Search Results (13)

Background: Chronic insomnia (CID) is a highly prevalent sleep disorder, yet the precise mechanisms underlying it remain incompletely understood. The aim of this study is to analyze effective connectivity between key regions of the default mode network (DMN), executive control network (ECN), and salience network (SN) in patients with CID as potential neurologic correlates of the hyperarousal state. Methods: Thirty-one CID patients and 24 healthy controls (HC) were recruited. All the subjects filled out the Insomnia severity index scale (ISI), Beck depression inventory (BDI), and Epworth sleepiness scale (ESS), underwent polysomnography, and were scanned on functional magnetic resonance imaging. Statistical Parametric Mapping 12 was used to analyze the results. Spectral dynamic causal modeling was applied to the chosen regions of interest. Results: There were three significant connections present in the CID group—inhibitory from the dorsolateral prefrontal cortex (DLPFC) to the right hippocampus (Hippocamp R); excitatory from the dorsomedial prefrontal cortex to the ventromedial prefrontal cortex; and excitatory from the common medial prefrontal cortex to the right anterior insula (AIR). Two statistically significant excitatory connections were lacking in the patients’ group—from the posterior cingulate cortex (PCC) to AIR, and from precuneus to PCC. CID patients scored higher on the ISI and BDI. Significant negative correlations between DLPFC-Hippocamp R connectivity and both ISI and BDI scores were identified. Conclusions: Disruptions within the DMN and between the DMN, SN, and ECN reflect an impaired ability to appropriately shift between internally and externally directed cognitive states—an imbalance that potentially underlies the hyperarousal state of CID. Full article

The brain receives information via sensory inputs through the peripheral nervous system and stores a small subset as memories within the central nervous system. Short-term, working memory is present in the hippocampus whereas long-term memories are distributed within neural networks throughout the brain. Elegant studies on the mechanisms for memory storage and the neuroeconomic formulation of human decision making have been recognized with Nobel Prizes in Physiology or Medicine and in Economics, respectively. There is a wide gap, however, in our understanding of how memories of disparate bits of information translate into “knowledge”, and the neural mechanisms by which knowledge is used to make decisions. I propose that the conceptualization of a “knowledge network” for the creation, storage and recall of knowledge is critical to start bridging this gap. Knowledge creation involves value-driven contextualization of memories through cross-validation via certainty-seeking behaviors, including rumination or reflection. Knowledge recall, like memory, may occur via oscillatory activity that dynamically links multiple networks. These networks may show correlated activity and interactivity despite their presence within widely separated regions of the nervous system, including the brainstem, spinal cord and gut. The hippocampal–amygdala complex together with the entorhinal and prefrontal cortices are likely components of multiple knowledge networks since they participate in the contextual recall of memories and action selection. Sleep and reflection processes and attentional mechanisms mediated by the habenula are expected to play a key role in knowledge creation and consolidation. Unlike a straightforward test of memory, determining the loci and mechanisms for the storage and recall of knowledge requires the implementation of a naturalistic decision-making paradigm. By formalizing a neuroscientific concept of knowledge networks, we can experimentally test their functionality by recording large-scale neural activity during decision making in awake, naturally behaving animals. These types of studies are difficult but important also for advancing knowledge-driven as opposed to big data-driven models of artificial intelligence. A knowledge network-driven understanding of brain function may have practical implications in other spheres, such as education and the treatment of mental disorders. Full article

Threat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories. Full article

Early cognitive decline in patients with Alzheimer’s (AD) is associated with quantifiable structural and functional connectivity changes in the brain. AD dysregulation of Aβ and tau metabolism progressively disrupt normal synaptic function, leading to loss of synapses, decreased hippocampal synaptic density and early hippocampal atrophy. Advances in brain imaging techniques in living patients have enabled the transition from clinical signs and symptoms-based AD diagnosis to biomarkers-based diagnosis, with functional brain imaging techniques, quantitative EEG, and body fluids sampling. The hippocampus has a central role in semantic and episodic memory processing. This cognitive function is critically dependent on normal intrahippocampal connections and normal hippocampal functional connectivity with many cortical regions, including the perirhinal and the entorhinal cortex, parahippocampal cortex, association regions in the temporal and parietal lobes, and prefrontal cortex. Therefore, decreased hippocampal synaptic density is reflected in the altered functional connectivity of intrinsic brain networks (aka large-scale networks), including the parietal memory, default mode, and salience networks. This narrative review discusses recent critical issues related to detecting AD-associated early cognitive decline with brain synaptic structural and functional markers in high-risk or neuropsychologically diagnosed patients with subjective cognitive impairment or mild cognitive impairment. Full article

