Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network

PubMed Central

Alústiza, Irene; Radua, Joaquim; Albajes-Eizagirre, Anton; Domínguez, Manuel; Aubá, Enrique; Ortuño, Felipe

2016-01-01

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile. PMID:26925013

Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity.

PubMed

Kaiser, Roselinde H; Andrews-Hanna, Jessica R; Wager, Tor D; Pizzagalli, Diego A

2015-06-01

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. To investigate network dysfunction in MDD through a meta-analysis of rsFC studies. Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data. Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis. Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network. Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

PubMed

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Large-scale network dysfunction in Major Depressive Disorder: Meta-analysis of resting-state functional connectivity

PubMed Central

Kaiser, Roselinde H.; Andrews-Hanna, Jessica R.; Wager, Tor D.; Pizzagalli, Diego A.

2015-01-01

IMPORTANCE Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. OBJECTIVE To investigate network dysfunction in MDD through the first meta-analysis of rsFC studies. DATA SOURCES Seed-based voxel-wise rsFC studies comparing MDD with healthy individuals (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web-of-Science, EMBASE), and authors contacted for additional data. STUDY SELECTION Twenty-seven datasets from 25 publications (556 MDD adults/teens; 518 controls) were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Coordinates of seed regions-of-interest and between-group effects were extracted. Seeds were categorized into “seed-networks” by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive, or reduced negative, connectivity) or hypoconnectivity (increased negative, or reduced positive, connectivity) with each seed-network. RESULTS MDD was characterized by hypoconnectivity within the frontoparietal network (FN), a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network (DAN) involved in attending to the external environment. MDD was also associated with hyperconnectivity within the default network (DN), a network believed to support internally-oriented and self-referential thought, and hyperconnectivity between FN control systems and regions of DN. Finally, MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. CONCLUSIONS AND RELEVANCE Reduced connectivity within frontoparietal control systems, and imbalanced connectivity between control systems and networks involved in internal- or external-attention, may reflect depressive biases towards internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression. PMID:25785575

Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

PubMed Central

Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

2016-01-01

Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease: a meta-analysis of 75 fMRI studies.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; He, Yong; Zuo, Xi-Nian

2015-03-01

Most of the previous task functional magnetic resonance imaging (fMRI) studies found abnormalities in distributed brain regions in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and few studies investigated the brain network dysfunction from the system level. In this meta-analysis, we aimed to examine brain network dysfunction in MCI and AD. We systematically searched task-based fMRI studies in MCI and AD published between January 1990 and January 2014. Activation likelihood estimation meta-analyses were conducted to compare the significant group differences in brain activation, the significant voxels were overlaid onto seven referenced neuronal cortical networks derived from the resting-state fMRI data of 1,000 healthy participants. Thirty-nine task-based fMRI studies (697 MCI patients and 628 healthy controls) were included in MCI-related meta-analysis while 36 task-based fMRI studies (421 AD patients and 512 healthy controls) were included in AD-related meta-analysis. The meta-analytic results revealed that MCI and AD showed abnormal regional brain activation as well as large-scale brain networks. MCI patients showed hypoactivation in default, frontoparietal, and visual networks relative to healthy controls, whereas AD-related hypoactivation mainly located in visual, default, and ventral attention networks relative to healthy controls. Both MCI-related and AD-related hyperactivation fell in frontoparietal, ventral attention, default, and somatomotor networks relative to healthy controls. MCI and AD presented different pathological while shared similar compensatory large-scale networks in fulfilling the cognitive tasks. These system-level findings are helpful to link the fundamental declines of cognitive tasks to brain networks in MCI and AD. © 2014 Wiley Periodicals, Inc.

Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease.

PubMed

Putcha, Deepti; Ross, Robert S; Cronin-Golomb, Alice; Janes, Amy C; Stern, Chantal E

2016-02-01

Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

PubMed

Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

PubMed

He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

2016-11-01

Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Global Efficiency of Structural Networks Mediates Cognitive Control in Mild Cognitive Impairment

PubMed Central

Berlot, Rok; Metzler-Baddeley, Claudia; Ikram, M. Arfan; Jones, Derek K.; O’Sullivan, Michael J.

2016-01-01

Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI). Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusion: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive control but not for episodic memory. Interventions to improve cognitive control will need to address both dysfunction of local circuitry and global network architecture to be maximally effective. PMID:28018208

Altered Effective Connectivity among Core Neurocognitive Networks in Idiopathic Generalized Epilepsy: An fMRI Evidence

PubMed Central

Wei, Huilin; An, Jie; Shen, Hui; Zeng, Ling-Li; Qiu, Shijun; Hu, Dewen

2016-01-01

Idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizures (GTCS) suffer long-term cognitive impairments, and present a higher incidence of psychosocial and psychiatric disturbances than healthy people. It is possible that the cognitive dysfunctions and higher psychopathological risk in IGE-GTCS derive from disturbed causal relationship among core neurocognitive brain networks. To test this hypothesis, we examined the effective connectivity across the salience network (SN), default mode network (DMN), and central executive network (CEN) using resting-state functional magnetic resonance imaging (fMRI) data collected from 27 IGE-GTCS patients and 29 healthy controls. In the study, a combination framework of time domain and frequency domain multivariate Granger causality analysis was firstly proposed, and proved to be valid and accurate by simulation experiments. Using this method, we then observed significant differences in the effective connectivity graphs between the patient and control groups. Specifically, between-group statistical analysis revealed that relative to the healthy controls, the patients established significantly enhanced Granger causal influence from the dorsolateral prefrontal cortex to the dorsal anterior cingulate cortex, which is coherent both in the time and frequency domains analyses. Meanwhile, time domain analysis also revealed decreased Granger causal influence from the right fronto-insular cortex to the posterior cingulate cortex in the patients. These findings may provide new evidence for functional brain organization disruption underlying cognitive dysfunctions and psychopathological risk in IGE-GTCS. PMID:27656137

From Shortage to Surge: A Developmental Switch in Hippocampal–Prefrontal Coupling in a Gene–Environment Model of Neuropsychiatric Disorders

PubMed Central

Hartung, Henrike; Cichon, Nicole; De Feo, Vito; Riemann, Stephanie; Schildt, Sandra; Lindemann, Christoph; Mulert, Christoph; Gogos, Joseph A.; Hanganu-Opatz, Ileana L.

2016-01-01

Cognitive deficits represent a major burden of neuropsychiatric disorders and result in part from abnormal communication within hippocampal–prefrontal circuits. While it has been hypothesized that this network dysfunction arises during development, long before the first clinical symptoms, experimental evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic and environmental risk factors of disease (dual-hit GE mice) have poorer recognition memory that correlates with augmented coupling by synchrony and stronger directed interactions between prefrontal cortex and hippocampus. The network dysfunction emerges already during neonatal development, yet it initially consists in a diminished hippocampal theta drive and consequently, a weaker and disorganized entrainment of local prefrontal circuits in discontinuous oscillatory activity in dual-hit GE mice when compared with controls. Thus, impaired maturation of functional communication within hippocampal–prefrontal networks switching from hypo- to hyper-coupling may represent a mechanism underlying the pathophysiology of cognitive deficits in neuropsychiatric disorders. PMID:27613435

Rethinking cognition and behavior in the new classification for childhood epilepsy: Examples from frontal lobe and temporal lobe epilepsies.

PubMed

Smith, Mary Lou

2016-11-01

The new approach to classification of the epilepsies emphasizes the role of dysfunction in networks in defining types of epilepsies. This paper reviews the structural and neuropsychological deficits in two types of childhood epilepsy: frontal lobe and temporal lobe epilepsy. The evidence for and against a pattern of specificity of deficits in executive function and memory associated with these two types of epilepsies is presented. The evidence varies with the methodologies used in the studies, but direct comparison of the two types of epilepsies does not suggest a clear-cut mapping of function onto structure. These findings are discussed in light of the concept of network dysfunction. The evidence supports the conceptualization of epilepsy as a network disease. Implications for future work in the neuropsychology of pediatric epilepsy are suggested. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Connectivity Estimated from Resting-State fMRI Reveals Selective Alterations in Male Adolescents with Pure Conduct Disorder

PubMed Central

Lu, Feng-Mei; Zhou, Jian-Song; Zhang, Jiang; Xiang, Yu-Tao; Zhang, Jian; Liu, Qi; Wang, Xiao-Ping; Yuan, Zhen

2015-01-01

Conduct disorder (CD) is characterized by a persistent pattern of antisocial behavior and aggression in childhood and adolescence. Previous task-based and resting-state functional magnetic resonance imaging (fMRI) studies have revealed widespread brain regional abnormalities in adolescents with CD. However, whether the resting-state networks (RSNs) are altered in adolescents with CD remains unknown. In this study, resting-state fMRI data were first acquired from eighteen male adolescents with pure CD and eighteen age- and gender-matched typically developing (TD) individuals. Independent component analysis (ICA) was implemented to extract nine representative RSNs, and the generated RSNs were then compared to show the differences between the CD and TD groups. Interestingly, it was observed from the brain mapping results that compared with the TD group, the CD group manifested decreased functional connectivity in four representative RSNs: the anterior default mode network (left middle frontal gyrus), which is considered to be correlated with impaired social cognition, the somatosensory network (bilateral supplementary motor area and right postcentral gyrus), the lateral visual network (left superior occipital gyrus), and the medial visual network (right fusiform, left lingual gyrus and right calcarine), which are expected to be relevant to the perceptual systems responsible for perceptual dysfunction in male adolescents with CD. Importantly, the novel findings suggested that male adolescents with pure CD were identified to have dysfunctions in both low-level perceptual networks (the somatosensory network and visual network) and a high-order cognitive network (the default mode network). Revealing the changes in the functional connectivity of these RSNs enhances our understanding of the neural mechanisms underlying the modulation of emotion and social cognition and the regulation of perception in adolescents with CD. PMID:26713867

Detecting social-cognitive deficits after traumatic brain injury: An ALE meta-analysis of fMRI studies.

PubMed

Xiao, Hui; Jacobsen, Andre; Chen, Ziqian; Wang, Yang

2017-01-01

Traumatic brain injury (TBI) can result in significant social dysfunction, which is represented by impairment to social-cognitive abilities (i.e. social cognition, social attention/executive function and communication). This study is aimed to explore brain networks mediating the social dysfunction after TBI and its underlying mechanisms. We performed a quantitative meta-analysis using the activation likelihood estimation (ALE) approach on functional magnetic resonance imaging (fMRI) studies of social-cognitive abilities following TBI. Sixteen studies fulfilled the inclusion criteria resulting in a total of 190 patients with TBI and 206 controls enrolled in the ALE meta-analysis. The temporoparietal junction (TPJ) and the medial prefrontal cortex (mPFC) were the specific regions that social cognition predominantly engaged. The cingulate gyrus, frontal gyrus and inferior parietal lobule were the main regions related to social attention/executive functions. Communication dysfunction, especially related to language deficits, was found to show greater activation of the temporal gyrus and fusiform gyrus in TBI. The current ALE meta-analytic findings provide evidence that patients have significant social-cognitive disabilities following TBI. The relatively limited pool of literature and the varied fMRI results from published studies indicate that social-cognitive abilities following TBI is an area that would greatly benefit from further investigation.

The default mode network and recurrent depression: a neurobiological model of cognitive risk factors.

PubMed

Marchetti, Igor; Koster, Ernst H W; Sonuga-Barke, Edmund J; De Raedt, Rudi

2012-09-01

A neurobiological account of cognitive vulnerability for recurrent depression is presented based on recent developments of resting state neural networks. We propose that alterations in the interplay between task positive (TP) and task negative (TN) elements of the Default Mode Network (DMN) act as a neurobiological risk factor for recurrent depression mediated by cognitive mechanisms. In the framework, depression is characterized by an imbalance between TN-TP components leading to an overpowering of TP by TN activity. The TN-TP imbalance is associated with a dysfunctional internally-focused cognitive style as well as a failure to attenuate TN activity in the transition from rest to task. Thus we propose the TN-TP imbalance as overarching neural mechanism involved in crucial cognitive risk factors for recurrent depression, namely rumination, impaired attentional control, and cognitive reactivity. During remission the TN-TP imbalance persists predisposing to vulnerability of recurrent depression. Empirical data to support this model is reviewed. Finally, we specify how this framework can guide future research efforts.

Structural network efficiency is associated with cognitive impairment in small-vessel disease.

PubMed

Lawrence, Andrew J; Chung, Ai Wern; Morris, Robin G; Markus, Hugh S; Barrick, Thomas R

2014-07-22

To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. © 2014 American Academy of Neurology.

Structural network efficiency is associated with cognitive impairment in small-vessel disease

PubMed Central

Chung, Ai Wern; Morris, Robin G.; Markus, Hugh S.; Barrick, Thomas R.

2014-01-01

Objective: To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. Methods: A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Results: Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Conclusions: Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. PMID:24951477

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PubMed

Huang, Ran-Ran; Jia, Bao-Hui; Xie, Lei; Ma, Shu-Hua; Yin, Jing-Jing; Sun, Zong-Bo; Le, Hong-Bo; Xu, Wen-Can; Huang, Jin-Zhuang; Luo, Dong-Xue

2016-01-01

To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction. © 2015 Wiley Periodicals, Inc.

Effects of amyloid and small vessel disease on white matter network disruption.

PubMed

Kim, Hee Jin; Im, Kiho; Kwon, Hunki; Lee, Jong Min; Ye, Byoung Seok; Kim, Yeo Jin; Cho, Hanna; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2015-01-01

There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: more than frontal lobe dysfunction.

PubMed

Tsermentseli, Stella; Leigh, P Nigel; Goldstein, Laura H

2012-02-01

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be significant heterogeneity. This article will review the current state of knowledge regarding the neuropathological and neuroanatomical basis for cognitive dysfunction in ALS. Neuropathological findings suggest that ALS does not selectively affect the frontotemporal network but rather is part of a broad clinico-pathological spectrum now known as TAR-DNA binding protein (TDP)-43 proteinopathies. Functional neuroimaging has supported neuropsychological findings of frontotemporal dysfunction but has also implied the involvement of somatosensory areas. Structural neuroimaging has not been able to establish a specific hypothesis of extra-motor cortical atrophy beyond the combination of various frontal, temporal and limbic areas. The finding of reduction in the integrity of white matter in the frontal, temporal and parietal lobes including long association fibers suggests that subcortical involvement may underlie both cognitive and functional changes in ALS. Future perspectives for further investigations are highlighted. Copyright © 2011 Elsevier Srl. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elman, Jeremy A.; Madison, Cindee M.; Baker, Suzanne L.

In Alzheimer's disease (AD), Beta-amyloid (Aβ) deposition is one of the hallmarks. However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [ 11 C]PIB-PET inmore » 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.« less

Decreased triple network connectivity in patients with post-traumatic stress disorder

NASA Astrophysics Data System (ADS)

Liu, Yang; Li, Liang; Li, Baojuan; Zhang, Xi; Lu, Hongbing

2017-03-01

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With arterial spin labeling sequence, three networks were identified using independent component analysis in 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. In PTSD patients, decreased connectivity was identified in left middle frontal gyrus of CEN, left precuneus and bilateral superior frontal gyrus of DMN, and right anterior insula of SN. The decreased connectivity in left middle frontal gyrus was identified to associate with clinical severity. These results indicated the decreased triple network connectivity, which not only supported the proposal of the triple network model, but also prompted possible neurobiology mechanism of cognitive dysfunction for this kind of PTSD.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

PubMed

Soloff, Paul H; Abraham, Kristy; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A

2017-05-01

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural network alterations and neurological dysfunction in cerebral amyloid angiopathy

PubMed Central

Reijmer, Yael D.; Fotiadis, Panagiotis; Martinez-Ramirez, Sergi; Salat, David H.; Schultz, Aaron; Shoamanesh, Ashkan; Ayres, Alison M.; Vashkevich, Anastasia; Rosas, Diana; Schwab, Kristin; Leemans, Alexander; Biessels, Geert-Jan; Rosand, Jonathan; Johnson, Keith A.; Viswanathan, Anand; Gurol, M. Edip

2015-01-01

Cerebral amyloid angiopathy is a common form of small-vessel disease and an important risk factor for cognitive impairment. The mechanisms linking small-vessel disease to cognitive impairment are not well understood. We hypothesized that in patients with cerebral amyloid angiopathy, multiple small spatially distributed lesions affect cognition through disruption of brain connectivity. We therefore compared the structural brain network in patients with cerebral amyloid angiopathy to healthy control subjects and examined the relationship between markers of cerebral amyloid angiopathy-related brain injury, network efficiency, and potential clinical consequences. Structural brain networks were reconstructed from diffusion-weighted magnetic resonance imaging in 38 non-demented patients with probable cerebral amyloid angiopathy (69 ± 10 years) and 29 similar aged control participants. The efficiency of the brain network was characterized using graph theory and brain amyloid deposition was quantified by Pittsburgh compound B retention on positron emission tomography imaging. Global efficiency of the brain network was reduced in patients compared to controls (0.187 ± 0.018 and 0.201 ± 0.015, respectively, P < 0.001). Network disturbances were most pronounced in the occipital, parietal, and posterior temporal lobes. Among patients, lower global network efficiency was related to higher cortical amyloid load (r = −0.52; P = 0.004), and to magnetic resonance imaging markers of small-vessel disease including increased white matter hyperintensity volume (P < 0.001), lower total brain volume (P = 0.02), and number of microbleeds (trend P = 0.06). Lower global network efficiency was also related to worse performance on tests of processing speed (r = 0.58, P < 0.001), executive functioning (r = 0.54, P = 0.001), gait velocity (r = 0.41, P = 0.02), but not memory. Correlations with cognition were independent of age, sex, education level, and other magnetic resonance imaging markers of small-vessel disease. These findings suggest that reduced structural brain network efficiency might mediate the relationship between advanced cerebral amyloid angiopathy and neurologic dysfunction and that such large-scale brain network measures may represent useful outcome markers for tracking disease progression. PMID:25367025

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

PubMed

Dinkelacker, Vera; Xin, Xu; Baulac, Michel; Samson, Séverine; Dupont, Sophie

2016-09-01

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity. Copyright © 2016. Published by Elsevier Inc.

Characterizing attention with predictive network models

PubMed Central

Rosenberg, M. D.; Finn, E. S.; Scheinost, D.; Constable, R. T.; Chun, M. M.

2017-01-01

Recent work shows that models based on functional connectivity in large-scale brain networks can predict individuals’ attentional abilities. Some of the first generalizable neuromarkers of cognitive function, these models also inform our basic understanding of attention, providing empirical evidence that (1) attention is a network property of brain computation, (2) the functional architecture that underlies attention can be measured while people are not engaged in any explicit task, and (3) this architecture supports a general attentional ability common to several lab-based tasks and impaired in attention deficit hyperactivity disorder. Looking ahead, connectivity-based predictive models of attention and other cognitive abilities and behaviors may potentially improve the assessment, diagnosis, and treatment of clinical dysfunction. PMID:28238605

Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability

DOE PAGES

Elman, Jeremy A.; Madison, Cindee M.; Baker, Suzanne L.; ...

2014-11-07

In Alzheimer's disease (AD), Beta-amyloid (Aβ) deposition is one of the hallmarks. However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [ 11 C]PIB-PET inmore » 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.« less

REVIEWING THE KETAMINE MODEL FOR SCHIZOPHRENIA

PubMed Central

Frohlich, Joel

2014-01-01

The observation that antagonists of the N-methyl-D-aspartate glutamate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory -aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal aberrations of NMDAR might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia. PMID:24257811

Mathematics, anxiety, and the brain.

PubMed

Moustafa, Ahmed A; Tindle, Richard; Ansari, Zaheda; Doyle, Margery J; Hewedi, Doaa H; Eissa, Abeer

2017-05-24

Given that achievement in learning mathematics at school correlates with work and social achievements, it is important to understand the cognitive processes underlying abilities to learn mathematics efficiently as well as reasons underlying the occurrence of mathematics anxiety (i.e. feelings of tension and fear upon facing mathematical problems or numbers) among certain individuals. Over the last two decades, many studies have shown that learning mathematical and numerical concepts relies on many cognitive processes, including working memory, spatial skills, and linguistic abilities. In this review, we discuss the relationship between mathematical learning and cognitive processes as well as the neural substrates underlying successful mathematical learning and problem solving. More importantly, we also discuss the relationship between these cognitive processes, mathematics anxiety, and mathematics learning disabilities (dyscalculia). Our review shows that mathematical cognition relies on a complex brain network, and dysfunction to different segments of this network leads to varying manifestations of mathematical learning disabilities.

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; Lu, Guang-Ming; Zuo, Xi-Nian

2015-10-01

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Graph theory network function in Parkinson's disease assessed with electroencephalography.

PubMed

Utianski, Rene L; Caviness, John N; van Straaten, Elisabeth C W; Beach, Thomas G; Dugger, Brittany N; Shill, Holly A; Driver-Dunckley, Erika D; Sabbagh, Marwan N; Mehta, Shyamal; Adler, Charles H; Hentz, Joseph G

2016-05-01

To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinson's disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D). EEG recordings were analyzed via graph theory network analysis to quantify changes in global efficiency and local integration. This included minimal spanning tree analysis. T-tests and correlations were used to assess differences between groups and assess the relationship with cognitive performance. Network measures showed increased local integration across all frequency bands between control and PD-CN; in contrast, decreased local integration occurred in PD-D when compared to PD-CN in the alpha1 frequency band. Differences found in PD-MCI mirrored PD-D. Correlations were found between network measures and assessments of global cognitive performance in PD. Our results reveal distinct patterns of band and network measure type alteration and breakdown for PD, as well as with cognitive decline in PD. These patterns suggest specific ways that interaction between cortical areas becomes abnormal and contributes to PD symptoms at various stages. Graph theory analysis by EEG suggests that network alteration and breakdown are robust attributes of PD cortical dysfunction pathophysiology. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease.

PubMed

Kobeleva, Xenia; Firbank, Michael; Peraza, Luis; Gallagher, Peter; Thomas, Alan; Burn, David J; O'Brien, John; Taylor, John-Paul

2017-07-01

Attention and executive dysfunction are features of Lewy body dementia (LBD) but their neuroanatomical basis is poorly understood. To investigate underlying dysfunctional attention-executive network (EXEC) interactions, we examined functional connectivity (FC) in 30 patients with LBD, 20 patients with Alzheimer's disease (AD), and 21 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a modified Attention Network Test (ANT), where they were instructed to press a button in response to the majority direction of arrows, which were either all pointing in the same direction or with one pointing in the opposite direction. Network activations during both target conditions and a baseline condition (no target) were derived by (ICA) Independent Component Analysis, and interactions between these networks were examined using the beta series correlations approach. Our study revealed that FC of ventral and dorsal attention networks DAN was reduced in LBD during all conditions, although most prominently during incongruent trials. These alterations in connectivity might be driven by a failure of engagement of ventral attention networks, and consequent over-reliance on the DAN. In contrast, when comparing AD patients with the other groups, we found hyperconnectivity between the posterior part of the default mode network (DMN) and the DAN in all conditions, particularly during incongruent trials. This might be attributable to either a compensatory effect to overcome DMN dysfunction, or be arising as a result of a disturbed transition of the DMN from rest to task. Our results demonstrate that dementia syndromes can be characterized both by hyper- and hypoconnectivity of distinct brain networks, depending on the interplay between task demand and available cognitive resources. However these are dependent upon the underlying pathology, which needs to be taken into account when developing specific cognitive therapies for LBD as compared to Alzheimer's. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cognitive dysfunction among newly diagnosed older patients with hematological malignancy: frequency, clinical indicators and predictors.

PubMed

Aiki, Sayo; Okuyama, Toru; Sugano, Koji; Kubota, Yosuke; Imai, Fuminobu; Nishioka, Masahiro; Ito, Yoshinori; Iida, Shinsuke; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Akechi, Tatsuo

2018-01-01

Medical staff often overlook or underestimate the presence or severity of cognitive dysfunction. The purpose of this study was to clarify the frequency, clinical indicators and predictors of cognitive dysfunction among newly diagnosed older patients with hematologic malignancy receiving first-line chemotherapy. Patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were consecutively recruited. Cognitive dysfunction was evaluated using the Mini-Mental State Examination (MMSE) twice: before starting chemotherapy (T1) and 1 month later (T2). Participants also underwent a comprehensive geriatric assessment at T1. Potential clinical indicators that were associated with cognitive dysfunction were explored via cross-sectional analysis at T1. Predictors of cognitive dysfunction at T2 were also investigated among patients without cognitive dysfunction at T1. A total of 145 participants participated in the study; cognitive dysfunction at T1 was present in 20%. Multivariate analysis demonstrated that lower educational attainment and poorer instrumental activities of daily living were significant clinical indicators of cognitive dysfunction. Among 99 patients who did not have cognitive dysfunction at T1 and underwent cognitive assessment at T2, 7% developed dysfunction. Subjective perception of difficulty remembering at T1 was the only factor which significantly predicted new-onset cognitive dysfunction at T2. The prevalence rate of cognitive dysfunction was non-negligible among older patients with hematologic malignancy before and immediately after initial chemotherapy. Attention to the clinical indicators and predictors found in this study may provide facilitate the identification of cognitive dysfunction in patients with cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An fMRI study of multimodal selective attention in schizophrenia

PubMed Central

Mayer, Andrew R.; Hanlon, Faith M.; Teshiba, Terri M.; Klimaj, Stefan D.; Ling, Josef M.; Dodd, Andrew B.; Calhoun, Vince D.; Bustillo, Juan R.; Toulouse, Trent

2015-01-01

Background Studies have produced conflicting evidence regarding whether cognitive control deficits in patients with schizophrenia result from dysfunction within the cognitive control network (CCN; top-down) and/or unisensory cortex (bottom-up). Aims To investigate CCN and sensory cortex involvement during multisensory cognitive control in patients with schizophrenia. Method Patients with schizophrenia and healthy controls underwent functional magnetic resonance imaging while performing a multisensory Stroop task involving auditory and visual distracters. Results Patients with schizophrenia exhibited an overall pattern of response slowing, and these behavioural deficits were associated with a pattern of patient hyperactivation within auditory, sensorimotor and posterior parietal cortex. In contrast, there were no group differences in functional activation within prefrontal nodes of the CCN, with small effect sizes observed (incongruent–congruent trials). Patients with schizophrenia also failed to upregulate auditory cortex with concomitant increased attentional demands. Conclusions Results suggest a prominent role for dysfunction within auditory, sensorimotor and parietal areas relative to prefrontal CCN nodes during multisensory cognitive control. PMID:26382953

A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway

PubMed Central

Pinault, Didier

2017-01-01

Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30–80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders. PMID:28350371

A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway.

PubMed

Pinault, Didier

2017-03-28

Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30-80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N - methyl -d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders.

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes.

PubMed

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong

2018-05-01

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.

Altered Brain Connectivity in Early Postmenopausal Women with Subjective Cognitive Impairment

PubMed Central

Vega, Jennifer N.; Zurkovsky, Lilia; Albert, Kimberly; Melo, Alyssa; Boyd, Brian; Dumas, Julie; Woodward, Neil; McDonald, Brenna C.; Saykin, Andrew J.; Park, Joon H.; Naylor, Magdalena; Newhouse, Paul A.

2016-01-01

Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50–60) in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance. PMID:27721740

Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

PubMed

Kesler, Shelli R; Adams, Marjorie; Packer, Melissa; Rao, Vikram; Henneghan, Ashley M; Blayney, Douglas W; Palesh, Oxana

2017-03-01

Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics ( p  = .046) and cognitive functioning ( p  < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering ( p  < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls ( p  = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction ( p  = .005). Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

Disrupted reward and cognitive control networks contribute to anhedonia in depression.

PubMed

Gong, Liang; He, Cancan; Zhang, Haisan; Zhang, Hongxing; Zhang, Zhijun; Xie, Chunming

2018-08-01

Neuroimaging studies have identified that anhedonia, a core feature of major depressive disorder (MDD), is associated with dysfunction in reward and cognitive control processing. However, it is still not clear how the reward network (β-network) and the cognitive control network (δ-network) are linked to biased anhedonia in MDD patients. Sixty-eight MDD patients and 64 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. A 2*2 ANCOVA analysis was used to explore the differences in the nucleus accumbens-based, voxelwise functional connectivity (FC) between the groups. Then, the β- and δ-networks were constructed, and the FC intensities were compared within and between theβ- and δ-networks across all subjects. Multiple linear regression analyses were also employed to investigate the relationships between the neural features of the β- and δ-networks and anhedonia in MDD patients. Compared to the CN subjects, the MDD patients showed synergistic functional decoupling in both the β- and δ-networks, as well as decreased FC intensities in the intra- and inter- β- and δ-networks. In addition, the FC in both the β- and δ-networks was significantly correlated with anhedonia severity in the MDD patients. Importantly, the integrated neural features of the β- and δ-networks could more precisely predict anhedonic symptoms. These findings initially demonstrated that the imbalance between β- and δ-network activity successfully predicted anhedonia severity and suggested that the neural features of both the β- and δ-networks could represent a fundamental mechanism that underlies anhedonia in MDD patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction

PubMed Central

Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

2016-01-01

Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It seems that the OT system is a critical factor for the development of addiction. So we then discuss strategies to treat drug addiction with OT, and suggest that future research should further investigate OT system interventions aiming to improve cognitive control and/or social cognition functions, in order to develop strategies designed to more effectively treat drug addiction. PMID:27713720

Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction.

PubMed

Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

2016-01-01

Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It seems that the OT system is a critical factor for the development of addiction. So we then discuss strategies to treat drug addiction with OT, and suggest that future research should further investigate OT system interventions aiming to improve cognitive control and/or social cognition functions, in order to develop strategies designed to more effectively treat drug addiction.

Neuropsychological Impairments in Schizophrenia and Psychotic Bipolar Disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study

PubMed Central

Hill, S. Kristian; Reilly, James L.; Keefe, Richard S.E.; Gold, James M.; Bishop, Jeffrey R.; Gershon, Elliot S.; Tamminga, Carol A.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Sweeney, John A.

2017-01-01

Objective Familial neuropsychological deficits are well established in schizophrenia but remain less well characterized in other psychotic disorders. This study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium 1) compares cognitive impairment in schizophrenia and bipolar disorder with psychosis, 2) tests a continuum model of cognitive dysfunction in psychotic disorders, 3) reports familiality of cognitive impairments across psychotic disorders, and 4) evaluates cognitive impairment among nonpsychotic relatives with and without cluster A personality traits. Method Participants included probands with schizophrenia (N=293), psychotic bipolar disorder (N=227), schizoaffective disorder (manic, N=110; depressed, N=55), their first-degree relatives (N=316, N=259, N=133, and N=64, respectively), and healthy comparison subjects (N=295). All participants completed the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery. Results Cognitive impairments among psychotic probands, compared to healthy comparison subjects, were progressively greater from bipolar disorder (z=−0.77) to schizoaffective disorder (manic z=−1.08; depressed z=−1.25) to schizophrenia (z=−1.42). Profiles across subtests of the BACS were similar across disorders. Familiality of deficits was significant and comparable in schizophrenia and bipolar disorder. Of particular interest were similar levels of neuropsychological deficits in relatives with elevated cluster A personality traits across proband diagnoses. Nonpsychotic relatives of schizophrenia probands without these personality traits exhibited significant cognitive impairments, while relatives of bipolar probands did not. Conclusions Robust cognitive deficits are present and familial in schizophrenia and psychotic bipolar disorder. Severity of cognitive impairments across psychotic disorders was consistent with a continuum model, in which more prominent affective features and less enduring psychosis were associated with less cognitive impairment. Cognitive dysfunction in first-degree relatives is more closely related to psychosis-spectrum personality disorder traits in psychotic bipolar disorder than in schizophrenia. PMID:23771174

Gestational Age is Dimensionally Associated with Structural Brain Network Abnormalities Across Development.

PubMed

Nassar, Rula; Kaczkurkin, Antonia N; Xia, Cedric Huchuan; Sotiras, Aristeidis; Pehlivanova, Marieta; Moore, Tyler M; Garcia de La Garza, Angel; Roalf, David R; Rosen, Adon F G; Lorch, Scott A; Ruparel, Kosha; Shinohara, Russell T; Davatzikos, Christos; Gur, Ruben C; Gur, Raquel E; Satterthwaite, Theodore D

2018-04-21

Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

Characterizing Attention with Predictive Network Models.

PubMed

Rosenberg, M D; Finn, E S; Scheinost, D; Constable, R T; Chun, M M

2017-04-01

Recent work shows that models based on functional connectivity in large-scale brain networks can predict individuals' attentional abilities. While being some of the first generalizable neuromarkers of cognitive function, these models also inform our basic understanding of attention, providing empirical evidence that: (i) attention is a network property of brain computation; (ii) the functional architecture that underlies attention can be measured while people are not engaged in any explicit task; and (iii) this architecture supports a general attentional ability that is common to several laboratory-based tasks and is impaired in attention deficit hyperactivity disorder (ADHD). Looking ahead, connectivity-based predictive models of attention and other cognitive abilities and behaviors may potentially improve the assessment, diagnosis, and treatment of clinical dysfunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large-Scale Brain Network Coupling Predicts Total Sleep Deprivation Effects on Cognitive Capacity

PubMed Central

Wang, Lubin; Zhai, Tianye; Zou, Feng; Ye, Enmao; Jin, Xiao; Li, Wuju; Qi, Jianlin; Yang, Zheng

2015-01-01

Interactions between large-scale brain networks have received most attention in the study of cognitive dysfunction of human brain. In this paper, we aimed to test the hypothesis that the coupling strength of large-scale brain networks will reflect the pressure for sleep and will predict cognitive performance, referred to as sleep pressure index (SPI). Fourteen healthy subjects underwent this within-subject functional magnetic resonance imaging (fMRI) study during rested wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Self-reported scores of sleepiness were higher for TSD than for RW. A subsequent working memory (WM) task showed that WM performance was lower after 36 h of TSD. Moreover, SPI was developed based on the coupling strength of salience network (SN) and default mode network (DMN). Significant increase of SPI was observed after 36 h of TSD, suggesting stronger pressure for sleep. In addition, SPI was significantly correlated with both the visual analogue scale score of sleepiness and the WM performance. These results showed that alterations in SN-DMN coupling might be critical in cognitive alterations that underlie the lapse after TSD. Further studies may validate the SPI as a potential clinical biomarker to assess the impact of sleep deprivation. PMID:26218521

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder.

PubMed

Konrad, Kerstin; Eickhoff, Simon B

2010-06-01

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. (c) 2010 Wiley-Liss, Inc.

Abnormal amyloid β42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease.

PubMed

Vinothkumar, G; Kedharnath, C; Krishnakumar, S; Sreedhar, S; Preethikrishnan, K; Dinesh, S; Sundaram, A; Balakrishnan, D; Shivashekar, G; Sureshkumar; Venkataraman, P

2017-12-01

Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aβ production. The aim of this study is to assess the antioxidant status and Aβ 42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction. A total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aβ 42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aβ level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects. Like AD subjects, significantly increased Aβ and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects. Results suggest that elevated plasma oxidative stress and Aβ were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.

Impaired orienting in youth with Internet Addiction: Evidence from the Attention Network Task (ANT).

