Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Initial oak regeneration responses to experimental warming along microclimatic and macroclimatic gradients.

Quercus spp. are one of the most important tree genera in temperate deciduous forests in terms of biodiversity, economic and cultural perspectives. However, natural regeneration of oaks, depending on specific environmental conditions, is still not sufficiently understood. Oak regeneration dynamics are impacted by climate change, but these climate impacts will depend on local forest management and light and temperature conditions. Here, we studied germination, survival and seedling performance (i.e. aboveground biomass, height, root collar diameter and specific leaf area) of four oak species (Q. cerris, Q. ilex, Q. robur and Q. petraea). Acorns were sown across a wide latitudinal gradient, from Italy to Sweden, and across several microclimatic gradients located within and beyond the species' natural ranges. Microclimatic gradients were applied in terms of forest structure, distance to the forest edge and experimental warming. We found strong interactions between species and latitude, as well as between microclimate and latitude or species. The species thus reacted differently to local and regional changes in light and temperature ; in southern regions the temperate Q. robur and Q. petraea performed best in plots with a complex structure, whereas the Mediterranean Q. ilex and Q. cerris performed better in simply structured forests with a reduced microclimatic buffering capacity. The experimental warming treatment only enhanced height and aboveground biomass of Mediterranean species. Our results show that local microclimatic gradients play a key role in the initial stages of oak regeneration; however, one needs to consider the species-specific responses to forest structure and the macroclimatic context.

Prosthetic gait of unilateral lower-limb amputees with current and novel prostheses: A pilot study.

BACKGROUND: Novel lower-limb prostheses aim to improve the quality of locomotion of individuals with an amputation. This study evaluates the biomechanics of a novel bionic foot during walking. METHODS: Able-bodied individuals (n = 7) and individuals with a transfemoral (n = 6) or transtibial amputation (n = 6) were included. Able-bodied individuals conducted one experimental trial, whereas individuals with transtibial and transfemoral amputations conducted a familiarization (with current prosthesis) and two experimental trials using a passive and bionic prosthesis. Each trial consisted of 3 bouts of 2 min of treadmill walking at different speeds. Biomechanical data were gathered using a force platform and motion capture system and analysed using Statistical Parametric Mapping and (non)-parametric tests. FINDINGS: Conventional prosthetic feet alter gait patterns and induce locomotion difficulties. While walking at a normal speed with the passive prosthesis, transtibial amputees display reduced maximum heel forces, increased ankle and trunk angular velocities at midstance, and increased knee angle during stance and swing phases on their effected side (P ≤ 0.026). Improved lower-limb kinematics was demonstrated during slow and normal speed walking with the bionic prosthesis; however, dynamic trunk stability was negatively impacted during this condition. The bionic prosthesis did not benefit transfemoral amputees at any walking speed. INTERPRETATION: Transtibial amputees can better approximate typical movement patterns at slow and normal walking speeds using the novel bionic prosthesis; however the same benefit was not observed in transfemoral amputees.

Acute cocoa flavanols intake improves cerebral hemodynamics while maintaining brain activity and cognitive performance in moderate hypoxia.

INTRODUCTION: Acute cocoa flavanols (CF) intake has been suggested to modulate cognitive function and neurovascular coupling (NVC). Whether increased NVC is solely driven by improved vascular responsiveness or also by neuronal activity remains unknown. This study investigated the effects of acute CF intake on cognitive performance, NVC, and neuronal activity in healthy subjects in normoxia and hypoxia (4000 m simulated altitude; 12.7% O2). METHODS: Twenty healthy subjects (age 23.2 ± 4.3 years) performed four trials. Participants performed a Stroop task and "cognition" battery 2 h after acute CF (530 mg CF, 100 mg epicatechin) or placebo intake, and 30 min after initial exposure to hypoxia or normoxia. Electroencephalogram and functional near-infrared spectroscopy were used to analyze hemodynamic changes and neuronal activity. RESULTS: CF enhanced NVC in the right prefrontal cortex during several tasks (risk decision making, visual tracking, complex scanning, spatial orientation), while neuronal activity was not affected. CF improved abstract thinking in normoxia, but not in hypoxia and did not improve other cognitive performances. Hypoxia decreased accuracy on the Stroop task, but performance on other cognitive tasks was preserved. NVC and neuronal activity during cognitive tasks were similar in hypoxia vs. normoxia, with the exception of increased ß activity in the primary motor cortex during abstract thinking. CONCLUSIONS: Acute CF intake improved NVC, but did not affect neuronal activity and cognitive performance in both normoxia and hypoxia. Most cognitive functions, as well as NVC and neuronal activity, did not decline by acute exposure to moderate hypoxia in healthy subjects.