Neurons in the medial entorhinal cortex exhibit multiple, periodically organized, firing fields which collectively appear to form an internal representation of space. Neuroimaging data suggest that this grid coding is also present in other cortical areas such as the prefrontal cortex, indicating that it may be a general principle of neural functionality in the brain. In a recent analysis through the lens of dynamical systems theory, we showed how grid coding can lead to the generation of a diversity of empirically observed sequential reactivations of hippocampal place cells corresponding to traversals of cognitive maps. Here, we extend this sequence generation model by describing how the synthesis of multiple dynamical systems can support compositional cognitive computations. To empirically validate the model, we simulate two experiments demonstrating compositionality in space or in time during sequence generation. Finally, we describe several neural network architectures supporting various types of compositionality based on grid coding and highlight connections to recent work in machine learning leveraging analogous techniques. Full article

Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption. Full article

Anxiety and depression exhibit high comorbidity and share the alteration of the amygdala–hippocampal–prefrontal network, playing different roles in the ventral and dorsal hippocampi. Deep brain stimulation of the infralimbic cortex in rodents or the human equivalent—the subgenual cingulate cortex—constitutes a fast antidepressant treatment. The aim of this work was: (1) to describe the oscillatory profile in a rodent model of anxiety, and (2) to deepen the therapeutic basis of infralimbic deep brain stimulation in mood disorders. First, the anxiogenic drug FG-7142 was administered to anaesthetized rats to characterize neural oscillations within the amygdala and the dorsoventral axis of the hippocampus. Next, deep brain stimulation was applied. FG-7142 administration drastically reduced the slow waves, increasing delta, low theta, and beta oscillations in the network. Moreover, FG-7142 altered communication in these bands in selective subnetworks. Deep brain stimulation of the infralimbic cortex reversed most of these FG-7142 effects. Cross-frequency coupling was also inversely modified by FG-7142 and by deep brain stimulation. Our study demonstrates that the hyperactivated amygdala–hippocampal network associated with the anxiogenic drug exhibits an oscillatory fingerprint. The study contributes to comprehending the neurobiological basis of anxiety and the effects of infralimbic deep brain stimulation. Full article

Goal-directed spatial learning is crucial for the survival of animals, in which the formation of the route from the current location to the goal is one of the central problems. A distributed brain network comprising the hippocampus and prefrontal cortex has been shown to support such capacity, yet it is not fully understood how the most similar brain regions in birds, the hippocampus (Hp) and nidopallium caudolaterale (NCL), cooperate during route formation in goal-directed spatial learning. Hence, we examined neural activity in the Hp-NCL network of pigeons and explored the connectivity dynamics during route formation in a goal-directed spatial task. We found that behavioral changes in spatial learning during route formation are accompanied by modifications in neural patterns in the Hp-NCL network. Specifically, as pigeons learned to solve the task, the spectral power in both regions gradually decreased. Meanwhile, elevated hippocampal theta (5 to 12 Hz) connectivity and depressed connectivity in NCL were also observed. Lastly, the interregional functional connectivity was found to increase with learning, specifically in the theta frequency band during route formation. These results provide insight into the dynamics of the Hp-NCL network during spatial learning, serving to reveal the potential mechanism of avian spatial navigation. Full article

Anodal transcranial direct current stimulation (anodal-tDCS) is known to improve cognition and normalize abnormal network configuration during resting-state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). We aimed to evaluate the impact of sequential anodal-tDCS on cognitive functions, functional segregation, and integration parameters in patients with MCI, according to high-risk factors for Alzheimer’s disease (AD): amyloid-beta (Aβ) deposition and APOE ε4-allele status. In 32 patients with MCI ([¹⁸ F] flutemetamol-: n = 10, [¹⁸ F] flutemetamol+: n = 22; APOE ε4-: n = 13, APOE ε4+: n = 19), we delivered anodal-tDCS (2 mA/day, five times/week, for 2 weeks) over the left dorsolateral prefrontal cortex and assessed the neuropsychological test battery and resting-state fMRI measurements before and after 2 weeks stimulation. We observed a non-significant impact of an anodal-tDCS on changes in neuropsychological battery scores between MCI patients with and without high-risk factors of AD, Aβ retention and APOE ε4-allele. However, there was a significant difference in brain functional segregation and integration parameters between MCI patients with and without AD high-risk factors. We also found a significant effect of tDCS-by-APOE ε4-allele interaction on changes in the functional segregation parameter of the temporal pole. In addition, baseline Aβ deposition significantly associated negatively with change in global functional integrity of hippocampal formation. Anodal-tDCS might help to enhance restorative and compensatory intrinsic functional changes in MCI patients, modulated by the presence of Aβ retention and the APOE ε4-allele. Full article

