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Impaired Grid-Like Representations at Theta Frequency in Schizophrenia
- Laura Convertino, Daniel Bush, Fanfan Zheng, Rick Adams, Neil Burgess
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- Journal:
- BJPsych Open / Volume 8 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 20 June 2022, p. S48
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Aims
Schizophrenia is a chronic brain disorder characterised by distortion of thoughts and perception. Several studies have shown a key role of the hippocampal formation in the pathophysiology of schizophrenia. Patients show impaired theta coherence between medial temporal lobe and medial prefrontal cortex (mPFC), and impairment of knowledge structuring and inferential processes. Both the hippocampal formation and mPFC contain hexadirectional modulation of activity, indicative of grid cell populations. Grid cells play an important role in mapping the environment and are believed to represent the transition structure between task states. With other cell populations in the hippocampal formation, they play a fundamental role in inference, episodic memory, and spatial navigation. Here, we investigate whether schizophrenia is associated with disrupted grid firing patterns.
MethodsTo test this hypothesis, we asked 18 participants with diagnoses of schizophrenia and 26 controls (matched for age, sex and IQ) to perform a spatial memory task in magnetoencephalography (MEG), while navigating a virtual reality environment. We first analysed theta (4–10 Hz) power during movement onset compared to stationary periods. We then source-localised the signal and looked for the hexadirectional modulation of theta band oscillatory activity by heading direction during movement onset. We also controlled for other symmetries in theta frequencies (four, five, and eight fold) and hexadirectional modulation in other frequencies. The same participants performed an inference task outside MEG, which we used for correlation analysis.
ResultsThe peak of theta power during movement onset was stronger in controls compared to patients (p < 0.05). In the control group, we found hexadirectional modulation of theta power by movement direction in the right entorhinal cortex (p < 0.005). This effect was absent in patients with a significant difference between groups (p < 0.05), suggesting that their entorhinal grid firing patterns may be disrupted. No other symmetry modulated theta power significantly in controls or patients, and hexadirectional modulation during movement onset was found only in theta frequencies in controls. Performance in the inference task was significantly impaired in schizophrenic patients, and spatial memory performance in both controls and patients was positively correlated with their performance in the inference task.
ConclusionThese results are consistent with the hypothesis that impairments in knowledge structuring and inference associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex. Although further work is needed to better understand the role of grid cells in health and disease, this work provides new insights into dysfunction of the hippocampal formation in schizophrenia.
Persistent depressive symptoms and cognitive decline in older adults
- Fanfan Zheng, Baoliang Zhong, Xiaoyu Song, Wuxiang Xie
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- Journal:
- The British Journal of Psychiatry / Volume 213 / Issue 5 / November 2018
- Published online by Cambridge University Press:
- 22 August 2018, pp. 638-644
- Print publication:
- November 2018
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Background
Little is known about the effect of persistent depressive symptoms on the trajectory of cognitive decline.
AimsWe aimed to investigate the longitudinal association between the duration of depressive symptoms and subsequent cognitive decline over a 10-year follow-up period.
MethodThe English Longitudinal Study of Ageing cohort is a prospective and nationally representative cohort of men and women living in England aged ≥50 years. We examined 7610 participants with two assessments of depressive symptoms at wave 1 (2002–2003) and wave 2 (2004–2005), cognitive data at wave 2 and at least one reassessment of cognitive function (wave 3 to wave 7, 2006–2007 to 2014–2015).
ResultsThe mean age of the 7610 participants was 65.2 ± 10.1 years, and 57.0% were women. Of these, 1157 (15.2%) participants had episodic depressive symptoms and 525 participants (6.9%) had persistent depressive symptoms. Compared with participants without depressive symptoms at wave 1 and wave 2, the multivariable-adjusted rates of global cognitive decline associated with episodic depressive symptoms and persistent depressive symptoms were faster by –0.065 points/year (95% CI –0.129 to –0.000) and –0.141 points/year (95% CI –0.236 to –0.046), respectively (P for trend < 0.001). Similarly, memory, executive and orientation function also declined faster with increasing duration of depressive symptoms (all P for trend < 0.05).
ConclusionsOur results demonstrated that depressive symptoms were significantly associated with subsequent cognitive decline over a 10-year follow-up period. Cumulative exposure of long-term depressive symptoms in elderly individuals could predict accelerated subsequent cognitive decline in a dose-response pattern.
Declaration of interestNone.
High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing
- Fanfan Zheng, Wuxiang Xie
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- Journal:
- Psychological Medicine / Volume 48 / Issue 8 / June 2018
- Published online by Cambridge University Press:
- 07 November 2017, pp. 1381-1389
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Background
High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent.
MethodWe employed data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3–7.
ResultsA total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9–4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [−0.048 points/year, 95% confidence interval (CI) −0.072 to −0.023], memory scores (−0.022 points/year, 95% CI −0.031 to −0.013), and executive function scores (−0.025 points/year, 95% CI −0.043 to −0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by −0.043 points/year (95% CI −0.116 to 0.029), −0.090 points/year (95% CI −0.166 to −0.015), −0.145 (95% CI −0.221 to −0.069), respectively (p for trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP.
ConclusionsA significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline.