Impacts of multiple anthropogenic stressors on the transcriptional response of Gammarus fossarum in a mesocosm field experiment.

BACKGROUND: Freshwaters are exposed to multiple anthropogenic stressors, leading to habitat degradation and biodiversity decline. In particular, agricultural stressors are known to result in decreased abundances and community shifts towards more tolerant taxa. However, the combined effects of stressors are difficult to predict as they can interact in complex ways, leading to enhanced (synergistic) or decreased (antagonistic) response patterns. Furthermore, stress responses may remain undetected if only the abundance changes in ecological experiments are considered, as organisms may have physiological protective pathways to counteract stressor effects. Therefore, we here used transcriptome-wide sequencing data to quantify single and combined effects of elevated fine sediment deposition, increased salinity and reduced flow velocity on the gene expression of the amphipod Gammarus fossarum in a mesocosm field experiment. RESULTS: Stressor exposure resulted in a strong transcriptional suppression of genes involved in metabolic and energy consuming cellular processes, indicating that G. fossarum responds to stressor exposure by directing energy to vitally essential processes. Treatments involving increased salinity induced by far the strongest transcriptional response, contrasting the observed abundance patterns where no effect was detected. Specifically, increased salinity induced the expression of detoxification enzymes and ion transporter genes, which control the membrane permeability of sodium, potassium or chloride. Stressor interactions at the physiological level were mainly antagonistic, such as the combined effect of increased fine sediment and reduced flow velocity. The compensation of the fine sediment induced effect by reduced flow velocity is in line with observations based on specimen abundance data. CONCLUSIONS: Our findings show that gene expression data provide new mechanistic insights in responses of freshwater organisms to multiple anthropogenic stressors. The assessment of stressor effects at the transcriptomic level and its integration with stressor effects at the level of specimen abundances significantly contribute to our understanding of multiple stressor effects in freshwater ecosystems.

From provocation to aggression: the neural network.

BACKGROUND: In-vivo observations of neural processes during human aggressive behavior are difficult to obtain, limiting the number of studies in this area. To address this gap, the present study implemented a social reactive aggression paradigm in 29 healthy men, employing non-violent provocation in a two-player game to elicit aggressive behavior in fMRI settings. RESULTS: Participants responded more aggressively after high provocation reflected in taking more money from their opponents. Comparing aggression trials after high provocation to those after low provocation revealed activations in neural circuits involved in aggression: the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), and the insula. In general, our findings indicate that aggressive behavior activates a complex, widespread brain network, reflecting a cortico-limbic interaction and overlapping with circuits underlying negative emotions and conflicting decision-making. Brain activation during provocation in the OFC was associated with the degree of aggressive behavior in this task. CONCLUSION: Therefore, data suggest there is greater susceptibility for provocation, rather than less inhibition of aggressive tendencies, in individuals with higher aggressive responses. This further supports the hypothesis that reactive aggression can be seen as a consequence of provocation of aggressive emotional responses and parallel evaluative regulatory processes mediated mainly by the insula and prefrontal areas (OFC, mPFC, dlPFC, and ACC) respectively.

Predicting Stability of Mild Cognitive Impairment (MCI): Findings of a Community Based Sample.

BACKGROUND: Mild Cognitive Impairment (MCI) is a risk factor for Alzheimer's disease (AD) and other forms of dementia. However, much heterogeneity concerning neuropsychological measures, prevalence and progression rates impedes distinct diagnosis and treatment implications. OBJECTIVE: Aim of the present study was the identification of specific tests providing a high certainty for stable MCI and factors that precipitate instability of MCI in a community based sample examined at three measurement points. METHOD: 130 participants were tested annually with an extensive test battery including measures of memory, language, executive functions, intelligence and dementia screening tests. Exclusion criteria at baseline comprised, severe cognitive deficits (e.g. diagnosis of dementia, psychiatric or neurological disease). Possible predictors for stability or instability of MCI-diagnosis were analyzed using Regression and Receiver Operating Characteristic (ROC) curve analysis. Age, IQ and APOE status were tested for moderating effects on the interaction of test performances and group membership. RESULTS: A high prevalence of MCI (49%) was observed at baseline with a reversion rate of 18% after two years. Stability of MCI was related to performances in four measures (VLMT: delayed recall, CERAD: recall drawings, CERAD: Boston Naming Test, Benton Visual Retention Test: number of mistakes). Conversion to MCI is associated with language functions. Reversion to 'normal' was primarily predicted by single domain impairment. There was no significant influence of demographic, medical or genetic variables. CONCLUSION: The results highlight the role of repeated measurements for a reliable identification of functional neuropsychological predictors and better diagnostic reliability. In cases of high uncertainty close monitoring over time is needed in order of estimating outcome.

