Characterizing Spatial Information Loss for Wastewater Surveillance Using crAssphage: Effect of Decay, Temperature, and Population Mobility.

Populations contribute information about their health status to wastewater. Characterizing how that information degrades in transit to wastewater sampling locations (e.g., wastewater treatment plants and pumping stations) is critical to interpret wastewater responses. In this work, we statistically estimate the loss of information about fecal contributions to wastewater from spatially distributed populations at the census block group resolution. This was accomplished with a hydrologically and hydraulically influenced spatial statistical approach applied to crAssphage (Carjivirus communis) load measured from the influent of four wastewater treatment plants in Hamilton County, Ohio. We find that we would expect to observe a 90% loss of information about fecal contributions from a given census block group over a travel time of 10.3 h. This work demonstrates that a challenge to interpreting wastewater responses (e.g., during wastewater surveillance) is distinguishing between a distal but large cluster of contributions and a near but small contribution. This work demonstrates new modeling approaches to improve measurement interpretation depending on sewer network and wastewater characteristics (e.g., geospatial layout, temperature variability, population distribution, and mobility). This modeling can be integrated into standard wastewater surveillance methods and help to optimize sewer sampling locations to ensure that different populations (e.g., vulnerable and susceptible) are appropriately represented.

Persistent neuronal firing in the medial temporal lobe supports performance and workload of visual working memory in humans.

The involvement of the medial temporal lobe (MTL) in working memory is controversially discussed. Recent findings suggest that persistent neural firing in the hippocampus during maintenance in verbal working memory is associated with workload. Here, we recorded single neuron firing in 13 epilepsy patients (7 male) while they performed a visual working memory task. The number of colored squares in the stimulus set determined the workload of the trial. Performance was almost perfect for low workload (1 and 2 squares) and dropped at high workload (4 and 6 squares), suggesting that high workload exceeded working memory capacity. We identified maintenance neurons in MTL neurons that showed persistent firing during the maintenance period. More maintenance neurons were found in the hippocampus for trials with correct compared to incorrect performance. Maintenance neurons increased and decreased firing in the hippocampus and increased firing in the entorhinal cortex for high compared to low workload. Population firing predicted workload particularly during the maintenance period. Prediction accuracy of workload based on single-trial activity during maintenance was strongest for neurons in the entorhinal cortex and hippocampus. The data suggest that persistent neural firing in the MTL reflects a domain-general process of maintenance supporting performance and workload of multiple items in working memory below and beyond working memory capacity. Persistent neural firing during maintenance in the entorhinal cortex may be associated with its preference to process visual-spatial arrays.

Persistent hippocampal neural firing and hippocampal-cortical coupling predict verbal working memory load.

The maintenance of items in working memory relies on persistent neural activity in a widespread network of brain areas. To investigate the influence of load on working memory, we asked human subjects to maintain sets of letters in memory while we recorded single neurons and intracranial encephalography (EEG) in the medial temporal lobe and scalp EEG. Along the periods of a trial, hippocampal neural firing differentiated between success and error trials during stimulus encoding, predicted workload during memory maintenance, and predicted the subjects' behavior during retrieval. During maintenance, neuronal firing was synchronized with intracranial hippocampal EEG. On the network level, synchronization between hippocampal and scalp EEG in the theta-alpha frequency range showed workload dependent oscillatory coupling between hippocampus and cortex. Thus, we found that persistent neural activity in the hippocampus participated in working memory processing that is specific to memory maintenance, load sensitive and synchronized to the cortex.

Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. METHODS: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. RESULTS: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. CONCLUSIONS: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.

Children and Adolescents Show Altered Visual Working Memory Related Brain Activity More Than One Decade After Arterial Switch Operation for D-Transposition of the Great Arteries.

This pilot study investigated neural correlates of visual working memory using functional magnetic resonance imaging (fMRI) in seven patients more than one decade after neonatal arterial switch operation for surgical correction of d-transposition of the great arteries (d-TGA, aged 10-18 years, 1 female). Compared with age and sex matched healthy controls patients showed similar visual working memory performance and a smaller increase in brain activity in the posterior parietal cortex with higher visual working memory load. These findings suggest that patients exhibit altered neural activity within a network that is known to support visuospatial memory and cognition.

Inter-hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces.

This study investigated how changes of functional connectivity over time accompany consolidation of face memories. Based on previous research, it was hypothesized that connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting-state functional connectivity was examined shortly before, shortly after and about 40 min after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting-state session. Results reveal that memory performance-related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. As the increase in connectivity in the two final resting-state sessions was associated with memory performance, the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following 40 min. It is discussed that the delayed increase in inter-hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes.

Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.

Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.

Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.

Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion.

This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

Occipital cortical thickness in very low birth weight born adolescents predicts altered neural specialization of visual semantic category related neural networks.

