Effects of Memantine on Event-Related Potential, Oscillations, and Complexity in Individuals With and Without Family Histories of Alcoholism

Narayanan, B. V. Sathia; Stevens, Michael C.; Jiantonio, Rachel E.; Krystal, John H.; Pearlson, Godfrey D.

doi:10.15288/jsad.2013.74.245

Cited by 14 publications

(10 citation statements)

References 61 publications

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“…In line with this region-specificity, previous studies showed that large-scale impairments in brain network communication and organization is closely associated with local efficiency declines [ 44 ]. Besides, considering that the EEG-derived fractal dimension is typically inversely related to low frequency spectral power of brain activity and positively associated with power in higher frequency bands [ 12 , 45 ], fractal dimension dependence on age seems to mirror the slowing of brain activity that is shown by elderly individuals in central and parietal areas [ 4 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

et al. 2016

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Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi’s fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20–89 years) and 67 Alzheimer’s Disease (AD) patients (age: 50–88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called “free” copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.

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Section: Discussionmentioning

confidence: 99%

Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

et al. 2016

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“…This is consistent with rodent studies that showed a low dose of memantine to have minimal effect on the auditory evoked potential 36 and with human studies which showed comparable but slightly lower evoked potential under memantine treatment in healthy subjects. 37 Therefore, the memantine treatment did not affect excitability.…”

Section: Excitabilitymentioning

confidence: 95%

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

et al. 2018

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Recent studies suggest that neurodegenerative diseases could affect brain structure and function in disease‐specific network patterns; however, how spontaneous activity affects structural covariance network (SC) is not clear. We hypothesized that hyper‐excitability in Huntington disease (HD) disrupts the coordinated structural and functional connectivity, and treatment with memantine helps to reduce excitotoxicity and normalize the connectivity. MRI was conducted to measure somatosensory activation, resting‐state functional‐connectivity (rsFC), SC, amplitude of low frequency fluctuation (ALFF) and ALFF covariance (ALFFC) in the YAC128 mouse model of HD. We found somatosensory activation was unchanged but the subcortical ALFF was increased in HD mice, indicating subcortical but not cortical hyperactivity. The reduced sensorimotor rsFC but spared hippocampal and default mode networks in the HD mice was consistent with the more pronounced impairment in motor function compared with cognitive performance. The disease suppressed SC globally and reduced ALFFC in the basal ganglia network as well as its anti‐correlation with the default mode network. By comparing these connectivity measures, we found that the originally coupled rsFC‐SC relationship was impaired whereas SC‐ALFFC correlation was increased by HD, suggesting disease facilitated covariation of brain volume and activity amplitude but not neural synchrony. The comparison with mono‐synaptic axonal projection supports the hypothesis that rsFC, but not SC or ALFFC, is highly dependent on structural connectivity under healthy conditions. Treatment with memantine had a strong effect on normalizing the SC and reducing ALFF while slightly increasing other connectivity measures and restoring the rsFC‐SC coupling, which is consistent with its effect on alleviating hyper‐excitability and improving the coordinated neural growth. These results indicate that HD affects the cerebral structure–function relationship which could be partially reverted by NMDA antagonism. These connectivity measures provide unique insights into pathological and pharmaceutical effects in brain circuitry, and could be translatable biomarkers for evaluating drug effect and refining its efficacy.

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“…Because family history of alcoholism moderates the response to NMDA receptor antagonists (Narayanan et al, 2013; Jamadar et al, 2012: Petrakis et al, 2004), we evaluated the moderating effect of family history on the effects of memantine. Furthermore, we also explored the modulating influence of impulsivity based on emerging evidence that the NMDA system may be involved in impulsive behaviors, which may influence the decision to drink (Jentsch and Taylor, 1999; Winstanley et al 2010), and that NMDA antagonists may alter impulsive choice by increasing preference for small immediate rewards (Cottone et al 2013); while these were planned exploratory analyses we did not have a specific hypothesis about the directionality of the response.…”

Section: Introductionmentioning

confidence: 99%

N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers

Krishnan‐Sarin

O’Malley

Franco

et al. 2015

Alcoholism Clin & Exp Res

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Objective To determine the effects of the NMDA receptor antagonist, memantine (0, 20, 40 mg/day), upon alcohol drinking and craving in heavy drinkers with or without a family history (FH) of alcoholism, and to explore the modulatory influence of the presence of impulsivity on these outcomes. Methods Ninety-two, non-treatment-seeking, heavy drinkers received memantine or placebo for eight days. On the eighth day, they received a priming dose of ethanol followed by a three-hour period of alcohol access. Results Memantine at a dose of 20 mg reduced alcohol craving but did not influence alcohol drinking. No effects of FH were observed. In participants with higher baseline levels of impulsivity, 40 mg of memantine reduced alcohol craving but increased alcohol drinking and alcohol-induced stimulation. Conclusions NMDA receptor signaling may play divergent roles in mediating alcohol cue-induced craving and alcohol drinking in heavy drinkers. The potential efficacy of memantine as monotherapy for alcohol use disorders may be limited by its tendency to disinhibit drinking in some individuals.

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Effects of Memantine on Event-Related Potential, Oscillations, and Complexity in Individuals With and Without Family Histories of Alcoholism

Cited by 14 publications

References 61 publications

Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers

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