Cerebrocortical activity during self-paced exercise in temperate, hot and hypoxic conditions.

AIM: Heat stress and hypoxia independently influence cerebrocortical activity and impair prolonged exercise performance. This study examined the relationship between electroencephalography (EEG) activity and self-paced exercise performance in control (CON, 18 °C, 40% RH), hot (HOT, 35 °C, 60% RH) and hypoxic (HYP, 18 °C, 40% RH FiO2 : 0.145) conditions. METHODS: Eleven well-trained cyclists completed a 750 kJ cycling time trial in each condition on separate days in a counterbalanced order. EEG activity was recorded with α- and ß-activity evaluated in the frontal (F3 and F4) and central (C3 and C4) areas. Standardized low-resolution brain electromagnetic tomography (sLORETA) was also utilized to localize changes in cerebrocortical activity. RESULTS: Both α- and ß-activity decreased in the frontal and central areas during exercise in HOT relative to CON (P < 0.05). α-activity was also lower in HYP compared with CON (P < 0.05), whereas ß-activity remained similar. ß-activity was higher in HYP than in HOT (P < 0.05). sLORETA revealed that α- and ß-activity increased at the onset of exercise in the primary somatosensory and motor cortices in CON and HYP, while only ß-activity increased in HOT. A decrease in α- and ß-activity occurred thereafter in all conditions, with α-activity being lower in the somatosensory and somatosensory association cortices in HOT relative to CON. CONCLUSION: High-intensity prolonged self-paced exercise induces cerebrocortical activity alterations in areas of the brain associated with the ability to inhibit conflicting attentional processing under hot and hypoxic conditions, along with the capacity to sustain mental readiness and arousal under heat stress.

Electro-physiological changes in the brain induced by caffeine or glucose nasal spray.

OBJECTIVE: A direct link between the mouth cavity and the brain for glucose (GLUC) and caffeine (CAF) has been established. The aim of this study is to determine whether a direct link for both substrates also exist between the nasal cavity and the brain. METHODS: Ten healthy male subjects (age 22 ± 1 years) performed three experimental trials, separated by at least 2 days. Each trial included a 20-s nasal spray (NAS) period in which solutions placebo (PLAC), GLUC, or CAF were provided in a double-blind, randomized order. During each trial, four cognitive Stroop tasks were performed: two familiarization trials and one pre- and one post-NAS trial. Reaction times and accuracy for different stimuli (neutral, NEUTR; congruent, CON; incongruent INCON) were determined. Electroencephalography was continuously measured throughout the trials. During the Stroop tasks pre- and post-NAS, the P300 was assessed and during NAS, source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA). RESULTS AND DISCUSSION: NAS activated the anterior cingulate cortex (ACC). CAF-NAS also increased θ and ß activity in frontal cortices. Furthermore, GLUC-NAS increased the ß activity within the insula. GLUC-NAS also increased the P300 amplitude with INCON (P = 0.046) and reduced P300 amplitude at F3-F4 and P300 latency at CP1-CP2-Cz with NEUTR (P = 0.001 and P = 0.016, respectively). The existence of nasal bitter and sweet taste receptors possibly induce these brain responses. CONCLUSION: Greater cognitive efficiency was observed with GLUC-NAS. CAF-NAS activated cingulate, insular, and sensorymotor cortices, whereas GLUC-NAS activated sensory, cingulate, and insular cortices. However, no effect on the Stroop task was found.

Neurophysiological effects of exercise in the heat.

Fatigue during prolonged exercise is a multifactorial phenomenon. The complex interplay between factors originating from both the periphery and the brain will determine the onset of fatigue. In recent years, electrophysiological and imaging tools have been fine-tuned, allowing for an improved understanding of what happens in the brain. In the first part of the review, we present literature that studied the changes in electrocortical activity during and after exercise in normal and high ambient temperature. In general, exercise in a thermo-neutral environment or at light to moderate intensity increases the activity in the ß frequency range, while exercising at high intensity or in the heat reduces ß activity. In the second part, we review literature that manipulated brain neurotransmission, through either pharmacological or nutritional means, during exercise in the heat. The dominant outcomes were that manipulations changing brain dopamine concentration have the potential to delay fatigue, while the manipulation of serotonin had no effect and noradrenaline reuptake inhibition was detrimental for performance in the heat. Research on the effects of neurotransmitter manipulations on brain activity during or after exercise is scarce. The combination of brain imaging techniques with electrophysiological measures presents one of the major future challenges in exercise physiology/neurophysiology.

Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.

An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine.

Effects of caffeine and maltodextrin mouth rinsing on P300, brain imaging, and cognitive performance.

Caffeine (CAF) and maltodextrin (MALT) mouth rinses (MR) improve exercise performance. The current experiment aims to determine the effect of CAF and MALT MR on cognitive performance and brain activity. Ten healthy male subjects (age 27 ± 3 yr) completed three experimental trials. Each trial included four Stroop tasks: two familiarization tasks, and one task before and one task after an MR period. The reaction time (in milliseconds) and accuracy (percent) of simple, congruent, and incongruent stimuli were assessed. Electroencephalography was applied throughout the experiment to record brain activity. The amplitudes and latencies of the P300 were determined during the Stroop tasks before and after the MR period. Subjects received MR with CAF (0.3 g/25 ml), MALT (1.6 g/25 ml), or placebo (PLAC) in a randomized, double-blind, crossover design. During MR, the brain imaging technique standardized low-resolution brain electromagnetic tomography was applied. Magnitude-based inferences showed that CAF MR is likely trivial (63.5%) and likely beneficial (36.4%) compared with PLAC MR, and compared with MALT MR likely beneficial to reaction time on incongruent stimuli (61.6%). Additionally, both the orbitofrontal and dorsolateral prefrontal cortex were activated only during CAF MR, potentially explaining the likely beneficial effect on reaction times. MALT MR increased brain activity only within the orbitofrontal cortex. However, this brain activation did not alter the reaction time. Furthermore, no significant differences in the accuracy of stimuli responses were observed between conditions. In conclusion, only CAF MR exerted a likely beneficial effect on reaction time due to the subsequent activation of both the orbitofrontal and dorsolateral prefrontal cortexes.

Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.

A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP). Only three other kindreds have been described world-wide with this mutation and only limited phenotypic information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.

[Psychotic realization of the "myth of return": a case study involving delusional misidentification]. / Psychotyczna realizacja "mitu powrotu do ojczyzny": studium przypadku urojeniowego, blednego rozpoznawania osób.

Case study of a Polish man who for many years was treated in hospitals in Great Britain, whose psychopathology forms at the same time a psychotic return to the fatherland.

Selecting an antidepressant for use in a patient with epilepsy. Safety considerations.

Depression is a common and disabling condition and is especially disabling for patients who also have epilepsy. Antidepressants, particularly the tricyclic antidepressants are well known to be associated with seizure activity, but this is a very neglected area of research. Most of the data on the proconvulsive effects of antidepressants come from either work in animal models or from research into the effects of antidepressants in overdose. Both of these situations may tell us little about the behaviour of antidepressants in patients with epilepsy. The selective serotonin [5-hydroxytryptamine; 5-HT] reuptake inhibitors have a low seizure propensity, are well tolerated in overdose and have a favourable adverse effect profile, making them suitable as first line treatments for depression in patients with epilepsy. Other antidepressants, e.g. trazodone, moclobemide, mirtazepine, are also likely to have minimal proconvulsive effects, but adverse effects, interactions with other drugs, especially anticonvulsants, or the lack of clinical data may make their use less attractive. Although this review has focused on these clinically important issues it is clear that considerably more research needs to be undertaken on the seizure propensity and clinical efficacy of antidepressants in patients with epilepsy.

Reduced autonomic responses to faces in Capgras delusion.

People experiencing the Capgras delusion claim that others, usually those quite close emotionally, have been replaced by near-identical impostors. Ellis & Young suggested in 1990 that the Capgras delusion results from damage to a neurological system involved in orienting responses to seen faces based on their personal significance. This hypothesis predicts that people suffering the Capgras delusion will be hyporesponsive to familiar faces. We tested this prediction in five people with Capgras delusion. Comparison data were obtained from five middle-aged members of the general public, and a psychiatric control group of five patients taking similar anti-psychotic medication. Capgras delusion patients did not reveal autonomic discrimination between familiar and unfamiliar faces, but orienting responses to auditory tones were normal in magnitude and rate of initial habituation, showing that the hyporesponsiveness is circumscribed.