PubMed

Fu, Jia; Xu, Peng; Zhao, Lun; Yu, Guoming

2018-06-01

An important theory of attention suggests that there are three separate networks that execute discrete cognitive functions: alerting, orienting and conflict networks. Recent studies showed that there was a dysfunction of attention in Internet Addiction. In order to investigate the underlying mechanism of attention dysfunction in Internet Addiction, we recorded performance related to the Attentional Network Test (ANT) in youth. The ANT, a behavioral assay of the functional integrity of attention networks, was used to examine the performance in Internet Addiction and healthy controls. Performance on the ANT clearly differentiated the participants with and without Internet Addiction in terms of mean reaction times (RTs). Compared with control group, the Internet Addiction group detected targets more slowly and this effect was evident only for spatial cue condition. The Internet Addiction group demonstrated deficits in the orienting network in terms of slower RT. There was no demonstration of a deficit in both the alerting and conflict network in Internet Addiction on this task. The youth with Internet Addiction demonstrated deficits in the orienting network but normal functioning of the alerting and conflict attention networks. Copyright © 2017 Elsevier B.V. All rights reserved.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

PubMed Central

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-01

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

PubMed

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-24

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

PubMed Central

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

PubMed

Rabinowitz, Amanda R; Arnett, Peter A

2009-09-01

Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

Multiple cortical thickness sub-networks and cognitive impairments in first episode, drug naïve patients with late life depression: A graph theory analysis.

PubMed

Shin, Jeong-Hyeon; Um, Yu Hyun; Lee, Chang Uk; Lim, Hyun Kook; Seong, Joon-Kyung

2018-03-15

Coordinated and pattern-wise changes in large scale gray matter structural networks reflect neural circuitry dysfunction in late life depression (LLD), which in turn is associated with emotional dysregulation and cognitive impairments. However, due to methodological limitations, there have been few attempts made to identify individual-level structural network properties or sub-networks that are involved in important brain functions in LLD. In this study, we sought to construct individual-level gray matter structural networks using average cortical thicknesses of several brain areas to investigate the characteristics of the gray matter structural networks in normal controls and LLD patients. Additionally, we investigated the structural sub-networks correlated with several clinical measurements including cognitive impairment and depression severity. We observed that small worldness, clustering coefficients, global and local efficiency, and hub structures in the brains of LLD patients were significantly different from healthy controls. We further found that a sub-network including the anterior cingulate, dorsolateral prefrontal cortex and superior prefrontal cortex is significantly associated with attention control and executive function. The severity of depression was associated with the sub-networks comprising the salience network, including the anterior cingulate and insula. We investigated cortico-cortical connectivity, but omitted the subcortical structures such as the striatum and thalamus. We report differences in patterns between several clinical measurements and sub-networks from large-scale and individual-level cortical thickness networks in LLD. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of Common Neural Circuit Disruptions in Cognitive Control Across Psychiatric Disorders.

PubMed

McTeague, Lisa M; Huemer, Julia; Carreon, David M; Jiang, Ying; Eickhoff, Simon B; Etkin, Amit

2017-07-01

Cognitive deficits are a common feature of psychiatric disorders. The authors investigated the nature of disruptions in neural circuitry underlying cognitive control capacities across psychiatric disorders through a transdiagnostic neuroimaging meta-analysis. A PubMed search was conducted for whole-brain functional neuroimaging articles published through June 2015 that compared activation in patients with axis I disorders and matched healthy control participants during cognitive control tasks. Tasks that probed performance or conflict monitoring, response inhibition or selection, set shifting, verbal fluency, and recognition or working memory were included. Activation likelihood estimation meta-analyses were conducted on peak voxel coordinates. The 283 experiments submitted to meta-analysis included 5,728 control participants and 5,493 patients with various disorders (schizophrenia, bipolar or unipolar depression, anxiety disorders, and substance use disorders). Transdiagnostically abnormal activation was evident in the left prefrontal cortex as well as the anterior insula, the right ventrolateral prefrontal cortex, the right intraparietal sulcus, and the midcingulate/presupplementary motor area. Disruption was also observed in a more anterior cluster in the dorsal cingulate cortex, which overlapped with a network of structural perturbation that the authors previously reported in a transdiagnostic meta-analysis of gray matter volume. These findings demonstrate a common pattern of disruption across major psychiatric disorders that parallels the "multiple-demand network" observed in intact cognition. This network interfaces with the anterior-cingulo-insular or "salience network" demonstrated to be transdiagnostically vulnerable to gray matter reduction. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology. Dysfunction in these networks may reflect an intermediate transdiagnostic phenotype, which could be leveraged to advance therapeutics.

Cognition and dementia in older patients with epilepsy

PubMed Central

Sen, Arjune; Capelli, Valentina

2018-01-01

Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising the possibility that better understanding of shared mechanisms in these conditions might help to ameliorate not just seizures, but also epileptogenesis and cognitive dysfunction. PMID:29506031

Regulatory RNAs and control of epigenetic mechanisms: expectations for cognition and cognitive dysfunction.

PubMed

Butler, Anderson A; Webb, William M; Lubin, Farah D

2016-01-01

The diverse functions of noncoding RNAs (ncRNAs) can influence virtually every aspect of the transcriptional process including epigenetic regulation of genes. In the CNS, regulatory RNA networks and epigenetic mechanisms have broad relevance to gene transcription changes involved in long-term memory formation and cognition. Thus, it is becoming increasingly clear that multiple classes of ncRNAs impact neuronal development, neuroplasticity, and cognition. Currently, a large gap exists in our knowledge of how ncRNAs facilitate epigenetic processes, and how this phenomenon affects cognitive function. In this review, we discuss recent findings highlighting a provocative role for ncRNAs including lncRNAs and piRNAs in the control of epigenetic mechanisms involved in cognitive function. Furthermore, we discuss the putative roles for these ncRNAs in cognitive disorders such as schizophrenia and Alzheimer's disease.

Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

PubMed

de Schipper, Laura J; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2017-01-01

In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data. 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD. The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = - 0.265, η p 2  = 0.070) and p = 0.001 (β = - 0.264, η p 2  = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks. We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

2012-03-01

Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

Transdiagnostic Associations Between Functional Brain Network Integrity and Cognition.

PubMed

Sheffield, Julia M; Kandala, Sridhar; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Sweeney, John A; Clementz, Brett A; Lerman-Sinkoff, Dov B; Hill, S Kristian; Barch, Deanna M

2017-06-01

Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs. To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains. A total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017. The Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested. The final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = -0.037; 95% CI, -0.076 to -0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009). These findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

PubMed

Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Neuroplasticity-based computerized cognitive remediation for geriatric depression.

PubMed

Morimoto, Sarah Shizuko; Wexler, Bruce E; Alexopoulos, George S

2012-12-01

This article describes a novel treatment model designed to target specific neurocognitive deficits in geriatric depression with neuroplasticity-based computerized cognitive remediation (NBCCR). The recent National Institute of Mental Health (NIMH) report "From Discovery to Cure" calls for studies focusing on mechanisms of treatment response with the goal of arriving at new interventions for those who do not respond to existing treatments. We describe the process that led to the identification of specific executive deficits and their underlying neurobiology, as well as the rationale for targeting these symptoms as a part of a strategy intended to improve both executive dysfunction and depression. We then propose a strategy for further research in this emerging area. Despite significant developments, conventional antidepressant treatments leave many older adults still depressed and suffering. Psychotherapy may be effective in some depressed elders, although a recent review concluded that none of the available treatment studies meets stringent criteria for efficacy in the acute treatment of geriatric depression. Appropriately developed and targeted NBCCR, has the potential to serve as a novel treatment intervention for geriatric depression. Pathophysiological changes associated with executive dysfunction may be an appropriate target for NBCCR. Examining both behavioral changes and indices of structural integrity and functional change of networks related to cognitive and emotional regulation may lead to a novel treatment and elucidate the role of specific cerebral networks in geriatric depression. Copyright © 2012 John Wiley & Sons, Ltd.

Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke

PubMed Central

Gottesman, Rebecca F; Hillis, Argye E

2013-01-01

Stroke remains a primary cause of morbidity throughout the world mainly because of its effect on cognition. Individuals can recover from physical disability resulting from stroke, but might be unable to return to their previous occupations or independent life because of cognitive impairments. Cognitive dysfunction ranges from focal deficits, resulting directly from an area of infarction or from hypoperfusion in adjacent tissue, to more global cognitive dysfunction. Global dysfunction is likely to be related to other underlying subclinical cerebrovascular disease, such as white-matter disease or subclinical infarcts. Study of cognitive dysfunction after stroke is complicated by varying definitions and lack of measurement of cognition before stroke. Additionally, stroke can affect white-matter connectivity, so newer imaging techniques, such as diffusion-tensor imaging and magnetisation transfer imaging, that can be used to assess this subclinical injury are important tools in the assessment of cognitive dysfunction after stroke. As research is increasingly focused on the role of preventable risk factors in the development of dementia, the role of stroke in the development of cognitive impairment and dementia could be another target for prevention. PMID:20723846

Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function.

PubMed

Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A

2014-05-01

Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. To test the hypothesis that the strength of coupling among 3 large-scale brain networks--salience, executive control, and default mode--will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. Twenty-four hours of abstinence vs smoking satiety. Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = -0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = -0.66, P = .003; posterior cingulate cortex, r = -0.65, P = .001). Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Meta-connectomics: human brain network and connectivity meta-analyses.

PubMed

Crossley, N A; Fox, P T; Bullmore, E T

2016-04-01

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors

PubMed Central

Ullrich, Nicole J.; Whelen, Megan J.; Lange, Beverly J.

2014-01-01

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes. PMID:25080574

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.

PubMed

Padula, Maria C; Schaer, Marie; Scariati, Elisa; Maeder, Johanna; Schneider, Maude; Eliez, Stephan

2017-04-01

Large-scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting-state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty-three patients with 22q11DS and sixty-eighty controls (age 6-33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between-network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177-2189, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Brain activation patterns elicited by the 'Faces Symbol Test' -- a pilot fMRI study.

PubMed

Grabner, Rh; Popotnig, F; Ropele, S; Neuper, C; Gorani, F; Petrovic, K; Ebner, F; Strasser-Fuchs, S; Fazekas, F; Enzinger, C

2008-04-01

The Faces Symbol Test (FST) has recently been proposed as a brief and patient-friendly screening instrument for the assessment of cognitive dysfunction in patients with multiple sclerosis (MS). However, in contrast to well-established MS screening tests such as the Paced Auditory Serial Addition Test, the neural correlates of the FST have not been investigated so far. In the present study, we developed a functional MRI (fMRI) version of the FST to provide first data on brain regions and networks involved in this test. A sample of 19 healthy participants completed a version of the FST adapted for fMRI, requiring matching of faces and symbols in a multiple choice test and two further experimental conditions drawing on cognitive subcomponents (face matching and symbol matching). Imaging data showed a differential involvement of a fronto-parieto-occipital network in the three conditions. The most demanding FST condition elicited brain activation patterns related with sustained attention and executive control. These results suggest that the FST recruits brain networks critical for higher-order cognitive functions often impaired in MS patients.

Deficient attention is hard to find: applying the perceptual load model of selective attention to attention deficit hyperactivity disorder subtypes.

PubMed

Huang-Pollock, Cynthia L; Nigg, Joel T; Carr, Thomas H

2005-11-01

Whether selective attention is a primary deficit in childhood Attention Deficit Hyperactivity Disorder (ADHD) remains in active debate. We used the perceptual load paradigm to examine both early and late selective attention in children with the Primarily Inattentive (ADHD-I) and Combined subtypes (ADHD-C) of ADHD. No evidence emerged for selective attention deficits in either of the subtypes, but sluggish cognitive tempo was associated with abnormal early selection. At least some, and possibly most, children with DSM-IV ADHD have normal selective attention. Results support the move away from theories of attention dysfunction as primary in ADHD-C. In ADHD-I, this was one of the first formal tests of posterior attention network dysfunction, and results did not support that theory. However, ADHD children with sluggish cognitive tempo (SCT) warrant more study for possible early selective attention deficits.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications.

PubMed

Christidi, Foteini; Migliaccio, Raffaella; Santamaría-García, Hernando; Santangelo, Gabriella; Trojsi, Francesca

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

PubMed Central

Santamaría-García, Hernando; Santangelo, Gabriella

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAβPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment

PubMed Central

Wang, Jian-hui; Cheng, Xiao-rui; Zhang, Xiao-rui; Wang, Tong-xing; Xu, Wen-jian; Li, Fei; Liu, Feng; Cheng, Jun-ping; Bo, Xiao-chen; Wang, Sheng-qi; Zhou, Wen-xia; Zhang, Yong-xiang

2016-01-01

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1β, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug. PMID:27049828

Informant Perceptions of the Cause of Activities of Daily Living Difficulties in Parkinson's Disease.

PubMed

Benge, Jared F; Balsis, Steve

2016-01-01

Individuals with Parkinson's disease (PD) can have difficulties with activities of daily living (ADL) that stem from cognitive, motor, or affective manifestations of the disease. Accurately attributing ADL difficulty specifically to cognitive decline is critical when conducting a neuropsychological evaluation of a person with PD. Informant description of ADL performance is frequently used for this purpose, but there has been little work assessing informants' ability to attribute ADL dysfunction to a specific symptom source in PD. Fifty community dwelling individuals with PD completed cognitive, motor, and affective measures. A knowledgeable informant completed an ADL scale that asked about degree and perceived source of difficulty (cognitive, motor, affective) for each task. Informants indicated that motor dysfunction was the most common source of ADL difficulty, but the informants viewed difficulty with certain tasks, such as financial management, as particularly related to cognitive dysfunction. Informant reports of the source of ADL dysfunction (cognitive, motor, affective) were consistent with clinical measures of those specific dysfunctions. ADL dysfunction attributed to cognition specifically (χ(2) = 9.80, p = .01) was higher in those with measurable cognitive impairment. Informant reports of the sources of ADL dysfunction correlate with clinical measures of these symptoms, suggesting that informants may provide useful clinical information about the cause of ADL dysfunction in persons with PD.

Analysing UK clinicians' understanding of cognitive symptoms in major depression: A survey of primary care physicians and psychiatrists.

PubMed

McAllister-Williams, R Hamish; Bones, Kate; Goodwin, Guy M; Harrison, John; Katona, Cornelius; Rasmussen, Jill; Strong, Sarah; Young, Allan H

2017-01-01

Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians. A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research. There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic. Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers. UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

PubMed

Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

2008-12-01

This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

Abnormal spontaneous brain activity is associated with impaired emotion and cognition in hyperthyroidism: A rs-fMRI study.

PubMed

Zhi, Mengmeng; Hou, Zhenghua; We, Qiong; Zhang, Yuqun; Li, Ling; Yuan, Yonggui

2018-06-07

Hyperthyroid patients undergo emotional and cognitive dysfunction. However, the neurological basis for it remains ambiguous. Amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to investigate abnormal spontaneous activity in hyperthyroidism for the first time. 29 hyperthyroid patients and 29 healthy controls (HC) received 3.0T magnetic resonance imaging (MRI) scans and neuropsychological assessments. Compared with HC, hyperthyroid patients showed decreased ALFF in left medial frontal gyrus (MeFG) and left posterior cingulate cortex (PCC). Hyperthyroidism group exhibited decreased ReHo in left MeFG. Within hyperthyroidism group, ALFF values in left MeFG were positively correlated with Hamilton Anxiety Rating Scale (HARS) Z-scores, but negatively correlated with processing speed Z-scores. Besides, ALFF values in left precuneus had a positive correlation with HARS Z-scores. As a result, abnormal brain spontaneous activity mainly in default mode network (DMN) implicated the neuro-pathological substrate of relevant emotional and cognitive dysfunction in hyperthyroid patients. Copyright © 2018 Elsevier B.V. All rights reserved.

A neural model of mechanisms of empathy deficits in narcissism

PubMed Central

Jankowiak-Siuda, Kamila; Zajkowski, Wojciech

2013-01-01

From a multidimensional perspective, empathy is a process that includes affective sharing and imagining and understanding the emotions of others. The primary brain structures involved in mediating the components of empathy are the anterior insula (AI), the anterior cingulate cortex (ACC), and specific regions of the medial prefrontal cortex (MPFC). The AI and ACC are the main nodes in the salience network (SN), which selects and coordinates the information flow from the intero- and exteroreceptors. AI might play a role as a crucial hub – a dynamic switch between 2 separate networks of cognitive processing: the central executive network (CEN), which is concerned with effective task execution, and the default mode network (DMN), which is involved with self-reflective processes. Given various classifications, a deficit in empathy may be considered a central dysfunctional trait in narcissism. A recent fMRI study suggests that deficit in empathy is due to a dysfunction in the right AI. Based on the acquired data, we propose a theoretical model of imbalanced SN functioning in narcissism in which the dysfunctional AI hub is responsible for constant DMN activation, which, in turn, centers one’s attention on the self. This might hinder the ability to affectively share and understand the emotions of others. This review paper on neural mechanisms of empathy deficits in narcissism aims to inspire and direct future research in this area. PMID:24189465

CAN NONINVASIVE BRAIN STIMULATION ENHANCE COGNITION IN NEUROPSYCHIATRIC DISORDERS?

PubMed Central

Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Pascual-Leone, Alvaro

2013-01-01

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient’s quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer’s disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. PMID:22749945

Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

PubMed

Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

2015-03-13

As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

PubMed

Srisurapanont, Manit; Mok, Yee Ming; Yang, Yen Kuang; Chan, Herng-Nieng; Della, Constantine D; Zainal, Nor Zuraida; Jambunathan, Stephen; Amir, Nurmiati; Kalita, Pranab

2018-05-01

Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ± 6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ± 16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

PubMed

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

GABA Neurons and the Mechanisms of Network Oscillations: Implications for Understanding Cortical Dysfunction in Schizophrenia

PubMed Central

Gonzalez-Burgos, Guillermo; Lewis, David A.

2008-01-01

Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical γ-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type–specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value. PMID:18586694

GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia.

PubMed

Gonzalez-Burgos, Guillermo; Lewis, David A

2008-09-01

Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical gamma-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type-specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

PubMed

Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

2017-09-12

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

Increased Resting-State Functional Connectivity in the Cingulo-Opercular Cognitive-Control Network after Intervention in Children with Reading Difficulties

PubMed Central

Horowitz-Kraus, Tzipi; Toro-Serey, Claudio; DiFrancesco, Mark

2015-01-01

Dyslexia, or reading difficulty, is characterized by slow, inaccurate reading accompanied by executive dysfunction. Reading training using the Reading Acceleration Program improves reading and executive functions in both children with dyslexia and typical readers. This improvement is associated with increased activation in and functional connectivity between the anterior cingulate cortex, part of the cingulo-opercular cognitive-control network, and the fusiform gyrus during a reading task after training. The objective of the current study was to determine whether the training also has an effect on functional connectivity of the cingulo-opercular and fronto-parietal cognitive-control networks during rest in children with dyslexia and typical readers. Fifteen children with reading difficulty and 17 typical readers (8-12 years old) were included in the study. Reading and executive functions behavioral measures and resting-state functional magnetic resonance imaging data were collected before and after reading training. Imaging data were analyzed using a graphical network-modeling tool. Both reading groups had increased reading and executive-functions scores after training, with greater gains among the dyslexia group. Training may have less effect on cognitive control in typical readers and a more direct effect on the visual area, as previously reported. Statistical analysis revealed that compared to typical readers, children with reading difficulty had significantly greater functional connectivity in the cingulo-opercular network after training, which may demonstrate the importance of cognitive control during reading in this population. These results support previous findings of increased error-monitoring activation after reading training in children with dyslexia and confirm greater gains with training in this group. PMID:26197049

Therapeutic impact of rHuEPO on abnormal platelet APP, BACE 1, presenilin 1, ADAM 10 and Aβ expressions in chronic kidney disease patients with cognitive dysfunction like Alzheimer's disease: A pilot study.

PubMed

G, Vinothkumar; S, Krishnakumar; Sureshkumar; G, Shivashekar; S, Sreedhar; Preethikrishnan; S, Dinesh; A, Sundaram; D, Balakrishnan; Riya; P, Venkataraman

2018-08-01

Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent. The aim of the study is to determine the impact of rHuEPO therapy on platelet APP processing in CKD with Cognitive Dysfunction. A total of 60 subjects comprising of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment. APP, BACE1, Presenilin 1, ADAM 10 (α secretase) and Aβ expressions in platelets were determined by western blotting and lipid peroxidation (LPO) in platelet rich plasma (PRP) was done by spectrophotometrically. The parameters were statistically compared with Alzheimer's disease (AD), Normocytic normochromic anemic and healthy subjects. Significantly (p < 0.05) decreased APP, ADAM 10 while increased BACE1, Presenilin 1, Aβ and LPO were observed in CKD with cognitive dysfunction like AD subjects compared to other groups. The parameters were reassessed in CKD with cognitive dysfunction subjects after rHuEPO (100 IU/ kg, weekly twice, 6 months) therapy. All the parameters were retrieved significantly (p < 0.05) along with improved neuropsychological tests scoring after rHuEPO therapy. This study demonstrated that rHuEPO is an effective neuroprotective agent in the context of CKD associated cognitive dysfunction and proved its clinical usefulness. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

PubMed

Ide, Kazuki; Yamada, Hiroshi; Takuma, Norikata; Park, Mijong; Wakamiya, Noriko; Nakase, Junpei; Ukawa, Yuuichi; Sagesaka, Yuko M

2014-09-29

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants' MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.

Cognitive-Behavioral Erectile Dysfunction Treatment for Gay Men

ERIC Educational Resources Information Center

Hart, Trevor A.; Schwartz, Danielle R.

2010-01-01

The purpose of the present paper is to assist cognitive-behavioral therapists who are treating erectile dysfunction among gay men. Little information is available to cognitive-behavioral therapists about the psychological and social effects of erectile dysfunction in this population, or how to incorporate the concerns of gay men with erectile…

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

PubMed

Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

2015-10-01

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

PubMed

Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M; Pascual-Leone, Alvaro

2013-01-01

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maternal Depressive Symptoms, Dysfunctional Cognitions, and Infant Night Waking: The Role of Maternal Nighttime Behavior

ERIC Educational Resources Information Center

Teti, Douglas M.; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via…

Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.

PubMed

Ruggero, Camilo J; Bain, Kathleen M; Smith, Patrick M; Kilmer, Jared N

2015-07-01

Individuals with bipolar disorder often endorse dysfunctional beliefs consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007). The present study sought to assess whether young adult offspring of those with bipolar disorder would also endorse these beliefs, independent of their own mood episode history. Participants (N = 89) were young adult college students with a parent with bipolar disorder (n = 27), major depressive disorder (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck and colleagues' (2006) and Mansell's (2007) cognitive models were assessed. Unlike offspring of parents with MDD or no mood disorder, those with a parent with bipolar disorder endorsed significantly more dysfunctional cognitions associated with extreme appraisal of mood states, even after controlling for their own mood diagnosis. Once affected by a bipolar or depressive disorder, offspring endorsed dysfunctional cognitions across measures. Dysfunctional cognitions, particularly those related to appraisals of mood states and their potential consequences, are evident in young adults with a parent who has bipolar disorder and may represent targets for psychotherapeutic intervention.

Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle

PubMed Central

Larson-Prior, Linda J.; Ju, Yo-El; Galvin, James E.

2014-01-01

Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. PMID:25309500

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

PubMed

Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun

2009-06-01

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Cognitive Dysfunction in Asian Patients with Depression (CogDAD): A Cross-Sectional Study

PubMed Central

Manit, Srisurapanont; Yee Ming, Mok; Yen Kuang, Yang; Herng-Nieng, Chan; Constantine D, Della; Zuraida, Zainal, Nor; Stephen, Jambunathan; Nurmiati, Amir; Pranabi, Kalita

2017-01-01

Background: Cognitive dysfunction is a predominant symptom of Major Depressive Disorder (MDD), contributing to functional impairment. Objective: The primary objective of this study was to assess and describe perceived cognitive dysfunction amongst Asian patients diagnosed with MDD. The secondary objective was to explore the associations between depression severity, perceived cognitive dysfunction and functional disability. Methods: This was a multi-country, multi-centre, cross-sectional study. Adults with a current episode of MDD were recruited from 9 university/general hospital clinics in Asia. During a single study visit, psychiatrists assessed depression severity (Clinical Global Impression-Severity, CGI-S); patients completed questionnaires assessing depression severity (Patient Health Questionnaire-9 items, PHQ-9), perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D) and functional disability (Sheehan Disability Scale, SDS). Results: Patients (n=664), predominantly women (66.3%), were aged 46.5±12.5 years, lived in urban areas (81.3%) and were employed (84.6%). 51.5% of patients were having their first depressive episode; 86.7% were receiving treatment; 82.2% had a current episode duration >8 weeks. Patients had mild-to-moderate depression (CGI-S=3.3±1.0; PHQ-9=11.3±6.9). Patients reported perceived cognitive dysfunction (PDQ-D=22.6±16.2) and functional disability (SDS=11.3±7.9). PHQ-9, PDQ-D and SDS were moderately-to-highly correlated (PHQ-9 and SDS: r=0.72; PHQ-9 and PDQ-D: r=0.69; PDQ-D and SDS, r=0.63). ANCOVA showed that after controlling for patient-reported depression severity (PHQ-9), perceived cognitive dysfunction (PDQ-D) was significantly associated with functional disability (SDS) (p<0.001). Conclusions: Asian patients with MDD reported perceived cognitive dysfunction. There is a need for physicians to evaluate cognitive dysfunction in the clinical setting in order to reach treatment goals, including functional recovery beyond remission of mood symptoms. PMID:29238395

Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease.

PubMed

Carter, S F; Embleton, K V; Anton-Rodriguez, J M; Burns, A; Ralph, M A L; Herholz, K

2014-06-01

The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment. © 2014 by American Journal of Neuroradiology.

X-Chromosome Effects on Attention Networks: Insights from Imaging Resting-State Networks in Turner Syndrome.

PubMed

Green, Tamar; Saggar, Manish; Ishak, Alexandra; Hong, David S; Reiss, Allan L

2017-07-18

Attention deficit hyperactivity disorder (ADHD) is strongly affected by sex, but sex chromosomes' effect on brain attention networks and cognition are difficult to examine in humans. This is due to significant etiologic heterogeneity among diagnosed individuals. In contrast, individuals with Turner syndrome (TS), who have substantially increased risk for ADHD symptoms, share a common genetic risk factor related to the absence of the X-chromosome, thus serving as a more homogeneous genetic model. Resting-state functional MRI was employed to examine differences in attention networks between girls with TS (n = 40) and age- sex- and Tanner-matched controls (n = 33). We compared groups on resting-state functional connectivity measures from data-driven independent components analysis (ICA) and hypothesis-based seed analysis. Using ICA, reduced connectivity was observed in both frontoparietal and dorsal attention networks. Similarly, using seeds in the bilateral intraparietal sulcus (IPS), reduced connectivity was observed between IPS and frontal and cerebellar regions. Finally, we observed a brain-behavior correlation between IPS-cerebellar connectivity and cognitive attention measures. These findings indicate that X-monosomy contributes affects to attention networks and cognitive dysfunction that might increase risk for ADHD. Our findings not only have clinical relevance for girls with TS, but might also serve as a biological marker in future research examining the effects of the intervention that targets attention skills. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

From Neurons to Social Beings: Short Review of the Mirror Neuron System Research and Its Socio-Psychological and Psychiatric Implications

PubMed Central

Jeon, Hyeonjin

2018-01-01

The mirror neuron system (MNS) is a brain network activated when we move our body parts and when we observe the actions of other agent. Since the mirror neuron’s discovery in research on monkeys, several studies have examined its network and properties in both animals and humans. This review discusses MNS studies of animals and human MNS studies related to high-order social cognitions such as emotion and empathy, as well as relations between MNS dysfunction and mental disorders. Finally, these evidences are understood from an evolutionary perspective. PMID:29397663

Modulation of the Metabiome by Rifaximin in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

PubMed Central

Bajaj, Jasmohan S.; Heuman, Douglas M.; Sanyal, Arun J.; Hylemon, Phillip B.; Sterling, Richard K.; Stravitz, R. Todd; Fuchs, Michael; Ridlon, Jason M.; Daita, Kalyani; Monteith, Pamela; Noble, Nicole A.; White, Melanie B.; Fisher, Andmorgan; Sikaroodi, Masoumeh; Rangwala, Huzefa; Gillevet, Patrick M.

2013-01-01

Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Methods Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. Results There was a significant improvement in cognition(six of seven tests improved,p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar. Conclusions Rifaximin is associated with improved cognitive function and endotoxemia in MHE, which is accompanied by alteration of gut bacterial linkages with metabolites without significant change in microbial abundance. Trial Registration ClinicalTrials.gov NCT01069133 PMID:23565181

Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.

PubMed

Avery, Suzanne N; Rogers, Baxter P; Heckers, Stephan

2018-05-01

Functional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision. We investigated the modularity of hippocampal resting-state functional networks in a sample of 45 patients with schizophrenia spectrum disorders and 38 healthy control subjects. Modularity was calculated for two distinct functional networks: a core hippocampal-medial temporal lobe cortex network and an extended hippocampal-cortical network. As hippocampal function differs along its longitudinal axis, follow-up analyses examined anterior and posterior networks separately. To explore effects of resting network function on behavior, we tested associations between modularity and relational memory ability. Age, sex, handedness, and parental education were similar between groups. Network modularity was lower in schizophrenia patients, especially in the posterior hippocampal network. Schizophrenia patients also showed markedly lower relational memory ability compared with control subjects. We found a distinct brain-behavior relationship in schizophrenia that differed from control subjects by network and anterior/posterior division-while relational memory in control subjects was associated with anterior hippocampal-cortical modularity, schizophrenia patients showed an association with posterior hippocampal-medial temporal lobe cortex network modularity. Our findings support a model of abnormal resting-state corticohippocampal network coherence in schizophrenia, which may contribute to relational memory deficits. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Towards systems neuroscience of ADHD: A meta-analysis of 55 fMRI studies

PubMed Central

Cortese, Samuele; Kelly, Clare; Chabernaud, Camille; Proal, Erika; Di Martino, Adriana; Milham, Michael P.; Castellanos, F. Xavier

2013-01-01

Objective To perform a comprehensive meta-analysis of task-based functional MRI studies of Attention-Deficit/Hyperactivity Disorder (ADHD). Method PubMed, Ovid, EMBASE, Web of Science, ERIC, CINHAL, and NeuroSynth were searched for studies published through 06/30/2011. Significant differences in activation of brain regions between individuals with ADHD and comparisons were detected using activation likelihood estimation meta-analysis (p<0.05, corrected). Dysfunctional regions in ADHD were related to seven reference neuronal systems. We performed a set of meta-analyses focused on age groups (children; adults), clinical characteristics (history of stimulant treatment; presence of psychiatric comorbidities), and specific neuropsychological tasks (inhibition; working memory; vigilance/attention). Results Fifty-five studies were included (39 in children, 16 in adults). In children, hypoactivation in ADHD vs. comparisons was found mostly in systems involved in executive functions (frontoparietal network) and attention (ventral attentional network). Significant hyperactivation in ADHD vs. comparisons was observed predominantly within the default, ventral attention, and somatomotor networks. In adults, ADHD-related hypoactivation was predominant in the frontoparietal system, while ADHD-related hyperactivation was present in the visual, dorsal attention, and default networks. Significant ADHD-related dysfunction largely reflected task features and was detected even in the absence of comorbid mental disorders or history of stimulant treatment. Conclusions A growing literature provides evidence of ADHD-related dysfunction within multiple neuronal systems involved in higher-level cognitive functions but also in sensorimotor processes, including the visual system, and in the default network. This meta-analytic evidence extends early models of ADHD pathophysiology focused on prefrontal-striatal circuits. PMID:22983386

Subjective cognitive dysfunction in rehabilitation outpatients with musculoskeletal disorders or chronic pain.

PubMed

Schrier, Ernst; Geertzen, Jan H; Dijkstra, Pieter U

2017-08-01

Rehabilitation patients, without brain damage, sometimes complain about poor concentration and problems with their memory. The magnitude and associations, of this cognitive dysfunction, with different factors is unclear. To determine the magnitude of cognitive dysfunction in rehabilitation outpatient and to explore its associations with patient characteristics, diagnosis, surgery, pain, stress, anxiety and depression. Cross-sectional. Rehabilitation outpatients. Between July 2009 and January 2012, 274 rehabilitation outpatients were included and divided in 8 different groups through diagnosis. Cognitive functioning was assessed using the cognitive failure questionnaire and compared with the general Dutch population. Associations of gender, age, diagnosis, recent surgery, pain and stress coping ability with cognitive function was explored. Mediation of depression and anxiety was explored. The rehabilitation patients had a significantly higher score on the CFQ (mean 35.9±13.4) when compared to the general Dutch population (mean 31.8±11.1). Mean difference is 4.1, 95% confidence interval 2.60 to 5.60. In the stepwise linear regression analysis only gender, diagnosis and stress coping ability were significantly associated. A significant mediation effect was found of anxiety (P≤0.001) and depression (P≤0.005) between stress coping ability and cognitive function. Rehabilitation outpatients experience more cognitive problems in comparison to the general Dutch population. Reported dysfunction of cognition in rehabilitation outpatients are associated with stress coping ability and for a small amount to gender and diagnosis. The association of stress coping ability and cognitive dysfunction is mediated by depression and anxiety. Women tend to report more dysfunctional cognition compared to men. Patient characteristics, surgery and experienced pain have no significant influence on the experienced cognitive dysfunction. Cognitive problems reported by patients should be addressed by adapting the rehabilitation program, for instance write down instructions, repeat explanations and take more time for instructions. Cognitive problems in rehabilitation patients without brain damage is probably a stress coping problem and can be addressed by boosting resilience. Targeting depression or anxiety is another option of treatment cognition if those are mediating between stress coping and cognitive problems.

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction

PubMed Central

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-01

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction. PMID:25206795

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction.

PubMed

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-15

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Clinical Epidemiology, Evaluation, and Management of Dementia in Parkinson Disease.

PubMed

Safarpour, Delaram; Willis, Allison W

2016-11-01

The prevalence of neurodegenerative diseases such as Parkinson disease (PD) will increase substantially, due to the aging of the population and improved treatments leading to better disease-related outcomes. Dementia is the most common nonmotor symptom in PD, and most patients with PD will have cognitive dysfunction and cognitive decline in the course of their disease. The development of cognitive dysfunction in PD greatly limits the ability to participate in activities of daily living and can be a tipping point for nursing home placement or major caregiver stress. Understanding the different causes of dementia and how to reduce the incidence and impact of secondary cognitive dysfunction in PD are necessary skills for primary care physicians and neurologists. In this review, we discuss the clinical epidemiology of dementia in PD with an emphasis on preventable cognitive dysfunction, present tools for outpatient evaluation of cognitive dysfunction, and describe current pharmacological treatments for dementia in PD. © The Author(s) 2016.

Association Between Cognitive Function and Health Care Costs 3 Months and 6 Months After Initiating Antidepressant Medication for Depressive Disorders.