Very low birth weight (VLBW) premature born infants have a high risk to develop visual perceptual and learning deficits as well as widespread functional and structural brain abnormalities during infancy and childhood. Whether and how prematurity alters neural specialization within visual neural networks is still unknown. We used functional and structural brain imaging to examine the visual semantic system of VLBW born (<1250 g, gestational age 25-32 weeks) adolescents (13-15 years, n = 11, 3 males) and matched term born control participants (13-15 years, n = 11, 3 males). Neurocognitive assessment revealed no group differences except for lower scores on an adaptive visuomotor integration test. All adolescents were scanned while viewing pictures of animals and tools and scrambled versions of these pictures. Both groups demonstrated animal and tool category related neural networks. Term born adolescents showed tool category related neural activity, i.e. tool pictures elicited more activity than animal pictures, in temporal and parietal brain areas. Animal category related activity was found in the occipital, temporal and frontal cortex. VLBW born adolescents showed reduced tool category related activity in the dorsal visual stream compared with controls, specifically the left anterior intraparietal sulcus, and enhanced animal category related activity in the left middle occipital gyrus and right lingual gyrus. Lower birth weight of VLBW adolescents correlated with larger thickness of the pericalcarine gyrus in the occipital cortex and smaller surface area of the superior temporal gyrus in the lateral temporal cortex. Moreover, larger thickness of the pericalcarine gyrus and smaller surface area of the superior temporal gyrus correlated with reduced tool category related activity in the parietal cortex. Together, our data suggest that very low birth weight predicts alterations of higher order visual semantic networks, particularly in the dorsal stream. The differences in neural specialization may be associated with aberrant cortical development of areas in the visual system that develop early in childhood.

Hippocampal and posterior parietal contributions to developmental increases in visual short-term memory capacity.

Developmental increases in visual short-term memory (VSTM) capacity have been associated with changes in attention processing limitations and changes in neural activity within neural networks including the posterior parietal cortex (PPC). A growing body of evidence suggests that the hippocampus plays a role in VSTM, but it is unknown whether the hippocampus contributes to the capacity increase across development. We investigated the functional development of the hippocampus and PPC in 57 children, adolescents and adults (age 8-27 years) who performed a visuo-spatial change detection task. A negative relationship between age and VSTM related activity was found in the right posterior hippocampus that was paralleled by a positive age-activity relationship in the right PPC. In the posterior hippocampus, VSTM related activity predicted individual capacity in children, whereas neural activity in the right anterior hippocampus predicted individual capacity in adults. The findings provide first evidence that VSTM development is supported by an integrated neural network that involves hippocampal and posterior parietal regions.

Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease.

Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.

Behind the scenes: how visual memory load biases selective attention during processing of visual streams.

We recorded ERPs to investigate whether the visual memory load can bias visual selective attention. Participants memorized one or four letters and then responded to memory-matching letters presented in a relevant color while ignoring distractor letters or letters in an irrelevant color. Stimuli in the relevant color elicited larger frontal selection positivities (FSP) and occipital selection negativities (OSN) compared to irrelevant color stimuli. Only distractors elicited a larger FSP in the high than in the low memory load task. Memory load prolonged the OSN for all letters. Response mapping complexity was also modulated but did not affect the FSP and OSN. Together, the FSP data suggest that high memory load increased distractability. The OSN data suggest that memory load sustained attention to letters in a relevant color until working memory processing was completed, independently of whether the letters were in working memory or not.

Neural activity in the hippocampus predicts individual visual short-term memory capacity.

Although the hippocampus had been traditionally thought to be exclusively involved in long-term memory, recent studies raised controversial explanations why hippocampal activity emerged during short-term memory tasks. For example, it has been argued that long-term memory processes might contribute to performance within a short-term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short-term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19-27 yr, nine males) while they performed a match-to-sample task requiring processing of object-location associations (delay period = 900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K-formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of "set size" in the posterior parietal cortex (PPC). In line with a "set size × group" interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity = 3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity = 5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance-related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object-location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating.

Frontal GABA levels change during working memory.

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

Neurodevelopment of the visual system in typically developing children.

A central question in developmental psychology is how a child acquires knowledge about the surrounding world. Is it important for learning to know what an object represents, before a child knows how to deal with it? Or does a child learn because it is improving haptic skills to act upon an object, to follow its actions and predict how it behaves? Behavioral research investigating such questions distinguished the role of dorsal and ventral visual streams in learning to "know how" and "know what" about objects, but these studies did not unequivocally resolve how these functions mature. Recent functional, structural, and microstructural neuroimaging research has shed a novel light on the normal development of the human visual system, particularly during later stages of child development. This chapter reviews these neuroimaging studies and interrogates them on the question of whether dorsal and ventral visual streams mature at different rates. Structural gray matter properties within the ventral visual stream show prolonged development compared to the dorsal stream, whereas white matter connectivity within dorsal visual stream structures matures later. Functionally specialized areas in the ventral visual stream show increased size during development, whereas parietal dorsal stream areas show increasing activity associated with high-order visual perception. Such results emphasize the importance of neuroimaging techniques for research on visual cognitive development. They suggest that high-order visual functions mature late and that dorsal and ventral visual streams follow different neurodevelopmental trajectories.

