for cognitive and neuroimaging studies of verbal and spatial working memory and highlight the importance of considering both task design and individual behavior.

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Maintaining fixation does not increase demands on working memory relative to free viewing

PeerJ ◽

10.7717/peerj.6839 ◽

2019 ◽

Vol 7 ◽

pp. e6839 ◽

Cited By ~ 6

Author(s):

Michael J. Armson ◽

Jennifer D. Ryan ◽

Brian Levine

Keyword(s):

Working Memory ◽

Eye Movements ◽

Response Times ◽

Memory Load ◽

Memory Performance ◽

Memory Task ◽

Oculomotor System ◽

Finger Tapping ◽

Long Term Memory ◽

Free Viewing

The comparison of memory performance during free and fixed viewing conditions has been used to demonstrate the involvement of eye movements in memory encoding and retrieval, with stronger effects at encoding than retrieval. Relative to conditions of free viewing, participants generally show reduced memory performance following sustained fixation, suggesting that unrestricted eye movements benefit memory. However, the cognitive basis of the memory reduction during fixed viewing is uncertain, with possible mechanisms including disruption of visual-mnemonic and/or imagery processes with sustained fixation, or greater working memory demands required for fixed relative to free viewing. To investigate one possible mechanism for this reduction, we had participants perform a working memory task—an auditory n-back task—during free and fixed viewing, as well as a repetitive finger tapping condition, included to isolate the effects of motor interference independent of the oculomotor system. As expected, finger tapping significantly interfered with n-back performance relative to free viewing, as indexed by a decrease in accuracy and increase in response times. By contrast, there was no evidence that fixed viewing interfered with n-back performance relative to free viewing. Our findings failed to support a hypothesis of increased working memory load during fixation. They are consistent with the notion that fixation disrupts long-term memory performance through interference with visual processes.

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Differential role of visuospatial working memory in the propensity toward uncertainty in patients with obsessive–compulsive disorder and in healthy subjects

Psychological Medicine ◽

10.1017/s0033291713002730 ◽

2013 ◽

Vol 44 (10) ◽

pp. 2113-2124 ◽

Cited By ~ 5

Author(s):

V. Lambrecq ◽

J.-Y. Rotge ◽

N. Jaafari ◽

B. Aouizerate ◽

N. Langbour ◽

...

Keyword(s):

Working Memory ◽

Obsessive Compulsive Disorder ◽

Healthy Subjects ◽

Memory Performance ◽

Continuous Performance ◽

Visuospatial Working Memory ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Temporal Direction

BackgroundObsessive–compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects.MethodBaseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups.ResultsBaseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects.ConclusionsThe present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients.

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Dissociation between MEG alpha modulation and performance accuracy on visual working memory task in obsessive compulsive disorder

Human Brain Mapping ◽

10.1002/hbm.20365 ◽

2007 ◽

Vol 28 (12) ◽

pp. 1401-1414 ◽

Cited By ~ 18

Author(s):

Kristina T. Ciesielski ◽

Matti S. Hämäläinen ◽

Daniel A. Geller ◽

Sabine Wilhelm ◽

Timothy E. Goldsmith ◽

...

Keyword(s):

Working Memory ◽

Obsessive Compulsive Disorder ◽

Visual Working Memory ◽

Memory Task ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Performance Accuracy ◽

And Performance

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A case-control association study of COMT rs4680 Polymorphism with Obsessive-Compulsive Disorder and Cognitive Functions: The role of sex

10.21203/rs.3.rs-34240/v1 ◽

2020 ◽

Author(s):

sajedeh hamidian ◽

Abbas Pourshahbaz ◽

atefeh moradkhani ◽

Behrooz Dolatshahi ◽

Esmaeil Shahsavand Ananloo ◽

...