PubMed

Walker, Valery; Patel, Haridarshan; Kurlander, Jonathan L; Essoi, Breanna; Yang, Jiao; Mahableshwarkar, Atul R; Samp, Jennifer C; Akhras, Kasem S

2015-09-01

Major depressive disorder is one of the most common and disabling mental health disorders and is associated with substantial costs in terms of direct health care utilization and workplace productivity. Cognitive dysfunction, which alone substantially increases health care costs, is commonly associated with major depressive disorder. However, the health care costs of cognitive dysfunction in the context of depressive disorder are unknown. Recovery from mood symptoms is not always associated with resolution of cognitive dysfunction. Thus, cognitive dysfunction may contribute to health care burden even with successful antidepressant therapy.  To compare health care utilization and costs for patients with a depressive disorder with and without cognitive dysfunction, at 3 and 6 months after initiation of antidepressant medication.  This was an observational study, combining a cross-sectional patient survey, administered during a telephone interview, with health care claims data from a large, geographically diverse U.S. health plan. Included patients had at least 1 pharmacy claim for an antidepressant medication between August 1 and September 30, 2012, and no claim for any antidepressant during the 6 months prior to the index date. In addition to other criteria assessed in the claims data, patients confirmed a diagnosis of depression or major depressive disorder and the absence of any exclusionary neurological diagnoses possibly associated with cognitive impairment. Eligible patients were administered validated cognitive function assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised, Delayed and Total); attention (Digit Span Forward Maximum Sequence Length); working memory (Digit Span Backward Maximum Sequence Length); and executive function (D-KEFS-Letter Fluency Test). Based on comparison of scores with normative data, patients were assigned to cognitive dysfunction or cognitive normal cohorts. All-cause (all diagnoses) and depressive disorder-related health care utilization and costs (all from a payer perspective) were assessed 6 months prior (baseline) to antidepressant initiation and 3 months and 6 months after (follow-up) initiation of antidepressant medication. Health care utilization and costs included ambulatory (office and hospital outpatient), emergency room, inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics), and total (all categories combined). All-cause and depressive disorder-related total costs during the 3- and 6-month follow-up periods were modeled with generalized linear modeling with gamma distribution and log link, while adjusting for potential confounders (age, race, gender, education, employment, and comorbidities). Of the 13,537 patients who were mailed an invitation, 824 (6%) were eligible and agreed to participate. Of these, 563 patients provided informed consent, completed the interview, maintained eligibility, and were included in the 3-month calculations. Among these, 255 (45%) were classified as having cognitive dysfunction. Mean patient age was 41.3 (± 12.5) years; 80% were female. Most patients were white and employed. More patients in the cognitive normal cohort were white (P  less than  0.001) and employed full time (P = 0.029), had higher education attainment (P  less than    0.001), and had fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort. Over the first 3 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive disorder-related costs ($718 vs. $406, P  less than  0.001) than patients without cognitive dysfunction. At 6 months, data from 4 patients were removed from the analysis because of exclusionary diagnoses. Over 6 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive disorder-related costs did not significantly differ between patients with ($771) and without cognitive dysfunction ($594, P = 0.071). The main drivers of all-cause costs were office visits, outpatient hospital visits, and inpatient costs, and the main driver of depressive disorder-related costs was inpatient costs. Cognitive dysfunction was associated with higher adjusted all-cause and depressive disorder-related costs 3 months after initiation of an antidepressant medication. This difference persisted for all-cause costs through 6 months. Identification and treatment of cognitive dysfunction in patients with depressive disorder might reduce health care costs.

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

PubMed Central

2013-01-01

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction. PMID:24156319

Discriminative analysis of non-linear brain connectivity for leukoaraiosis with resting-state fMRI

NASA Astrophysics Data System (ADS)

Lai, Youzhi; Xu, Lele; Yao, Li; Wu, Xia

2015-03-01

Leukoaraiosis (LA) describes diffuse white matter abnormalities on CT or MR brain scans, often seen in the normal elderly and in association with vascular risk factors such as hypertension, or in the context of cognitive impairment. The mechanism of cognitive dysfunction is still unclear. The recent clinical studies have revealed that the severity of LA was not corresponding to the cognitive level, and functional connectivity analysis is an appropriate method to detect the relation between LA and cognitive decline. However, existing functional connectivity analyses of LA have been mostly limited to linear associations. In this investigation, a novel measure utilizing the extended maximal information coefficient (eMIC) was applied to construct non-linear functional connectivity in 44 LA subjects (9 dementia, 25 mild cognitive impairment (MCI) and 10 cognitively normal (CN)). The strength of non-linear functional connections for the first 1% of discriminative power increased in MCI compared with CN and dementia, which was opposed to its linear counterpart. Further functional network analysis revealed that the changes of the non-linear and linear connectivity have similar but not completely the same spatial distribution in human brain. In the multivariate pattern analysis with multiple classifiers, the non-linear functional connectivity mostly identified dementia, MCI and CN from LA with a relatively higher accuracy rate than the linear measure. Our findings revealed the non-linear functional connectivity provided useful discriminative power in classification of LA, and the spatial distributed changes between the non-linear and linear measure may indicate the underlying mechanism of cognitive dysfunction in LA.

The social brain in psychiatric and neurological disorders

PubMed Central

Kennedy, Daniel P.; Adolphs, Ralph

2013-01-01

Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the ‘social brain’. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks. PMID:23047070

Cognitive medicine - a new approach in health care science.

PubMed

Wallin, Anders; Kettunen, Petronella; Johansson, Per M; Jonsdottir, Ingibjörg H; Nilsson, Christer; Nilsson, Michael; Eckerström, Marie; Nordlund, Arto; Nyberg, Lars; Sunnerhagen, Katharina S; Svensson, Johan; Terzis, Beata; Wahlund, Lars-Olof; Georg Kuhn, H

2018-02-08

The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course. Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction. Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status.

PubMed

da Luz, Felipe Q; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A; Swinbourne, Jessica; da Silva, Dhiordan C; da S Oliveira, Margareth

2017-02-28

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants-53 with morbid obesity and 58 of normal weight-were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight.

Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly.

PubMed

Hogan, Kirk J; Bratzke, Lisa C; Hogan, Kendra L

2018-02-01

Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%-15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

PubMed Central

Bi, Yanlin; Liu, Shuyun; Yu, Xinjuan; Wang, Mingshan; Wang, Yuelan

2014-01-01

Inflammation may play a role in postoperative cognitive dysfunction. 5′ Adenosine monophosphate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-α are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5′ adenosine monophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1–7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis factor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats. PMID:25206851

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Cognitive dysfunction in patients with Systemic Lupus Erythematosus.

PubMed

Butt, Bilal Azeem; Farman, Sumaira; Khan, Saira Elaine Anwer; Saeed, Muhammad Ahmed; Ahmad, Nighat Mir

2017-01-01

To determine the frequency of cognitive dysfunction in patients with Systemic Lupus Erythematosus in a Pakistani population, presenting at a tertiary care Rheumatology setting. This cross-sectional study was conducted at the Division of Rheumatology, Fatima Memorial Hospital, Lahore, from March to June 2016. A total of 43 consecutive patients, who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for Systemic Lupus Erythematosus (SLE), were enrolled. Cognitive function was assessed using Montréal Cognitive Assessment (MoCA) questionnaire. Demographic data and disease dynamics were collected in a proforma. Cognitive dysfunction was defined as score < 26/30, adjusted for duration of formal education. SPSS version 16.0 for windows was used to analyse data and to calculate frequency of cognitive dysfunction. Out of 43 enrolled patients, 95.3% were females and 4.7% were males, with mean age of 28.72 ± 9.25 years and mean formal education duration of 10.98 ± 3.29 years. The mean disease duration was 24.21 ± 30.46 months. Anti-nuclear antibodies (ANA) were present in all patients and anti-ds DNA in 93% patients. Cognitive dysfunction according to MoCA score was found in 65.1% (n=28) patients. For patients with disease duration more than two years, cognitive dysfunction was found in 60% patients [p>0.05] and for duration of formal education less than 12 years in 74.1% patients [p>0.05]. In this study, two third of SLE patients had Cognitive dysfunction. Hence, there is an increasing need to recognise and initiate early therapy for this overlooked aspect of SLE with an aim to achieve better quality of life.

Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects on Craving and Cognitive Function

PubMed Central

Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A.

2014-01-01

IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks–salience, executive control, and default mode–will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety. MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = −0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = −0.66, P = .003; posterior cingulate cortex, r = −0.65, P = .001). CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence. PMID:24622915

A cross-sectional study of functional disabilities and perceived cognitive dysfunction in patients with major depressive disorder in South Korea: The PERFORM-K study.

PubMed

Kim, Jae Min; Chalem, Ylana; di Nicola, Sylvia; Hong, Jin Pyo; Won, Seung Hee; Milea, Dominique

2016-05-30

PERFORM-K was a cross-sectional observational study that investigated functional disability, productivity and quality of life in MDD outpatients in South Korea, and the associations of these with depressive symptoms, perceived cognitive dysfunction and other factors. A total of 312 outpatients who started antidepressant monotherapy underwent a single study interview. Physicians and patients assessed depression severity. Patients also assessed: perceived cognitive dysfunction, functional disability, impaired productivity and quality of life. Patients had moderate to severe depression (MADRS mean total score: 28.9±7.3), and reported marked functional disability (SDS mean total score: 16.7±8.6), impaired productivity (WPAI mean overall work productivity loss: 52.4±31.8%), perceived cognitive dysfunction (PDQ-D mean total score: 29.9±18.6) and impaired quality of life (EQ-5D mean utility index score of 0.726±0.192). Greater functional disability and impairment in daily activities were associated with more severe depression and greater perceived cognitive dysfunction. Irrespective of depression severity, patients with more severe perceived cognitive dysfunction reported worse work-related productivity outcomes (higher presenteeism and greater overall work productivity loss). PERFORM-K confirms the impact of MDD on functional status and well-being in South Korean patients, and highlights the importance of recognising cognitive dysfunction in clinical practice. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia.

PubMed

Dermody, Nadene; Wong, Stephanie; Ahmed, Rebekah; Piguet, Olivier; Hodges, John R; Irish, Muireann

2016-05-30

Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.

Meta-analytically informed network analysis of resting state FMRI reveals hyperconnectivity in an introspective socio-affective network in depression.

PubMed

Schilbach, Leonhard; Müller, Veronika I; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

2014-01-01

Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.

Meta-Analytically Informed Network Analysis of Resting State fMRI Reveals Hyperconnectivity in an Introspective Socio-Affective Network in Depression

PubMed Central

Schilbach, Leonhard; Müller, Veronika I.; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto

2014-01-01

Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology. PMID:24759619

Cognitive Rehabilitation for Executive Dysfunction in Parkinson's Disease: Application and Current Directions

PubMed Central

Calleo, Jessica; Burrows, Cristina; Levin, Harvey; Marsh, Laura; Lai, Eugene; York, Michele K.

2012-01-01

Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patient's strengths and deficits. PMID:22135762

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

PubMed

Sachs, G; Katschnig, H

2001-03-01

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

Default Network Modulation and Large-Scale Network Interactivity in Healthy Young and Old Adults

PubMed Central

Schacter, Daniel L.

2012-01-01

We investigated age-related changes in default, attention, and control network activity and their interactions in young and old adults. Brain activity during autobiographical and visuospatial planning was assessed using multivariate analysis and with intrinsic connectivity networks as regions of interest. In both groups, autobiographical planning engaged the default network while visuospatial planning engaged the attention network, consistent with a competition between the domains of internalized and externalized cognition. The control network was engaged for both planning tasks. In young subjects, the control network coupled with the default network during autobiographical planning and with the attention network during visuospatial planning. In old subjects, default-to-control network coupling was observed during both planning tasks, and old adults failed to deactivate the default network during visuospatial planning. This failure is not indicative of default network dysfunction per se, evidenced by default network engagement during autobiographical planning. Rather, a failure to modulate the default network in old adults is indicative of a lower degree of flexible network interactivity and reduced dynamic range of network modulation to changing task demands. PMID:22128194

Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

PubMed

Yamamoto, Hiroshi; Ogawa, Kenichi; Huaman Battifora, Henry; Yamamuro, Kaori; Ishitake, Tatsuya

2018-05-24

Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status

PubMed Central

da Luz, Felipe Q.; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A.; Swinbourne, Jessica; da Silva, Dhiordan C.; da S. Oliveira, Margareth

2017-01-01

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants—53 with morbid obesity and 58 of normal weight—were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight. PMID:28264484

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

PubMed

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial.

PubMed

Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren

2015-10-24

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up. Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive training has the potential to reduce cognitive dysfunctions and to become a new treatment option, which can promote a more normal neural development in young children with ADHD and thus reduce cognitive dysfunctions and symptoms. This could help children with ADHD to perform better in everyday life and school. ClinicalTrials.gov: NCT01752530 , date of registration: 10 December 2012.

Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy.

PubMed

Han, Chuanlai; Fu, Rong; Lei, Weifu

2018-07-01

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

PubMed

Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

2017-06-01

Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus.

PubMed

Massardo, L; Bravo-Zehnder, M; Calderón, J; Flores, P; Padilla, O; Aguirre, J M; Scoriels, L; González, A

2015-05-01

Autoantibodies against N-methyl-D-aspartate receptor (anti-NMDAR) and ribosomal-P (anti-P) antigens are potential pathogenic factors in the frequently observed diffuse brain dysfunctions in patients with systemic lupus erythematosus (SLE). Although studies have been conducted in this area, the role of anti-NMDAR antibodies in SLE cognitive dysfunction remains elusive. Moreover, the specific contribution of anti-P antibodies has not been reported yet. The present study attempts to clarify the contribution of anti-NMDAR and anti-P antibodies to cognitive dysfunction in SLE. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess a wide range of cognitive function areas in 133 Chilean women with SLE. ANCOVA models included autoantibodies, patient and disease features. Cognitive deficit was found in 20%. Higher SLEDAI-2K scores were associated with impairment in spatial memory and learning abilities, whereas both anti-NMDAR and anti-P antibodies contributed to deficits in attention and spatial planning abilities, which reflect fronto-parietal cortex dysfunctions. These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

PubMed

Osawa, Aiko; Maeshima, Shinichiro

2016-04-01

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

PubMed

Zhang, Sheng; Hu, Sien; Sinha, Rajita; Potenza, Marc N; Malison, Robert T; Li, Chiang-Shan R

2016-01-01

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.

Raven's Coloured Progressive Matrices as a Measure of Cognitive Functioning in Cerebral Palsy

ERIC Educational Resources Information Center

Pueyo, R.; Junque, C.; Vendrell, P.; Narberhaus, A.; Segarra, D.

2008-01-01

Background: Cognitive dysfunction is frequent in Cerebral Palsy (CP). CP motor impairment and associated speech deficits often hinder cognitive assessment, with the result being that not all CP studies consider cognitive dysfunction. Raven's Coloured Progressive Matrices is a simple, rapid test which can be used in persons with severe motor…

Cognitive reactivity versus dysfunctional cognitions and the prediction of relapse in recurrent major depressive disorder.

PubMed

Figueroa, Caroline A; Ruhé, Henricus G; Koeter, Maarten W; Spinhoven, Philip; Van der Does, Willem; Bockting, Claudi L; Schene, Aart H

2015-10-01

Major depressive disorder (MDD) is a burdensome disease that has a high risk of relapse/recurrence. Cognitive reactivity appears to be a risk factor for relapse. It remains unclear, however, whether dysfunctional cognitions alone or the reactivity of such cognitions to mild states of sadness (ie, cognitive reactivity) is the crucial factor that increases relapse risk. We aimed to assess the long-term predictive value of cognitive reactivity versus dysfunctional cognitions and other risk factors for depressive relapse. In a prospective cohort of outpatients (N = 116; studied between 2000-2005) who had experienced ≥ 2 previous major depressive episodes (MDEs) and were in remission (DSM-IV) at the start of follow-up, we measured cognitive reactivity, with the Leiden Index of Depression Sensitivity (LEIDS), and dysfunctional cognitions, with the Dysfunctional Attitudes Scale, simultaneously. Course of illness (with the primary outcome of MDE assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) and time to relapse were monitored prospectively for 3.5 years. Cognitive reactivity scores were associated with time to relapse over the 3.5-year follow-up and also when corrected for the number of previous MDEs and concurrent depressive symptoms (hazard ratio for 1 standard deviation [(HR(SD)); 20 points of the LEIDS, measuring cognitive reactivity] = 1.47; 95% CI, 1.04-2.09; P = .031). Rumination appeared to be a particularly strong predictor of relapse (HR(SD) = 1.60; 95% CI, 1.13-2.26; P = .007). Dysfunctional cognitions did not predict relapse over 3.5 years (HR(SD) = 1.00; 95% CI, 0.74-1.37; P = .93). Every 20-point increase on the cognitive reactivity scale resulted in a 10% to 15% increase in risk of relapse (corrected for previous MDEs and concurrent depressive symptoms). Cognitive reactivity--and particularly rumination--is a long-term predictor of relapse. Future research should address whether psychological interventions can improve cognitive reactivity scores and thereby prevent depressive relapses. ISRCTN Identifier: 68246470. © Copyright 2015 Physicians Postgraduate Press, Inc.

Should general anaesthesia be avoided in the elderly?

PubMed Central

Strøm, C.; Rasmussen, L. S.; Sieber, F. E.

2016-01-01

Summary Surgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, manifest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cognitive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderly surgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with a particular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitive decline, and describe the treatment strategies by which such decline may be prevented. PMID:24303859

Mild Cognitive Dysfunction: An Epidemiological Perspective with an Emphasis on African Americans

PubMed Central

Unverzagt, Frederick W.; Gao, Sujuan; Lane, Kathleen A.; Callahan, Christopher; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hall, Kathleen S.; Hendrie, Hugh C.

2009-01-01

In this review, we begin with a historical accounting of the evolution of the concept of mild cognitive dysfunction including nomenclature and criteria from Kral to Petersen. A critical analysis of the main elements relating to assessment and diagnosis of mild cognitive dysfunction are described. Methodological limitations in design, measurement, and characterization, especially as they relate to older African Americans, are identified. Data from a 15-year longitudinal study of community-dwelling, African Americans in Indianapolis indicate 23% prevalence of all-cause mild cognitive dysfunction with approximately 25% progressing to dementia in 2 years and another 25% reverting to normal in the same interval. Factors contributing to this longitudinal variability in outcome are reviewed including the role of medical health factors. We close with suggestions for next steps in the epidemiological research of mild cognitive impairment. PMID:18004008

Cognitive disorders in children's hydrocephalus.

PubMed

Zielińska, Dorota; Rajtar-Zembaty, Anna; Starowicz-Filip, Anna

Hydrocephalus is defined as an increase of volume of cerebrospinal fluid in the ventricular system of the brain. It develops as a result of cerebrospinal fluid flow disorder due to dysfunctions of absorption or, less frequently, as a result of the increase of its production. Hydrocephalus may lead to various cognitive dysfunctions in children. In order to determine cognitive functioning in children with hydrocephalus, the authors reviewed available literature while investigating this subject. The profile of cognitive disorders in children with hydrocephalus may include a wide spectrum of dysfunctions and the process of neuropsychological assessment may be very demanding. The most frequently described cognitive disorders within children's hydrocephalus include attention, executive, memory, visual, spatial or linguistic dysfunctions, as well as behavioral problems. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation.

PubMed

Matt, Stephanie M; Johnson, Rodney W

2016-02-01

Microglia, the resident immune cells of the brain, are at the center of communication between the central nervous system and immune system. While these brain-immune interactions are balanced in healthy adulthood, the ability to maintain homeostasis during aging is impaired. Microglia develop a loss of integrated regulatory networks including aberrant signaling from other brain cells, immune sensors, and epigenetic modifiers. The low-grade chronic neuroinflammation associated with this dysfunctional activity likely contributes to cognitive deficits and susceptibility to age-related pathologies. A better understanding of the underlying mechanisms responsible for neuro-immune dysregulation with age is crucial for providing targeted therapeutic strategies to support brain repair and healthy aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder.

PubMed

Aupperle, Robin L; Allard, Carolyn B; Grimes, Erin M; Simmons, Alan N; Flagan, Taru; Behrooznia, Michelle; Cissell, Shadha H; Twamley, Elizabeth W; Thorp, Steven R; Norman, Sonya B; Paulus, Martin P; Stein, Murray B

2012-04-01

Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. Case-control, cross-sectional study. General community and hospital and community psychiatric clinics. Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Differential Patterns of Dysconnectivity in Mirror Neuron and Mentalizing Networks in Schizophrenia

PubMed Central

Schilbach, Leonhard; Derntl, Birgit; Aleman, Andre; Caspers, Svenja; Clos, Mareike; Diederen, Kelly M. J.; Gruber, Oliver; Kogler, Lydia; Liemburg, Edith J.; Sommer, Iris E.; Müller, Veronika I.; Cieslik, Edna C.; Eickhoff, Simon B.

2016-01-01

Impairments of social cognition are well documented in patients with schizophrenia (SCZ), but the neural basis remains poorly understood. In light of evidence that suggests that the “mirror neuron system” (MNS) and the “mentalizing network” (MENT) are key substrates of intersubjectivity and joint action, it has been suggested that dysfunction of these neural networks may underlie social difficulties in SCZ patients. Additionally, MNS and MENT might be associated differently with positive vs negative symptoms, given prior social cognitive and symptom associations. We assessed resting state functional connectivity (RSFC) in meta-analytically defined MNS and MENT networks in this patient group. Magnetic resonance imaging (MRI) scans were obtained from 116 patients and 133 age-, gender- and movement-matched healthy controls (HC) at 5 different MRI sites. Network connectivity was analyzed for group differences and correlations with clinical symptoms. Results demonstrated decreased connectivity within the MNS and also the MENT in patients compared to controls. Notably, dysconnectivity of the MNS was related to symptom severity, while no such relationship was observed for the MENT. In sum, these findings demonstrate that differential patterns of dysconnectivity exist in SCZ patients, which may contribute differently to the interpersonal difficulties commonly observed in the disorder. PMID:26940699

Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

PubMed

Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

2018-06-01

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Functional Magnetic Resonance Imaging Methods

PubMed Central

Chen, Jingyuan E.; Glover, Gary H.

2015-01-01

Since its inception in 1992, Functional Magnetic Resonance Imaging (fMRI) has become an indispensible tool for studying cognition in both the healthy and dysfunctional brain. FMRI monitors changes in the oxygenation of brain tissue resulting from altered metabolism consequent to a task-based evoked neural response or from spontaneous fluctuations in neural activity in the absence of conscious mentation (the “resting state”). Task-based studies have revealed neural correlates of a large number of important cognitive processes, while fMRI studies performed in the resting state have demonstrated brain-wide networks that result from brain regions with synchronized, apparently spontaneous activity. In this article, we review the methods used to acquire and analyze fMRI signals. PMID:26248581

Physiologic Dysfunction Scores and Cognitive Function Test Performance in United States Adults

PubMed Central

Kobrosly, Roni W; Seplaki, Christopher L; Jones, Courtney M; van Wijngaarden, Edwin

2013-01-01

Objective To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. Methods We examined a summary score measuring physiological dysfunction, a multisystem measure of the body’s ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the third National Health and Nutrition Examination Survey (1988–1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. ‘Physiologic dysfunction’ scores summarizing measures of cardiovascular, immunologic, kidney, and liver function were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiological dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. Results We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% CI = (0.066, 0.348), p < 0.0001) that persisted after adjustment for all covariates (p = 0.03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = 0.37) or perceptual-motor ability (p = 0.33). Conclusions Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains. PMID:22155941

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia.

PubMed

Caminiti, Silvia P; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F

2015-01-01

bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.

A pilot study of cognitive insight and structural covariance in first-episode psychosis.

PubMed

Kuang, Corin; Buchy, Lisa; Barbato, Mariapaola; Makowski, Carolina; MacMaster, Frank P; Bray, Signe; Deighton, Stephanie; Addington, Jean

2017-01-01

Cognitive insight is described as a balance between one's self-reflectiveness (recognition and correction of dysfunctional reasoning), and self-certainty (overconfidence). Neuroimaging studies have linked the ventrolateral prefrontal cortex (VLPFC) to cognitive insight in people with psychosis. However, the relationship between cognitive insight and structural connectivity between the VLPFC and other brain areas is unknown. Here, we investigated the modulation of cognitive insight on structural covariance networks involving the VLPFC in a first-episode psychosis sample. Fifteen patients with a first-episode psychosis provided magnetic resonance (MR) scans and completed the Beck Cognitive Insight Scale (BCIS). MR scans were also available for 15 historical controls. Seed-based analysis of structural covariance was conducted using the Mapping Anatomical Correlations Across the Cerebral Cortex (MACACC) methodology, whereby Pearson correlation coefficients were extracted between seed regions in left and right VLPFC and cortical thickness across the brain. Structural covariance maps between groups were compared at each vertex. In first-episode subjects, we evaluated the modulation of BCIS scores on cortical covariance between VLPFC and every other vertex. Findings showed no significant group difference between first-episode psychosis subjects and controls in thickness covariance seeded from left or right VLPFC. However, in first-episode psychosis subjects, a positive association with self-certainty was found in networks seeded from both left and right VLPFC with thickness in medial frontal cortex and right pars triangularis. No significant associations were found for self-reflectiveness. These results suggest that self-certainty, but not self-reflectiveness, positively modulated cortical covariance in a frontal network in patients with a first-episode psychosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy.

PubMed

A Yassine, Imane; M Eldeeb, Waleed; A Gad, Khaled; A Ashour, Yossri; A Yassine, Inas; O Hosny, Ahmed

2018-07-01

Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.

PubMed

Frittoli, Renan Bazuco; de Oliveira Peliçari, Karina; Bellini, Bruna Siqueira; Marini, Roberto; Fernandes, Paula Teixeira; Appenzeller, Simone

2016-01-01

To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Heading in Soccer: Integral Skill or Grounds for Cognitive Dysfunction?

ERIC Educational Resources Information Center

Kirkendall, Donald T.; Garrett, William E., Jr.

2001-01-01

Discusses how purposeful heading of soccer balls and head injuries affect soccer players' cognitive dysfunction. Cognitive deficits may occur for many reasons. Heading cannot be blamed when details of the actual event and impact are unknown. Concussions are the most common head injury in soccer and a factor in cognitive deficits and are probably…

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease.

PubMed

Njomboro, Progress

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease

PubMed Central

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments. PMID:28729755

Impulsive aggression and response inhibition in attention-deficit/hyperactivity disorder and disruptive behavioral disorders: Findings from a systematic review.

PubMed

Puiu, Andrei A; Wudarczyk, Olga; Goerlich, Katharina S; Votinov, Mikhail; Herpertz-Dahlmann, Beate; Turetsky, Bruce; Konrad, Kerstin

2018-04-22

Although impulsive aggression (IA) and dysfunctional response inhibition (RI) are hallmarks of attention-deficit/hyperactivity disorder (ADHD) and disrupted behavioral disorders (DBDs), little is known about their shared and distinct deviant neural mechanisms. Here, we selectively reviewed s/fMRI ADHD and DBD studies to identify disorder-specific and shared IA and RI aberrant neural mechanisms. In ADHD, deviant prefrontal and cingulate functional activity was associated with increased IA. Structural alterations were most pronounced in the cingulate cortex. Subjects with DBDs showed marked cortico-subcortical dysfunctions. ADHD and DBDs share similar cortico-limbic structural and functional alterations. RI deficits in ADHD highlighted hypoactivity in the dorso/ventro-lateral PFC, insula, and striatum, while the paralimbic system was primarily dysfunctional in DBDs. Across disorders, extensively altered cortico-limbic dysfunctions underlie IA, while RI was mostly associated with aberrant prefrontal activity. Control network deficits were evidenced across clinical phenotypes in IA and RI. Dysfunctions at any level within these cortico-subcortical projections lead to deficient cognitive-affective control by ascribing emotional salience to otherwise irrelevant stimuli. The clinical implications of these findings are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia.

PubMed

Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

2016-01-01

As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. Copyright © 2016. Published by Elsevier Ltd.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

PubMed Central

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles.

PubMed

Blasczyk-Schiep, Sybilla; Sokoła, Kaja; Fila-Witecka, Karolina; Kazén, Miguel

2016-06-01

We investigated dysfunctional cognitions about eating and body image in relation to personality styles in a group of professional models. Dysfunctional cognitions in professional models (n = 43) and a control group (n = 43) were assessed with the 'Eating Disorder Cognition Questionnaire' (EDCQ), eating attitudes with the 'Eating Attitudes Test' (EAT), and personality with the 'Personality Styles and Disorders Inventory' (PSDI-S). Models had higher scores than controls on the EDCQ and EAT and on nine scales of the PSDI-S. Moderation analyses showed significant interactions between groups and personality styles in predicting EDCQ scales: The ambitious/narcissistic style was related to "negative body and self-esteem", the conscientious/compulsive style to "dietary restraint", and the spontaneous/borderline style to "loss of control in eating". The results indicate that not all models are susceptible to dysfunctional cognitions about eating and body image. Models are at a higher risk of developing negative automatic thoughts and dysfunctional assumptions relating to body size, shape and weight, especially if they have high scores on the above personality styles.

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

PubMed

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

Neuroanatomical Substrates of Social Cognition Dysfunction in Autism

ERIC Educational Resources Information Center

Pelphrey, Kevin; Adolphs, Ralph; Morris, James P.

2004-01-01

In this review article, we summarize recent progress toward understanding the neural structures and circuitry underlying dysfunctional social cognition in autism. We review selected studies from the growing literature that has used the functional neuroimaging techniques of cognitive neuroscience to map out the neuroanatomical substrates of social…

Three screening methods for cognitive dysfunction using the Mini-Mental State Examination and Korean Dementia Screening Questionnaire.

PubMed

Choi, Seong Hye; Park, Moon Ho

2016-02-01

To screen for and determine cognitive dysfunction, cognitive tests and/or informant reports are commonly used. However, these cognitive tests and informant reports are not always available. The present study investigated three screening methods using the Mini-Mental State Examination (MMSE) as the cognitive test, and the Korean dementia screening questionnaire (KDSQ) as the informant report. Participants were recruited from the Korea Clinical Research Center for Dementia of South Korea, and included 2861 patients with Alzheimer's disease (dementia), 3519 patients with mild cognitive impairment and 1375 controls with no cognitive dysfunction. Three screening methods were tested: (i) MMSE alone (MMSE(cut-off) ); (ii) a conventional combination of MMSE and KDSQ (MMSE+KDSQ(cut-off) ); and (iii) a decision tree with MMSE and KDSQ (MMSE+KDSQ(decision tree) ). For discriminating any cognitive dysfunction from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.784). For discriminating dementia from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.899). For discriminating mild cognitive impairment from controls, MMSE(cut-off) had the highest area under the receiver operating characteristic curve (0.683). MMSE+KDSQ(decision tree) showed the highest sensitivity for all discriminations. For overall classification accuracy, MMSE+KDSQ(decision tree) had the highest value (70.0%). These three methods had different advantageous properties for screening and staging cognitive dysfunction. As there might be different availability across clinical settings, these three methods can be selected and used according to situational needs. © 2015 Japan Geriatrics Society.

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

Stability of Cognitive Vulnerabilities to Depression: A Short-Term Prospective Multiwave Study

PubMed Central

Hankin, Benjamin L.

2009-01-01

The stability of 3 cognitive vulnerabilities—a negative cognitive style, dysfunctional attitudes, and rumination—as well as depressive symptoms as a benchmark were examined to investigate whether cognitive vulnerabilities are stable, enduring risks for depression. A sample of adolescents (6th–10th graders) completed measures of these 3 cognitive vulnerabilities and depressive symptoms every 5 weeks for 4 waves of data across 5 months. Mean-level and differential stability were examined for the sample overall and by age subgroups. A negative cognitive style exhibited mean-level stability, whereas rumination and dysfunctional attitudes showed some mean-level change. Absolute magnitudes of test–retest reliabilities were strong for depressive symptoms (mean r = .70), moderately high for a negative cognitive style (mean r = .52), and more modest for rumination (mean r = .28) and dysfunctional attitudes (mean r = .26). Structural equation modeling showed that primarily enduring processes, but not contextual forces, contributed to the patterning of these test–retest reliabilities over time for a negative cognitive style and dysfunctional attitudes, whereas both enduring and contextual dynamics appeared to underlie the stability for rumination. Theoretical and clinical implications of these findings are discussed. PMID:18489208

4C.05: PWV IS AN INDEPENDENT DETERMINANT OF COGNITIVE DYSFUNCTION IN CKD PATIENTS.

PubMed

Karasavvidou, D; Pappas, K; Stagikas, D; Makridis, D; Katsinas, C; Kalaitzidis, R

2015-06-01

Cognitive dysfunction has long been recognized as a complication of chronic kidney disease (CKD), through several putative mechanisms, including high BP, large and small artery damage. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function in CKD patients.(Figure is included in full-text article.) : Two hundred seventeen patients (50 with CKD stage 1; 67 stage 2; 53 stage 3; 47 stage 4), with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive function was assessed using Mini Mental State Examination (MMSE). Full score on the MMSE is 30; cognitive impairment was defined as <26 and cognitive dysfunction as <19. Educational level was categorized as lower versus higher education. Using the Sphygmocor system and an oscillometric device, we directly measured brachial SBP (bSBP) and pulse pressure (bPP), carotid SBP (cSBP) and pulse pressure (cPP) and estimated aortic SBP (aSBP) and pulse pressure (aPP) from the radial pressure waveform. Pulse Pressure Amplification (PPA), augmentation index (AIx) and carotid-femoral pulse wave velocity (cfPWV) were calculated. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p < 0.01). Table. In univariate analysis, age (p < 0.001), education level (p < 0.001) stages of CKD (p < 0.004), cfPWV (p < 0.029), AIx (p < 0.03), bSBP (p < 0.002), aSBP (p < 0.012), cSBP (p < 0.015) and cPP (p < 0.002) were significantly and negatively associated with MMSE. In multivariate regression analysis, adjusted for CKD stages, the remaining independent factor significantly (p < 0.02) associated with cognitive dysfunction was cfPWV. Carotid-femoral PWV may be a more sensitive marker of cognitive dysfunction than other parameters of central blood pressure. Since high cfPWV is associated with high pressure pulsatility at the cerebrovascular level, these data suggest that the later could play a pathophysiological role in cognitive dysfunction. In clinical practice, measuring aortic stiffness may help predicting the cognitive decline. Whether, the reduction in aortic stiffness following treatment translates into improved cognitive outcomes remains to be determined.

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

Vision science and schizophrenia research: toward a re-view of the disorder. Editors' introduction to special section.

PubMed

Silverstein, Steven M; Keane, Brian P

2011-07-01

This theme section on vision science and schizophrenia research demonstrates that our understanding of the disorder could be significantly accelerated by a greater adoption of the methods of vision science. In this introduction, we briefly describe what vision science is, how it has advanced our understanding of schizophrenia, and what challenges and opportunities lay ahead regarding schizophrenia research. We then summarize the articles that follow. These include reviews of abnormal form perception (perceptual organization and backward masking) and motion processing, and an article on reduced size contrast illusions experienced by hearing but not deaf persons with schizophrenia. These articles reveal that the methods of basic vision research can provide insights into a number of aspects of the disorder, including pathophysiology, development, cognition, social cognition, and phenomenology. Importantly, studies of visual processing in schizophrenia make it clear that there are impairments in the functioning of basic neural mechanisms (e.g., center-surround modulation, contextual modulation of feedforward processing, reentrant processing) that are found throughout the cortex and that are operative in multiple forms of cognitive dysfunction in the illness. Such evidence allows for an updated view of schizophrenia as a condition involving generalized failures in neural network formation and maintenance, as opposed to a primary failure in a higher level factor (e.g., cognitive control) that accounts for all other types of perceptual and cognitive dysfunction. Finally, studies of vision in schizophrenia can identify sensitive probes of neural functioning that can be used as biomarkers of treatment response.