The relations between the developing mind and developing brain are explored. We outline a theory of intellectual development postulating that the mind comprises four systems of processes (domain-specific, attention and working memory, reasoning, and cognizance) developing in four cycles (episodic, realistic, rule-based, and principle-based representations, emerging at birth, 2, 6, and 11 years, respectively), with two phases in each. Changes in reasoning relate to processing efficiency in the first phase and working memory in the second phase. Awareness of mental processes is recycled with the changes in each cycle and drives their integration into the representational unit of the next cycle. Brain research shows that each type of processes is served by specialized brain networks. Domain-specific processes are rooted in sensory cortices; working memory processes are mainly rooted in hippocampal, parietal, and prefrontal cortices; abstraction and alignment processes are rooted in parietal, frontal, and prefrontal and medial cortices. Information entering these networks is available to awareness processes. Brain networks change along the four cycles, in precision, connectivity, and brain rhythms. Principles of mind-brain interaction are discussed. Full article

Anxiety disorders that develop in adolescence represent a significant burden and are particularly challenging to treat, due in no small part to the high occurrence of relapse in this age group following exposure therapy. This pattern of persistent fear is preserved across species; relative to those younger and older, adolescents consistently show poorer extinction, a key process underpinning exposure therapy. This suggests that the neural processes underlying fear extinction are temporarily but profoundly compromised during adolescence. The formation, retrieval, and modification of fear- and extinction-associated memories are regulated by a forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the hippocampus. These regions undergo robust maturational changes in early life, with unique alterations in structure and function occurring throughout adolescence. In this review, we focus primarily on two of these regions—the PFC and the amygdala—and discuss how changes in plasticity, synaptic transmission, inhibition/excitation, and connectivity (including modulation by hippocampal afferents to the PFC) may contribute to transient deficits in extinction retention. We end with a brief consideration of how exposure to stress during this adolescent window of vulnerability can permanently disrupt neurodevelopment, leading to lasting impairments in pathways of emotional regulation. Full article

Background: Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess the available neuroimaging studies exploring CBT’s effects in adult patients with MDD. Methods: Computerized databases were consulted till April 2018 and a research was conducted according to PRISMA guidelines in order to identify original research articles published at any time in English and French languages on this topic. Results: Seventeen studies were identified. Only one study was randomized comparing CBT to pharmacological interventions, and none included an effective control. Following CBT, changes occurred in cerebral areas that are part of the fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala-hippocampal complex. However, the pattern of activation and connectivity in these areas varied across the studies. Conclusion: A considerable heterogeneity exists with regard to study design, adapted CBT type and intensity, and employed neuroimaging paradigms, all of which may partly explain the difference in studies’ outcomes. The lack of randomization and effective controls in most of them makes it difficult to draw formal conclusion whether the observed effects are CBT mediated or due to spontaneous recovery. Despite the observed inconsistencies and dearth of data, CBT appears to exert its anti-depressant effects mainly by modulating the function of affective and cognitive networks devoted to emotions generation and control, respectively. This concept remains to be validated in large scale randomized controlled trials. Full article

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a necessary part of the memory system. These findings challenge the conventional characterizations of hippocampus and PFC as being circumscribed to traditional cognitive domains. Here, we emphasize that the ability to parsimoniously account for the breadth of hippocampal and PFC contributions to behavior, in terms of memory function and beyond, requires theoretical advances in our understanding of their characteristic processing features and mental representations. Notably, several literatures exist that touch upon this issue, but have remained disjointed because of methodological differences that necessarily limit the scope of inquiry, as well as the somewhat artificial boundaries that have been historically imposed between domains of cognition. In particular, this article focuses on the contribution of relational memory theory as an example of a framework that describes both the representations and processes supported by the hippocampus, and further elucidates the role of the hippocampal–PFC network to a variety of behaviors. Full article