Keyword(s):

Working Memory ◽

Obsessive Compulsive Disorder ◽

Cognitive Functions ◽

Memory Performance ◽

Total Sample ◽

Control Group ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Genetic Components

Abstract Background Previous studies have emphasized the role of genetic components in obsessive-compulsive disorder (OCD) and cognitive functions. One of the most controversial markers in this area is the COMT rs4680 polymorphism. In the present study, we aimed to investigate the effect of rs4680 on susceptibility to OCD and cognitive functions with respect to the moderating role of sex. Methods The subjects included 127 patients with OCD and 145 healthy controls. Genotyping was carried out by ARMS-PCR. The subjects underwent cognitive evaluations using the Wechsler Memory Scale-III. Data were analyzed using SPSS 22 and R package software. Results The results showed a significantly higher frequency of the AA genotype in the OCD group than in the healthy control group. Cognitive assessments showed weaker Immediate Memory and General Memory performance in the patients with OCD than in the control group. No significant association was found between rs4680 and memory dimensions in the total sample, whereas analysis by sex revealed a significant association of rs4680 with Working Memory only in females. Conclusions The results of this study confirm previous findings about the association of the AA genotype with OCD. These findings also corroborate previous assumptions about impaired episodic memory in patients with OCD. Moreover, the association of rs4680 with Working Memory only in females endorses the hypothesis of the sexual dimorphism of the effects of this COMT gene polymorphism.

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Positivity Effect and Working Memory Performance Remains Intact in Older Adults After Sleep Deprivation

10.31219/osf.io/nkaqr ◽

2018 ◽

Author(s):

Andreas Gerhardsson ◽

Håkan Fischer ◽

Mats Lekander ◽

Göran Kecklund ◽

John Axelsson ◽

...

Keyword(s):

Older Adults ◽

Working Memory ◽

Sleep Deprivation ◽

Memory Load ◽

Memory Performance ◽

Memory Task ◽

Reaction Times ◽

Positivity Effect ◽

As Stress ◽

Positive Stimuli

Background: Older adults perform better in tasks which include positive stimuli, referred to as the positivity effect. However, recent research suggests that the positivity effect could be attenuated when additional challenges such as stress or cognitive demands are introduced. Moreover, it is well established that older adults are relatively resilient to many of the adverse effects of sleep deprivation. Our aim was to investigate if the positivity effect in older adults is affected by one night of total sleep deprivation using an emotional working memory task. Methods: A healthy sample of 48 older adults (60-72 years) was either sleep deprived for one night (n = 24) or had a normal night’s sleep (n = 24). They performed an emotional working memory n-back (n = 1 & 3) task containing positive, negative and neutral pictures. Results: Performance in terms of accuracy and reaction times was best for positive stimuli and worst for negative stimuli. This positivity effect was not altered by sleep deprivation. Results also showed that, despite significantly increased sleepiness, there was no effect of sleep deprivation on working memory performance. A working memory load × valence interaction on the reaction times revealed that the beneficial effect of positive stimuli was only present in the 1-back condition. Conclusion: While the positivity effect and general working memory abilities in older adults are intact after one night of sleep deprivation, increased cognitive demand attenuates the positivity effect on working memory speed.

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Everyday memory functioning in obsessive– compulsive disorder

Journal of the International Neuropsychological Society ◽

10.1017/s1355617706060899 ◽

2006 ◽

Vol 12 (5) ◽

pp. 746-749 ◽

Cited By ~ 17

Author(s):

LENA JELINEK ◽

STEFFEN MORITZ ◽

DEIKE HEEREN ◽

DIETER NABER

Keyword(s):

Obsessive Compulsive Disorder ◽

Prospective Memory ◽

Memory Performance ◽

Memory Task ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Everyday Functioning ◽

Compulsive Disorder ◽

Wide Range ◽

Compulsive Checking

Memory performance in obsessive–compulsive disorder (OCD) is discussed as a pathogenetic risk factor for the emergence of OCD, particularly checking compulsions. At present, however, findings are mixed and little is known about memory performance in tasks relevant to everyday functioning in patients with OCD. For the present study, memory performance was assessed in 31 patients diagnosed with OCD and 33 healthy controls with the Rivermead Behavioural Memory Test (RBMT), which covers a wide range of verbal and nonverbal memory components as well as prospective memory. OCD patients performed comparably to healthy controls on the memory task for verbal, nonverbal, and prospective memory (p > .1). According to norm values, memory performance was unimpaired in most OCD patients. The present findings further challenge a broad account of the “memory deficit” hypothesis of OCD and compulsive checking, respectively (JINS, 2006, 12, 746–749.)

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