Vision Science and Schizophrenia Research: Toward a Re-view of the Disorder Editors’ Introduction to Special Section

PubMed Central

Silverstein, Steven M.; Keane, Brian P.

2011-01-01

This theme section on vision science and schizophrenia research demonstrates that our understanding of the disorder could be significantly accelerated by a greater adoption of the methods of vision science. In this introduction, we briefly describe what vision science is, how it has advanced our understanding of schizophrenia, and what challenges and opportunities lay ahead regarding schizophrenia research. We then summarize the articles that follow. These include reviews of abnormal form perception (perceptual organization and backward masking) and motion processing, and an article on reduced size contrast illusions experienced by hearing but not deaf persons with schizophrenia. These articles reveal that the methods of basic vision research can provide insights into a number of aspects of the disorder, including pathophysiology, development, cognition, social cognition, and phenomenology. Importantly, studies of visual processing in schizophrenia make it clear that there are impairments in the functioning of basic neural mechanisms (eg, center-surround modulation, contextual modulation of feedforward processing, reentrant processing) that are found throughout the cortex and that are operative in multiple forms of cognitive dysfunction in the illness. Such evidence allows for an updated view of schizophrenia as a condition involving generalized failures in neural network formation and maintenance, as opposed to a primary failure in a higher level factor (eg, cognitive control) that accounts for all other types of perceptual and cognitive dysfunction. Finally, studies of vision in schizophrenia can identify sensitive probes of neural functioning that can be used as biomarkers of treatment response. PMID:21700588

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

PubMed

Calabrese, Massimiliano; Gajofatto, Alberto; Gobbin, Francesca; Turri, Giulia; Richelli, Silvia; Matinella, Angela; Oliboni, Eugenio Simone; Benedetti, Maria Donata; Monaco, Salvatore

2015-04-01

Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs. © The Author(s), 2014.

Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Tay, Sen Hee; Mak, Anselm

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. PMID:25955648

Attachment, dysfunctional attitudes, self-esteem, and association to depressive symptoms in patients with mood disorders.

PubMed

Fuhr, Kristina; Reitenbach, Ivanina; Kraemer, Jan; Hautzinger, Martin; Meyer, Thomas D

2017-04-01

Cognitive factors might be the link between early attachment experiences and later depression. Similar cognitive vulnerability factors are discussed as relevant for both unipolar and bipolar disorders. The goals of the study were to test if there are any differences concerning attachment style and cognitive factors between remitted unipolar and bipolar patients compared to controls, and to test if the association between attachment style and depressive symptoms is mediated by cognitive factors. A path model was tested in 182 participants (61 with remitted unipolar and 61 with remitted bipolar disorder, and 60 healthy subjects) in which adult attachment insecurity was hypothesized to affect subsyndromal depressive symptoms through the partial mediation of dysfunctional attitudes and self-esteem. No differences between patients with remitted unipolar and bipolar disorders concerning attachment style, dysfunctional attitudes, self-esteem, and subsyndromal depressive symptoms were found, but both groups reported a more dysfunctional pattern than healthy controls. The path models confirmed that the relationship between attachment style and depressive symptoms was mediated by the cognitive variables 'dysfunctional attitudes' and 'self-esteem'. With the cross-sectional nature of the study, results cannot explain causal development over time. The results emphasize the relevance of a more elaborate understanding of cognitive and interpersonal factors in mood disorders. It is important to address cognitive biases and interpersonal experiences in treatment of mood disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

PubMed Central

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

PubMed

Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

2015-06-01

Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

PubMed

Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

2010-05-01

Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

PubMed

Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

2014-10-03

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

PubMed

Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

2017-10-01

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

"Don't Look Now": The Role of Self-Focus in Sexual Dysfunction.

ERIC Educational Resources Information Center

Wiederman, Michael W.

2001-01-01

Couples and family counselors may aid in the remedy of sexual dysfunction when it has a cognitive or psychological basis. One important source of sexual dysfunction is cognitive distraction that results from certain forms of self-focus during sexual activity with a partner, a phenomenon sex therapists have labeled spectatoring. Introduces sensate…

Early-stage attenuation of phase-amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of Alzheimer's disease.

PubMed

Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

2018-03-01

Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of gamma-aminobutyric acid-ergic signaling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABA A ) receptor subunits α1 , α5, and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is part of the Special Issue "Vascular Dementia". © 2017 Her Majesty the Queen in Right of Canada Journal of Neurochemistry © 2017 International Society for Neurochemistry.

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

PubMed Central

Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.

2012-01-01

Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469

A comprehensive assessment of cognitive function in the common genetic generalized epilepsy syndromes.

PubMed

Loughman, A; Bowden, S C; D'Souza, W J

2017-03-01

Considered to be benign conditions, the common genetic generalized epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction. A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities. Scores on tests of overall cognitive ability, acquired knowledge, long-term retrieval and speed of information processing were significantly below the normative mean. Long-term retrieval was a pronounced weakness with a large reduction in scores (d = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function. This study confirms previous meta-analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE. © 2016 EAN.

Cognitive Developmental Therapy: Aiding Adult Children of Dysfunctional Families.

ERIC Educational Resources Information Center

Towers, David A.

The works of Kegan and Guidano have presented cognition and emotion as complementary modes of knowing that develop together. Cognition is conceived of as being concerned with the knowledge of reality, and emotions are conceptualized as people's system for knowing of their relationship to that reality. Adult children of dysfunctional families are a…

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation

PubMed Central

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment. PMID:29651240

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation.

PubMed

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.

Lateral specialization in unilateral spatial neglect: a cognitive robotics model.

PubMed

Conti, Daniela; Di Nuovo, Santo; Cangelosi, Angelo; Di Nuovo, Alessandro

2016-08-01

In this paper, we present the experimental results of an embodied cognitive robotic approach for modelling the human cognitive deficit known as unilateral spatial neglect (USN). To this end, we introduce an artificial neural network architecture designed and trained to control the spatial attentional focus of the iCub robotic platform. Like the human brain, the architecture is divided into two hemispheres and it incorporates bio-inspired plasticity mechanisms, which allow the development of the phenomenon of the specialization of the right hemisphere for spatial attention. In this study, we validate the model by replicating a previous experiment with human patients affected by the USN and numerical results show that the robot mimics the behaviours previously exhibited by humans. We also simulated recovery after the damage to compare the performance of each of the two hemispheres as additional validation of the model. Finally, we highlight some possible advantages of modelling cognitive dysfunctions of the human brain by means of robotic platforms, which can supplement traditional approaches for studying spatial impairments in humans.

Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson's disease.

PubMed

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson's disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) "Parkinson disease"; "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson disease"; "depression," "major depressive disorder," "drug therapy." We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.

Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

PubMed

Babakhani, Anet; Startup, Mike

2012-01-01

Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

PubMed

Daulatzai, Mak Adam

2016-10-01

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

[Discipline styles and co-morbid disorders of adolescents with attention deficit hyperactivity disorder: a longitudinal study].

PubMed

Colomer-Diago, Carla; Berenguer-Forner, Carmen; Tárraga-Mínguez, Raúl; Miranda-Casas, Ana

2014-02-24

Problems in cognitive functioning, social and educational development of children with attention deficit hyperactivity disorder (ADHD) continue to be present in adolescence and adulthood. Although the literature shows a significant relationship between the use of dysfunctional discipline methods and severity in the course of ADHD, follow-up studies have been rare. To analyze parenting style and ADHD symptomatology assessed in childhood (time 1) to predict the oppositional behavior and cognitive problems in early adolescence (time 2), and to study, depending on the use of dysfunctional parenting style, the course of oppositional behavior and cognitive problems. Forty-five children with ADHD-combined presentation were assessed in two different moments: time 1 (ages: 6-13) and time 2 (ages: 8-16). Oppositionism and cognitive problems in the follow-up were predicted by dysfunctional discipline styles and ADHD severity (assessed in time 1). Oppositional behavior increased between time 1 and time 2 in children with a dysfunctional parenting, whereas a decrease on oppositional symptoms was observed in the functional parenting group (time x discipline interaction effect). Dysfunctional parenting practices in childhood predicted cognitive and behavioral problems associated in adolescence. The findings have implications for the planning of interventions.

Disrupted Structural Brain Network in AD and aMCI: A Finding of Long Fiber Degeneration.

PubMed

Fang, Rong; Yan, Xiao-Xiao; Wu, Zhi-Yuan; Sun, Yu; Yin, Qi-Hua; Wang, Ying; Tang, Hui-Dong; Sun, Jun-Feng; Miao, Fei; Chen, Sheng-Di

2015-01-01

Although recent evidence has emerged that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients show both regional brain abnormalities and topological degeneration in brain networks, our understanding of the effects of white matter fiber aberrations on brain network topology in AD and aMCI is still rudimentary. In this study, we investigated the regional volumetric aberrations and the global topological abnormalities in AD and aMCI patients. The results showed a widely distributed atrophy in both gray and white matters in the AD and aMCI groups. In particular, AD patients had weaker connectivity with long fiber length than aMCI and normal control (NC) groups, as assessed by fractional anisotropy (FA). Furthermore, the brain networks of all three groups exhibited prominent economical small-world properties. Interestingly, the topological characteristics estimated from binary brain networks showed no significant group effect, indicating a tendency of preserving an optimal topological architecture in AD and aMCI during degeneration. However, significantly longer characteristic path length was observed in the FA weighted brain networks of AD and aMCI patients, suggesting dysfunctional global integration. Moreover, the abnormality of the characteristic path length was negatively correlated with the clinical ratings of cognitive impairment. Thus, the results therefore suggested that the topological alterations in weighted brain networks of AD are induced by the loss of connectivity with long fiber lengths. Our findings provide new insights into the alterations of the brain network in AD and may indicate the predictive value of the network metrics as biomarkers of disease development.

Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks

PubMed Central

Menniti, Frank S.; Lindsley, Craig W.; Conn, P. Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A.

2013-01-01

Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved. PMID:23409764

Efficiently Assessing Negative Cognition in Depression: An Item Response Theory Analysis of the Dysfunctional Attitude Scale

ERIC Educational Resources Information Center

Beevers, Christopher G.; Strong, David R.; Meyer, Bjorn; Pilkonis, Paul A.; Miller, Ivan R.

2007-01-01

Despite a central role for dysfunctional attitudes in cognitive theories of depression and the widespread use of the Dysfunctional Attitude Scale, form A (DAS-A; A. Weissman, 1979), the psychometric development of the DAS-A has been relatively limited. The authors used nonparametric item response theory methods to examine the DAS-A items and…

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: advances, gaps, and needs in current research.

PubMed

Goschke, Thomas

2014-01-01

Disadvantageous decision-making and impaired volitional control over actions, thoughts, and emotions are characteristics of a wide range of mental disorders such as addiction, eating disorders, depression, and anxiety disorders and may reflect transdiagnostic core mechanisms and possibly vulnerability factors. Elucidating the underlying neurocognitive mechanisms is a precondition for moving from symptom-based to mechanism-based disorder classifications and ultimately mechanism-targeted interventions. However, despite substantial advances in basic research on decision-making and cognitive control, there are still profound gaps in our current understanding of dysfunctions of these processes in mental disorders. Central unresolved questions are: (i) to which degree such dysfunctions reflect transdiagnostic mechanisms or disorder-specific patterns of impairment; (ii) how phenotypical features of mental disorders relate to dysfunctional control parameter settings and aberrant interactions between large-scale brain systems involved in habit and reward-based learning, performance monitoring, emotion regulation, and cognitive control; (iii) whether cognitive control impairments are consequences or antecedent vulnerability factors of mental disorders; (iv) whether they reflect generalized competence impairments or context-specific performance failures; (v) whether not only impaired but also chronic over-control contributes to mental disorders. In the light of these gaps, needs for future research are: (i) an increased focus on basic cognitive-affective mechanisms underlying decision and control dysfunctions across disorders; (ii) longitudinal-prospective studies systematically incorporating theory-driven behavioural tasks and neuroimaging protocols to assess decision-making and control dysfunctions and aberrant interactions between underlying large-scale brain systems; (iii) use of latent-variable models of cognitive control rather than single tasks; (iv) increased focus on the interplay of implicit and explicit cognitive-affective processes; (v) stronger focus on computational models specifying neurocognitive mechanisms underlying phenotypical expressions of mental disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Insular subdivisions functional connectivity dysfunction within major depressive disorder.

PubMed

Peng, Xiaolong; Lin, Pan; Wu, Xiaoping; Gong, Ruxue; Yang, Rui; Wang, Jue

2018-02-01

Major depressive disorder (MDD) is a mental disorder characterized by cognitive and affective deficits. Previous studies suggested that insula is a crucial node of the salience network for initiating network switching, and dysfunctional connection to this region may be related to the mechanism of MDD. In this study, we systematically investigated and quantified the altered functional connectivity (FC) of the specific insular subdivisions and its relationship to psychopathology of MDD. Resting-state FC of insular subdivisions, including bilateral ventral/dorsal anterior insula and posterior insula, were estimated in 19 MDD patients and 19 healthy controls. Abnormal FC was quantified between groups. Additionally, we investigated the relationships between insular connectivity and depressive symptom severity. MDD patients demonstrated aberrant FC for insular subdivisions to superior temporal sulcus, inferior prefrontal gyrus, amygdala and posterior parietal cortex. Moreover, depression symptoms (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scorers) were associated with the FC values of insular subdivisions. First, the sample size of our current study is relatively small, which may affect the statistic power. Second, using standardized insular subdivision seeds for FC analyses may neglect subtle natural differences in size and location of functional area across individuals and may thus affect connectivity maps. Abnormal FC of insular subdivisions to default network and central executive network may represent impaired intrinsic networks switching which may affect the underlying emotional and sensory disturbances in MDD. And our findings can help to understand the pathophysiology and underlying neural mechanisms of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal depressive symptoms, dysfunctional cognitions, and infant night waking: the role of maternal nighttime behavior.

PubMed

Teti, Douglas M; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via their impact on mothers' bedtime and nighttime behavior with infants (from video). Two infant-driven mediational models were also examined, in which infant night waking predicted maternal depressive symptoms, or dysfunctional cognitions, via their impact on nighttime maternal behavior. Stronger support for the mother-driven model was obtained, which was further supported by qualitative observations from video-recordings. This study provides important insights about maternal depression's effects on nighttime parenting, and how such parenting affects infant sleep. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

PubMed

Samat, Nor A; Abdul Murad, Nor A; Mohamad, Khairiyah; Abdul Razak, Mohd R; Mohamed Ibrahim, Norlinah

2017-01-01

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E ( ApoE ) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGEL APoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA ( p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. The ApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction ( p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

Semi-metric analysis of the functional brain network: Relationship with familial risk for psychotic disorder

PubMed Central

Peeters, Sanne; Simas, Tiago; Suckling, John; Gronenschild, Ed; Patel, Ameera; Habets, Petra; van Os, Jim; Marcelis, Machteld

2015-01-01

Background Dysconnectivity in schizophrenia can be understood in terms of dysfunctional integration of a distributed network of brain regions. Here we propose a new methodology to analyze complex networks based on semi-metric behavior, whereby higher levels of semi-metricity may represent a higher level of redundancy and dispersed communication. It was hypothesized that individuals with (increased risk for) psychotic disorder would have more semi-metric paths compared to controls and that this would be associated with symptoms. Methods Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 unaffected siblings and 72 controls. Semi-metric percentages (SMP) at the whole brain, hemispheric and lobar level were the dependent variables in a multilevel random regression analysis to investigate group differences. SMP was further examined in relation to symptomatology (i.e., psychotic/cognitive symptoms). Results At the whole brain and hemispheric level, patients had a significantly higher SMP compared to siblings and controls, with no difference between the latter. In the combined sibling and control group, individuals with high schizotypy had intermediate SMP values in the left hemisphere with respect to patients and individuals with low schizotypy. Exploratory analyses in patients revealed higher SMP in 12 out of 42 lobar divisions compared to controls, of which some were associated with worse PANSS symptomatology (i.e., positive symptoms, excitement and emotional distress) and worse cognitive performance on attention and emotion processing tasks. In the combined group of patients and controls, working memory, attention and social cognition were associated with higher SMP. Discussion The results are suggestive of more dispersed network communication in patients with psychotic disorder, with some evidence for trait-based network alterations in high-schizotypy individuals. Dispersed communication may contribute to the clinical phenotype in psychotic disorder. In addition, higher SMP may contribute to neuro- and social cognition, independent of psychosis risk. PMID:26740914

Objective Cognitive Functioning in Self-reported Habitual Short Sleepers not Reporting Daytime Dysfunction: Examination of Impulsivity via Delay Discounting.

PubMed

Curtis, Brian J; Williams, Paula G; Anderson, Jeffrey S

2018-05-30

1) Examine performance on an objective measure of reward-related cognitive impulsivity (delay discounting) among self-reported habitual short sleepers and medium (i.e., recommended 7-9 hours) length sleepers either reporting or not reporting daytime dysfunction; 2) Inform the debate regarding what type and duration of short sleep (e.g., 21 to 24 hours of total sleep deprivation, self-reported habitual short sleep duration) meaningfully influences cognitive impulsivity; 3) Compare the predictive utility of sleep duration and perceived dysfunction to other factors previously shown to influence cognitive impulsivity via delay discounting performance (age, income, education, and fluid intelligence). We analyzed data from 1,190 adults from the Human Connectome Project database. Participants were grouped on whether they reported habitual short (≤ 6 hours) vs. medium length (7-9 hours) sleep duration and whether they perceived daytime dysfunction using the Pittsburgh Sleep Quality Index. All short sleepers exhibited increased delay discounting compared to all medium length sleepers, regardless of perceived dysfunction. Of the variables examined, self-reported sleep duration was the strongest predictor of delay discounting behavior between groups and across all 1,190 participants. Individuals who report habitual short sleep are likely to exhibit increased reward-related cognitive impulsivity regardless of perceived sleep-related daytime impairment. Therefore, there is reason to suspect that these individuals exhibit more daytime dysfunction, in the form of reward-related cognitive impulsivity, than they may assume. Current findings suggest that assessment of sleep duration over the prior month has meaningful predictive utility for human reward-related impulsivity.

Gap junctional intercellular communication dysfunction mediates the cognitive impairment induced by cerebral ischemia-reperfusion injury: PI3K/Akt pathway involved.

PubMed

Zhou, Shujun; Fang, Zheng; Wang, Gui; Wu, Song

2017-01-01

Cerebral ischemia/reperfusion (I/R) injury causes hippocampal apoptosis and cognitive impairment, and the dysfunction of gap junction intercellular communication (GJIC) may contribute to the cognitive impairment. We aim to examine the impact of cerebral I/R injury on cognitive impairment, the role of GJIC dysfunction in the rat hippocampus and the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway. Rats were subjected to a cerebral I/R procedure and underwent cognitive assessment with the novel object recognition and Morris Water Maze tasks. The distance of Lucifer Yellow dye transfer and the Cx43 protein were examined to measure GJIC. Neural apoptosis was assessed with the terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. After rats received inhibitors of the PI3K/Akt pathway, GJIC and cognitive ability were measured again. GJIC promotion by ZP123 significantly reversed cognitive impairment and hippocampal apoptosis induced by cerebral I/R, while the inhibition of GJIC by octanol significantly facilitated cognitive impairment and hippocampal apoptosis. The phosphorylation of Akt was enhanced by cerebral I/R and octanol but inhibited by ZP123. The inhibition of the PI3K/Akt pathway significantly suppressed GJIC and cognitive impairment. The PI3K/Akt pathway is involved in cognitive impairment caused by gap junctional communication dysfunction in the rat hippocampus after ischemia-reperfusion injury.

Dysfunctions in brain networks supporting empathy: An fMRI study in adults with autism spectrum disorders

PubMed Central

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J.; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R.; Piefke, Martina

2010-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's “emotional bond” with other persons’ emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions. PMID:20945256

Dysfunctions in brain networks supporting empathy: an fMRI study in adults with autism spectrum disorders.

PubMed

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R; Piefke, Martina

2011-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's "emotional bond" with other persons' emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions.

Psychometric Properties of the German Version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER).

PubMed

de Haan, Anke; Petermann, Franz; Meiser-Stedman, Richard; Goldbeck, Lutz

2016-02-01

Dysfunctional trauma-related cognitions are associated with posttraumatic stress disorder (PTSD). The psychometric properties of the German version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223 children and adolescents (7-16 years) with a history of different traumatic events. Confirmatory factor analyses supported the original two-factor structure--permanent and disturbing change (CPTCI-PC) and fragile person in a scary world (CPTCI-SW). The total scale and both subscales showed good internal consistency. Participants with PTSD had significantly more dysfunctional trauma-related cognitions than those without PTSD. Dysfunctional posttraumatic cognitions correlated significantly with posttraumatic stress symptoms (PTSS; r = .62), depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric properties and may facilitate evaluation of treatments and further research on the function of trauma-related cognitions in children and adolescents. (Partial) correlations provide empirical support for the combined DSM-5 symptom cluster negative alterations in cognitions and mood.

Working Memory-Related Effective Connectivity in Huntington's Disease Patients.

PubMed

Lahr, Jacob; Minkova, Lora; Tabrizi, Sarah J; Stout, Julie C; Klöppel, Stefan; Scheller, Elisa

2018-01-01

Huntington's disease (HD) is a genetically caused neurodegenerative disorder characterized by heterogeneous motor, psychiatric, and cognitive symptoms. Although motor symptoms may be the most prominent presentation, cognitive symptoms such as memory deficits and executive dysfunction typically co-occur. We used functional magnetic resonance imaging (fMRI) and task fMRI-based dynamic causal modeling (DCM) to evaluate HD-related changes in the neural network underlying working memory (WM). Sixty-four pre-symptomatic HD mutation carriers (preHD), 20 patients with early manifest HD symptoms (earlyHD), and 83 healthy control subjects performed an n -back fMRI task with two levels of WM load. Effective connectivity was assessed in five predefined regions of interest, comprising bilateral inferior parietal cortex, left anterior cingulate cortex, and bilateral dorsolateral prefrontal cortex. HD mutation carriers performed less accurately and more slowly at high WM load compared with the control group. While between-group comparisons of brain activation did not reveal differential recruitment of the cortical WM network in mutation carriers, comparisons of brain connectivity as identified with DCM revealed a number of group differences across the whole WM network. Most strikingly, we observed decreasing connectivity from several regions toward right dorsolateral prefrontal cortex (rDLPFC) in preHD and even more so in earlyHD. The deterioration in rDLPFC connectivity complements results from previous studies and might mirror beginning cortical neural decline at premanifest and early manifest stages of HD. We were able to characterize effective connectivity in a WM network of HD mutation carriers yielding further insight into patterns of cognitive decline and accompanying neural deterioration.

Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

PubMed Central

D'Angelo, Egidio; Casali, Stefano

2013-01-01

Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the “timing and learning machine” capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression. PMID:23335884

Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

PubMed

Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

2013-05-01

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Copyright © 2011 Wiley Periodicals, Inc.

The influence of personality and dysfunctional sleep-related cognitions on the severity of insomnia.

PubMed

Park, Jang Ho; An, Hoyoung; Jang, Eun Sook; Chung, Seockhoon

2012-05-30

Previous findings suggest that personality traits and dysfunctional sleep-related cognitions may perpetuate insomnia, but findings concerning this have been scarce. Thus, we hypothesized that personality and sleep-related cognitions influence the severity of insomnia, and investigated the association personality and sleep-related cognitions had with various sleep-related parameters, including severity of insomnia. Forty-four patients with psychophysiological insomnia were assessed using The Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was significantly and positively correlated with harm avoidance, self-transcendence and sleep-related cognitions, and negatively correlated with novelty seeking, reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions were positively correlated with insomnia severity and sleep quality. Stepwise multiple regression analysis showed that sleep-related cognitions, depression and reward dependence scores were significant determinants of insomnia severity, and that sleep-related cognitions and self-transcendence were significant positive determinants of sleep quality. Reward dependence, depression and sleep-related cognitions were associated with insomnia severity, and comparison with previous findings implied that 'internalizing behavior' and depression may be more plausible candidates for the link between personality and insomnia than anxiety. Considering the major role of cognitive-behavioral treatment (CBT) in the treatment of insomnia, assessment of these factors and management of sleep-related cognitions may help alleviate symptoms in patients with insomnia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

PubMed Central

Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

2016-01-01

Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

The Basal Ganglia and Adaptive Motor Control

NASA Astrophysics Data System (ADS)

Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

1994-09-01

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease

PubMed Central

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs. PMID:25873910

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia

PubMed Central

Caminiti, Silvia P.; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F.

2015-01-01

Background bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. Objective To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). Methods We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Results Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Conclusions Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms. PMID:26594631

Applying a cognitive neuroscience perspective to the disorder of psychopathy.

PubMed

Blair, R J R

2005-01-01

Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered.

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

PubMed Central

Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

2016-01-01

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task.

PubMed

Lee, Seung Jae; Kang, Do Hyung; Kim, Chi-Won; Gu, Bon Mi; Park, Ji-Young; Choi, Chi-Hoon; Shin, Na Young; Lee, Jong-Min; Kwon, Jun Soo

2010-02-28

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice

PubMed Central

Furukawa-Hibi, Yoko; Alkam, Tursun; Nitta, Atsumi; Matsuyama, Akihiro; Mizoguchi, Hiroyuki; Suzuki, Kazuhiko; Moussaoui, Saliha; Yu, Qian-Sheng; Greig, Nigel H.; Nagai, Taku; Yamada, Kiyofumi

2016-01-01

The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethylnorcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ1–40 or the control peptide Aβ40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ1–40 induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0–3 inclusively, ameliorated the cognitive dysfunction in Aβ1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ1–40 induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD. PMID:21820013

Development and initial validation of a brief self-report measure of cognitive dysfunction in fibromyalgia.

PubMed

Kratz, Anna L; Schilling, Stephen G; Goesling, Jenna; Williams, David A

2015-06-01

Pain is often the focus of research and clinical care in fibromyalgia (FM); however, cognitive dysfunction is also a common, distressing, and disabling symptom in FM. Current efforts to address this problem are limited by the lack of a comprehensive, valid measure of subjective cognitive dysfunction in FM that is easily interpretable, accessible, and brief. The purpose of this study was to leverage cognitive functioning item banks that were developed as part of the Patient Reported Outcomes Measurement Information System (PROMIS) to devise a 10-item short form measure of cognitive functioning for use in FM. In study 1, a nationwide (U.S.) sample of 1,035 adults with FM (age range = 18-82, 95.2% female) completed 2 cognitive item pools. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. A recommended 10-item measure, called the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) was created. In study 2, 232 adults with FM completed the MISCI and a legacy measure of cognitive functioning that is used in FM clinical trials, the Multiple Ability Self-Report Questionnaire (MASQ). The MISCI showed excellent internal reliability, low ceiling/floor effects, and good convergent validity with the MASQ (r = -.82). This paper presents the MISCI, a 10-item measure of cognitive dysfunction in FM, developed through classical test theory and item response theory. This brief but comprehensive measure shows evidence of excellent construct validity through large correlations with a lengthy legacy measure of cognitive functioning. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

PubMed

Flouri, Eirini; Panourgia, Constantina

2012-10-01

The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

Executive Dysfunction and Depressive Symptoms Associated With Reduced Participation of People With Severe Congestive Heart Failure

PubMed Central

Foster, Erin R.; Cunnane, Kathleen B.; Edwards, Dorothy F.; Morrison, M. Tracy; Ewald, Gregory A.; Geltman, Edward M.; Zazulia, Allyson R.

2011-01-01

OBJECTIVE We investigated participation levels and relationships among cognition, depression, and participation for people with severe congestive heart failure (CHF). METHOD People with severe CHF (New York Heart Association Class III or IV) awaiting heart transplantation (N = 27) completed standardized tests of cognition and self-report measures of executive dysfunction, depressive symptoms, and participation. RESULTS Possible depression (64%) and cognitive impairment (15%–59%) were prevalent. Participants reported significant reductions in participation across all activity domains since CHF diagnosis (ps < .001). Worse executive dysfunction and depressive symptoms were associated with reduced participation and together accounted for 35%–46% of the variance in participation (ps < .01). CONCLUSION Participation restrictions associated with CHF are not limited to physically demanding activities and are significantly associated with executive dysfunction and depression. Cardiac rehabilitation should address cognitive and psychological functioning in the context of all life situations instead of focusing solely on physical function and disability. PMID:21675336

Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach

PubMed Central

Lin, Angela H.; Patel, Saumil S.; Sereno, Anne B.

2013-01-01

Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction. PMID:23460843

Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?

PubMed

Solowij, Nadia; Michie, Patricia T

2007-01-01

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

Clinical, functional, and neurophysiologic assessment of dysplastic cortical networks: Implications for cortical functioning and surgical management.

PubMed

Duchowny, Michael

2009-10-01

Cortical malformations are highly epileptogenic lesions associated with complex, unanticipated, and often aberrant electrophysiologic and functional relationships. These relationships are inextricably linked to widespread cortical networks subserving eloquent functions, particularly language and motor ability. Cytomegalic neurons but not balloon cells in Palmini type 2 dysplastic cortex are intrinsically hyperexcitable and contribute to local epileptogenesis and functional responsiveness. However, there is much evidence that focal cortical dysplasia is rarely a localized or even regional process, and is a functionally, electrophysiologically, and ultimately clinically integrated neural network disorder. Not surprisingly, malformed cortex is implicated in cognitive dysfunction, particularly disturbances of linguistic processing. An understanding of these relationships is critical for successful epilepsy surgery. Gains in surgical prognosis rely on multiple diagnostic modalities to delineate complex anatomic, electrophysiologic, and functional relationships in magnetic resonance imaging (MRI)-negative patients with rates of seizure-freedom roughly comparable to lesional patients.

Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

PubMed

Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

2010-08-18

The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

Executive dysfunction predicts social cognition impairment in amyotrophic lateral sclerosis.

PubMed

Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Catherine M; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H

2015-07-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor system with recognised extra-motor and cognitive involvement. This cross-sectional study examined ALS patients' performance on measures requiring social inference, and determined the relationship between such changes and variations in mood, behaviour, personality, empathy and executive function. Fifty-five ALS patients and 49 healthy controls were compared on tasks measuring social cognition and executive function. ALS patients also completed measures examining mood, behaviour and personality. Regression analyses explored the contribution of executive function, mood, behaviour and personality to social cognition scores within the ALS sample. A between-group MANOVA revealed that, the ALS group was impaired relative to controls on two composite scores for social cognition and executive function. Patients also performed worse on individual tests of executive function measuring cognitive flexibility, response inhibition and concept formation, and on individual aspects of social cognition assessing the attribution of emotional and mental states. Regression analyses indicated that ALS-related executive dysfunction was the main predictor of social cognition performance, above and beyond demographic variables, behaviour, mood and personality. On at least some aspects of social cognition, impaired performance in ALS appears to be secondary to executive dysfunction. The profile of cognitive impairment in ALS supports a cognitive continuum between ALS and frontotemporal dementia.

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies

PubMed Central

Lewis, Alan S.; van Schalkwyk, Gerrit I.; Bloch, Michael H.

2017-01-01

Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer’s disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen’s d = −0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d = −1.18 to −0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR. PMID:28065843

Comparison of a gratitude-based and cognitive restructuring intervention for body dissatisfaction and dysfunctional eating behavior in college women.

PubMed

Wolfe, Wendy L; Patterson, Kaitlyn

2017-01-01

Researchers have investigated the efficacy of a gratitude intervention for decreasing body dissatisfaction (BD) in an internet treatment-seeking sample and demonstrated it worked equally well to decrease BD as cognitive restructuring. We extend this research by testing the efficacy of a gratitude intervention on BD, along with common sequelae of BD: dysfunctional eating, negative mood, and depressive symptoms. Females were randomly assigned to Gratitude, Cognitive Restructuring, or Control conditions. Pre- to post-intervention period comparisons found the gratitude intervention to perform better than the other conditions at increasing body esteem, decreasing BD, reducing dysfunctional eating, and reducing depressive symptoms.

Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

PubMed Central

Clark, Duncan B.; Chung, Tammy; Martin, Christopher S.; Hasler, Brant P.; Fitzgerald, Douglas H.; Luna, Beatriz; Brown, Sandra A.; Tapert, Susan F.; Brumback, Ty; Cummins, Kevin; Pfefferbaum, Adolf; Sullivan, Edith V.; Pohl, Kilian M.; Colrain, Ian M.; Baker, Fiona C.; De Bellis, Michael D.; Nooner, Kate B.; Nagel, Bonnie J.

2017-01-01

During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use. PMID:29180956

Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice.

PubMed

Zhan, Gaofeng; Yang, Ning; Li, Shan; Huang, Niannian; Fang, Xi; Zhang, Jie; Zhu, Bin; Yang, Ling; Yang, Chun; Luo, Ailin

2018-06-10

Alzheimer's disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer's disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer's disease.

Persistent activation of microglia and NADPH drive hippocampal dysfunction in experimental multiple sclerosis

PubMed Central

Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

2016-01-01

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID:26887636

Relationship between maladaptive cognitions about sleep and recovery in patients with borderline personality disorder

PubMed Central

Plante, David T.; Frankenburg, Frances R.; Fitzmaurice, Garrett M.; Zanarini, Mary C.

2013-01-01

Borderline personality disorder (BPD) has been associated with maladaptive cognitive processes including dysfunctional attitudes and a negative attribution style. Comorbid insomnia affects the course of multiple psychiatric disorders, and has been associated with absence of recovery from BPD. Because dysfunctional beliefs and attitudes are common among patients with insomnia, the purpose of this study was to evaluate the association between maladaptive sleep-related cognitions and recovery status (symptomatic remission plus good concurrent psychosocial functioning) in patients with BPD. 223 BPD patients participating in the McLean Study of Adult Development (MSAD) were administered the Dysfunctional Beliefs and Attitudes about Sleep questionnaire (DBAS-16) as part of the 16-year follow-up wave. Maladaptive sleep cognitions were compared between recovered (n=105) and non-recovered (n=118) BPD participants, in analyses that adjusted for age, sex, depression, anxiety, and primary sleep disorders. Results demonstrated non-recovered BPD patients had significantly more severe maladaptive sleep-related cognitions as measured by the overall DBAS-16 score. These results demonstrate an association between dysfunctional beliefs and attitudes about sleep and recovery status among BPD patients. Further research is warranted to evaluate treatments targeted towards maladaptive sleep-related cognitions, and their subsequent effects on the course of BPD. PMID:23972789

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

PubMed

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

[The Effects of Mobile Social Networking Service-Based Cognitive Behavior Therapy on Insomnia in Nurses].

PubMed

Kim, Ji Eun; Kim, Suk Sun

2017-08-01

This study aimed to examine the effects of cognitive behavior therapy for insomnia (CBT-I) based on the mobile social networking service (SNS) on dysfunctional beliefs and attitudes about sleep, sleep quality, daytime sleepiness, depression, and quality of life among rotating-shift nurses in a hospital in Korea. A nonequivalent control group pre-post test design was used. The participants included 55 nurses with rotating three-shift work (25 in the experimental group and 30 in the control group). For the experimental group, CBT-I using mobile SNS was provided once a week for 60 minutes over six weeks. Data were analyzed using descriptive statistics, χ²-test, independent samples t-test, and Mann-whitney U test with the SPSS 21.0 program. In the homogeneity test of the general characteristics and study variables, there were no significant differences between the two groups. Nurses in the experimental group had significantly lower scores on dysfunctional beliefs and attitudes regarding sleep and sleepiness than nurses in the control group. Nurses in the experimental group had significantly higher scores on sleep quality and quality of life than nurses in the control group. These findings indicate that using the mobile SNS-based CBT-I is feasible and has significant and positive treatment-related effects on rotating-shift nurses' irrational thoughts and beliefs in association with sleep, sleep quality, daytime sleepiness, and quality of life. These contribute to expanding our knowledge of rotating-shift nurses' sleep issues and their preferences for intervention. © 2017 Korean Society of Nursing Science

[Postoperative cognitive deficits].

PubMed

Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System

PubMed Central

Steininger, Stefanie C.; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M.; Prüssmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. Methods: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Results: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Conclusion: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD. PMID:24672483

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

PubMed

Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

2014-01-01

Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

PubMed

Cotman, Carl W; Head, Elizabeth; Muggenburg, Bruce A; Zicker, S; Milgram, Norton W

2002-01-01

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies. Copyright 2002 Elsevier Science Inc.

Neurocognitive function in obstructive sleep apnoea: a meta-review.

PubMed

Bucks, Romola S; Olaithe, Michelle; Eastwood, Peter

2013-01-01

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta-analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand-searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short-term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long-term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

PubMed Central

Cardin, Velia

2016-01-01

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors.

PubMed

Kesler, Shelli R; Blayney, Douglas W

2016-02-01

Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain's default mode network. The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non-chemotherapy-treated controls. These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.

Cognitive correlates of frontoparietal network connectivity 'at rest' in individuals with differential risk for psychotic disorder.

PubMed

Peeters, S C T; van Bronswijk, S; van de Ven, V; Gronenschild, E H B M; Goebel, R; van Os, J; Marcelis, M

2015-11-01

Altered frontoparietal network functional connectivity (FPN-fc) has been associated with neurocognitive dysfunction in individuals with (risk for) psychotic disorder. Cannabis use is associated with cognitive and FPN-fc alterations in healthy individuals, but it is not known whether cannabis exposure moderates the FPN-fc-cognition association. We studied FPN-fc in relation to psychosis risk, as well as the moderating effects of psychosis risk and cannabis use on the association between FPN-fc and (social) cognition. This was done by collecting resting-state fMRI scans and (social) cognitive test results from 63 patients with psychotic disorder, 73 unaffected siblings and 59 controls. Dorsolateral prefrontal cortex (DLPFC) seed-based correlation analyses were used to estimate FPN-fc group differences. Additionally, group×FPN-fc and cannabis×FPN-fc interactions in models of cognition were assessed with regression models. Results showed that DLPFC-fc with the left precuneus, right inferior parietal lobule, right middle temporal gyrus (MTG), inferior frontal gyrus (IFG) regions and right insula was decreased in patients compared to controls. Siblings had reduced DLPFC-fc with the right MTG, left middle frontal gyrus, right superior frontal gyrus, IFG regions, and right insula compared to controls, with an intermediate position between patients and controls for DLPFC-IFG/MTG and insula-fc. There were no significant FPN-fc×group or FPN-fc×cannabis interactions in models of cognition. Reduced DLPFC-insula-fc was associated with worse social cognition in the total sample. In conclusion, besides patient- and sibling-specific FPN-fc alterations, there was evidence for trait-related alterations. FPN-fc-cognition associations were not conditional on familial liability or cannabis use. Lower FPN-fc was associated with lower emotion processing in the total group. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Modulating the processing of emotional stimuli by cognitive demand

PubMed Central

Sternkopf, Melanie A.; Schneider, Frank; Habel, Ute; Turetsky, Bruce I.; Zilles, Karl; Eickhoff, Simon B.

2012-01-01

Emotional processing is influenced by cognitive processes and vice versa, indicating a profound interaction of these domains. The investigation of the neural mechanisms underlying this interaction is not only highly relevant for understanding the organization of human brain function. Rather, it may also help in understanding dysregulated emotions in affective disorders and in elucidating the neurobiology of cognitive behavioural therapy (e.g. in borderline personality disorder), which aims at modulating dysfunctional emotion processes by cognitive techniques, such as restructuring. In the majority of earlier studies investigating the interaction of emotions and cognition, the main focus has been on the investigation of the effects of emotional stimuli or, more general, emotional processing, e.g. instituted by emotional material that needed to be processed, on cognitive performance and neural activation patterns. Here we pursued the opposite approach and investigated the modulation of implicit processing of emotional stimuli by cognitive demands using an event-related functional magnetic resonance imaging––study on a motor short-term memory paradigm with emotional interferences. Subjects were visually presented a finger-sequence consisting either of four (easy condition) or six (difficult condition) items, which they had to memorize. After a short pause positive, negative or neutral International affective picture system pictures or a green dot (as control condition) were presented. Subjects were instructed to reproduce the memorized sequence manually as soon as the picture disappeared. Analysis showed that with increasing cognitive demand (long relative to short sequences), neural responses to emotional pictures were significantly reduced in amygdala and orbitofrontal cortex. In contrast, the more difficult task evoked stronger activation in a widespread frontoparietal network. As stimuli were task-relevant go-cues and hence had to be processed perceptually, we would interpret this as a specific attenuation of affective responses by concurrent cognitive processing––potentially reflecting a relocation of resources mediated by the frontoparietal network. PMID:21258093

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

PubMed

Tarantini, Stefano; Valcarcel-Ares, M Noa; Yabluchanskiy, Andriy; Tucsek, Zsuzsanna; Hertelendy, Peter; Kiss, Tamas; Gautam, Tripti; Zhang, Xin A; Sonntag, William E; de Cabo, Rafael; Farkas, Eszter; Elliott, Michael H; Kinter, Michael T; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-14

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

BEHAVIORAL AND LEARNING DISABILITIES ASSOCIATED WITH COGNITIVE-MOTOR DYSFUNCTION. INTERIM REPORT.

ERIC Educational Resources Information Center

BRAUN, JEAN S.; RUBIN, ELI Z.

THIS REPORT EXAMINES THE RELATIONSHIP BETWEEN BEHAVIORAL AND ACADEMIC DISABILITIES AND COGNITIVE-MOTOR DYSFUNCTION AS REVEALED BY DATA ON 400 ELEMENTARY SCHOOL CHILDREN. THE BEHAVIOR CHECKLIST WAS USED AS A BASIS FOR SAMPLE SELECTION. BEHAVIOR CLUSTERS REFLECTING BOTH ANTI-SOCIAL TENDENCIES AND UNASSERTIVE, WITHDRAWN BEHAVIOR WERE IDENTIFIED. A…

Dorso-Lateral Prefrontal Cortex MRI Measurements and Cognitive Performance in Autism

PubMed Central

Griebling, Jessica; Minshew, Nancy J.; Bodner, Kimberly; Libove, Robin; Bansal, Rahul; Konasale, Prasad; Keshavan, Matcheri S.; Hardan, Antonio

2012-01-01

This study examined the relationships between volumetric measurements of frontal lobe structures and performance on executive function tasks in individuals with autism. MRI scans were obtained from 38 individuals with autism and 40 matched controls between the ages of 8 and 45 years. Executive function was assessed using neuropsychological measures including the Wisconsin Card Sorting Test and Tower of Hanoi. Differences in performance on the neuropsychological tests were found between the two groups. However, no differences in dorsolateral prefrontal cortex volumes were observed between groups. No correlations between volumetric measurements and performance on the neuropsychological tests were found. Findings from this study suggest that executive function deficits observed in autism are related to functional but not anatomical abnormalities of the frontal lobe. The absence of correlations suggests that executive dysfunction is not the result of focal brain alterations but, rather, is the result of a distributed neural network dysfunction. PMID:20097663

The evolution of the cognitive model of depression and its neurobiological correlates.

PubMed

Beck, Aaron T

2008-08-01

Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression--probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.

Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression

PubMed Central

Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

2017-01-01

Abstract Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = −0.21, P = 0.046) and rumination (r = −0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. PMID:28981917

Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression.

PubMed

Figueroa, Caroline A; Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

2017-11-01

Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = -0.21, P = 0.046) and rumination (r = -0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. © The Author (2017). Published by Oxford University Press.

Counterfactual thinking in Tourette's syndrome: a study using three measures.

PubMed

Zago, Stefano; Delli Ponti, Adriana; Mastroianni, Silvia; Solca, Federica; Tomasini, Emanuele; Poletti, Barbara; Inglese, Silvia; Sartori, Giuseppe; Porta, Mauro

2014-01-01

Pathophysiological evidence suggests an involvement of frontostriatal circuits in Tourette syndrome (TS) and cognitive abnormalities have been detected in tasks sensitive to cognitive deficits associated with prefrontal damage (verbal fluency, planning, attention shifting, working memory, cognitive flexibility, and social reasoning). A disorder in counterfactual thinking (CFT), a behavioural executive process linked to the prefrontal cortex functioning, has not been investigated in TS. CFT refers to the generation of a mental simulation of alternatives to past factual events, actions, and outcomes. It is a pervasive cognitive feature in everyday life and it is closely related to decision-making, planning, problem-solving, and experience-driven learning-cognitive processes that involve wide neuronal networks in which prefrontal lobes play a fundamental role. Clinical observations in patients with focal prefrontal lobe damage or with neurological and psychiatric diseases related to frontal lobe dysfunction (e.g., Parkinson's disease, Huntington's disease, and schizophrenia) show counterfactual thinking impairments. In this work, we evaluate the performance of CFT in a group of patients with Tourette's syndrome compared with a group of healthy participants. Overall results showed no statistical differences in counterfactual thinking between TS patients and controls in the three counterfactual measures proposed. The possible explanations of this unexpected result are discussed below.

Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI

PubMed Central

Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo

2014-01-01

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441

Selective impairment of attention networks during propofol anesthesia after gynecological surgery in middle-aged women.

PubMed

Chen, Chen; Xu, Guang-hong; Li, Yuan-hai; Tang, Wei-xiang; Wang, Kai

2016-04-15

Postoperative cognitive dysfunction is a common complication of anesthesia and surgery. Attention networks are essential components of cognitive function and are subject to impairment after anesthesia and surgery. It is not known whether such impairment represents a global attention deficit or relates to a specific attention network. We used an Attention Network Task (ANT) to examine the efficiency of the alerting, orienting, and executive control attention networks in middle-aged women (40-60 years) undergoing gynecologic surgery. A matched group of medical inpatients were recruited as a control. Fifty female patients undergoing gynecologic surgery (observation group) and 50 female medical inpatients (control group) participated in this study. Preoperatively patients were administered a mini-mental state examination as a screening method. The preoperative efficiencies of three attention networks in an attention network test were compared to the 1st and 5th post-operative days. The control group did not have any significant attention network impairments. On the 1st postoperative day, significant impairment was shown in the alerting (p=0.003 vs. control group, p=0.015 vs. baseline), orienting (p<0.001 vs. both baseline level and control group), and executive control networks (p=0.007 vs. control group, p=0.002 vs. baseline) of the observation group. By the 5th postoperative day, the alerting network efficiency had recovered to preoperative levels (p=0.464 vs. baseline) and the orienting network efficiency had recovered partially (p=0.031 vs. 1st post-operative day), but not to preoperative levels (p=0.01 vs. baseline). The executive control network did not recover by the 5th postoperative day (p=0.001 vs. baseline, p=0.680 vs. 1st post-operative day). Attention networks of middle-aged women show a varying degree of significant impairment and differing levels of recovery after surgery and propofol anesthetic. Copyright © 2016 Elsevier B.V. All rights reserved.

Learning temporal statistics for sensory predictions in mild cognitive impairment.

PubMed

Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-08-01

Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Disrupted insula-based neural circuit organization and conflict interference in trauma-exposed youth.

PubMed

Marusak, Hilary A; Etkin, Amit; Thomason, Moriah E

2015-01-01

Childhood trauma exposure is a potent risk factor for psychopathology. Emerging research suggests that aberrant saliency processing underlies the link between early trauma exposure and later cognitive and socioemotional deficits that are hallmark of several psychiatric disorders. Here, we examine brain and behavioral responses during a face categorization conflict task, and relate these to intrinsic connectivity of the salience network (SN). The results demonstrate a unique pattern of SN dysfunction in youth exposed to trauma (n = 14) relative to comparison youth (n = 19) matched on age, sex, IQ, and sociodemographic risk. We find that trauma-exposed youth are more susceptible to conflict interference and this correlates with higher fronto-insular responses during conflict. Resting-state functional connectivity data collected in the same participants reveal increased connectivity of the insula to SN seed regions that is associated with diminished reward sensitivity, a critical risk/resilience trait following stress. In addition to altered intrinsic connectivity of the SN, we observed altered connectivity between the SN and default mode network (DMN) in trauma-exposed youth. These data uncover network-level disruptions in brain organization following one of the strongest predictors of illness, early life trauma, and demonstrate the relevance of observed neural effects for behavior and specific symptom dimensions. SN dysfunction may serve as a diathesis that contributes to illness and negative outcomes following childhood trauma.

The Activation of Incompetence Schemas in Response to Negative Sexual Events in Heterosexual and Lesbian Women: The Moderator Role of Personality Traits and Dysfunctional Sexual Beliefs.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-01-01

Personality traits and dysfunctional sexual beliefs have been described as vulnerability factors for sexual dysfunction in women, and have also been proposed as dispositional variables for the activation of incompetence schemas in response to negative sexual events. However, no study has tested the role of personality traits and dysfunctional sexual beliefs in the activation of incompetence schemas. The current study aimed to assess the moderator role of neuroticism, extraversion, and dysfunctional sexual beliefs in the association between frequency of unsuccessful sexual episodes and activation of incompetence schemas in heterosexual and lesbian women. An online survey was completed by 1,121 women (831 heterosexual; 290 lesbian). Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Sexual Dysfunctional Beliefs Questionnaire-Female Version (SDBQ), and the Questionnaire of Cognitive Schemas Activated in Sexual Context (QCSASC). Findings indicate that neuroticism moderates the association between frequency of negative sexual events and activation of incompetence schemas in heterosexual women. Moreover, several sexual beliefs also act as moderators of the relationship between negative sexual episodes and the activation of cognitive schemas in both heterosexual and lesbian women. Overall, findings support the cognitive-emotional model of sexual dysfunctions, emphasizing the role of personality traits and dysfunctional sexual beliefs as facilitators of the activation of incompetence schemas in response to negative events in women.

Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients.

PubMed

Kozora, Elizabeth; Erkan, Doruk; Zhang, Lening; Zimmerman, Robert; Ramon, Glendalee; Ulug, Aziz M; Lockshin, Michael D

2014-01-01

The aim of this study was to compare the cognitive function of antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and aPL-positive non-SLE patients. Twenty aPL-negative SLE and 20 aPL-positive non-SLE female patients with no history of overt neuropsychiatric manifestations took standardised cognitive tests of learning and memory, attention and working memory, executive functions, verbal fluency, visuoconstruction, and motor function. The primary outcome measure was an established global cognitive impairment index (CII). Cranial magnetic resonance imaging (MRI) was also obtained on all patients. Twelve of 20 (60%) of the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive impairment on CII; there were no group differences on CII or on individual measures. Cognitive impairment was not associated with duration of disease, level of disease activity, or prednisone use. No correlations were found between clinical disease factors and cognitive impairment, and neither group showed an association between incidental or major MRI abnormalities and cognitive dysfunction. Both aPL-negative SLE and aPL-positive non-SLE patients, without other overt neuropsychiatric disease, demonstrated high levels of cognitive impairment. No clinical, serologic, or radiologic characteristics were associated with cognitive impairment. Cognitive dysfunction is common in APS and in SLE, but its mechanisms remain unknown.

Chronic methamphetamine self-administration disrupts cortical control of cognition.

PubMed

Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

2016-10-01

Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

The social brain hypothesis of schizophrenia.

PubMed

Burns, Jonathan

2006-06-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected.

The social brain hypothesis of schizophrenia

PubMed Central

BURNS, JONATHAN

2006-01-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected. PMID:16946939

Cognitive Visual Dysfunctions in Preterm Children with Periventricular Leukomalacia

ERIC Educational Resources Information Center

Fazzi, Elisa; Bova, Stefania; Giovenzana, Alessia; Signorini, Sabrina; Uggetti, Carla; Bianchi, Paolo

2009-01-01

Aim: Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method: We studied 22 children born preterm (12 males, 10 females;…

Cerebellar Dysfunction, Cognitive Flexibility and Autistic Traits in a Non-Clinical Sample

ERIC Educational Resources Information Center

Ridley, Nicole J.; Homewood, Judi; Walters, Jenny

2011-01-01

Cerebellar dysfunction and impaired cognitive flexibility are key features of autism spectrum disorders (ASD). However, despite the increasing interest in subclinical autism, no research has yet examined the relationship between these signs and autistic traits in the wider population. This study used the Autism-Spectrum Quotient (AQ) questionnaire…

Specificity of spontaneous EEG associated with different levels of cognitive and communicative dysfunctions in children.

PubMed

Kozhushko, Nadezhda Ju; Nagornova, Zhanna V; Evdokimov, Sergey A; Shemyakina, Natalia V; Ponomarev, Valery A; Tereshchenko, Ekaterina P; Kropotov, Jury D

2018-06-01

This study aimed to reveal electrophysiological markers of communicative and cognitive dysfunctions of different severity in children with autism spectrum disorder (ASD). Eyes-opened electroencephalograms (EEGs) of 42 children with ASD, divided into two groups according to the severity of their communicative and cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and 70 age-matched controls aged 4-9 years were examined by means of spectral and group independent component (gIC) analyses. A predominance of theta and beta EEG activity in both groups of children with ASD compared to the activity in the control group was found in the global gIC together with a predominance of beta EEG activity in the right occipital region. The quantity of local gICs with enhanced slow and high-frequency EEG activity (within the frontal, temporal, and parietal cortex areas) in children 4-9 years of age might be considered a marker of cognitive and communicative dysfunction severity. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuroprotective effects of voluntary running on cognitive dysfunction in an α-synuclein rat model of Parkinson's disease.

PubMed

Crowley, Erin K; Nolan, Yvonne M; Sullivan, Aideen M

2018-05-01

Parkinson's disease (PD) is no longer primarily classified as a motor disorder due to increasing recognition of the impact on patients of several nonmotor PD symptoms, including cognitive dysfunction. These nonmotor symptoms are highly prevalent and greatly affect the quality of life of patients with PD, and so, therapeutic interventions to alleviate these symptoms are urgently needed. The aim of this study was to investigate the potential neuroprotective effects of voluntary running on cognitive dysfunction in an adeno-associated virus-α-synuclein rat model of PD. Bilateral intranigral administration of adeno-associated virus-α-synuclein was found to induce motor dysfunction and a significant loss of nigral dopaminergic neurons, neither of which were rescued by voluntary running. Overexpression of α-synuclein also resulted in significant impairment on hippocampal neurogenesis-dependent pattern separation, a cognitive task; this was rescued by voluntary running. This was substantiated by an effect of running on neurogenesis levels in the dorsal dentate gyrus, suggesting that the functional effects of running on pattern separation were mediated via increased neurogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

PubMed

Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

2016-09-01

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

Relationship Between Self-reported Apathy and Executive Dysfunction in Nondemented Patients With Parkinson Disease

PubMed Central

Zgaljardic, Dennis J.; Borod, Joan C.; Foldi, Nancy S.; Rocco, Mary; Mattis, Paul J.; Gordon, Mark F.; Feigin, Andrew S.; Eidelberg, David

2015-01-01

Objective The prevalence of apathy was assessed across select cognitive and psychiatric variables in 32 nondemented patients with Parkinson disease (PD) and 29 demographically matched healthy control participants. Background Apathy is common in PD, although differentiating apathy from motor, cognitive, and/or other neuropsychiatric symptoms can be challenging. Previous studies have reported a positive relationship between apathy and cognitive impairment, particularly executive dysfunction. Method Patients were categorized according to apathy symptom severity. Stringent criteria were used to exclude patients with dementia. Results Approximately 44% of patients endorsed significant levels of apathy. Those patients performed worse than patients with nonsignificant levels of apathy on select measures of verbal fluency and on a measure of verbal and nonverbal conceptualization. Further, they reported a greater number of symptoms related to depression and behavioral disturbance than did those patients with nonsignificant levels of apathy. Apathy was significantly related to self-report of depression and executive dysfunction. Performance on cognitive tasks assessing verbal fluency, working memory, and verbal abstraction and also on a self-report measure of executive dysfunction was shown to significantly predict increasing levels of apathy. Conclusions Our findings suggest that apathy in nondemented patients with PD seems to be strongly associated with executive dysfunction. PMID:17846518

Modification of dysfunctional thoughts about caregiving in dementia family caregivers: description and outcomes of an intervention programme.

PubMed

Márquez-González, M; Losada, A; Izal, M; Pérez-Rojo, G; Montorio, I

2007-11-01

Among the diverse group of interventions developed to help dementia family caregivers cognitive-behavioural approaches show especially promising results. This study describes a cognitive-behavioural group intervention aimed principally at the modification of dysfunctional thoughts associated with caregiving (MDTC). The efficacy of the MDTC intervention in reducing caregivers' depressive symptomatology, together with the frequency and appraisal of problem behaviours, is compared to that of a waiting-list control group (WL). Furthermore, the potential mediating role of the dysfunctional thoughts in the relationship between this intervention and caregivers' depressive symptomatology is analyzed. Of the 74 dementia caregivers who were randomized to one of two conditions (MDTC and WL), 39 completed the post-intervention assessment. Statistical analyses were performed on an intention-to-treat basis, using last observation carried forward. The results reveal that the MDTC intervention is successful in reducing caregivers' level of depressive symptomatology and dysfunctional thoughts about caregiving, as well as in modifying their appraisal of their relative's problem behaviours. Furthermore, a mediating role for dysfunctional thoughts was found in the relationship between the MDTC intervention and levels of depressive symptomatology. The relevance of addressing dysfunctional thoughts and cognitive distortions in group interventions with caregivers is highlighted.

Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users

PubMed Central

Harding, Ian H; Solowij, Nadia; Harrison, Ben J; Takagi, Michael; Lorenzetti, Valentina; Lubman, Dan I; Seal, Marc L; Pantelis, Christos; Yücel, Murat

2012-01-01

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes. PMID:22534625

Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast Exposed/TBI Service Members

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-15-1-0490 TITLE: Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast-Exposed/ TBI...3. DATES COVERED 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Diagnosing Contributions of Sensory and Cognitive Deficits to...installed at WRNMMC, and is running finalized versions of both the auditory and visual selective attention tasks. Subject recruitment has started, and

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

PubMed

Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

PubMed

Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

2012-09-01

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy.

PubMed

Packer, Rowena M A; McGreevy, Paul D; Salvin, Hannah E; Valenzuela, Michael J; Chaplin, Chloe M; Volk, Holger A

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

PubMed Central

McGreevy, Paul D.; Salvin, Hannah E.; Valenzuela, Michael J.; Chaplin, Chloe M.; Volk, Holger A.

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments. PMID:29420639

Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

PubMed Central

Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

2016-01-01

Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

Cognitive structures in women with sexual dysfunction: the role of early maladaptive schemas.

PubMed

Oliveira, Cátia; Nobre, Pedro J

2013-07-01

Cognitive schemas are often related to psychological problems. However, the role of these structures within sexual problems is not yet well established. The aim of this study was to evaluate the presence and importance of early maladaptive schemas on women's sexual functioning and cognitive schemas activated in response to negative sexual events. A total of 228 women participated in the study: a control sample of 167 women without sexual problems, a subclinical sample of 37 women with low sexual functioning, and a clinical sample of 24 women with sexual dysfunction. Participants completed several self-reported measures: the Schema Questionnaire, the Questionnaire of Cognitive Schema Activation in Sexual Context, the Brief Symptom Inventory, the Beck Depression Inventory, and the Female Sexual Function Index. Findings indicated that women with sexual dysfunction presented significantly more early maladaptive schemas from the Impaired Autonomy and Performance domain, particularly failure (P < 0.001, η(2) = 0.08), dependence/incompetence (P < 0.05, η(2) = 0.03), and vulnerability to danger (P < 0.05, η(2) = 0.04). Additionally, in response to negative sexual events, women with sexual dysfunction presented significantly higher scores on incompetence (P < 0.001, η(2) = 0.16), self-depreciation (P < 0.01, η(2) = 0.05), and difference/loneliness (P < 0.01, η(2) = 0.05) schemas. Results supported differences between women with and without sexual problems regarding cognitive factors. This may have implications for the knowledge, assessment, and treatment of sexual dysfunction in women. © 2012 International Society for Sexual Medicine.

Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study.

PubMed

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M; Cappola, Anne R; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs > or =65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P<.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P<.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61+/-6.88 vs 24.72+/-4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.

No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.

PubMed

Lex, Claudia; Meyer, Thomas D; Marquart, Barbara; Thau, Kenneth

2008-03-01

Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.

Cognitive Dysfunction in Patients with Renal Failure Requiring Hemodialysis

PubMed Central

Thimmaiah, Rohini; Murthy, K. Krishna; Pinto, Denzil

2012-01-01

Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis. PMID:23439613

Vascular cognitive impairment, a cardiovascular complication.

PubMed

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-06-22

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

Vascular cognitive impairment, a cardiovascular complication

PubMed Central

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-01-01

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961

COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

PubMed Central

Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

2013-01-01

Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

Obesity Reduces Cognitive and Motor Functions across the Lifespan

PubMed Central

Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095

Obesity Reduces Cognitive and Motor Functions across the Lifespan.

PubMed

Wang, Chuanming; Chan, John S Y; Ren, Lijie; Yan, Jin H

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition.

PubMed

Stip, Emmanuel; Caron, Jean; Tousignant, Michel; Lecomte, Yves

2017-10-01

To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Dong-mei; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province; Lu, Jun, E-mail: lu-jun75@163.com

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitivemore » deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.« less

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition

PubMed Central

Stip, Emmanuel; Caron, Jean; Tousignant, Michel

2017-01-01

Objective: To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. Method: The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. Results: The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). Conclusion: The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders. PMID:28673099

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

PubMed

Li, Zhenguang; Yu, Zhancai; Zhang, Jinbiao; Wang, Jing; Sun, Chao; Wang, Pengfei; Zhang, Jiangshan

2015-01-01

The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients. © 2015 S. Karger AG, Basel.

Changes in cognitive control in pre-manifest Huntington's disease examined using pre-saccadic EEG potentials - a longitudinal study.

PubMed

Ness, Vanessa; Bestgen, Anne-Kathrin; Saft, Carsten; Beste, Christian

2014-01-01

It is well-known that Huntington's disease (HD) affects saccadic processing. However, saccadic dysfunctions in HD may be seen as a result of dysfunctional processes occurring at the oculomotor level prior to the execution of saccades, i.e., at a pre-saccadic level. Virtually nothing is known about possible changes in pre-saccadic processes in HD. This study examines pre-saccadic processing in pre-manifest HD gene mutation carriers (pre-HDs) by using clinically available EEG measures. Error rates, pre-saccadic EEG potentials and saccade onset EEG potentials were measured in 14 pre-HDs and case-matched controls performing prosaccades and antisaccades in a longitudinal study over a 15-month period. The results show that pre-saccadic potentials were changed in pre-HDs, relative to controls and also revealed changes across the 15-month longitudinal period. In particular, pre-saccadic ERP in pre-HDs were characterized by lower amplitudes and longer latencies, which revealed longitudinal changes. These changes were observed for anti-saccades, but not for pro-saccades. Overt saccadic trajectories (potentials) were not different to those in controls, showing that pre-saccadic processes are sensitive to subtle changes in fronto-striatal networks in pre-HDs. Deficits in pre-saccadic processes prior the execution of an erroneous anti-saccade can be seen as an effect of dysfunctional cognitive control in HD. This may underlie saccadic abnormalities and hence a major phenotype of HD. Pre-saccadic EEG potentials preceding erroneous anti-saccades are sensitive to pre-manifest disease progression in HD.

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

PubMed Central

SIMON, TONY J.; BISH, JOEL P.; BEARDEN, CARRIE E.; DING, LIJUN; FERRANTE, SAMANTHA; NGUYEN, VY; GEE, JAMES C.; McDONALD–McGINN, DONNA M.; ZACKAI, ELAINE H.; EMANUEL, BEVERLY S.

2006-01-01

We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. PMID:16262991

Cognitive Dysfunction, Locus of Control and Treatment Outcome among Chronic Alcoholics.

ERIC Educational Resources Information Center

Abbott, Max W.

While alcoholism is no longer regarded as a unitary disorder, conventional measures of congition and personality have yet to be shown capable of consistently predicting clinical outcomes. To investigate cognitive dysfunction and locus of control as predictors of post treatment outcome in a large sample of alcoholics, 106 alcoholics (74 men, 32…

[Social dysfunction in schizotypy].

PubMed

de Wachter, O; De La Asuncion, J; Sabbe, B; Morrens, M

2016-01-01

Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. To describe schizotypy and its influence on social functioning. We reviewed the literature systematically using the online databases PubMed and PsycINFO. The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Qingyu; Department of Neurology, Zengcheng People's Hospital, Guangzhou; Lin, Focai

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitivemore » function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN. The number of temporal CMBs is independently associated with increased likelihood of cognitive dysfunction in patients with RN.« less

Theory of mind and empathy in preclinical and clinical Huntington’s disease

PubMed Central

Adjeroud, Najia; Besnard, Jérémy; Massioui, Nicole El; Verny, Christophe; Prudean, Adriana; Scherer, Clarisse; Gohier, Bénédicte; Bonneau, Dominique

2016-01-01

We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington’s disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054–67) that examines first- and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first- and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy. PMID:26211015

Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure.

PubMed

Barnes, Abigail K; Smith, Summer B; Datta, Subimal

2017-01-01

Cognitive dysfunction in depression has recently been given more attention and legitimacy as a core symptom of the disorder. However, animal investigations of depression-related cognitive deficits have generally focused on emotional or spatial memory processing. Additionally, the relationship between the cognitive and affective disturbances that are present in depression remains obscure. Interestingly, sleep disruption is one aspect of depression that can be related both to cognition and affect, and may serve as a link between the two. Previous studies have correlated sleep disruption with negative mood and impaired cognition. The present study investigated whether a long photoperiod-induced depressive phenotype showed cognitive deficits, as measured by novel object recognition, and displayed a cognitive vulnerability to an acute period of total sleep deprivation. Adult male Wistar rats were subjected to a long photoperiod (21L:3D) or a normal photoperiod (12L:12D) condition. Our results indicate that our long photoperiod exposed animals showed behaviors in the forced swim test consistent with a depressive phenotype, and showed significant deficits in novel object recognition. Three hours of total sleep deprivation, however, did not significantly change novel object recognition in either group, but the trends suggest that the long photoperiod and normal photoperiod groups had different cognitive responses to total sleep deprivation. Collectively, these results underline the extent of cognitive dysfunction present in depression, and suggest that altered sleep plays a role in generating both the affective and cognitive symptoms of depression.

Brain imaging and cognitive dysfunctions in Huntington's disease

PubMed Central

Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

2006-01-01

Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial.

PubMed

Hassani, Soghra; Alipour, Abbas; Darvishi Khezri, Hadi; Firouzian, Abolfazl; Emami Zeydi, Amir; Gholipour Baradari, Afshin; Ghafari, Rahman; Habibi, Wali-Allah; Tahmasebi, Homeyra; Alipour, Fatemeh; Ebrahim Zadeh, Pooneh

2015-03-01

We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure

PubMed Central

Park, Bumhee; Roy, Bhaswati; Woo, Mary A.; Palomares, Jose A.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2016-01-01

Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID:27203600

Functional changes in the cortical semantic network in amnestic mild cognitive impairment.

PubMed

Pineault, Jessica; Jolicoeur, Pierre; Grimault, Stephan; Bermudez, Patrick; Brambati, Simona Maria; Lacombe, Jacinthe; Villalpando, Juan Manuel; Kergoat, Marie-Jeanne; Joubert, Sven

2018-05-01

Semantic memory impairment has been documented in individuals with amnestic Mild cognitive impairment (aMCI), who are at risk of developing Alzheimer's disease (AD), yet little is known about the neural basis of this breakdown. The aim of this study was to investigate the brain mechanisms associated with semantic performance in aMCI patients. A group of aMCI patients and a group of healthy controls carried out a semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). During the task, participants were shown famous faces and had to determine whether each famous person matched a given occupation. The main hypotheses were that (a) semantic processing should be compromised for aMCI patients, and (b) these deficits should be associated with cortical dysfunctions within specific areas of the semantic network. Behavioral results showed that aMCI participants were significantly slower and less accurate than controls at the semantic task. Additionally, relative to controls, a significant pattern of hyperactivation was found in the aMCI group within specific regions of the extended semantic network, including the right anterior temporal lobe (ATL) and fusiform gyrus. Abnormal functional activation within key areas of the semantic network suggests that it is compromised early in the disease process. Moreover, this pattern of right ATL and fusiform gyrus hyperactivation was positively associated with gray matter integrity in specific areas, but was not associated with any pattern of atrophy, suggesting that this pattern of hyperactivation may precede structural alteration of the semantic network in aMCI. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex.

PubMed

Ruiz-Mejias, Marcel; Martinez de Lagran, Maria; Mattia, Maurizio; Castano-Prat, Patricia; Perez-Mendez, Lorena; Ciria-Suarez, Laura; Gener, Thomas; Sancristobal, Belen; García-Ojalvo, Jordi; Gruart, Agnès; Delgado-García, José M; Sanchez-Vives, Maria V; Dierssen, Mara

2016-03-30

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the prefrontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressingDyrk1A(TgDyrk1A). Usingin vivoextracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awakeTgDyrk1Amice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parvalbumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC ofTgDyrk1Amice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. DYRK1Ais a major candidate gene in Down syndrome. Its overexpression results into altered cognitive abilities, explained by defective cortical microarchitecture and excitation/inhibition imbalance. An open question is how these deficits impact the functionality of the prefrontal cortex network. Combining functional, anatomical, and computational approaches, we identified decreased neuronal firing rate and deficits in gamma frequency in the prefrontal cortices of transgenic mice overexpressingDyrk1A We also identified a reduction of vesicular GABA transporter punctae specifically on parvalbumin positive interneurons. Using a conductance-based computational model, we demonstrate that this decreased inhibition on interneurons recapitulates the observed functional deficits, including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. Copyright © 2016 the authors 0270-6474/16/363649-12$15.00/0.

Thyroid Function Abnormalities and Cognitive Impairment in the Elderly. Results of the InCHIANTI Study

PubMed Central

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M.; Cappola, Anne R.; Valenti, Giorgio; Ferrucci, Luigi

2008-01-01

Objectives To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Design Cross-sectional study Setting Community-based Participants 1171 men and women aged 23-102 yrs Measurements Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated by the Mini Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 versus ≥65 years). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association of thyroid dysfunction with MMSE score was evaluated adjusting for confounders. Results Both subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (Subclinical hypothyroidism, 0.4 % vs 3.5 % in younger vs older participants, respectively, P<.03 Subclinical hyperthyroidism, 1.9 % vs 7.8 % in younger vs older participants, respectively, P<.002). In euthyroid participants TSH and FT3 declined with age while FT4 increased. Old participants with subclinical hyperthyroidism had a lower MMSE score than euthyroid subjects (22.61 ± 6.88 vs 24.72 ± 4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (HR: 2.26, P= .003). Conclusion Subtle age-related changes in FT3, FT4 and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. PMID:19054181

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

PubMed Central

Chen, Yeong-Chang; Wei, Tsui-Shan; Sun, Ding-Ping; Wang, Jhi-Joung; Yeh, Ching-Hua

2015-01-01

Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID:26273133

Hemodynamic Profiles of Functional and Dysfunctional Forms of Repetitive Thinking.

PubMed

Ottaviani, Cristina; Brosschot, Jos F; Lonigro, Antonia; Medea, Barbara; Van Diest, Ilse; Thayer, Julian F

2017-04-01

The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease.

Role of Language-Related Functional Connectivity in Patients with Benign Childhood Epilepsy with Centrotemporal Spikes

PubMed Central

Kim, Hyeon Jin; Lee, Jung Hwa; Park, Chang-hyun; Hong, Hye-Sun; Choi, Yun Seo; Yoo, Jeong Hyun

2018-01-01

Background and Purpose Benign childhood epilepsy with centrotemporal spikes (BECTS) does not always have a benign cognitive outcome. We investigated the relationship between cognitive performance and altered functional connectivity (FC) in the resting-state brain networks of BECTS patients. Methods We studied 42 subjects, comprising 19 BECTS patients and 23 healthy controls. Cognitive performance was assessed using the Korean version of the Wechsler Intelligence Scale for Children-III, in addition to verbal and visuospatial memory tests and executive function tests. Resting-state functional magnetic resonance imaging was acquired in addition to high-resolution structural data. We selected Rolandic and language-related areas as regions of interest (ROIs) and analyzed the seed-based FC to voxels throughout the brain. We evaluated the correlations between the neuropsychological test scores and seed-based FC values using the same ROIs. Results The verbal intelligence quotient (VIQ) and full-scale intelligence quotient (FSIQ) were lower in BECTS patients than in healthy controls (p<0.001). The prevalence of subjects with a higher performance IQ than VIQ was significantly higher in BECTS patients than in healthy controls (73.7% vs. 26.1%, respectively; p=0.002). Both the Rolandic and language-related ROIs exhibited more enhanced FC to voxels in the left inferior temporal gyrus in BECTS patients than in healthy controls. A particularly interestingly finding was that the enhanced FC was correlated with lower cognitive performance as measured by the VIQ and the FSIQ in both patients and control subjects. Conclusions Our findings suggest that the FC alterations in resting-state brain networks related to the seizure onset zone and language processing areas could be related to adaptive plasticity for coping with cognitive dysfunction. PMID:29629540

Does Joe influence Fred's action? Not if Fred has autism spectrum disorder.

PubMed

Welsh, Timothy N; Ray, Matthew C; Weeks, Daniel J; Dewey, Deborah; Elliott, Digby

2009-01-12

It has been proposed that the deficits in social interaction seen in autism spectrum disorder (ASD) arise from problems in action perception stemming from a dysfunction of the mirror neuron system (MNS)--a neural network that becomes active during the performance and observation of action. A dysfunction of this system could have a cascading effect leading to deficits in social cognition because poor activation of the MNS during action observation may lead to an incomplete understanding of another person's actions, intentions and, ultimately, mental states. The present study tested the MNS dysfunction explanation by determining if people with ASD demonstrate a between-person inhibition of return (BP-IOR) effect. The BP-IOR effect, longer reaction times to targets presented at the location of another person's previous response relative to an unresponded-to location, has been hypothesized to be the result of the MNS co-representing the observed response and subsequently activating the mechanisms that cause IOR when individuals respond on their own (within-person IOR [WP-IOR]). Consistent with the MNS dysfunction hypothesis, participants with ASD did not demonstrate a BP-IOR effect in a condition in which they only observed the movement of the partner. The participants with ASD did demonstrate a WP-IOR effect suggesting that the mechanisms underlying IOR are intact in ASD. The contrast between the BP- and WP-IOR effects in the participants with ASD provides significant behavioural evidence for MNS dysfunction in ASD and has important implications for understanding this disorder.

Role of fruits, nuts, and vegetables in maintaining cognitive health.

PubMed

Miller, Marshall G; Thangthaeng, Nopporn; Poulose, Shibu M; Shukitt-Hale, Barbara

2017-08-01

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; however, these foods, which contain a variety of neuroprotective phytochemicals, are widely under-consumed. Surprisingly few studies have investigated the effects of individual plant foods on cognitive health but recent clinical trials have shown that dietary supplementation with individual foods, or switching to a diet rich in several of these foods, can improve cognitive ability. While additional research is needed, increasing fruit, nut, and vegetable intake may be an effective strategy to prevent or delay the onset of cognitive dysfunction during aging. Published by Elsevier Inc.

Awareness of financial skills in dementia.

PubMed

Van Wielingen, L E; Tuokko, H A; Cramer, K; Mateer, C A; Hultsch, D F

2004-07-01

The present study examined the relations among levels of cognitive functioning, executive dysfunction, and awareness of financial management capabilities among a sample of 42 community-dwelling persons with dementia. Financial tasks on the Measure of Awareness of Financial Skills (MAFS) were dichotomized as simple or complex based on Piaget's operational levels of childhood cognitive development. Severity of global cognitive impairment and executive dysfunction were significantly related to awareness of financial abilities as measured by informant-participant discrepancy scores on the MAFS. For persons with mild and moderate/severe dementia, and persons with and without executive dysfunction, proportions of awareness within simple and complex financial task categories were tabulated. Significantly less awareness of financial abilities occurred on complex compared with simple tasks. Individuals with mild dementia were significantly less aware of abilities on complex items, whereas persons with moderate/severe dementia were less aware of abilities, regardless of task complexity. Similar patterns of awareness were observed for individuals with and without executive dysfunction. These findings support literature suggesting that deficits associated with dementia first occur for complex cognitive tasks involving inductive reasoning or decision-making in novel situations, and identify where loss of function in the financial domain may first be expected. Copyright Taylor & Francis Ltd

Dopamine and the Development of Executive Dysfunction in Autism Spectrum Disorders

PubMed Central

Kriete, Trenton; Noelle, David C.

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life. PMID:25811610

Dopamine and the development of executive dysfunction in autism spectrum disorders.

PubMed

Kriete, Trenton; Noelle, David C

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

Predictors of Smoking Cessation in Old–Old Age

PubMed Central

2016-01-01

Introduction: There is a dearth of knowledge on smoking cessation in older adults. This study examined predictors of smoking cessation in persons over age 75. Methods: This study is a secondary analysis of a prospective longitudinal study. A sample of 619 older persons aged 75–94 was drawn from a representative cohort of older persons in Israel and was examined longitudinally. By means of interviews, we assessed smoking, health, Activities of Daily Living (ADL), Instrumental ADL, cognitive dysfunction, and well-being. Results: Continuing smokers tended to be lonelier. Participants who quit smoking took more medications and had greater cognitive dysfunction compared to those who continued smoking. Conclusions: Greater cognitive dysfunction and high medication use or the physical causes for high medication use may precipitate smoking cessation in persons aged 75–94, potentially through a greater influence of caregivers on one’s lifestyle. Implications: Cognitive dysfunction and high medication use predicted smoking cessation. Smoking cessation for long time smokers may be influenced by greater ill health. Influence of caregivers may augment smoking cessation. Given these findings, for persistent smokers into old age, smoking cessation may occur at the time of physical and functional decline during the end of life period. PMID:26783294

The effect of a negative mood priming challenge on dysfunctional attitudes, explanatory style, and explanatory flexibility.

PubMed

Fresco, David M; Heimberg, Richard G; Abramowitz, Adrienne; Bertram, Tara L

2006-06-01

Ninety-seven undergraduates, 48 of whom had a history of self-reported major depression, completed measures of mood and cognitive style (e.g. explanatory style, explanatory flexibility, dysfunctional attitudes) prior to and directly after a negative mood priming challenge that consisted of listening to sad music and thinking about an upsetting past event. Eighteen of the previously depressed participants endorsed baseline levels of depression, explanatory style for negative events, and dysfunctional attitudes higher than levels reported by never depressed participants or euthymic participants with a history of depression. All three groups (never depressed participants, dysphoric participants with a history of depression, euthymic participants with a history of depression) demonstrated increases in dysphoria and dysfunctional attitudes in response to the negative mood priming challenge. Dysphoric participants with a history of depression, but not the other two groups, evidenced modest increases in explanatory style following the negative mood priming challenge. Finally, euthymic participants with a history of depression, but not the other two groups, evidenced drops in explanatory flexibility. Findings from the present study suggest that the cognitive theories of depression may benefit from examining both cognitive content and cognitive flexibility when assessing risk for depression.

Understanding marijuana's effects on functional connectivity of the default mode network in patients with schizophrenia and co-occurring cannabis use disorder: A pilot investigation.

PubMed

Whitfield-Gabrieli, Susan; Fischer, Adina S; Henricks, Angela M; Khokhar, Jibran Y; Roth, Robert M; Brunette, Mary F; Green, Alan I

2018-04-01

Nearly half of patients with schizophrenia (SCZ) have co-occurring cannabis use disorder (CUD), which has been associated with decreased treatment efficacy, increased risk of psychotic relapse, and poor global functioning. While reports on the effects of cannabis on cognitive performance in patients with SCZ have been mixed, study of brain networks related to executive function may clarify the relationship between cannabis use and cognition in these dual-diagnosis patients. In the present pilot study, patients with SCZ and CUD (n=12) and healthy controls (n=12) completed two functional magnetic resonance imaging (fMRI) resting scans. Prior to the second scan, patients smoked a 3.6% tetrahydrocannabinol (THC) cannabis cigarette or ingested a 15mg delta-9-tetrahydrocannabinol (THC) pill. We used resting-state functional connectivity to examine the default mode network (DMN) during both scans, as connectivity/activity within this network is negatively correlated with connectivity of the network involved in executive control and shows reduced activity during task performance in normal individuals. At baseline, relative to controls, patients exhibited DMN hyperconnectivity that correlated with positive symptom severity, and reduced anticorrelation between the DMN and the executive control network (ECN). Cannabinoid administration reduced DMN hyperconnectivity and increased DMN-ECN anticorrelation. Moreover, the magnitude of anticorrelation in the controls, and in the patients after cannabinoid administration, positively correlated with WM performance. The finding that DMN brain connectivity is plastic may have implications for future pharmacotherapeutic development, as treatment efficacy could be assessed through the ability of therapies to normalize underlying circuit-level dysfunction. Copyright © 2017. Published by Elsevier B.V.

Self-reported personality variability across the social network is associated with interpersonal dysfunction.

PubMed

Clifton, Allan; Kuper, Laura E

2011-04-01

We describe 2 studies (n=52 and n=82) examining variability in perceptions of personality using a social network methodology. Undergraduate participants completed self-report measures of personality and interpersonal dysfunction and then subsequently reported on their personalities with each of 30 members of their social networks. Results across the 2 studies found substantial variability in participants' perceived personalities within their social networks. Measures of interpersonal dysfunction were associated with the amount of variability in dyadic ratings of personality, specifically Agreeableness and Openness to Experience. Results suggest that personality variability across interpersonal contexts may be an important individual difference related to social behavior and dysfunction. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

The relationship between cognitive dysfunction and coping abilities in schizophrenia.

PubMed

Wilder-Willis, Kelly E; Shear, Paula K; Steffen, John J; Borkin, Joyce

2002-06-01

Cognitive dysfunction is a core feature of schizophrenia [Psychiatr. Clin. North Am., 16 (1993) 295; Psychopharmacology: The fourth generation of progress, Raven Press, New York (1995) 1171; Clinical Neuropsychology, Oxford University Press, New York (1993) 449] and is related to psychosocial functioning in this population [Am. J. Psychiatry, 153 (1996) 321]. It is unclear whether cognitive dysfunction is related to specific areas of functioning in schizophrenia, such as coping abilities. Individuals with schizophrenia have deficient coping skills, which may contribute to their difficulties dealing with stressors [Am. J. Orthopsychiatry, 62 (1992) 117; J. Abnorm. Psychol., 82 (1986) 189]. The current study examined the relationship between coping abilities and cognitive dysfunction in a community sample of individuals with schizophrenia. It was hypothesized that executive dysfunction and mnemonic impairments would be positively related to deficiencies in active coping efforts involving problem solving and self-initiation (e.g. advocating for oneself and others with mental illness and becoming involved in meaningful activities, such as work), independent of the contributions of the general intellectual deficits associated with the disorder and psychiatric symptoms. The results indicated that both executive dysfunction and mnemonic impairments were related to decreased usage of active coping mechanisms after controlling for general intellectual deficits. Further, recognition memory made independent contributions to the prediction of coping involving action and help seeking after controlling for the effects of negative symptoms. These findings suggest that individuals with schizophrenia may be less flexible in their use of coping strategies, which may in turn contribute to their difficulties in coping with mental illness and its consequences.

Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

PubMed

Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

2017-12-01

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools.

PubMed

Tyler, Patrick M; White, Stuart F; Thompson, Ronald W; Blair, R J R

2018-02-12

A cognitive neuroscience perspective seeks to understand behavior, in this case disruptive behavior disorders (DBD), in terms of dysfunction in cognitive processes underpinned by neural processes. While this type of approach has clear implications for clinical mental health practice, it also has implications for school-based assessment and intervention with children and adolescents who have disruptive behavior and aggression. This review articulates a cognitive neuroscience account of DBD by discussing the neurocognitive dysfunction related to emotional empathy, threat sensitivity, reinforcement-based decision-making, and response inhibition. The potential implications for current and future classroom-based assessments and interventions for students with these deficits are discussed.

Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

PubMed Central

Reynolds, Conner D.; Jefferson, Taylor S.; Volquardsen, Meagan; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Lugo, Joaquin N.

2017-01-01

Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects.  Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction. PMID:29946420

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

PubMed

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

2009-12-01

High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

Brain-Based Biomarkers for the Treatment of Depression: Evolution of an Idea.

PubMed

Waters, Allison C; Mayberg, Helen S

2017-10-01

An ambition of depression biomarker research is to augment psychometric and cognitive assessment of clinically relevant phenomena with neural measures. Although such applications have been slow to arrive, we observe a steady evolution of the idea and anticipate emerging technologies with some optimism. To highlight critical themes and innovations in depression biomarker research, we take as our point of reference a specific research narrative. We begin with an early model of frontal-limbic dysfunction, which represents a conceptual shift from localized pathology to understanding symptoms as an emergent property of distributed networks. Over the decades, this model accommodates perspectives from neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past insight as more complex methods become available. We also track the expanding mission of brain biomarker research: from the development of diagnostic tools to treatment selection algorithms, measures of neurocognitive functioning and novel targets for neuromodulation. To conclude, we draw from this particular research narrative future directions for biomarker research. We emphasize integration of measurement modalities to describe dynamic change in domain-general networks, and we speculate that a brain-based framework for psychiatric problems may dissolve classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870-880).

Altered effective connectivity of default model brain network underlying amnestic MCI

NASA Astrophysics Data System (ADS)

Yan, Hao; Wang, Yonghui; Tian, Jie

2012-02-01

Mild cognitive impairment (MCI) is the transitional, heterogeneous continuum from healthy elderly to Alzheimer's disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in MCI patients. However, the altered effective connectivity of the DMN in MCI patients remains largely unknown. The present study combined an independent component analysis (ICA) approach with Granger causality analysis (mGCA) to investigate the effective connectivity within the DMN in 12 amnestic MCI patients and 12 age-matched healthy elderly. Compared to the healthy control, the MCI exhibited decreased functional activity in the posterior DMN regions, as well as a trend towards activity increases in anterior DMN regions. Results from mGCA further supported this conclusion that the causal influence projecting to the precuneus/PCC became much weaker in MCI, while stronger interregional interactions emerged within the frontal-parietal cortices. These findings suggested that abnormal effective connectivity within the DMN may elucidate the dysfunctional and compensatory processes in MCI brain networks.

Cognitive Attentional Syndrome and Metacognitive Beliefs in Male Sexual Dysfunction: An Exploratory Study.

PubMed

Giuri, Simona; Caselli, Gabriele; Manfredi, Chiara; Rebecchi, Daniela; Granata, Antonio; Ruggiero, Giovanni Maria; Veronese, Guido

2017-05-01

Erectile dysfunction (ED) and premature ejaculation (PE) are two forms of male sexual disorder with both psychological and physical features. While their cognitive, attentional, and affective components have been investigated separately, there is a lack of knowledge about the role played by cognitive attentional syndrome in their onset and maintenance. The aim of the present study was to investigate the possible contribution of perseverative thinking styles and thought control strategies to the development and maintenance of ED and PE. The authors hypothesized that such modes of processing might constitute a cognitive attentional syndrome specific to these disorders and sustained by particular metacognitive beliefs. A semistructured interview was administered to 11 participants with ED and 10 with PE in order to assess their metacognitive beliefs and cognitive attentional processes. The results suggest that individuals with ED and PE adopt a range of cognitive attentional strategies aimed at improving their sexual performance, and endorse both positive and negative metacognitive beliefs about these thinking responses. Overall, their cognitive and attentional patterns worsened negative internal states, reduced sexual excitement, detached them from their bodily sensations, and hindered sexual functioning. These preliminary findings suggest that perseverative thinking, thought control strategies, and metacognitive beliefs may play a key role in the onset and maintenance of male sexual dysfunction.

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

PubMed

Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Identifying major depressive disorder using Hurst exponent of resting-state brain networks.

PubMed

Wei, Maobin; Qin, Jiaolong; Yan, Rui; Li, Haoran; Yao, Zhijian; Lu, Qing

2013-12-30

Resting-state functional magnetic resonance imaging (fMRI) studies of major depressive disorder (MDD) have revealed abnormalities of functional connectivity within or among the resting-state networks. They provide valuable insight into the pathological mechanisms of depression. However, few reports were involved in the "long-term memory" of fMRI signals. This study was to investigate the "long-term memory" of resting-state networks by calculating their Hurst exponents for identifying depressed patients from healthy controls. Resting-state networks were extracted from fMRI data of 20 MDD and 20 matched healthy control subjects. The Hurst exponent of each network was estimated by Range Scale analysis for further discriminant analysis. 95% of depressed patients and 85% of healthy controls were correctly classified by Support Vector Machine with an accuracy of 90%. The right fronto-parietal and default mode network constructed a deficit network (lower memory and more irregularity in MDD), while the left fronto-parietal, ventromedial prefrontal and salience network belonged to an excess network (longer memory in MDD), suggesting these dysfunctional networks may be related to a portion of the complex of emotional and cognitive disturbances. The abnormal "long-term memory" of resting-state networks associated with depression may provide a new possibility towards the exploration of the pathophysiological mechanisms of MDD. © 2013 Elsevier Ireland Ltd. All rights reserved.

Dedifferentiation Does Not Account for Hyperconnectivity after Traumatic Brain Injury.

PubMed

Bernier, Rachel Anne; Roy, Arnab; Venkatesan, Umesh Meyyappan; Grossner, Emily C; Brenner, Einat K; Hillary, Frank Gerard

2017-01-01

Changes in functional network connectivity following traumatic brain injury (TBI) have received increasing attention in recent neuroimaging literature. This study sought to understand how disrupted systems adapt to injury during resting and goal-directed brain states. Hyperconnectivity has been a common finding, and dedifferentiation (or loss of segregation of networks) is one possible explanation for this finding. We hypothesized that individuals with TBI would show dedifferentiation of networks (as noted in other clinical populations) and these effects would be associated with cognitive dysfunction. Graph theory was implemented to examine functional connectivity during periods of task and rest in 19 individuals with moderate/severe TBI and 14 healthy controls (HCs). Using a functional brain atlas derived from 83 functional imaging studies, graph theory was used to examine network dynamics and determine whether dedifferentiation accounts for changes in connectivity. Regions of interest were assigned to one of three groups: task-positive, default mode, or other networks. Relationships between these metrics were then compared with performance on neuropsychological tests. Hyperconnectivity in TBI was most commonly observed as increased within-network connectivity. Network strengths within networks that showed differences between TBI and HCs were correlated with performance on five neuropsychological tests typically sensitive to deficits commonly reported in TBI. Hyperconnectivity within the default mode network (DMN) during task was associated with better performance on Digit Span Backward, a measure of working memory [ R 2 (18) = 0.28, p  = 0.02]. In other words, increased differentiation of networks during task was associated with better working memory. Hyperconnectivity within the task-positive network during rest was not associated with behavior. Negative correlation weights were not associated with behavior. The primary hypothesis that hyperconnectivity occurs through increased segregation of networks, rather than dedifferentiation, was not supported. Instead, enhanced connectivity post injury was observed within network. Results suggest that the relationship between increased connectivity and cognitive functioning may be both state (rest or task) and network dependent. High-cost network hubs were identical for both rest and task, and cost was negatively associated with performance on measures of psychomotor speed and set-shifting.

Correlates of Real World Executive Dysfunction in Bipolar I Disorder

PubMed Central

Peters, Amy T.; Peckham, Andrew D.; Stange, Jonathan P.; Sylvia, Louisa G.; Hansen, Natasha S.; Salcedo, Stephanie; Rauch, Scott L.; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo

2014-01-01

Background Bipolar disorder is characterized by impairments in cognitive functioning, both during acute mood episodes and periods of euthymia, which interfere with functioning. Cognitive functioning is typically assessed using laboratory-based tests, which may not capture how cognitive dysfunction is experienced in real-life settings. Little is known about the specific illness characteristics of bipolar disorder that contribute to cognitive dysfunction in everyday life. Methods Participants met DSM-IV criteria for bipolar I disorder (n = 68) in a depressed or euthymic state. Everyday executive functioning was evaluated using the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Frontal Systems Behavior Rating Scale (FrSBe). Participants completed clinician rated measures of mood state (Hamilton Depression Rating Scale, Young Mania Rating Scale), prior illness course and co-morbidities (Mini International Neuropsychiatric Interview), as well as self-report measures of psychotropic medication use and medical co-morbidity. Results Individuals in this study reported significant impairment in every domain of executive functioning. These deficits were associated with a multitude of illness factors, some directly impacted by mood symptoms and others shaped by illness chronicity, psychiatric comorbidity, medical co-morbidity, and medication use. Discussion Executive functioning problems observed in everyday functioning in bipolar disorder are not entirely mood-state dependent. Cognitive rehabilitation for executive dysfunction should be considered an important adjunctive treatment for many individuals with bipolar disorder. PMID:24655587

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

PubMed

Di Paola, Margherita; Phillips, Owen; Costa, Alberto; Ciurli, Paola; Bivona, Umberto; Catani, Sheila; Formisano, Rita; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-01-01

Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. Neuropsychological scores and hippocampal volumes. We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

PubMed

Skvarc, David R; Berk, Michael; Byrne, Linda K; Dean, Olivia M; Dodd, Seetal; Lewis, Matthew; Marriott, Andrew; Moore, Eileen M; Morris, Gerwyn; Page, Richard S; Gray, Laura

2018-01-01

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Beyond "Facebook Addiction": The Role of Cognitive-Related Factors and Psychiatric Distress in Social Networking Site Addiction.

PubMed

Pontes, Halley M; Taylor, Megan; Stavropoulos, Vasileios

2018-04-01

The use of social networking sites (SNSs) is rapidly increasing as billions of individuals use SNS platforms regularly to communicate with other users, follow the news, and play browser games. Given the widespread use of SNS platforms, investigating the potential predictors of addictive SNS use beyond Facebook use has become paramount given that most studies so far focused on "Facebook addiction." In this study, a total of 511 English-speaking SNS users (58.1% young adults aged 20-35 years; 64.6% female) were recruited online and asked to complete a battery of standardized psychometric tools assessing participants' sociodemographic characteristics, SNS preferences and patterns of use, SNS addiction, preference for online social interaction, maladaptive cognitions, fear of missing out (FoMo), dysfunctional emotion regulation, and general psychiatric distress. Overall, about 4.9% (n = 25) of all participants could be classed as having a high SNS addiction risk profile. Moreover, the results further indicated that FoMo (β = 0.38), maladaptive cognitions (β = 0.25), and psychiatric distress (β = 0.12) significantly predicted SNS addiction (i.e., p < 0.0001) and accounted for about 61% of the total variance in SNS addiction, with FoMo providing the strongest predictive contribution over and above the effects of sociodemographic variables and patterns of SNS use. The implications of the present findings were discussed in light of extant literature on behavioral addictions and Facebook addiction and further considerations were provided regarding the potential clinical implications for cognitive-based psychological treatment approaches to SNS addiction.

How do you make me feel better? Social cognitive emotion regulation and the default mode network.

PubMed

Xie, Xiyao; Mulej Bratec, Satja; Schmid, Gabriele; Meng, Chun; Doll, Anselm; Wohlschläger, Afra; Finke, Kathrin; Förstl, Hans; Zimmer, Claus; Pekrun, Reinhard; Schilbach, Leonhard; Riedl, Valentin; Sorg, Christian

2016-07-01

Socially-induced cognitive emotion regulation (Social-Reg) is crucial for emotional well-being and social functioning; however, its brain mechanisms remain poorly understood. Given that both social cognition and cognitive emotion regulation engage key regions of the default-mode network (DMN), we hypothesized that Social-Reg would rely on the DMN, and that its effectiveness would be associated with social functioning. During functional MRI, negative emotions were elicited by pictures, and - via short instructions - a psychotherapist either down-regulated participants' emotions by employing reappraisal (Reg), or asked them to simply look at the pictures (Look). Adult Attachment Scale was used to measure social functioning. Contrasting Reg versus Look, aversive emotions were successfully reduced during Social-Reg, with increased activations in the prefrontal and parietal cortices, precuneus and the left temporo-parietal junction. These activations covered key nodes of the DMN and were associated with Social-Reg success. Furthermore, participants' attachment security was positively correlated with both Social-Reg success and orbitofrontal cortex involvement during Social-Reg. In addition, specificity of the neural correlates of Social-Reg was confirmed by comparisons with participants' DMN activity at rest and their brain activations during a typical emotional self-regulation task based on the same experimental paradigm without a psychotherapist. Our results provide first evidence for the specific involvement of the DMN in Social-Reg, and the association of Social-Reg with individual differences in attachment security. The findings suggest that DMN dysfunction, found in many neuropsychiatric disorders, may impair the ability to benefit from Social-Reg. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study

PubMed Central

Newsom-Davis, I; Lyall, R; Leigh, P; Moxham, J; Goldstein, L

2001-01-01

OBJECTIVES—Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS.
METHODS—Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated.
RESULTS—Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test.
CONCLUSIONS—Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.

 PMID:11561031

Altered intra- and inter-network functional coupling of resting-state networks associated with motor dysfunction in stroke.

PubMed

Zhao, Zhiyong; Wu, Jie; Fan, Mingxia; Yin, Dazhi; Tang, Chaozheng; Gong, Jiayu; Xu, Guojun; Gao, Xinjie; Yu, Qiurong; Yang, Hao; Sun, Limin; Jia, Jie

2018-04-24

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra- and inter-network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty-three left subcortical chronic stroke patients and 34 healthy controls underwent resting-state functional magnetic resonance imaging. Eleven resting-state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl-Meyer Assessment (FMA) scores (hand + wrist). With respect to inter-network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra- and inter-network alterations associated with motor-visual attention and high-order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke. © 2018 Wiley Periodicals, Inc.

A Competing Neurobehavioral Decision Systems Model of SES-Related Health and Behavioral Disparities

PubMed Central

Bickel, W. K.; Moody, L.; Quisenberry, A. J.; Ramey, C. T.; Sheffer, C. E.

2014-01-01

We propose that executive dysfunction is an important component relating the socioeconomic status gradient of select health behaviors. We review and find evidence supporting an SES gradient associated with (1) negative health behaviors (e.g., obesity, excessive use of alcohol, tobacco and other substances), and (2) executive dysfunction. Moreover, the evidence supports that stress and insufficient cognitive resources contribute to executive dysfunction and that executive dysfunction is evident among individuals who smoke cigarettes, are obese, abuse alcohol, and use illicit drugs. Collectively these data supports the dual system model of cognitive control, referred to here as the Competing Neurobehavioral Decision Systems hypothesis. The implications of these relationships for intervention and social justice considerations are discussed. PMID:25008219

Relationships between self-reported sleep quality components and cognitive functioning in breast cancer survivors up to 10 years following chemotherapy.

PubMed

Henneghan, Ashley M; Carter, Patricia; Stuifbergan, Alexa; Parmelee, Brennan; Kesler, Shelli

2018-04-23

Links have been made between aspects of sleep quality and cognitive function in breast cancer survivors (BCS), but findings are heterogeneous. The objective of this study is to examine relationships between specific sleep quality components (latency, duration, efficiency, daytime sleepiness, sleep disturbance, use of sleep aids) and cognitive impairment (performance and perceived), and determine which sleep quality components are the most significant contributors to cognitive impairments in BCS 6 months to 10 years post chemotherapy. Women 21 to 65 years old with a history of non-metastatic breast cancer following chemotherapy completion were recruited. Data collection included surveys to evaluate sleep quality and perceived cognitive impairments, and neuropsychological testing to evaluate verbal fluency and memory. Descriptive statistics, bivariate correlations, and hierarchical multiple regression were calculated. 90 women (mean age 49) completed data collection. Moderate significant correlations were found between daytime dysfunction, sleep efficiency, sleep latency, and sleep disturbance and perceived cognitive impairment (Rs = -0.37 to -0.49, Ps<.00049), but not objective cognitive performance of verbal fluency, memory or attention. After accounting for individual and clinical characteristics, the strongest predictors of perceived cognitive impairments were daytime dysfunction, sleep efficiency, and sleep disturbance. Findings support links between sleep quality and perceived cognitive impairments in BCS and suggest specific components of sleep quality (daytime dysfunction, sleep efficiency, and sleep disturbance) are associated with perceived cognitive functioning in this population. Findings can assist clinicians in guiding survivors to manage sleep and cognitive problems and aid in the design of interventional research. This article is protected by copyright. All rights reserved.

Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

PubMed

Lee, M; Sehatpour, P; Hoptman, M J; Lakatos, P; Dias, E C; Kantrowitz, J T; Martinez, A M; Javitt, D C

2017-11-01

Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

The Effects of a Cognitive Information Processing Career Intervention on the Dysfunctional Career Thoughts, Locus of Control, and Career Decision Self-Efficacy of Underprepared College Students

ERIC Educational Resources Information Center

Henderson, Kristina M.

2009-01-01

This study investigated the impact of a seven-session career intervention in a First Year Experience course on the dysfunctional career thoughts, locus of control, and career decision self-efficacy of underprepared college students. The career intervention was based on the cognitive information processing approach to career decision making…

Personality and cognitive vulnerability in remitted recurrently depressed patients.

PubMed

van Rijsbergen, Gerard D; Kok, Gemma D; Elgersma, Hermien J; Hollon, Steven D; Bockting, Claudi L H

2015-03-01

Personality disorders (PDs) have been associated with a poor prognosis of Major Depressive Disorder (MDD). The aim of the current study was to examine cognitive vulnerability (i.e., dysfunctional beliefs, extremity of beliefs, cognitive reactivity, and rumination) that might contribute to this poor prognosis of patients with PD comorbidity. 309 outpatients with remitted recurrent MDD (SCID-I; HAM-D17 ≤ 10) were included within two comparable RCTs and were assessed at baseline with the Personality Diagnostic Questionnaire-4(+) (PDQ-4(+)), the Dysfunctional Attitude Scale Version-A (DAS-A), the Leiden Index of Depression Sensitivity (LEIDS), the Ruminative Response Scale (RRS), and the Inventory of Depressive Symptomatology-Self Report (IDS-SR). We found an indication that the PD prevalence was 49.5% in this remitted recurrently depressed sample. Having a PD (and higher levels of personality pathology) was associated with dysfunctional beliefs, cognitive reactivity, and rumination. Extreme 'black and white thinking' on the DAS was not associated with personality pathology. Brooding was only associated with a Cluster C classification (t(308) = 4.03, p < .001) and with avoidant PD specifically (t(308) = 4.82, p < .001), while surprisingly not with obsessive-compulsive PD. PDs were assessed by questionnaire and the analyses were cross-sectional in nature. Being the first study to examine cognitive reactivity and rumination in patients with PD and remitted MDD, we demonstrated that even after controlling for depressive symptomatology, dysfunctional beliefs, cognitive reactivity, and rumination were associated with personality pathology. Rumination might be a pathway to relapse for patients with avoidant PD. Replication of our findings concerning cognitive vulnerability and specific PDs is necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

PubMed

Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

2014-06-30

Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

PubMed

Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

2017-12-01

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Rumination, distraction and mindful self-focus: effects on mood, dysfunctional attitudes and cortisol stress response.

PubMed

Kuehner, C; Huffziger, S; Liebsch, K

2009-02-01

Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses. Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session. Compared to induced rumination, distraction showed a clear beneficial effect on the course of dysphoric mood, whereas a mindful self-focus did not. In contrast to distraction and mindful self-focus, participants induced to ruminate showed significant increases in dysfunctional attitudes from baseline to post-induction. Although rumination was not itself linked to higher cortisol responses, participants scoring high on the Beck Depression Inventory (BDI)-II who were induced to ruminate showed a smaller decrease in cortisol levels than those scoring low on the BDI-II. This study indicates that rumination as a dysfunctional mode of cognitive processing is able to maintain depression-linked dysfunctional thought content. Furthermore, our study revealed preliminary indications for a link between induced rumination and the cortisol stress response in vulnerable individuals.

Applications of the Morris water maze in translational traumatic brain injury research.

PubMed

Tucker, Laura B; Velosky, Alexander G; McCabe, Joseph T

2018-05-01

Acquired traumatic brain injury (TBI) is frequently accompanied by persistent cognitive symptoms, including executive function disruptions and memory deficits. The Morris Water Maze (MWM) is the most widely-employed laboratory behavioral test for assessing cognitive deficits in rodents after experimental TBI. Numerous protocols exist for performing the test, which has shown great robustness in detecting learning and memory deficits in rodents after infliction of TBI. We review applications of the MWM for the study of cognitive deficits following TBI in pre-clinical studies, describing multiple ways in which the test can be employed to examine specific aspects of learning and memory. Emphasis is placed on dependent measures that are available and important controls that must be considered in the context of TBI. Finally, caution is given regarding interpretation of deficits as being indicative of dysfunction of a single brain region (hippocampus), as experimental models of TBI most often result in more diffuse damage that disrupts multiple neural pathways and larger functional networks that participate in complex behaviors required in MWM performance. Published by Elsevier Ltd.

Cognitive radio wireless sensor networks: applications, challenges and research trends.

PubMed

Joshi, Gyanendra Prasad; Nam, Seung Yeob; Kim, Sung Won

2013-08-22

A cognitive radio wireless sensor network is one of the candidate areas where cognitive techniques can be used for opportunistic spectrum access. Research in this area is still in its infancy, but it is progressing rapidly. The aim of this study is to classify the existing literature of this fast emerging application area of cognitive radio wireless sensor networks, highlight the key research that has already been undertaken, and indicate open problems. This paper describes the advantages of cognitive radio wireless sensor networks, the difference between ad hoc cognitive radio networks, wireless sensor networks, and cognitive radio wireless sensor networks, potential application areas of cognitive radio wireless sensor networks, challenges and research trend in cognitive radio wireless sensor networks. The sensing schemes suited for cognitive radio wireless sensor networks scenarios are discussed with an emphasis on cooperation and spectrum access methods that ensure the availability of the required QoS. Finally, this paper lists several open research challenges aimed at drawing the attention of the readers toward the important issues that need to be addressed before the vision of completely autonomous cognitive radio wireless sensor networks can be realized.

Pharmacological modulation of pulvinar resting-state regional oscillations and network dynamics in major depression

PubMed Central

Tadayonnejad, Reza; Ajilore, Olusola; Mickey, Brian J.; Crane, Natania A.; Hsu, David T.; Kumar, Anand; Zubieta, Jon-Kar; Langenecker, Scott A.

2016-01-01

The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment. PMID:27148894

BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

PubMed

Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

2016-05-15

Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. Copyright © 2016 Elsevier B.V. All rights reserved.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined ‘Timed Up and Go’ Test (iTUG)

PubMed Central

Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

2017-01-01

Background Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. Objective To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. Methods TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. Results The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. Conclusion These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction. PMID:28125616

Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined 'Timed Up and Go' Test (iTUG).

PubMed

Geiger, Maxime; Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

2017-01-01

Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction.

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

PubMed

Liu, Jiankang

2008-01-01

We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults.

PubMed

Hampstead, B M; Khoshnoodi, M; Yan, W; Deshpande, G; Sathian, K

2016-01-01

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns. Published by Elsevier Inc.

Myopia and cognitive dysfunction among elderly Chinese adults: a propensity score matching analysis.

PubMed

Sun, Hong-Peng; Liu, Hu; Xu, Yong; Pan, Chen-Wei

2016-03-01

The association between myopia and cognitive dysfunction among elderly adults was assessed by applying a Propensity Score Matching (PSM) approach. This is a statistical method which allows investigators to estimate causal treatment effects using observational or nonrandomised data. The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years or older in China. Objective refraction was measured using an autorefractor and subjective refraction was used to refine vision, using the results of the objective refraction as the starting point. Myopia was defined as a spherical equivalent value of less than -0.50 dioptre (D) in the right eye. The Abbreviated Mental Test (AMT) was used for cognitive assessment. The propensity scores for myopia were formulated using 13 potential confounders. We matched the propensity scores for subjects with and without myopia within a caliper of 0.01 of logit function of propensity scores. About 4123 elderly adults who successfully completed the AMT were included in this analysis. The odds ratio (OR) of cognitive dysfunction for myopia before matching was 1.98 (95% confidence interval [CI] 1.61, 2.44; p < 0.001). There were significant covariate imbalances between comparison groups and after propensity score matching, covariate imbalance was significantly reduced. After propensity score matching, the OR of cognitive dysfunction was marginally significant and the magnitude of association was reduced (OR: 1.31 95% CI 1.00, 1.71; p = 0.05). Traditional multivariate logistic regression modelling found an OR of 1.52 (95% CI 1.23, 2.06; p < 0.001) after adjusting for the 13 potential confounders. Myopia was associated with a higher prevalence of cognitive dysfunction among elderly Chinese aged 60 years or older in China. The PSM approach may be a useful method to address selection bias in observational studies when randomised trials cannot ethically be conducted. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Effect of Area-Level Socioeconomic Deprivation on Risk of Cognitive Dysfunction in Older Adults.

PubMed

McCann, Adrian; McNulty, Helene; Rigby, Jan; Hughes, Catherine F; Hoey, Leane; Molloy, Anne M; Cunningham, Conal J; Casey, Miriam C; Tracey, Fergal; O'Kane, Maurice J; McCarroll, Kevin; Ward, Mary; Moore, Katie; Strain, J J; Moore, Adrian

2018-02-12

To investigate the relationship between area-level deprivation and risk of cognitive dysfunction. Cross-sectional analysis. The Trinity, Ulster, and Department of Agriculture (TUDA) study from 2008 to 2012. Community-dwelling adults aged 74.0 ± 8.3 without dementia (N = 5,186; 67% female). Adopting a cross-jurisdictional approach, geo-referenced address-based information was used to map and link participants to official socioeconomic indicators of deprivation within the United Kingdom and the Republic of Ireland. Participants were assigned an individual deprivation score related to the smallest administrative area in which they lived. These scores were categorized into comparable quintiles, that were then used to integrate the datasets from both countries. Cognitive health was assessed using the Mini-Mental State Examination (MMSE); cognitive dysfunction was defined as a MMSE score of 24 or less. Approximately one-quarter of the cohort resided within the most-deprived districts in both countries. Greater area-level deprivation was associated with significantly lower MMSE scores; fewer years of formal education; greater anxiety, depression, smoking and alcohol use, and obesity; and more adverse outcomes, including higher blood pressure and diabetes risk. After adjustment for relevant covariates, area deprivation was associated with significantly higher risk of cognitive dysfunction (odds ratio =1.40, 95% confidence interval = 1.05-1.87, P = .02, for most vs least deprived). This analysis combining data from two health systems shows that area deprivation is an independent risk factor for cognitive dysfunction in older adults. Adults living in areas of greatest socioeconomic deprivation may benefit from targeted strategies aimed at improving modifiable risk factors for dementia. Further cross-national analysis investigating the impact of area-level deprivation is needed to address socioeconomic disparities and shape future policy to improve health outcomes in older adults. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Interplay Among Psychopathologic Variables, Personal Resources, Context-Related Factors, and Real-life Functioning in Individuals With Schizophrenia: A Network Analysis.

PubMed

Galderisi, Silvana; Rucci, Paola; Kirkpatrick, Brian; Mucci, Armida; Gibertoni, Dino; Rocca, Paola; Rossi, Alessandro; Bertolino, Alessandro; Strauss, Gregory P; Aguglia, Eugenio; Bellomo, Antonello; Murri, Martino Belvederi; Bucci, Paola; Carpiniello, Bernardo; Comparelli, Anna; Cuomo, Alessandro; De Berardis, Domenico; Dell'Osso, Liliana; Di Fabio, Fabio; Gelao, Barbara; Marchesi, Carlo; Monteleone, Palmiero; Montemagni, Cristiana; Orsenigo, Giulia; Pacitti, Francesca; Roncone, Rita; Santonastaso, Paolo; Siracusano, Alberto; Vignapiano, Annarita; Vita, Antonio; Zeppegno, Patrizia; Maj, Mario

2018-04-01

Enhanced understanding of factors associated with symptomatic and functional recovery is instrumental to designing personalized treatment plans for people with schizophrenia. To date, this is the first study using network analysis to investigate the associations among cognitive, psychopathologic, and psychosocial variables in a large sample of community-dwelling individuals with schizophrenia. To assess the interplay among psychopathologic variables, cognitive dysfunctions, functional capacity, personal resources, perceived stigma, and real-life functioning in individuals with schizophrenia, using a data-driven approach. This multicenter, cross-sectional study involved 26 university psychiatric clinics and/or mental health departments. A total of 921 community-dwelling individuals with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic treatment were recruited from those consecutively presenting to the outpatient units of the sites between March 1, 2012, and September 30, 2013. Statistical analysis was conducted between July 1 and September 30, 2017. Measures covered psychopathologic variables, neurocognition, social cognition, functional capacity, real-life functioning, resilience, perceived stigma, incentives, and service engagement. Of 740 patients (221 women and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core symptoms). The network analysis showed that functional capacity and everyday life skills were the most central and highly interconnected nodes in the network. Psychopathologic variables split in 2 domains, with positive symptoms being one of the most peripheral and least connected nodes. Functional capacity bridged cognition with everyday life skills; the everyday life skills node was connected to disorganization and expressive deficits. Interpersonal relationships and work skills were connected to avolition; the interpersonal relationships node was also linked to social competence, and the work skills node was linked to social incentives and engagement with mental health services. A case-dropping bootstrap procedure showed centrality indices correlations of 0.75 or greater between the original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No difference in the network structure was found between men and women. The high centrality of functional capacity and everyday life skills in the network suggests that improving the ability to perform tasks relevant to everyday life is critical for any therapeutic intervention in schizophrenia. The pattern of network node connections supports the implementation of personalized interventions.

Theory of mind impairment and its clinical correlates in patients with schizophrenia, major depressive disorder and bipolar disorder.

PubMed

Wang, Yan-Yu; Wang, Yi; Zou, Ying-Min; Ni, Ke; Tian, Xue; Sun, Hong-Wei; Lui, Simon S Y; Cheung, Eric F C; Suckling, John; Chan, Raymond C K

2017-11-06

Although Theory of Mind (ToM) impairment has been observed in patients with a wide range of mental disorders, the similarity and uniqueness of these deficits across diagnostic groups has not been thoroughly investigated. We recruited 35 participants with schizophrenia (SCZ), 35 with bipolar disorder (BD), 35 with major depressive disorder (MDD), and 35 healthy controls in this study. All participants were matched in age, gender proportion and IQ estimates. The Yoni task, capturing both the cognitive and affective components of ToM at the first- and second-order level was administered. Repeated-measure ANOVA and MANOVA were conducted to compare the group differences in ToM performance. A network was then constructed with ToM performances, psychotic and depressive symptoms, and executive function as nodes exploring the clinical correlates of ToM. Overall, ToM impairments were observed in all patient groups compared with healthy controls, with patients with SCZ performing worse than those with BD. In second-order conditions, patients with SCZ and MDD showed deficits in both cognitive and affective conditions, while patients with BD performed significantly poorer in cognitive conditions. Network analysis showed that second-order affective ToM performance was associated with psychotic and depressive symptoms as well as executive dysfunction, while second-order affective ToM performance and negative symptoms showed relatively high centrality in the network. Patients with SCZ, MDD and BD exhibited different types and severity of impairments in ToM sub-components. Impairment in higher-order affective ToM appears to be closely related to clinical symptoms in both psychotic and affective disorders. Copyright © 2017. Published by Elsevier B.V.

Negative Mood States or Dysfunctional Cognitions: Their Independent and Interactional Effects in Influencing Severity of Gambling Among Chinese Problem Gamblers in Hong Kong.

PubMed

Wong, Daniel Fu Keung; Zhuang, Xiao Yu; Jackson, Alun; Dowling, Nicki; Lo, Herman Hay Ming

2017-09-04

Gambling-related cognitions and negative psychological states have been proposed as major factors in the initiation and maintenance of problem gambling (PG). While there are a substantial number of studies supporting the role of cognitive dysfunctions in the initiation and maintenance of PG, very few empirical studies have explored the specific role of negative psychological states in influencing PG behaviours. In addition, very few studies have examined the interaction effects of cognitive dysfunctions and negative psychological states in exerting influence on PG behaviours. Therefore, the present study aims to examine the main and interaction effects of gambling-related cognitions and psychological states on the gambling severity among a group of problem gamblers in Hong Kong. A cross-sectional research design was adopted. A purposive sample of 177 problem gamblers who sought treatment from a social service organization in Hong Kong completed a battery of standardised questionnaires. While gambling-related cognitions were found to exert significant effects on gambling severity, negative psychological states (i.e. stress) significantly moderated the relationship between gambling cognitions and gambling severity. In essence, those participants who reported a higher level of stress had more stable and serious gambling problems than those who reported a lower level of stress irrespective of the level of gambling-related cognitions. The findings of the moderating role of negative emotions in the relationship between cognitive distortions and severity of gambling provide insight towards developing an integrated intervention model which includes both cognitive-behavioural and emotion regulation strategies in helping people with PG.

Cognitive deficits in recent-onset and chronic schizophrenia☆

PubMed Central

Sponheim, S.R.; Jung, R.E.; Seidman, L.J.; Mesholam-Gately, R.I.; Manoach, D.S.; O'Leary, D.S.; Ho, B.C.; Andreasen, N.C.; Lauriello, J.; Schulz, S.C.

2014-01-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. PMID:19878956

Cognitive deficits in recent-onset and chronic schizophrenia.

PubMed

Sponheim, S R; Jung, R E; Seidman, L J; Mesholam-Gately, R I; Manoach, D S; O'Leary, D S; Ho, B C; Andreasen, N C; Lauriello, J; Schulz, S C

2010-05-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. Published by Elsevier Ltd.

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Protein Kinase A Deregulation in the Medial Prefrontal Cortex Impairs Working Memory in Murine Oligophrenin-1 Deficiency.

PubMed

Zhang, Chun-Lei; Aime, Mattia; Laheranne, Emilie; Houbaert, Xander; El Oussini, Hajer; Martin, Christelle; Lepleux, Marilyn; Normand, Elisabeth; Chelly, Jamel; Herzog, Etienne; Billuart, Pierre; Humeau, Yann

2017-11-15

Classical and systems genetics have identified wide networks of genes associated with cognitive and neurodevelopmental diseases. In parallel to deciphering the role of each of these genes in neuronal or synaptic function, evaluating the response of neuronal and molecular networks to gene loss of function could reveal some pathophysiological mechanisms potentially accessible to nongenetic therapies. Loss of function of the Rho-GAP oligophrenin-1 is associated with cognitive impairments in both human and mouse. Upregulation of both PKA and ROCK has been reported in Ophn1 -/ y mice, but it remains unclear whether kinase hyperactivity contributes to the behavioral phenotypes. In this study, we thoroughly characterized a prominent perseveration phenotype displayed by Ophn1 -deficient mice using a Y-maze spatial working memory (SWM) test. We report that Ophn1 deficiency in the mouse generated severe cognitive impairments, characterized by both a high occurrence of perseverative behaviors and a lack of deliberation during the SWM test. In vivo and in vitro pharmacological experiments suggest that PKA dysregulation in the mPFC underlies cognitive dysfunction in Ophn1 -deficient mice, as assessed using a delayed spatial alternation task results. Functionally, mPFC neuronal networks appeared to be affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved in SWM were not affected in Ophn1 -/y mice. Thus, we propose that discrete gene mutations in intellectual disability might generate "secondary" pathophysiological mechanisms, which are prone to become pharmacological targets for curative strategies in adult patients. SIGNIFICANCE STATEMENT Here we report that Ophn1 deficiency generates severe impairments in performance at spatial working memory tests, characterized by a high occurrence of perseverative behaviors and a lack of decision making. This cognitive deficit is consecutive to PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly acquired rule. Functionally, mPFC neuronal networks appear to be affected in a PKA-dependent manner, whereas behaviorally important hippocampal projections were preserved by the mutation. Thus, we propose that discrete gene mutations in intellectual disability can generate "secondary" pathophysiological mechanisms prone to become pharmacological targets for curative strategies in adults. Copyright © 2017 the authors 0270-6474/17/3711114-13$15.00/0.

Vascular Neural Network phenotypic transformation after traumatic injury: potential role in long-term sequelae

PubMed Central

Badaut, J.; Bix, G.J.

2014-01-01

The classical neurovascular unit (NVU), composed primarily of endothelium, astrocytes and neurons, could be expanded to include smooth muscle and perivascular nerves present in both the up and down stream feeding blood vessels (arteries and veins). The extended NVU, which can be defined as the vascular neural network (VNN), may represent a new physiological unit to consider for therapeutic development in stroke, traumatic brain injury, and other brain disorders [1]. This review is focused on traumatic brain injury and resultant post-traumatic changes in cerebral blood-flow, smooth muscle cells, matrix, BBB structures and function and the association of these changes with cognitive outcomes as described in clinical and experimental reports. We suggest that studies characterizing TBI outcomes should increase their focus on changes to the VNN as this may yield meaningful therapeutic targets to resolve post-traumatic dysfunction. PMID:24323723

Anterior insular cortex regulation in autism spectrum disorders

PubMed Central

Caria, Andrea; de Falco, Simona

2015-01-01

Autism spectrum disorders (ASDs) comprise a heterogeneous set of neurodevelopmental disorders characterized by dramatic impairments of interpersonal behavior, communication, and empathy. Recent neuroimaging studies suggested that ASD are disorders characterized by widespread abnormalities involving distributed brain network, though clear evidence of differences in large-scale brain network interactions underlying the cognitive and behavioral symptoms of ASD are still lacking. Consistent findings of anterior insula cortex hypoactivation and dysconnectivity during tasks related to emotional and social processing indicates its dysfunctional role in ASD. In parallel, increasing evidence showed that successful control of anterior insula activity can be attained using real-time fMRI paradigms. More importantly, successful regulation of this region was associated with changes in behavior and brain connectivity in both healthy individuals and psychiatric patients. Building on these results we here propose and discuss the use of real-time fMRI neurofeedback in ASD aiming at improving emotional and social behavior. PMID:25798096

Traumatic stress symptoms after the November 13th 2015 Terrorist Attacks among Young Adults: The relation to media and emotion regulation.

PubMed

Monfort, Emmanuel; Afzali, Mohammad Hassan

2017-05-01

A major terror attack occurred in the Paris region on 13th November 2015. This event was widely showed, described, and commented in the media. Media consumption may lead to a widespread diffusion of trauma-related symptoms following a collective trauma. These effects may depend on the type of media and emotion regulation strategies used by the media consumer. Trauma history, traumatic symptoms, media consumption, psychological distress, and emotion regulation strategies of 451 young adults were assessed by an online survey. Findings reveal the joint role of social networks use and dysfunctional emotion regulation strategies on anxiety, depression, and somatization symptoms and also on cognitive and emotional alteration among traumatic symptoms. Consistent with the emotional contagion hypothesis, individuals who reported spending more time on social networks were also those who were experiencing more psychological distress. Copyright © 2017 Elsevier Inc. All rights reserved.

Theory of mind and empathy in preclinical and clinical Huntington's disease.

PubMed

Adjeroud, Najia; Besnard, Jérémy; El Massioui, Nicole; Verny, Christophe; Prudean, Adriana; Scherer, Clarisse; Gohier, Bénédicte; Bonneau, Dominique; Allain, Philippe

2016-01-01

We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington's disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054-67) that examines first- and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first- and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cognitive Radio Wireless Sensor Networks: Applications, Challenges and Research Trends

PubMed Central

Joshi, Gyanendra Prasad; Nam, Seung Yeob; Kim, Sung Won

2013-01-01

A cognitive radio wireless sensor network is one of the candidate areas where cognitive techniques can be used for opportunistic spectrum access. Research in this area is still in its infancy, but it is progressing rapidly. The aim of this study is to classify the existing literature of this fast emerging application area of cognitive radio wireless sensor networks, highlight the key research that has already been undertaken, and indicate open problems. This paper describes the advantages of cognitive radio wireless sensor networks, the difference between ad hoc cognitive radio networks, wireless sensor networks, and cognitive radio wireless sensor networks, potential application areas of cognitive radio wireless sensor networks, challenges and research trend in cognitive radio wireless sensor networks. The sensing schemes suited for cognitive radio wireless sensor networks scenarios are discussed with an emphasis on cooperation and spectrum access methods that ensure the availability of the required QoS. Finally, this paper lists several open research challenges aimed at drawing the attention of the readers toward the important issues that need to be addressed before the vision of completely autonomous cognitive radio wireless sensor networks can be realized. PMID:23974152

Diagnosis and treatment of vascular damage in dementia.

PubMed

Biessels, Geert Jan

2016-05-01

This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.

PubMed

Chiaravalloti, Nancy D; DeLuca, John

2015-10-01

This study examined the influence of processing speed (PS) on benefit from treatment with the modified Story Memory Technique(©) (mSMT), a behavioral intervention shown to improve new learning and memory in multiple sclerosis (MS). This double-blind, placebo-controlled, randomized clinical trial included 85 participants with clinically definite MS, 45 assigned to the treatment group and 40 to the placebo-control group. Participants completed baseline and follow-up neuropsychological assessment. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. The treatment group showed a significantly improved CVLT learning slope relative to the placebo group post-treatment, after co-varying PS performance. SDMT performance was a significant predictor of benefit from mSMT treatment, beyond group assignment. Post-hoc analysis indicated a significant correlation between the SDMT and overall cognition, indicating that the SDMT may be serving as a proxy for overall cognitive impairment. Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit of mSMT treatment. While the current study focused on PS as a critical factor, PS may be serving as a marker for generalized cognitive dysfunction. Implications for cognitive rehabilitation in MS are discussed. © The Author(s), 2015.

Neural Substrates of Inhibitory Control Deficits in 22q11.2 Deletion Syndrome†

PubMed Central

Montojo, C.A.; Jalbrzikowski, M.; Congdon, E.; Domicoli, S.; Chow, C.; Dawson, C.; Karlsgodt, K.H.; Bilder, R.M.; Bearden, C.E.

2015-01-01

22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. PMID:24177988

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Role of physical and mental training in brain network configuration

PubMed Central

Foster, Philip P.

2015-01-01

It is hypothesized that the topology of brain networks is constructed by connecting nodes which may be continuously remodeled by appropriate training. Efficiency of physical and/or mental training on the brain relies on the flexibility of networks' architecture molded by local remodeling of proteins and synapses of excitatory neurons producing transformations in network topology. Continuous remodeling of proteins of excitatory neurons is fine-tuning the scaling and strength of excitatory synapses up or down via regulation of intra-cellular metabolic and regulatory networks of the genome-transcriptome-proteome interface. Alzheimer's disease is a model of “energy cost-driven small-world network disorder” with dysfunction of high-energy cost wiring as the network global efficiency is impaired by the deposition of an informed agent, the amyloid-β, selectively targeting high-degree nodes. In schizophrenia, the interconnectivity and density of rich-club networks are significantly reduced. Training-induced homeostatic synaptogenesis-enhancement, presumably via reconfiguration of brain networks into greater small-worldness, appears essential in learning, memory, and executive functions. A macroscopic cartography of creation-removal of synaptic connections in a macro-network, and at the intra-cellular scale, micro-networks regulate the physiological mechanisms for the preferential attachment of synapses. The strongest molecular relationship of exercise and functional connectivity was identified for brain-derived neurotrophic factor (BDNF). The allele variant, rs7294919, also shows a powerful relationship with the hippocampal volume. How the brain achieves this unique quest of reconfiguration remains a puzzle. What are the underlying mechanisms of synaptogenesis promoting communications brain ↔ muscle and brain ↔ brain in such trainings? What is the respective role of independent mental, physical, or combined-mental-physical trainings? Physical practice seems to be playing an instrumental role in the cognitive enhancement (brain ↔ muscle com.). However, mental training, meditation or virtual reality (films, games) require only minimal motor activity and cardio-respiratory stimulation. Therefore, other potential paths (brain ↔ brain com.) molding brain networks are nonetheless essential. Patients with motor neuron disease/injury (e.g., amyotrophic lateral sclerosis, traumatism) also achieve successful cognitive enhancement albeit they may only elicit mental practice. PMID:26157387

Role of physical and mental training in brain network configuration.

PubMed

Foster, Philip P

2015-01-01

It is hypothesized that the topology of brain networks is constructed by connecting nodes which may be continuously remodeled by appropriate training. Efficiency of physical and/or mental training on the brain relies on the flexibility of networks' architecture molded by local remodeling of proteins and synapses of excitatory neurons producing transformations in network topology. Continuous remodeling of proteins of excitatory neurons is fine-tuning the scaling and strength of excitatory synapses up or down via regulation of intra-cellular metabolic and regulatory networks of the genome-transcriptome-proteome interface. Alzheimer's disease is a model of "energy cost-driven small-world network disorder" with dysfunction of high-energy cost wiring as the network global efficiency is impaired by the deposition of an informed agent, the amyloid-β, selectively targeting high-degree nodes. In schizophrenia, the interconnectivity and density of rich-club networks are significantly reduced. Training-induced homeostatic synaptogenesis-enhancement, presumably via reconfiguration of brain networks into greater small-worldness, appears essential in learning, memory, and executive functions. A macroscopic cartography of creation-removal of synaptic connections in a macro-network, and at the intra-cellular scale, micro-networks regulate the physiological mechanisms for the preferential attachment of synapses. The strongest molecular relationship of exercise and functional connectivity was identified for brain-derived neurotrophic factor (BDNF). The allele variant, rs7294919, also shows a powerful relationship with the hippocampal volume. How the brain achieves this unique quest of reconfiguration remains a puzzle. What are the underlying mechanisms of synaptogenesis promoting communications brain ↔ muscle and brain ↔ brain in such trainings? What is the respective role of independent mental, physical, or combined-mental-physical trainings? Physical practice seems to be playing an instrumental role in the cognitive enhancement (brain ↔ muscle com.). However, mental training, meditation or virtual reality (films, games) require only minimal motor activity and cardio-respiratory stimulation. Therefore, other potential paths (brain ↔ brain com.) molding brain networks are nonetheless essential. Patients with motor neuron disease/injury (e.g., amyotrophic lateral sclerosis, traumatism) also achieve successful cognitive enhancement albeit they may only elicit mental practice.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

PubMed

Krishnan, Syam; Justus, Sunitha; Meluveettil, Radhamani; Menon, Ramshekhar N; Sarma, Sankara P; Kishore, Asha

2015-01-01

The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P < 0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001) scores. This study establishes the reliability of cross-cultural adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam-speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

Postoperative cognitive dysfunction in older adults: a call for nursing involvement.

PubMed

Sorrell, Jeanne M

2014-11-01

As the population continues to age and new medical developments make surgery at advanced ages increasingly possible, it is important to consider how older adults tolerate surgery and anesthesia. Considerable evidence shows that older adults have a higher risk of developing postoperative cognitive dysfunction (POCD), which leads to transient and sometimes long-term cognitive changes that may affect quality of life. Because little is known about how to prevent or treat POCD, it is important that nurses identify ways in which they can intervene to help patients who experience this disorder. Copyright 2014, SLACK Incorporated.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

PubMed

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-05-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

PubMed Central

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-01-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

The cycle of schizoaffective disorder, cognitive ability, alcoholism, and suicidality.

PubMed

Goldstein, Gerald; Haas, Gretchen L; Pakrashi, Manish; Novero, Ada M; Luther, James F

2006-02-01

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-TV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a history of suicide attempts or suicidal ideation. Discriminant analysis was used to identify cognitive test performance measures that distinguished those with versus those without suicidal behavior. None of the cognitive measures discriminated between the two groups. The rates of suicidal behavior (suicidal ideation and suicide attempts) did not differ between participants with versus those without comorbid alcohol use. An association was found between suicidal behavior and the diagnosis of schizoaffective disorder. It was concluded that the history of prominent mood syndromes characteristic of schizoaffective disorder contributes to increased risk of suicidal behaviors. Cognitive dysfunction and/or alcoholism did not contribute additionally to risk in this study.

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

PubMed

Butler, Christopher R; Miller, Thomas D; Kaur, Manveer S; Baker, Ian W; Boothroyd, Georgie D; Illman, Nathan A; Rosenthal, Clive R; Vincent, Angela; Buckley, Camilla J

2014-04-01

Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

PubMed

Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W

2015-09-30

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction.

PubMed

Moore, Halle C F; Parsons, Michael W; Yue, Guang H; Rybicki, Lisa A; Siemionow, Wlodzimierz

2014-08-01

Persistent fatigue and cognitive dysfunction are poorly understood potential long-term effects of adjuvant chemotherapy. In this pilot study, we assessed the value of electroencephalogram (EEG) power measurements as a means to evaluate physical and mental fatigue associated with chemotherapy. Women planning to undergo adjuvant chemotherapy for breast cancer and healthy controls underwent neurophysiologic assessments at baseline, during the time of chemotherapy treatment, and at 1 year. Repeated measures analysis of variance was used to analyze the data. Compared with controls, patients reported more subjective fatigue at baseline that increased during chemotherapy and did not entirely resolve by 1 year. Performance on endurance testing was similar in patients versus controls at all time points; however, values of EEG power increased after a physical task in patients during chemotherapy but not controls. Compared with controls, subjective mental fatigue was similar for patients at baseline and 1 year but worsened during chemotherapy. Patients performed similarly to controls on formal cognitive testing at all time points, but EEG activity after the cognitive task was increased in patients only during chemotherapy. EEG power measurement has the potential to provide a sensitive neurophysiologic correlate of cancer treatment-related fatigue and cognitive dysfunction.

Does True Neurocognitive Dysfunction Contribute to Minnesota Multiphasic Personality Inventory-2nd Edition-Restructured Form Cognitive Validity Scale Scores?

PubMed

Martin, Phillip K; Schroeder, Ryan W; Heinrichs, Robin J; Baade, Lyle E

2015-08-01

Previous research has demonstrated RBS and FBS-r to identify non-credible reporters of cognitive symptoms, but the extent that these scales might be influenced by true neurocognitive dysfunction has not been previously studied. The present study examined the relationship between these cognitive validity scales and neurocognitive performance across seven domains of cognitive functioning, both before and after controlling for PVT status in 120 individuals referred for neuropsychological evaluations. Variance in RBS, but not FBS-r, was significantly accounted for by neurocognitive test performance across most cognitive domains. After controlling for PVT status, however, relationships between neurocognitive test performance and validity scales were no longer significant for RBS, and remained non-significant for FBS-r. Additionally, PVT failure accounted for a significant proportion of the variance in both RBS and FBS-r. Results support both the convergent and discriminant validity of RBS and FBS-r. As neither scale was impacted by true neurocognitive dysfunction, these findings provide further support for the use of RBS and FBS-r in neuropsychological evaluations. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

USDA-ARS?s Scientific Manuscript database

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Neural bases of different cognitive strategies for facial affect processing in schizophrenia.

PubMed

Fakra, Eric; Salgado-Pineda, Pilar; Delaveau, Pauline; Hariri, Ahmad R; Blin, Olivier

2008-03-01

To examine the neural basis and dynamics of facial affect processing in schizophrenic patients as compared to healthy controls. Fourteen schizophrenic patients and fourteen matched controls performed a facial affect identification task during fMRI acquisition. The emotional task included an intuitive emotional condition (matching emotional faces) and a more cognitively demanding condition (labeling emotional faces). Individual analysis for each emotional condition, and second-level t-tests examining both within-, and between-group differences, were carried out using a random effects approach. Psychophysiological interactions (PPI) were tested for variations in functional connectivity between amygdala and other brain regions as a function of changes in experimental conditions (labeling versus matching). During the labeling condition, both groups engaged similar networks. During the matching condition, schizophrenics failed to activate regions of the limbic system implicated in the automatic processing of emotions. PPI revealed an inverse functional connectivity between prefrontal regions and the left amygdala in healthy volunteers but there was no such change in patients. Furthermore, during the matching condition, and compared to controls, patients showed decreased activation of regions involved in holistic face processing (fusiform gyrus) and increased activation of regions associated with feature analysis (inferior parietal cortex, left middle temporal lobe, right precuneus). Our findings suggest that schizophrenic patients invariably adopt a cognitive approach when identifying facial affect. The distributed neocortical network observed during the intuitive condition indicates that patients may resort to feature-based, rather than configuration-based, processing and may constitute a compensatory strategy for limbic dysfunction.

Neurological Manifestations Among US Government Personnel Reporting Directional Audible and Sensory Phenomena in Havana, Cuba.

PubMed

Swanson, Randel L; Hampton, Stephen; Green-McKenzie, Judith; Diaz-Arrastia, Ramon; Grady, M Sean; Verma, Ragini; Biester, Rosette; Duda, Diana; Wolf, Ronald L; Smith, Douglas H

2018-03-20

From late 2016 through August 2017, US government personnel serving on diplomatic assignment in Havana, Cuba, reported neurological symptoms associated with exposure to auditory and sensory phenomena. To describe the neurological manifestations that followed exposure to an unknown energy source associated with auditory and sensory phenomena. Preliminary results from a retrospective case series of US government personnel in Havana, Cuba. Following reported exposure to auditory and sensory phenomena in their homes or hotel rooms, the individuals reported a similar constellation of neurological symptoms resembling brain injury. These individuals were referred to an academic brain injury center for multidisciplinary evaluation and treatment. Report of experiencing audible and sensory phenomena emanating from a distinct direction (directional phenomena) associated with an undetermined source, while serving on US government assignments in Havana, Cuba, since 2016. Descriptions of the exposures and symptoms were obtained from medical record review of multidisciplinary clinical interviews and examinations. Additional objective assessments included clinical tests of vestibular (dynamic and static balance, vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of convergence, saccadic, and smooth pursuit eye movements), cognitive (comprehensive neuropsychological battery), and audiometric (pure tone and speech audiometry) functioning. Neuroimaging was also obtained. Of 24 individuals with suspected exposure identified by the US Department of State, 21 completed multidisciplinary evaluation an average of 203 days after exposure. Persistent symptoms (>3 months after exposure) were reported by these individuals including cognitive (n = 17, 81%), balance (n = 15, 71%), visual (n = 18, 86%), and auditory (n = 15, 68%) dysfunction, sleep impairment (n = 18, 86%), and headaches (n = 16, 76%). Objective findings included cognitive (n = 16, 76%), vestibular (n = 17, 81%), and oculomotor (n = 15, 71%) abnormalities. Moderate to severe sensorineural hearing loss was identified in 3 individuals. Pharmacologic intervention was required for persistent sleep dysfunction (n = 15, 71%) and headache (n = 12, 57%). Fourteen individuals (67%) were held from work at the time of multidisciplinary evaluation. Of those, 7 began graduated return to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation. In this preliminary report of a retrospective case series, persistent cognitive, vestibular, and oculomotor dysfunction, as well as sleep impairment and headaches, were observed among US government personnel in Havana, Cuba, associated with reports of directional audible and/or sensory phenomena of unclear origin. These individuals appeared to have sustained injury to widespread brain networks without an associated history of head trauma.

The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

PubMed

van Rijsbergen, M W A; Mark, R E; Kop, W J; de Kort, P L M; Sitskoorn, M M

2017-03-01

Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (β = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (β = -0.34, P < 0.001). Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke. © 2016 EAN.

Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

PubMed

Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

2016-10-01

Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

Cognitive Impairment in Chronic Alcoholics: Some Cause for Optimism.

ERIC Educational Resources Information Center

Goldman, Mark S.

1983-01-01

It appears that, although the cognitive functioning of many alcoholics remains impaired even after drinking has stopped, considerable recovery can occur. New findings now suggest the possibility of reducing cognitive dysfunction and enhancing alcoholism treatment outcomes. (CMG)

Postoperative Structural Brain Changes and Cognitive Dysfunction in Patients with Breast Cancer.