Delusional misidentification of inanimate objects: a literature review and neuropsychological analysis of cognitive deficits in two cases.

Following a brief review of the literature on Delusions of Inanimate Doubles (DID), compared with other similar delusions, two cases are presented. Each completed a battery of tests designed to explore their cognitive abilities. In both cases, familiar and unfamiliar face-processing skills remained intact and word memory was unaffected. Their abilities to identify famous buildings and recognise unfamiliar houses were impaired. We propose that an extension of Ellis and Young's (1990) account of Capgras delusion can explain the cognitive impairments in case of DID. A comparison of the hypotheses of Staton et el. (1982), Ellis and Young (1990), and Van Lancker (1991) is also made. The last two have obvious similarities and seem to provide the best general approach. Finally, we caution the need to consider how a mood of suspiciousness may be needed to distort attribution processes that sustain delusional thinking.

Refined genetic and physical mapping of BPES type II.

BPES is a genetic disorder including blepharophimosis, ptosis of the eyelids, epicanthus inversus and telecanthus. Type I is associated with female infertility, whereas type II presents without other symptoms. Both types I and II occur sporadically or are inherited as an autosomal dominant trait. We present a molecular genetic and cytogenetic study in a large four-generation Belgian family with BPES type II. Karyotype analysis on high-resolution banded chromosomes yielded normal results. Fluorescence in situ hybridization (FISH) with cosmid probes spanning 3q22-q24 revealed normal hybridization patterns. Sixteen polymorphic CA repeats encompassing region 3q13-q25 were analysed. Linkage analysis in this large four-generation family provides conclusive evidence for the presence of a BPES gene in this region. Two-point lod scores greater than 3.0 between the disease and the following markers were seen: D3S1589 (4.67), D3S1292 (3.52), D3S1290 (3.59) and D3S1549 (3.65). By FISH, D3S1290, D3S1292 and D3S1549 were assigned to chromosome 3q23 using YACs positive for these markers.

Delusional misidentification: a plea for an agreed terminology and classification.

Since the publication of the seminal paper by Capgras and Reboul-Lachaux more than a dozen varieties of delusional misidentification have been reported in the psychiatric and neurological literature. Although subjected to increasingly sophisticated scrutiny, continuing confusion and disagreement over terminology, delineation of phenomenology and nosology hamper the systematic study of these phenomena.

Psychodynamic approaches to the Capgras delusion: a critical historical review.

Over the last eight decades a plethora of psychodynamic explanations have been invoked to account for the Capgras delusion. While often ill-founded and convoluted, these formulations have, until recently, dominated many theoretical approaches to the phenomenon. Generally post hoc and teleological in nature, they postulate motives that are not introspectable and defence mechanisms that cannot be observed, measured or refuted. While psychosocial factors can and often do play a part in the development, content and course of the Capgras delusion in individual patients it remains to be proven that such factors are necessary and sufficient to account for delusional misidentification in general and the Capgras delusion in particular.

Responses to facial and non-facial stimuli presented tachistoscopically in either or both visual fields by patients with the Capgras delusion and paranoid schizophrenics.

An experiment was carried out designed primarily to test A B Joseph's suggestion that patients with Capgras delusion may have problems integrating information between the two cortical hemispheres; and at the same time it was meant to examine J Cutting's ideas linking schizophrenia in general, and the Capgras delusion in particular, to right hemisphere dysfunction. Three patients with the Capgras delusion and three matched controls diagnosed as paranoid schizophrenics were briefly presented pairs of line-drawn object and photographs of faces randomly in the left visual field, the right visual field or bilaterally. The results with objects revealed no particular pattern of performance for either group; but, when faces were shown, the controls revealed the usual left visual field/right hemisphere advantage while for the Capgras group this was reversed. The results are not consistent with a simple prediction from Joseph's hypothesis but they are in accord with Cutting's theory-though they also pose some problems for it, which are discussed.

Cotard delusion after brain injury.

A right-handed young man with contusions affecting temporo-parietal areas of the right cerebral hemisphere and some bilateral frontal lobe damage became convinced that he was dead (the Cotard delusion), and experienced difficulties in recognizing familiar faces, buildings and places, as well as feelings of derealization. Neuropsychological investigation while these symptoms were resolving revealed impairment on face processing tests. We suggest that these impairments contributed to his Cotard delusion by heightening feelings of unreality, and that the underlying pathophysiology and neuropsychology of the Cotard delusion may be related to other problems involving delusional misidentification.