Carola Romberg

Alpha power modulations and slow negative potentials have previously been associated with anticipatory processes in spatial and temporal top‐down attention. In typical experimental designs, however, neural responses triggered by transient stimulus onsets can interfere with attention‐driven activity patterns and our interpretation of such. Here, we investigated these signatures of spatio‐temporal attention in a dynamic paradigm free from potentially confounding stimulus‐driven activity using electroencephalography. Participants attended the cued side of a bilateral stimulus rotation and mentally counted how often one of two remembered sample orientations (i.e., the target) was displayed while ignoring the uncued side and non‐target orientation. Afterwards, participants performed a delayed match‐to‐sample task, in which they indicated if the orientation of a probe stimulus matched the corresponding sample orientation (previously target or non‐target). We observed dynamic alpha power reductions and slow negative waves around task‐relevant points in space and time (i.e., onset of the target orientation in the cued hemifield) over posterior electrodes contralateral to the locus of attention. In contrast to static alpha power lateralization, these dynamic signatures correlated with subsequent memory performance (primarily detriments for matching probes of the non‐target orientation), suggesting a preferential allocation of attention to task‐relevant locations and time points at the expense of reduced resources and impaired performance for information outside the current focus of attention. Our findings suggest that humans can naturally and dynamically focus their attention at relevant points in space and time and that such spatio‐temporal attention shifts can be reflected by dynamic alpha power modulations and slow negative potentials.

Chronic stress is a major risk factor for developing Alzheimer's disease (AD) and promotes the processing of amyloid precursor protein (APP) to β‐amyloid (Aβ). However, the precise relationship of stress and disease‐typical cognitive decline is presently not well understood. The aim of this study was to investigate how early life stress may affect cognition in adult mice with and without soluble Aβ pathology typical for the early stages of the disease. We focussed on sustained attention and response control, aspects of cognition mediated by the prefrontal cortex that are consistently impaired both in early AD and after chronic stress exposure. Young wild‐type mice as well as transgenic arcAβ mice overexpressing the hAPParc/swe transgene were exposed to a chronic unpredictable stress paradigm (age 3–8 weeks). At 15 weeks, these mice were tested on the 5‐choice serial reaction time task, a test of sustained attention and executive control. We found that, expectedly, chronic stress increased impulsive choices and impaired sustained attention in wild‐type mice. However, the same treatment reduced impulsivity and did not interfere with sustained attention in arcAβ mice. These findings suggest an unexpected interaction between chronic stress and Aβ whereby Aβ‐pathology caused by the hAPParc/swe mutation prevented and/or reversed stress‐induced cognitive changes through mechanisms that deserve further investigation. They also indicate that Aβ, in modest amounts, may have a beneficial role for cognitive stability, for example by protecting neural networks from the impact of further physiological or behavioural stress.

Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood.

Nesting of fast rhythmical brain activity (gamma) into slower brain waves (theta) has frequently been suggested as a core mechanism of multi‐item working memory (WM) retention. It provides a better understanding of WM capacity limitations, and, as we discuss in this review article, it can lead to applications for modulating memory capacity. However, could cross‐frequency coupling of brain oscillations also constructively contribute to a better understanding of the neuronal signatures of working memory compatible with theoretical approaches that assume flexible capacity limits? Could a theta‐gamma code also be considered as a neural mechanism of flexible sharing of cognitive resources between memory representations in multi‐item WM? Here, we propose potential variants of theta‐gamma coupling that could explain WM retention beyond a fixed memory capacity limit of a few visual items. Moreover, we suggest how to empirically test these predictions in the future.

Rationale The hippocampus is implicated in many of the cognitive impairments observed in conditions such as Alzheimer’s disease (AD) and schizophrenia (SCZ). Often, mice are the species of choice for models of these diseases and the study of the relationship between brain and behaviour more generally. Thus, automated and efficient hippocampal-sensitive cognitive tests for the mouse are important for developing therapeutic targets for these diseases, and understanding brain-behaviour relationships. One promising option is to adapt the touchscreen-based trial-unique nonmatching-to-location (TUNL) task that has been shown to be sensitive to hippocampal dysfunction in the rat. Objectives This study aims to adapt the TUNL task for use in mice and to test for hippocampus-dependency of the task. Methods TUNL training protocols were altered such that C57BL/6 mice were able to acquire the task. Following acquisition, dysfunction of the dorsal hippocampus (dHp) was induced using a fibre-sparing excitotoxin, and the effects of manipulation of several task parameters were examined. Results Mice could acquire the TUNL task using training optimised for the mouse (experiments 1). TUNL was found to be sensitive to dHp dysfunction in the mouse (experiments 2, 3 and 4). In addition, we observed that performance of dHp dysfunction group was somewhat consistently lower when sample locations were presented in the centre of the screen. Conclusions This study opens up the possibility of testing both mouse and rat models on this flexible and hippocampus-sensitive touchscreen task.

Perineuronal nets (PNNs) are extracellular matrix structures surrounding cortical neuronal cell bodies and proximal dendrites and are involved in the control of brain plasticity and the closure of critical periods. Expression of the link protein Crtl1/Hapln1 in neurons has recently been identified as the key event triggering the formation of PNNs. Here we show that the genetic attenuation of PNNs in adult brain Crtl1 knock-out mice enhances long-term object recognition memory and facilitates long-term depression in the perirhinal cortex, a neural correlate of object recognition memory. Identical prolongation of memory follows localized digestion of PNNs with chondroitinase ABC, an enzyme that degrades the chondroitin sulfate proteoglycan components of PNNs. The memory-enhancing effect of chondroitinase ABC treatment attenuated over time, suggesting that the regeneration of PNNs gradually restored control plasticity levels. Our findings indicate that PNNs regulate both memory and experience-driven synaptic plasticity in adulthood.

Alzheimer’s disease is commonly regarded as a loss of memory for past events. However, patients with Alzheimer’s disease seem not only to forget events but also to express false confidence in remembering events that have never happened. How and why false recognition occurs in such patients is currently unknown, and treatments targeting this specific mnemonic abnormality have not been attempted. Here, we used a modified object recognition paradigm to show that the tgCRND8 mouse—which overexpresses amyloid β and develops amyloid plaques similar to those in the brains of patients with Alzheimer’s disease—exhibits false recognition. Furthermore, we found that false recognition did not occur when tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling previous findings in patients with mild cognitive impairment, which is often considered to be prodromal Alzheimer’s disease. Additionally, false recognition did not occur when mice were treated with the partial N-methyl-d-aspartic acid receptor antagonist memantine. In a subsequent experiment, we found abnormally enhanced N-methyl-d-aspartic acid receptor-dependent long-term depression in these mice, which could be normalized by treatment with memantine. We suggest that Alzheimer’s disease typical amyloid β pathology leads to aberrant synaptic plasticity, thereby making memory representations more susceptible to interfering sensory input, thus increasing the likelihood of false recognition. Parallels between these findings and those from the literature on Alzheimer’s disease and mild cognitive impairment suggest a mechanism underlying false recognition in these patients. The false recognition phenomenon may provide a novel paradigm for the discovery of potential therapies to treat the mnemonic dysfunction characteristic of this disease.