BackgroundPrenatal and early postnatal choline supplementation reduces cognitive and behavioral deficits in animal models of Fetal Alcohol Spectrum Disorder. In a previously published 9-month clinical trial of choline supplementation in children with FASD, we reported that postnatal choline was associated with improved performance on a hippocampal-dependent recognition memory task. The current paper describes the neurophysiological correlates of that memory performance for trial completers.MethodsChildren with FASD who were enrolled in a clinical trial of choline supplementation were followed for 9 months. Delayed (...) recall on a 9-step elicited imitation task served as the behavioral measure of recognition memory. Neurophysiological correlates of memory were assessed via event-related potentials.ResultsDelayed recall on EI was correlated with two ERP components commonly associated with recognition memory in young children: middle latency negative component and positive slow wave. No significant ERP differences were observed between the choline and placebo groups at the conclusion of the trial.ConclusionAlthough the small sample size limits the ability to draw clear conclusions about the treatment effect of choline on ERP, the results suggest a relationship between memory performance and underlying neurophysiological status in FASD. This trial was registered.1. (shrink)

Disturbances of consciousness, including fluctuations in attention and awareness, are a common and clinically important symptom in dementia with Lewy bodies. In the present study we investigate potential mechanisms of such disturbances of consciousness in a clinicopathological study evaluating specific components of the cholinergic system. [3H]Epibatidine binding to the high-affinity nicotinic receptor in the temporal cortex differentiated DLB cases with and without DOC, being 62–66% higher in those with DOC. The were no differences between DLB patients with or without DOC (...) in 125I-labeled α-bungaratoxin binding to the low-affinity nicotinic receptor, [3H]pirenzepine binding to the muscarinic M1 receptor, or in choline acetyltransferase activity. These findings provide support for the hypothesis that cholinergic activity is an important neural correlate if consciousness and suggest a mechanism of DOC in DLB involving alterations in the nicotinic receptor, composed of predominantly α4 and β2 subunits. (shrink)

Recent studies have provided evidence of associations between neurochemistry and reading (dis)ability (Pugh et al., 2014). Based on a long history of studies indicating that fluent reading entails the automatic convergence of the written and spoken forms of language and our recently proposed Neural Noise Hypothesis (Hancock et al., 2017), we hypothesized that individual differences in cross-modal integration would mediate, at least partially, the relationship between neurochemical concentrations and reading. Cross-modal integration was measured in 231 children using a two-alternative forced (...) choice cross-modal matching task with three language conditions (letters, words, and pseudowords) and two levels of difficulty within each language condition. Neurometabolite concentrations of Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl-aspartate (NAA) were then measured in a subset of this sample (n = 70) with Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model revealed that the effect of cross-modal word matching mediated the relationship between increased Glu (which has been proposed to be an index of neural noise) and poorer reading ability. In addition, the effect of cross-modal word matching fully mediated a relationship between increased Cho and poorer reading ability. Multilevel mixed effects models confirmed that lower Cho predicted faster cross-modal matching reaction time, specifically in the hard word condition. These Cho... (shrink)

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (...) (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity. (shrink)

Carbon monoxide intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. 1 H magnetic resonance spectroscopy may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO (...) poisoning assessed by gray and white matter MRS, magnetic resonance imaging and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1–6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline and decreased N -acetyl aspartate ratios to creatine, predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by 1 H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed. (shrink)

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease. A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex, a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD, as well as PD participants (...) with either normal cognition, mild cognitive impairment, or dementia. Ratios to Creatine resonance were obtained for glutamate, glutamine and glutamate combined, N-acetylaspartate, myoinositol, and total choline, and correlated with cognitive scores across multiple domains administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups. (shrink)