Hemostatic parameters in newborn--I. Effect of gestation and rate of intrauterine growth

The present study comprises of 208 term, 159 preterm and 18 post-term neonates born to mothers with no history of drug intake or any disease likely to effect coagulation of the newborn. PT, TT and KCCT were relatively prolonged and plasma fibrinogen reduced to varying degree in newborns (as compared to adults). There was further prolongation of TT and reduction in plasma fibrinogen levels amongst preterm newborns as compared to term babies; TT was more prolonged amongst post-term babies also. PT was significantly more prolonged till 30 weeks of gestation, after which a near plateau was formed. KCCT showed significant improvement after 33 weeks and a further trend to normalisation after 38 weeks of gestation. Serum FDP values showed too much of variation for any meaningful statistical analysis but generally FDPs were higher in preterm babies. Intrauterine growth rate had no significant effect on these parameters amongst preterms - similar values for SGA (small for gestational age), AGA (appropriate for gestational age) and LGA (large for gestational age). On the other hand, amongst term babies SGA neonates had significantly prolonged PT and low plasma fibrinogen as compared to AGA; LGA babies also showed more prolongation of TT as compared to AGA.     

GABAA receptor expression and white matter disruption in intrauterine growth restricted piglets

Intrauterine growth restriction (IUGR) is one of the most common causes of perinatal mortality and morbidity. White matter and neuronal injury are major pathophysiological features of the IUGR neonatal brain. GABA_A (γ-aminobutyric acid type A) receptors have been shown to play a role in oligodendrocyte differentiation and proliferation in the neonatal brain and may be a key factor in white matter injury and myelination in IUGR neonates. Whether there are impairments to the GABAergic system and neuronal cytoskeleton in IUGR brain has yet to be elucidated. This study aims to examine GABA_A receptor α₁ and α₃ subunit protein expression and distribution in parietal cortex and hippocampus of the IUGR piglet at four different ages (term = 115 d – days gestational age), 100 d, 104 d, birth (postnatal day 0–P0) and P7 and to examine neuronal and myelination patterns. Significant alterations to GABA_A receptor α₁ and α₃ protein expression levels were observed in the IUGR piglet brain of P7 IUGR piglets with significantly greater α₃ expression compared to α₁ expression in the hippocampus while there was virtually no difference between the two subunits in the parietal cortex. However a significantly lower α₁/α₃ ratio was evident in P7 IUGR cortex when compared with P7 NG cortex. Neuronal somatodendrites studied using MAP2 immunohistochemistry showed reduced and disrupted somatodendrites while MBP immunolabelling showed loss of axonal fibres from gestational day 104 d through to P7. These findings provide insights into the effects of IUGR on the development of the GABA system, altered developmental maturation of GABA_A receptor subunit expression in the IUGR brain may influence myelination and may partly explain the cognitive disabilities observed in IUGR. Understanding the mechanisms behind grey and white matter injury in the IUGR infant is essential to identifying targets for treatments to improve long-term outcomes for IUGR infants.     

Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats

Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)-1, -2 and -5, commonly referred to as dihydropyrimidinase-related proteins (DPYLs) – playing a role in axon guidance, invasive growth and cell migration – and compare it to the corresponding expression in control rats. Two-dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP-1, CRMP-2 and CRMP-5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress-induced programming.     

Auditory responsivity and intrauterine growth retardation in small for gestational age human newborns

Auditory responsivity in term small for gestational age (SGA) compared to term appropriate for gestational age (AGA) human newborns reflects functional differences which may be attributable to intrauterine growth retardation (IUGR). Between-group comparisons of percent of responses of averaged late component auditory evoked events (AEEs) to pure tone stimuli (500, 1000, 2000, 4000, 6000 and 8000 Hz) at 63 and 80 dB SPL revealed significantly greater AGA responsivity at 80 dB SPL. Conversely, the AEE mean latencies were significantly shorter for SGA infants at both intensity levels. Between-group responsivity differences suggest developmental retardation in term (38-42 weeks) SGA newborns, but the faster SGA latencies may reflect 'induced' acceleration in auditory neurophysiologic function.     