Visual working memory capacity and stimulus categories: a behavioral and electrophysiological investigation.

It has recently been suggested that visual working memory capacity may vary depending on the type of material that has to be memorized. Here, we use a delayed match-to-sample paradigm and event-related potentials (ERP) to investigate the neural correlates that are linked to these changes in capacity. A variable number of stimuli (1-4) were presented in each visual hemifield. Participants were required to selectively memorize the stimuli presented in one hemifield. Following memorization, a test stimulus was presented that had to be matched against the memorized item(s). Two types of stimuli were used: one set consisting of discretely different objects (discrete stimuli) and one set consisting of more continuous variations along a single dimension (continuous stimuli). Behavioral results indicate that memory capacity was much larger for the discrete stimuli, when compared with the continuous stimuli. This behavioral effect correlated with an increase in a contralateral negative slow wave ERP component that is known to be involved in memorization. We therefore conclude that the larger working memory capacity for discrete stimuli can be directly related to an increase in activity in visual areas and propose that this increase in visual activity is due to interactions with other, non-visual representations.

The left occipitotemporal system in reading: disruption of focal fMRI connectivity to left inferior frontal and inferior parietal language areas in children with dyslexia.

Developmental dyslexia is a severe reading disorder, which is characterized by dysfluent reading and impaired automaticity of visual word processing. Adults with dyslexia show functional deficits in several brain regions including the so-called "Visual Word Form Area" (VWFA), which is implicated in visual word processing and located within the larger left occipitotemporal VWF-System. The present study examines functional connections of the left occipitotemporal VWF-System with other major language areas in children with dyslexia. Functional connectivity MRI was used to assess connectivity of the VWF-System in 18 children with dyslexia and 24 age-matched controls (age 9.7-12.5 years) using five neighboring left occipitotemporal regions of interest (ROIs) during a continuous reading task requiring phonological and orthographic processing. First, the results revealed a focal origin of connectivity from the VWF-System, in that mainly the VWFA was functionally connected with typical left frontal and parietal language areas in control children. Adjacent posterior and anterior VWF-System ROIs did not show such connectivity, confirming the special role that the VWFA plays in word processing. Second, we detected a significant disruption of functional connectivity between the VWFA and left inferior frontal and left inferior parietal language areas in the children with dyslexia. The current findings add to our understanding of dyslexia by showing that functional disconnection of the left occipitotemporal system is limited to the small VWFA region crucial for automatic visual word processing, and emerges early during reading acquisition in children with dyslexia, along with deficits in orthographic and phonological processing of visual word forms.

Microstructural development: organizational differences of the fiber architecture between children and adults in dorsal and ventral visual streams.

Visual perceptual skills are basically mature by the age of 7 years. White matter, however, continues to develop until late adolescence. Here, we examined children (aged 5-7 years) and adults (aged 20-30 years) using diffusion tensor imaging (DTI) fiber tracking to investigate the microstructural maturation of the visual system. We characterized the brain volumes, DTI indices, and architecture of visual fiber tracts passing through white matter structures adjacent to occipital and parietal cortex (dorsal stream), and to occipital and temporal cortex (ventral stream). Dorsal, but not ventral visual stream pathways were found to increase in volume during maturation. DTI indices revealed expected maturational differences, manifested as decreased mean and radial diffusivities and increased fractional anisotropy in both streams. Additionally, fractional anisotropy was increased and radial diffusivity was decreased in the adult dorsal stream, which can be explained by specific dorsal stream myelination or increasing fiber compaction. Adult dorsal stream architecture showed additional intra- and interhemispheric connections: Dorsal fibers penetrated into contralateral hemispheres via commissural structures and projection fibers extended to the superior temporal gyrus and ventral association pathways. Moreover, intra-hemispheric connectivity was particularly strong in adult dorsal stream of the right hemisphere. Ventral stream architecture also differed between adults and children. Adults revealed additional connections to posterior lateral areas (occipital-temporal gyrus), whereas children showed connections to posterior medial areas (posterior parahippocampal and lingual gyrus). Hence, in addition to dorsal stream myelination or fiber compaction, progressing maturation of intra- and interhemispheric connectivity may contribute to the development of the visual system.