Effect of MAOA Genotype on Resting-State Networks in Healthy Participants.

Up to now, it remains unclear how monoamine oxidase A (MAOA), which has been repeatedly linked to aggression, affects brain activity within resting-state networks (RSN). Here, we used functional magnetic resonance imaging (fMRI) to test whether the MAOA genotype might influence activity within the common RSN. Our results demonstrate that during rest, participants with the low-activity genotype (MAOA-L) exhibit more activity within frontoparietal and temporal parts of the default mode network (DMN) and the cerebellum. The executive control and salience RSN revealed reduced activity for the MAOA-L group in several areas related to executive control, namely the right middle frontal gyrus (BA 6 and BA 9), and the dorsal part of the anterior cingulate cortex. Participants with the high-activity genotype (MAOA-H) showed increased activity in the posterior cingulate part of the DMN. Taken together, we found widespread hyperactivity within the DMN and reduced activity in brain areas related to executive and inhibitory control for the MAOA-L group. We discuss how these first results examining the influence of MAOA on the resting brain might be related to previous findings regarding the genetics of aggression, while acknowledging that this is an exploratory study which needs further confirmation.

Neural correlates of the core facets of empathy in schizophrenia.

Empathy is a multidimensional construct composed of several components such as emotion recognition, emotional perspective taking and affective responsiveness. Even though patients with schizophrenia demonstrate deficits in all core components of this basic social ability, the neural underpinnings of these dysfunctions are less clear. Using fMRI, we analyzed data from 15 patients meeting the DSM-IV criteria for schizophrenia and 15 matched healthy volunteers performing three separate paradigms tapping the core components of empathy, i.e. emotion recognition, perspective taking and affective responsiveness. Behavioral data analysis indicated a significant empathic deficit in patients, reflected in worse performance in all three domains. Analysis of functional data revealed hypoactivation in a fronto-temporo-parietal network including the amygdala in patients. Moreover, amygdala activation correlated negatively with severity of negative symptoms. The results suggest that schizophrenia patients not only suffer from a broad range of emotional deficits but also show cortical and subcortical abnormalities, extending previous findings on fronto-temporal cortical dysfunctions. Since empathy is related to psychosocial functioning and hence of high clinical relevance in schizophrenia, a more detailed understanding of the exact nature of these impairments is mandatory.

Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects.

The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.

Neural correlates of the attention network test in schizophrenia.

Attentional deficits are prominent in schizophrenia, affecting nearly all cognitive functions. Human attention comprises three essential components: alerting, orienting and executive control. For the assessment of these functions, the attention network test (ANT) has been proposed and used in healthy controls and patients. In schizophrenia, the ANT has revealed behavioral deficits; however, the corresponding neural correlates have not been examined. In the present study, neural correlates of attention were investigated in 17 schizophrenia patients and 17 healthy controls using the ANT with fMRI. Behavioral deficits emerged in the alertness system with a reduced efficiency for temporal cues. In fMRI, changes were observed for all three domains-alerting, orienting and conflict-and revealed hyper- as well as hypoactivation in patients. Affected regions during alerting comprised a broad fronto-temporo-parieto-occipito-cerebellar network, while differences during orienting mainly tapped fronto-parietal regions and during conflict processing a thalamo-frontal-temporal occipital network including the postcentral regions. In general, hyperactivations were positively correlated with more severe psychopathologial symptoms.

Cognitive performance and cholinergic transmission: influence of muscarinic and nicotinic receptor blockade.

The cholinergic system is essential in mediating cognitive processes. Although there has been extensive research regarding cholinergic receptor subsystems, the specific contribution of the muscarinic and nicotinic receptor system to cognitive processes still has not been sufficiently explored. In the present study, we examined the selective contribution of muscarinic and nicotinic antagonism to cognitive performance in healthy human subjects. A single-blind, double-dummy, time-elapsed, repeated measures cross-over design was used on 15 healthy males. Subjects completed a neuropsychological test battery assessing a wide range of cognitive domains after 0.4 mg scopolamine (intravenous), 0.2 mg/kg mecamylamine (max. 15 mg; oral) or placebo. Subjects were tested under three conditions: placebo/placebo (PP), scopolamine/placebo (SP) and mecamylamine/placebo (MP). Results show that scopolamine significantly impaired the free recall and recognition performance in the verbal learning test. No other cognitive domain was affected, neither by scopolamine nor by mecamylamine. In line with the existing literature, antagonism of muscarinic receptors resulted in specific cognitive impairments, predominantly memory performance.

Muscarinic antagonist effects on executive control of attention.

Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.

Nicotinic antagonist effects on functional attention networks.

Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.