Effect of cholinergic stimulation in early Alzheimer's disease - functional imaging during a recognition memory task

Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to be involved in face recognition memory processing demonstrated greater fMRI activity in both the acute and chronic rivastigmine conditions compared to the placebo condition. In the same brain areas, differences in both fMRI activation at the map level and regional fMRI signal intensity measures between the placebo and chronic treatment conditions correlated negatively with the Mini- Mental State Examination score. In the chronic rivastigmine condition, patients with better preserved cognitive abilities demonstrated less enhanced prefrontal activity, whereas patients with poorer cognition showed greater prefrontal activity. These findings suggest that the prefrontal attention/working memory systems are already impaired in the early stages of AD and that the effect of cholinergic medication in the brain areas involved in recognition memory, i.e., increased or decreased fMRI activation patterns, depends on the severity of the disease. These findings also suggest the importance of early AChEI treatment in the course of AD, at the point when there is still some cognitive reserve available and the therapy has the highest potential efficacy.     

Maximum length sequence BAER at term in low-risk babies born at 30-32 week gestation

Thirty babies born at 30-32 week gestation without any major perinatal problems were studied at term with brainstem auditory evoked response (BAER) to detect any abnormalities in central auditory function in low-risk very preterm babies. The BAER was recorded and analyzed at 37-42 week postconceptional age using maximum length sequence technique (MLS). The data obtained were compared with those of 38 normal term controls. Wave I and III latencies in the very preterm babies did not show any significant differences from the controls at all repetition rates of click stimuli used (91-910 s(-1)). Wave V latency and I-V interpeak interval tended to increase at all click rates, and differed significantly from the controls at the highest rate 910 s(-1) (P < 0.05). Both III-V interval and III-V/I-III interval ratio increased significantly at all click rates, particularly at 455 and 910 s(-1) (P < 0.05-0.001). On the other hand, I-III interval tended to decrease. None of wave I, III and V amplitudes showed any abnormalities. Neither did V/I nor V/III amplitude ratios. These results suggest that development of the central auditory system is slightly delayed, which can be shown by MLS BAER at very high rate-stimulation, in low-risk very preterm babies.     

Dissociation of recognition memory and associative learning by a restricted lesion of the chick forebrain

Bilateral lesions of a restricted part of the chick forebrain (IMHV) have been shown to impair the acquisition and retention of imprinting preferences. The present study sought to determine the effects of such lesions on an operant conditioning task in which the reward was the presentation of one of two conspicuous objects, a stuffed jungle fowl or an illuminated red box. Twelve hours after hatching 28 domestic chicks received bilateral lesions of IMHV. Thirty-two chicks served as sham-operated controls. On the following day all birds underwent two sessions of operant training. After the second session the chicks were given a preference test. In this test the reinforcing object (box or fowl) and a novel object (fowl or box, whichever had not been seen before) were simultaneously presented. One test was given 2 hr and a second 24 hr after the termination of the operant task. The lesioned birds were not impaired on the operant task or on measures of general activity. In contrast, these birds failed to show a preference for the reinforcing object whereas the sham-operated controls strongly preferred this object. These results suggest that object recognition and associative learning can be dissociated in young chicks. This dissociation is reminiscent of certain human amnesias. The lesion did not impair an expected increase in preference for the stuffed fowl which developed in all birds between the 2-hr and 24-hr preference tests.     

A multimodal imaging study of recognition memory in very preterm born adults

Very preterm (<32 weeks of gestation) birth is associated with structural brain alterations and memory impairments throughout childhood and adolescence. Here, we used functional MRI (fMRI) to study the neuroanatomy of recognition memory in 49 very preterm‐born adults and 50 controls (mean age: 30 years) during completion of a task involving visual encoding and recognition of abstract pictures. T1‐weighted and diffusion‐weighted images were also collected. Bilateral hippocampal volumes were calculated and tractography of the fornix and cingulum was performed and assessed in terms of volume and hindrance modulated orientational anisotropy (HMOA). Online recognition memory task performance, assessed with A scores, was poorer in the very preterm compared with the control group. Analysis of fMRI data focused on differences in neural activity between the recognition and encoding trials. Very preterm born adults showed decreased activation in the right middle frontal gyrus and posterior cingulate cortex/precuneus and increased activation in the left inferior frontal gyrus and bilateral lateral occipital cortex (LOC) compared with controls. Hippocampi, fornix and cingulum volume was significantly smaller and fornix HMOA was lower in very preterm adults. Among all the structural and functional brain metrics that showed statistically significant group differences, LOC activation was the best predictor of online task performance (P = 0.020). In terms of association between brain function and structure, LOC activation was predicted by fornix HMOA in the preterm group only (P = 0.020). These results suggest that neuroanatomical alterations in very preterm born individuals may be underlying their poorer recognition memory performance. Hum Brain Mapp 38:644–655, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Psychomotor status--a female case in the 34th week of pregnancy

A case report is presented here. A 33-year-old female who had been medicated with Chinese medicine showed a typical psychomotor status which conformed to all items of Heintel's and Treiman and Delgado-Escueta's diagnostic criteria of psychomotor status. When she was 33 years old in the 34th week of pregnancy on April 11, 1981, she was found to be in an epileptic twilight state during which a delirious state and some automatisms were observed. As the incidence of automatisms gradually increased, she was finally seized with a typical psychomotor status in which automatisms were quite periodically and frequently repeated without complete recovery of consciousness between seizures. This status still continued despite an intravenous injection of diazepam and phenytoin and barely ceased with the medication of clonazepam and carbamazepine four days after the beginning of the status.     

The cephalization index: a screening device for brain maturity and vulnerability in normal and intrauterine growth retarded newborns

Predictive estimates of future neurological maldevelopment as a result of vascular induced intrauterine injury are based on the assumption that the body is more affected than the brain resulting in asymmetrical intrauterine growth retarded (IUGR) newborns. The higher the brain:body ratio, the more severe the IUGR process and the greater the risk for the brain to be affected. This prompted us to study in human newborns, a cephalization index based on the ratio of head circumference to body weight to express the degree of brain maturity and possible vulnerability in relation to gestational age. The newborn cephalization index was correlated with neurodevelopment. A trend could be delineated; in the later gestational age, the higher the cephalization index reflecting a greater degree of brain vulnerability, the more severe the clinical pathology; especially the likelihood of cerebral palsy and severe psychomotor retardation. The cephalization index may serve as an additional screening device for high risk intrauterine growth retarded newborns.     

Spontaneous resolution of atraumatic intrauterine ping-pong fractures in newborns delivered by cesarean section

Two cases of spontaneous intrauterine ping-pong fractures are reported in newborns delivered by cesarean section. Skull fractures occurred with no evidence of extrinsic trauma or cephalopelvic disproportion. Subsequent clinical follow-up at 6 and 12 months revealed normal skull reshaping and growth, with no associated neurological deficits. Spontaneous intrauterine ping-pong fractures in newborns delivered by cesarean section is a distinctly rare condition. These 2 cases demonstrate that, even without complicated spontaneous vaginal delivery or history of external trauma, congenital ping-pong fracture of the skull can occur. The existence of this clinical condition and its spontaneous resolution is important knowledge that can assist in the prepartum and postpartum management of children with this pathology.     

Serial measurement of memory and diffusion tensor imaging changes within the first week following uncomplicated mild traumatic brain injury

Patients (n = 8) with uncomplicated mild traumatic brain injury (mTBI) underwent serial assessments (4) with diffusion tensor imaging (DTI) and neuropsychological testing within the first 8 days post-injury. Using a multi-case study design, we examined changes in brain parenchyma (via DTI-derived fractional anisotropy [FA], apparent diffusion coefficient [ADC], axial diffusivity [AD] and radial diffusivity [RD] in the left cingulum bundle) and in memory performance (via Hopkins Verbal Learning Test-Revised). Qualitative inspection of the results indicated that memory performance was transiently affected in most participants over the course of the week, with performance most negatively impacted on the second assessment (days 3–4 or 97–144 h post-injury), and then returning to within normal limits by 8 days post-injury. Alternatively, FA and other DTI metrics showed a more complex pattern, with the trajectory of some participants changing more prominently than others. For example, FA transiently increased in some participants over the study period, but the pattern was heterogeneous. Memory performance appeared to mirror changes in FA in certain cases, supporting a pathophysiological basis to memory impairment following mTBI. However, the pattern and the degree of symmetry between FA and memory performance was complex and did not always correspond. Serial imaging over the semi-acute recovery period may be important in reconciling conflicting findings in mTBI utilizing memory and/or DTI. Serial use of imaging modalities including DTI may aid understanding of underlying pathophysiological changes in the semi-acute post-injury period. Should a consistent pattern emerge that allows identification of patients at-risk for acute and/or persistent symptoms, such knowledge could guide development of therapeutic targets in mTBI and in understanding the most effective administration time window for these agents.     

Influence of emotional expression on memory recognition bias: a functional magnetic resonance imaging study.

BACKGROUND: Most studies of the influence of emotion on memory performance have focused on accuracy. However, there is evidence that emotion can influence other aspects of memory, in particular response bias (overall tendency to classify items as new or old regardless of the accuracy of the response). Here we investigated the behavioral and neural-related modulation of response bias by emotion. METHODS: Nineteen healthy individuals performed a recognition memory task on faces with happy, sad, and neutral expressions while undergoing functional magnetic resonance imaging (fMRI). RESULTS: We observed a familiarity (tendency to say "old") and novelty (tendency to say "new") bias for sad and happy faces, respectively. Novelty response bias was associated with amygdala and prefrontal cortex activity, whereas familiarity bias correlated with superior temporal gyrus activation. CONCLUSIONS: These results show that emotional expressions can have an influence on memory beyond simple accuracy and that this effect is in part mediated by the amygdala, a region previously implicated in emotional perception and memory. Our findings might have important clinical relevance, because they could help explain some of the inconsistencies in the literature regarding emotional memory deficits in psychiatric populations.     

轻度认知障碍老年人情节记忆功能的磁共振成像研究

目的 运用核磁共振(MRI)技术探讨轻度认知障碍(MCI)老人与健康老人脑结构和功能的异同.方法 对14例MCI老人(MCI组)和15名健康老人(正常对照组)进行神经心理学检查,并应用基于体素的形态测量方法 ,测定两组的灰质体积,并用事件相关功能MRI技术,测定两组在执行情节记忆提取任务时相关脑区的功能变化.结果 (1)神经心理学:MCI组听觉词语记忆测试[(2.1±1.7)分]和画钟试验[(7.8±1.2)分]成绩差于正常对照组[分别为(9.2±1.3)分和(9.2±0.8)分;P＜0.05].(2)结构影像:MCI组的灰质体积小于正常对照组,主要位于情节记忆相关脑区(P＜0.001).(3)功能影像:MCI组与正常对照组任务正确率和反应时间的差别无统计学意义;MCI组激活降低的脑区主要是海马旁回,而增强激活的脑区主要是前额叶前侧、背外侧、右侧颞上回、右侧颞下回、枕叶皮层(P＜0.005).结论 MCI组内侧颞叶记忆系统结构萎缩、功能下降,在任务难度适当的情节记忆提取任务中,MCI组动员额外脑区激活,以代偿颞叶内侧记忆系统的损害.     

Oscillatory correlates of retrieval-induced forgetting in recognition memory

Retrieval practice on a subset of previously studied material enhances later memory for practiced material but can inhibit memory for related unpracticed material. The present study examines the effects of prior retrieval practice on evoked (ERPs) and induced (oscillatory power) measures of electrophysiological activity underlying recognition of practiced and unpracticed words. Compared to control material, recognition of unpracticed words was characterized by reduced amplitudes of the P2 ERP component and by reduced early (200-400 msec) oscillatory theta power. The reduction in P2 amplitude was associated with decreased evoked theta power but not with decreased theta phase locking (phase-locking index). Recognition of unpracticed material was further accompanied by a reduction in occipital gamma power (>250 msec). In contrast, the beneficial effects of retrieval practice on practiced words were reflected by larger parietal ERP positivity (>500 msec) and by a stronger decrease in oscillatory alpha power in a relatively late time window (>700 msec). The results suggest that the beneficial and detrimental effects of retrieval practice are mediated by different processes. In particular, they suggest that reduced theta (4-7 Hz) and gamma (60-90 Hz) power reflect the specific effects of inhibitory processes on the unpracticed material's memory representation.