PubMed

Sato, Chiho; Sekiguchi, Atsushi; Kawai, Masaaki; Kotozaki, Yuka; Nouchi, Rui; Tada, Hiroshi; Takeuchi, Hikaru; Ishida, Takanori; Taki, Yasuyuki; Kawashima, Ryuta; Ohuchi, Noriaki

2015-01-01

The primary purpose of this study was to clarify the influence of the early response to surgery on brain structure and cognitive function in patients with breast cancer. It was hypothesized that the structure of the thalamus would change during the early response after surgery due to the effects of anesthesia and would represent one aspect of an intermediate phenotype of postoperative cognitive dysfunction (POCD). We examined 32 postmenopausal females with breast cancer and 20 age-matched controls. We assessed their cognitive function (attention, memory, and executive function), and performed brain structural MRI 1.5 ± 0.5 days before and 5.6 ± 1.2 days after surgery. We found a significant interaction between regional grey matter volume (rGMV) in the thalamus (P < 0.05, familywise error (FWE), small volume correction (SVC)) and one attention domain subtest (P = 0.001, Bonferroni correction) after surgery in the patient group compared with the control group. Furthermore, the changes in attention were significantly associated with sevoflurane anesthetic dose (r2 = 0.247, β = ‒0.471, P = 0.032) and marginally associated with rGMV changes in the thalamus (P = 0.07, FWE, SVC) in the Pt group. Our findings suggest that alterations in brain structure, particularly in the thalamus, may occur shortly after surgery and may be associated with attentional dysfunction. This early postoperative response to anesthesia may represent an intermediate phenotype of POCD. It was assumed that patients experiencing other risk factors of POCD, such as the severity of surgery, the occurrence of complications, and pre-existing cognitive impairments, would develop clinical POCD with broad and multiple types of cognitive dysfunction.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

PubMed

Li, Min; Zhang, Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Gu, Hong-Feng; Tang, Xiao-Qing

2017-04-01

Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2

PubMed Central

Li, Min; Zhang, Ping; Wei, Hai-jun; Li, Man-Hong; Li, Xiang; Gu, Hong-Feng

2017-01-01

Abstract Background: Homocysteine, a risk factor for Alzheimer’s disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. Methods: The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. Results: The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Conclusion: Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. PMID:27988490

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

PubMed Central

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

2017-01-01

Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait

PubMed Central

Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Nutt, John G.; Fair, Damian A.

2013-01-01

Freezing of gait is one of the most debilitating symptoms in Parkinson’s disease as it causes falls and reduces mobility and quality of life. The pedunculopontine nucleus is one of the major nuclei of the mesencephalic locomotor region and has neurons related to anticipatory postural adjustments preceding step initiation as well as to the step itself, thus it may be critical for coupling posture and gait to avoid freezing. Because freezing of gait and postural impairments have been related to frontal lesions and frontal dysfunction such as executive function, we hypothesized that freezing is associated with disrupted connectivity between midbrain locomotor regions and medial frontal cortex. We used diffusion tensor imaging to quantify structural connectivity of the pedunculopontine nucleus in patients with Parkinson’s disease with freezing of gait, without freezing, and healthy age-matched controls. We also included behavioural tasks to gauge severity of freezing of gait, quantify gait metrics, and assess executive cognitive functions to determine whether between-group differences in executive dysfunction were related to pedunculopontine nucleus structural network connectivity. Using seed regions from the pedunculopontine nucleus, we were able to delineate white matter connections between the spinal cord, cerebellum, pedunculopontine nucleus, subcortical and frontal/prefrontal cortical regions. The current study is the first to demonstrate differences in structural connectivity of the identified locomotor pathway in patients with freezing of gait. We report reduced connectivity of the pedunculopontine nucleus with the cerebellum, thalamus and multiple regions of the frontal cortex. Moreover, these structural differences were observed solely in the right hemisphere of patients with freezing of gait. Finally, we show that the more left hemisphere-lateralized the pedunculopontine nucleus tract volume, the poorer the performance on cognitive tasks requiring the initiation of appropriate actions and/or the inhibition of inappropriate actions, specifically within patients with freezing. These results support the notion that freezing of gait is strongly related to structural deficits in the right hemisphere’s locomotor network involving prefrontal cortical areas involved in executive inhibition function. PMID:23824487

T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

PubMed Central

Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal

2004-01-01

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions. PMID:15141078

Neurofeedback and its possible relevance for the treatment of Tourette syndrome.

PubMed

Farkas, Aniko; Bluschke, Annet; Roessner, Veit; Beste, Christian

2015-04-01

Neurofeedback is an increasingly recognized therapeutic option in various neuropsychiatric disorders to treat dysfunctions in cognitive control as well as disorder-specific symptoms. In this review we propose that neurofeedback may also reflect a valuable therapeutic option to treat executive control functions in Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions when ADHD symptoms appear in GTS likely reflect pathophysiological processes in cortico-thalamic-striatal circuits and may also underlie the motor symptoms in GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on neurophysiological processes well-known to be modifiable by neurofeedback. However, so far efforts to use neurofeedback to treat cognitive dysfunctions are scarce. We outline why neurofeedback should be considered a promising treatment option, what forms of neurofeedback may prove to be most effective and how neurofeedback may be implemented in existing intervention strategies to treat comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be most useful in this frequent combination of disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unifying the field: developing an integrative paradigm for behavior therapy.

PubMed

Eifert, G H; Forsyth, J P; Schauss, S L

1993-06-01

The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.

Protective effect of curcumin (Curcuma longa) against D-galactose-induced senescence in mice.

PubMed

Kumar, Anil; Prakash, Atish; Dogra, Samrita

2011-01-01

Brain senescence plays an important role in cognitive dysfunction and neurodegenerative disorders. Curcumin was reported to have beneficial effect against several neurodegenerative disorders including Alzheimer's disease. Therefore, the present study was conducted in order to explore the possible role of curcumin against D-galactose-induced cognitive dysfunction, oxidative damage, and mitochondrial dysfunction in mice. Chronic administration of D-galactose for 6 weeks significantly impaired cognitive function (both in Morris water maze and elevated plus maze), locomotor activity, oxidative defense (raised lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity), and mitochondrial enzyme complex activities (I, II, and III) as compared to vehicle treated group. Curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment for 6 weeks significantly improved cognitive tasks, locomotor activity, oxidative defense, and restored mitochondrial enzyme complex activity as compared to control (D-galactose). Chronic D-galactose treatment also significantly increased acetylcholine esterase activity that was attenuated by curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment. In conclusion, the present study highlights the therapeutic potential of curcumin against d-galactose induced senescence in mice.

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

PubMed

Sánchez, Stella M; Abulafia, Carolina; Duarte-Abritta, Barbara; de Guevara, M Soledad Ladrón; Castro, Mariana N; Drucaroff, Lucas; Sevlever, Gustavo; Nemeroff, Charles B; Vigo, Daniel E; Loewenstein, David A; Villarreal, Mirta F; Guinjoan, Salvador M

2017-01-01

We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

Event-related-potential low-resolution brain electromagnetic tomography (ERP-LORETA) suggests decreased energetic resources for cognitive processing in narcolepsy.

PubMed

Saletu, Michael; Anderer, Peter; Saletu-Zyhlarz, Gerda Maria; Mandl, Magdalena; Zeitlhofer, Josef; Saletu, Bernd

2008-08-01

Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography. In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF). In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity. Narcoleptic patients showed prolonged information processing, as indexed by N2 and P300 latencies and decreased energetic resources for cognitive processing. Electrophysiological aberrations in brain areas related to the 'executive attention network' and the 'limbic system' may contribute to a deterioration in mental performance and mood at the behavioral level.

[Minimal emotional dysfunction and first impression formation in personality disorders].

PubMed

Linden, M; Vilain, M

2011-01-01

"Minimal cerebral dysfunctions" are isolated impairments of basic mental functions, which are elements of complex functions like speech. The best described are cognitive dysfunctions such as reading and writing problems, dyscalculia, attention deficits, but also motor dysfunctions such as problems with articulation, hyperactivity or impulsivity. Personality disorders can be characterized by isolated emotional dysfunctions in relation to emotional adequacy, intensity and responsivity. For example, paranoid personality disorders can be characterized by continuous and inadequate distrust, as a disorder of emotional adequacy. Schizoid personality disorders can be characterized by low expressive emotionality, as a disorder of effect intensity, or dissocial personality disorders can be characterized by emotional non-responsivity. Minimal emotional dysfunctions cause interactional misunderstandings because of the psychology of "first impression formation". Studies have shown that in 100 ms persons build up complex and lasting emotional judgements about other persons. Therefore, minimal emotional dysfunctions result in interactional problems and adjustment disorders and in corresponding cognitive schemata.From the concept of minimal emotional dysfunctions specific psychotherapeutic interventions in respect to the patient-therapist relationship, the diagnostic process, the clarification of emotions and reality testing, and especially an understanding of personality disorders as impairment and "selection, optimization, and compensation" as a way of coping can be derived.

TRPV1 may increase the effectiveness of estrogen therapy on neuroprotection and neuroregeneration.

PubMed

Ramírez-Barrantes, Ricardo; Marchant, Ivanny; Olivero, Pablo

2016-08-01

Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases. Then, restoring neuroendocrine axes during aging can be key to enhance brain health through neuroprotection and neuroregeneration, depending on the modulation of plasticity mechanisms. Estrogen-dependent transient receptor potential cation channel, subfamily V, member 1 (TRPV1) expression induces neuroprotection, neurogenesis and regeneration on damaged tissues. Agonists of TRPV1 can modulate neuroprotection and repair of sensitive neurons, while modulators as other cognitive enhancers may improve the survival rate, differentiation and integration of neural stem cell progenitors in functional neural network. Menopause constitutes a relevant clinical model of steroidal production decline associated with progressive cognitive and mental impairment, which allows exploring the effects of hormone therapy in health outcomes such as dysfunction of CNS. Simulating the administration of hormone therapy to virtual menopausal individuals allows assessing its hypothetical impact and sensitivity to conditions that modify the effectiveness and efficiency.

Neural systems for social cognition in Klinefelter syndrome (47,XXY): evidence from fMRI.

PubMed

van Rijn, Sophie; Swaab, Hanna; Baas, Daan; de Haan, Edward; Kahn, René S; Aleman, André

2012-08-01

Klinefelter syndrome (KS) is a chromosomal condition (47, XXY) that may help us to unravel gene-brain behavior pathways to psychopathology. The phenotype includes social cognitive impairments and increased risk for autism traits. We used functional MRI to study neural mechanisms underlying social information processing. Eighteen nonclinical controls and thirteen men with XXY were scanned during judgments of faces with regard to trustworthiness and age. While judging faces as untrustworthy in comparison to trustworthy, men with XXY displayed less activation than controls in (i) the amygdala, which plays a key role in screening information for socio-emotional significance, (ii) the insula, which plays a role in subjective emotional experience, as well as (iii) the fusiform gyrus and (iv) the superior temporal sulcus, which are both involved in the perceptual processing of faces and which were also less involved during age judgments in men with XXY. This is the first study showing that KS can be associated with reduced involvement of the neural network subserving social cognition. Studying KS may increase our understanding of the genetic and hormonal basis of neural dysfunctions contributing to abnormalities in social cognition and behavior, which are considered core abnormalities in psychiatric disorders such as autism and schizophrenia.

Executive Dysfunction in Obsessive-Compulsive Disorder and Anterior Cingulate-Based Resting State Functional Connectivity

PubMed Central

Yun, Je-Yeon; Jang, Joon Hwan; Jung, Wi Hoon; Shin, Na Young; Kim, Sung Nyun; Hwang, Jae Yeon

2017-01-01

Objective Executive dysfunction might be an important determinant for response to pharmacotherapy in obsessive-compulsive disorder (OCD), and could be sustained independently of symptom relief. The anterior cingulate cortex (ACC) has been indicated as a potential neural correlate of executive functioning in OCD. The present study examined the brain-executive function relationships in OCD from the ACC-based resting state functional connectivity networks (rs-FCNs), which reflect information processing mechanisms during task performance. Methods For a total of 58 subjects [OCD, n=24; healthy controls (HCs), n=34], four subdomains of executive functioning were measured using the Rey-Osterrieth Complex Figure Test (RCFT), the Stroop Color-Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Trail Making Test part B (TMT-B). To probe for differential patterns of the brain-cognition relationship in OCD compared to HC, the ACC-centered rs-FCN were calculated using five seed regions systemically placed throughout the ACC. Results Significant differences between the OCD group and the HCs with respect to the WCST perseverative errors, SCWT interference scores, and TMT-B reaction times (p<0.05) were observed. Moreover, significant interactions between diagnosis×dorsal ACC [S3]-based rs-FCN strength in the right dorsolateral prefrontal cortex for RCFT organization summary scores as well as between diagnosis×perigenual ACC [S7]-based rs-FCN strength in the left frontal eye field for SCWT color-word interference scores were unveiled. Conclusion These network-based neural foundations for executive dysfunction in OCD could become a potential target of future treatment, which could improve global domains of functioning broader than symptomatic relief. PMID:28539952

Interactions of the Salience Network and Its Subsystems with the Default-Mode and the Central-Executive Networks in Normal Aging and Mild Cognitive Impairment.

PubMed

Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab; Qiu, Deqiang

2017-09-01

Previous functional magnetic resonance imaging (fMRI) investigations suggest that the intrinsically organized large-scale networks and the interaction between them might be crucial for cognitive activities. A triple network model, which consists of the default-mode network, salience network, and central-executive network, has been recently used to understand the connectivity patterns of the cognitively normal brains versus the brains with disorders. This model suggests that the salience network dynamically controls the default-mode and central-executive networks in healthy young individuals. However, the patterns of interactions have remained largely unknown in healthy aging or those with cognitive decline. In this study, we assess the patterns of interactions between the three networks using dynamical causal modeling in resting state fMRI data and compare them between subjects with normal cognition and mild cognitive impairment (MCI). In healthy elderly subjects, our analysis showed that the salience network, especially its dorsal subnetwork, modulates the interaction between the default-mode network and the central-executive network (Mann-Whitney U test; p < 0.05), which was consistent with the pattern of interaction reported in young adults. In contrast, this pattern of modulation by salience network was disrupted in MCI (p < 0.05). Furthermore, the degree of disruption in salience network control correlated significantly with lower overall cognitive performance measured by Montreal Cognitive Assessment (r = 0.295; p < 0.05). This study suggests that a disruption of the salience network control, especially the dorsal salience network, over other networks provides a neuronal basis for cognitive decline and may be a candidate neuroimaging biomarker of cognitive impairment.

Altered inhibition-related frontolimbic connectivity in obsessive-compulsive disorder.

PubMed

van Velzen, Laura S; de Wit, Stella J; Ćurĉić-Blake, Branislava; Cath, Daniëlle C; de Vries, Froukje E; Veltman, Dick J; van der Werf, Ysbrand D; van den Heuvel, Odile A

2015-10-01

Recent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings. Forty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved. Patients, and to a lesser extent also their unaffected siblings, show altered connectivity between the inferior frontal gyrus and the amygdala during response inhibition. The follow-up dynamic causal modeling suggests a bottom-up influence of the amygdala on the inferior frontal gyrus in healthy controls, whereas processing occurs top-down in patients with obsessive-compulsive, and in both directions in siblings. Our findings suggest that amygdala activation in obsessive-compulsive disorder interferes differently with the task-related recruitment of the inhibition network, underscoring the role of limbic disturbances in cognitive dysfunctions in obsessive-compulsive disorder. © 2015 Wiley Periodicals, Inc.

A Neurocomputational model of tonic and phasic dopamine in action selection: A comparison with cognitive deficits in Parkinson’s disease

PubMed Central

Guthrie, M.; Myers, C.E.; Gluck, M.A.

2015-01-01

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson’s disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson’s disease are not solely due to either the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status. PMID:19162084

Cerebrovascular Complications of Diabetes: Focus on Cognitive Dysfunction

PubMed Central

Hardigan, Trevor; Ward, Rebecca; Ergul, Adviye

2017-01-01

The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity--mediated inflammation in neurovascular changes in diabetes. PMID:27634842

Morphological differences in the mirror neuron system in Williams syndrome.

PubMed

Ng, Rowena; Brown, Timothy T; Erhart, Matthew; Järvinen, Anna M; Korenberg, Julie R; Bellugi, Ursula; Halgren, Eric

2016-01-01

Williams syndrome (WS) is a genetic condition characterized by an overly gregarious personality, including high empathetic concern for others. Although seemingly disparate from the profile of autism spectrum disorder (ASD), both are associated with deficits in social communication/cognition. Notably, the mirror neuron system (MNS) has been implicated in social dysfunction for ASD; yet, the integrity of this network and its association with social functioning in WS remains unknown. Magnetic resonance imaging (MRI) methods were used to examine the structural integrity of the MNS of adults with WS versus typically developing (TD) individuals. The Social Responsiveness Scale (SRS), a tool typically used to screen for social features of ASD, was also employed to assess the relationships between social functioning with the MNS morphology in WS participants. WS individuals showed reduced cortical surface area of MNS substrates yet relatively preserved cortical thickness as compared to TD adults. Increased cortical thickness of the inferior parietal lobule (IPL) was associated with increased deficits in social communication, social awareness, social cognition, and autistic mannerisms. However, social motivation was not related to anatomical features of the MNS. Our findings indicate that social deficits typical to both ASD and WS may be attributed to an aberrant MNS, whereas the unusual social drive marked in WS is subserved by substrates distinct from this network.

Morphological differences in the mirror neuron system in Williams Syndrome

PubMed Central

Ng, Rowena; Brown, Timothy T.; Erhart, Matthew; Järvinen, Anna M.; Korenberg, Julie R.; Bellugi, Ursula; Halgren, Eric

2015-01-01

Williams syndrome (WS) is a genetic condition characterized by an overly gregarious personality, including high empathetic concern for others. Although seemingly disparate from the profile of autism spectrum disorder (ASD), both are associated with deficits in social communication/cognition. Notably, the mirror neuron system (MNS) has been implicated in social dysfunction for ASD; yet, the integrity of this network and its association with social functioning in WS remains unknown. Magnetic resonance imaging methods were used to examine the structural integrity of the MNS of adults with WS versus typically developing (TD) individuals. The Social Responsiveness Scale (SRS), a tool typically used to screen for social features of ASD, was also employed to assess the relationships between social functioning with the MNS morphology in WS participants. WS individuals showed reduced cortical surface area of MNS substrates yet relatively preserved cortical thickness as compared to TD adults. Increased cortical thickness of the inferior parietal lobule was associated with increased deficits in social communication, social awareness, social cognition, and autistic mannerisms. However, social motivation was not related to anatomical features of the MNS. Our findings indicate that social deficits typical to both ASD and WS may be attributed to an aberrant MNS, whereas the unusual social drive marked in WS is subserved by substrates distinct from this network. PMID:26230578

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

Psychometrics of the AAN Caregiver Driving Safety Questionnaire and contributors to caregiver concern about driving safety in older adults.

PubMed

Carvalho, Janessa O; Springate, Beth; Bernier, Rachel A; Davis, Jennifer

2018-03-01

ABSTRACTBackground:The American Academy of Neurology (AAN) updated their practice parameters in the evaluation of driving risk in dementia and developed a Caregiver Driving Safety Questionnaire, detailed in their original manuscript (Iverson Gronseth, Reger, Classen, Dubinsky, & Rizzo, 2010). They described four factors associated with decreased driving ability in dementia patients: history of crashes or citations, informant-reported concerns, reduced mileage, and aggressive driving. An informant-reported AAN Caregiver Driving Safety Questionnaire was designed with these elements, and the current study was the first to explore the factor structure of this questionnaire. Additionally, we examined associations between these factors and cognitive and behavioral measures in patients with mild cognitive impairment or early Alzheimer's disease and their informants. Exploratory factor analysis revealed a four-component structure, consistent with the theory behind the AAN scale composition. These four factor scores also were significantly associated with performance on cognitive screening instruments and informant reported behavioral dysfunction. Regressions revealed that behavioral dysfunction predicted caregiver concerns about driving safety beyond objective patient cognitive dysfunction. In this first known quantitative exploration of the scale, our results support continued use of this scale in office driving safety assessments. Additionally, patient behavioral changes predicted caregiver concerns about driving safety over and above cognitive status, which suggests that caregivers may benefit from psychoeducation about cognitive factors that may negatively impact driving safety.

Insulin-like growth factor-1: a possible marker for emotional and cognitive disturbances, and treatment effectiveness in major depressive disorder.

PubMed

Levada, Oleg A; Troyan, Alexandra S

2017-01-01

Depression and cognitive dysfunction share a common neuropathological platform. Abnormal neural plasticity in the frontolimbic circuits has been linked to changes in the expression of neurotrophic factors, including IGF-1. These changes may result in clinical abnormalities observed over the course of major depressive disorder (MDD), including cognitive dysfunction. The present review aimed to summarize evidence regarding abnormalities of peripheral IGF-1 in MDD patients and assess a marker and predictive role of the neurotrophin for emotional and cognitive disturbances, and treatment effectiveness. A literature search of the PubMed database was conducted for studies, in which peripheral IGF-1 levels were evaluated. Our analysis revealed four main findings: (1) IGF-1 levels in MDD patients mismatch across the studies, which may arise from various factors, e.g., age, gender, the course of the disease, presence of cognitive impairment, ongoing therapy, or general health conditions; (2) the initial peripheral IGF-1 levels may predict the occurrence of depression in future; (3) peripheral IGF-1 levels may reflect cognitive dysfunction, although the data is limited; (4) it is difficult to evaluate the influence of treatment on IGF-1 levels as there is discrepancy of this growth factor among the studies at baseline, although most of them showed a decrease in IGF-1 levels after treatment.

Conversion of elderly to Alzheimer's dementia: role of confluence of hypothermia and senescent stigmata--the plausible pathway.

PubMed

Daulatzai, Mak Adam

2010-01-01

Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. Additionally, anesthesia in elderly also promotes hypothermia; anesthetics not only cause consciousness (sensory and motor) changes, but memory impairment as well. Anesthesia inhibits cholinergic pathways, reticular and thalamocortical systems, cortico-cortical connectivity, and causes post-operative delirium and cognitive dysfunction. Increasing evidence indicates that anesthetic exposures may contribute to dementia onset and Alzheimer's disease (AD) in hypothermic elderly. Inhaled anesthetics potentiate caspases, BACE, tau hyperphosphorylation, and apoptosis. This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

PubMed

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

PubMed

Bezdicek, O; Michalec, J; Vaneckova, M; Klempir, J; Liskova, I; Seidl, Z; Janikova, B; Miovsky, M; Hubacek, J; Diblik, P; Kuthan, P; Pilin, A; Kurcova, I; Fenclova, Z; Petrik, V; Navratil, T; Pelclova, D; Zakharov, S; Ruzicka, E

2017-03-01

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress.

PubMed

Tang, Yi-Yun; Wang, Ai-Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

2018-04-16

Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H 2 S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H 2 S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H 2 S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H 2 S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H 2 S in Hcy-induced cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Coping with cancer-related cognitive dysfunction: a scoping review of the literature.

PubMed

Sleight, Alix

2016-01-01

Cancer-related cognitive dysfunction (CRCD) impacts memory, attention, concentration, language, multi-tasking, and organizational skills and decreases participation and quality of life for cancer survivors. The objectives of this article are: (1) to outline the neuroscience of CRCD, its risk factors, and its effect on participation; and (2) to identify and summarize the literature on rehabilitation interventions and coping techniques for CRCD in cancer survivors. A scoping review of articles cited in PubMed, MEDLINE, PsychINFO, and CINAHL was performed. To be included, articles must have been published in a peer-reviewed scientific journal between 1996 and 2014, written in English, and included a quantitative or qualitative non-pharmacological study of interventions and/or coping strategies for adult cancer survivors experiencing CRCD. Ten articles met the inclusion criteria for final review. Six studies tested the efficacy of rehabilitation treatments on CRCD. Three involved cognitive-behavioral therapy (CBT), while three tested neuropsychological and/or cognitive training interventions. Four qualitative studies investigated coping strategies used by survivors with CRCD. CBT-based treatments and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most commonly-reported coping strategy is utilization of assistive technology and memory aids. Further research is needed about efficacious rehabilitation techniques for this population. Implications for Rehabilitation Cancer-related cognitive dysfunction (CRCD) may impact up to 50% of cancer survivors. CRCD can significantly decrease participation and quality of life during survivorship. Cognitive-behavioral therapy (CBT) and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most common coping strategy reported by cancer survivors with CRCD is the use of assistive technology and memory aids.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients.

PubMed

Zhang, Yan; Wang, Wanhua; Cai, Sijie; Sheng, Qi; Pan, Shenggui; Shen, Fang; Tang, Qing; Liu, Yang

2017-05-01

Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiential Avoidance as a Mediator of Relationships between Cognitions and Hair-Pulling Severity

ERIC Educational Resources Information Center

Norberg, Melissa M.; Wetterneck, Chad T.; Woods, Douglas W.; Conelea, Christine A.

2007-01-01

Cognitive-behavioral models suggest that certain cognitions and beliefs are functionally related to hair pulling in persons with trichotillomania (TTM), but little empirical data have been collected to test such claims. This study assessed dysfunctional beliefs about appearance, shameful cognitions, and fear of negative evaluation and their…

Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review.

PubMed

Thorsen, Anders Lillevik; Johansson, Kyrre; Løberg, Else-Marie

2014-01-01

Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.

Apollo’s gift: new aspects of neurologic music therapy

PubMed Central

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

Apollo's gift: new aspects of neurologic music therapy.

PubMed

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

Caspase-2 cleavage of tau reversibly impairs memory.

PubMed

Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

PubMed

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard

2017-08-01

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Reduced Physical Fitness in Patients With Heart Failure as a Possible Risk Factor for Impaired Driving Performance

PubMed Central

Alosco, Michael L.; Penn, Marc S.; Spitznagel, Mary Beth; Cleveland, Mary Jo; Ott, Brian R.

2015-01-01

OBJECTIVE. Reduced physical fitness secondary to heart failure (HF) may contribute to poor driving; reduced physical fitness is a known correlate of cognitive impairment and has been associated with decreased independence in driving. No study has examined the associations among physical fitness, cognition, and driving performance in people with HF. METHOD. Eighteen people with HF completed a physical fitness assessment, a cognitive test battery, and a validated driving simulator scenario. RESULTS. Partial correlations showed that poorer physical fitness was correlated with more collisions and stop signs missed and lower scores on a composite score of attention, executive function, and psychomotor speed. Cognitive dysfunction predicted reduced driving simulation performance. CONCLUSION. Reduced physical fitness in participants with HF was associated with worse simulated driving, possibly because of cognitive dysfunction. Larger studies using on-road testing are needed to confirm our findings and identify clinical interventions to maximize safe driving. PMID:26122681

Piracetam improves children's memory after general anaesthesia.

PubMed

Fesenko, Ułbołgan A

2009-01-01

Surgery and anaesthesia may account for postoperative complications including cognitive impairment. The purpose of the study was to assess the influence of general anaesthetics on children's memory and effectiveness of piracetam for prevention of postoperative cognitive dysfunction. The study included patients receiving different kinds of anaesthesia for various surgical procedures, randomly allocated to two groups. According to immediate postoperative treatment, the study group received intravenous piracetam 30 mg kg(-1) and the control group--placebo. The cognitive functions were examined preoperatively and within 10 consecutive postoperative days using the ten-word memory test. The study group consisted of 123 children, the control one--of 127. Declines in memory indexes were observed in all anaesthetized patients. The most injured function was long-term memory. The intravenous administration of piracetam improved this cognitive function. The study results confirm that general anaesthesia affects the memory function in children. Piracetam is effective for prevention of postoperative cognitive dysfunction after anaesthesia.

The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

PubMed

Phillips, Cristy; Baktir, Mehmet Akif; Das, Devsmita; Lin, Bill; Salehi, Ahmad

2015-07-01

Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed. © 2015 American Physical Therapy Association.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PubMed

Lawrence, J A; Griffin, L; Balcueva, E P; Groteluschen, D L; Samuel, T A; Lesser, G J; Naughton, M J; Case, L D; Shaw, E G; Rapp, S R

2016-02-01

Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Affective and cognitive reactivity to mood induction in chronic depression.

PubMed

Guhn, Anne; Sterzer, Philipp; Haack, Friderike H; Köhler, Stephan

2018-03-15

Chronic depression (CD) is strongly associated with childhood maltreatment, which has been proposed to lead to inefficient coping styles that are characterized by abnormal affective responsiveness and dysfunctional cognitive attitudes. However, while this notion forms an important basis for psychotherapeutic strategies in the treatment of CD, there is still little direct empirical evidence for a role of altered affective and cognitive reactivity in CD. The present study therefore experimentally investigated affective and cognitive reactivity to two forms of negative mood induction in CD patients versus a healthy control sample (HC). For the general mood induction procedure, a combination of sad pictures and sad music was used, while for individualized mood induction, negative mood was induced by individualized scripts with autobiographical content. Both experiments included n = 15 CD patients versus n = 15 HC, respectively. Interactions between affective or cognitive reactivity and group were analyzed by repeated measurements ANOVAs. General mood induction neither revealed affective nor cognitive reactivity in the patient group while the control group reported the expected decrease of positive affect [interaction (IA) affective reactivity x group: p = .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood induction specifically increased affective reactivity (IA: p = .037) as well as the amount of dysfunctional cognitions in patients versus controls (IA: p = .014). The experiments were not balanced in a crossover design, causal conclusions are thus limited. Additionally, the differences to non-chronic forms of depression are still outstanding. The results suggest that in patients with CD, specific emotional activation through autobiographical memories is a key factor in dysfunctional coping styles. Psychotherapeutic interventions aimed at modifying affective and cognitive reactivity are thus of high relevance in the treatment of CD. Copyright © 2018 Elsevier B.V. All rights reserved.

Kant, cognitive psychotherapy, and the hardening of the categories.

PubMed

Nevid, Jeffrey S

2007-12-01

Contemporary models of psychotherapy owe a considerable intellectual debt to philosophy, even though the contributions of philosophers to contemporary practice in the field often go unrecognized. A case in point is Kant's epistemology, which is foundational to cognitive approaches to psychotherapy. Here, it is argued that the rigid use of certain judgments represented in Kant's conceptual scheme underlies patterns of distorted or dysfunctional thinking associated with emotional disorders. Kantian judgments of necessity, disjunction, particularity and universality have counterpoints in contemporary conceptions of cognitive distortions. Moreover, Kantian epistemology has important therapeutic implications with respect to helping people with emotional disorders recognize and challenge rigidly held judgments or categories of understanding. The Kantian perspective also leads us to consider the cognitive frameworks or thought structures that underlie dysfunctional thinking patterns.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

PubMed

Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

2017-01-15

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

PubMed

Nelson, Ashley M; Jim, Heather S L; Small, Brent J; Nishihori, Taiga; Gonzalez, Brian D; Cessna, Julie M; Hyland, Kelly A; Rumble, Meredith E; Jacobsen, Paul B

2018-03-01

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

PubMed

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-09-01

Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: protective effect of alpha-lipoic acid.

PubMed

Manda, Kailash; Ueno, Megumi; Moritake, Takashi; Anzai, Kazunori

2007-02-12

Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa

PubMed Central

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-01-01

Background Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Methods Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Results Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis. PMID:27904421

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome.

PubMed

Zhou, Li; Chen, Ping; Peng, Yating; Ouyang, Ruoyun

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies

PubMed Central

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2016-01-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits. PMID:27940353

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

PubMed

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

PubMed

Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

2017-06-01

Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

PubMed Central

Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

2015-01-01

Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

Age-Associated Differences in Cognitive Performance in Older Community Dwelling Schizophrenia Patients: Differential Sensitivity of Clinical Neuropsychological and Experimental Information Processing Tests

PubMed Central

Bowie, Christopher R.; Reichenberg, Abraham; McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.

2008-01-01

Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed. PMID:18053687

Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

PubMed

Sahakian, Barbara J; Morein-Zamir, Sharon

2015-04-01

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics.

PubMed

Woldemichael, Bisrat T; Mansuy, Isabelle M

2016-03-15

Micro-RNAs (miRNAs) are small regulatory non-coding RNAs involved in the regulation of many biological functions. In the brain, they have distinct expression patterns depending on region, cell-type and developmental stage. Their expression profile is altered by neuronal activation in response to behavioral training or chemical/electrical stimulation. The dynamic changes in miRNA level regulate the expression of genes required for cognitive processes such as learning and memory. In addition, in cognitive dysfunctions such as dementias, expression levels of many miRNAs are perturbed, not only in brain areas affected by the pathology, but also in peripheral body fluids such as serum and cerebrospinal fluid. This presents an opportunity to utilize miRNAs as biomarkers for early detection and assessment of cognitive dysfunctions. Further, since miRNAs target many genes and pathways, they may represent key molecular signatures that can help understand the mechanisms of cognitive disorders and the development of potential therapeutic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive outcome of cerebral fat embolism.

PubMed

Manousakis, Georgios; Han, Dong Y; Backonja, Miroslav

2012-11-01

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

PubMed Central

Conti, Fabrizio; Alessandri, Cristiano; Perricone, Carlo; Scrivo, Rossana; Rezai, Soheila; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Ortona, Elena; Marianetti, Massimo; Mina, Concetta; Valesini, Guido

2012-01-01

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients. PMID:22461897

Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer's disease.

PubMed

Redel, P; Bublak, P; Sorg, C; Kurz, A; Förstl, H; Müller, H J; Schneider, W X; Perneczky, R; Finke, K

2012-01-01

Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Nicotine effects on brain function and functional connectivity in schizophrenia.

PubMed

Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

2004-04-15

Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

PubMed Central

Millet, Bruno; Dondaine, Thibaut; Reymann, Jean-Michel; Bourguignon, Aurélie; Naudet, Florian; Jaafari, Nematollah; Drapier, Dominique; Turmel, Valérie; Mesbah, Habiba; Vérin, Marc; Le Jeune, Florence

2013-01-01

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes. PMID:23326403

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Grey-matter network disintegration as predictor of cognitive and motor function with aging.

PubMed

Koini, Marisa; Duering, Marco; Gesierich, Benno G; Rombouts, Serge A R B; Ropele, Stefan; Wagner, Fabian; Enzinger, Christian; Schmidt, Reinhold

2018-06-01

Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20-87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration.

Does improvement of cognitive functioning by cognitive remediation therapy effect work outcomes in severe mental illness? A secondary analysis of a randomized controlled trial.

PubMed

Ikebuchi, Emi; Sato, Sayaka; Yamaguchi, Sosei; Shimodaira, Michiyo; Taneda, Ayano; Hatsuse, Norifumi; Watanabe, Yukako; Sakata, Masuhiro; Satake, Naoko; Nishio, Masaaki; Ito, Jun-Ichiro

2017-05-01

The aim of this study was to clarify whether improvement of cognitive functioning by cognitive remediation therapy can improve work outcome in schizophrenia and other severe mental illnesses when combined with supported employment. The subjects of this study were persons with severe mental illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD-10) and cognitive dysfunction who participated in both cognitive remediation using the Thinking Skills for Work program and a supported employment program in a multisite, randomized controlled study. Logistic and multiple linear regression analyses were performed to clarify the influence of cognitive functioning on vocational outcomes, adjusting for demographic and clinical variables. Improvement of cognitive functioning with cognitive remediation significantly contributed to the total days employed and total earnings of competitive employment in supported employment service during the study period. Any baseline demographic and clinical variables did not significantly contribute to the work-related outcomes. A cognitive remediation program transferring learning skills into the real world is useful to increase the quality of working life in supported employment services for persons with severe mental illness and cognitive dysfunction who want to work competitively. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Successful group psychotherapy of depression in adolescents alters fronto-limbic resting-state connectivity.

PubMed

Straub, J; Metzger, C D; Plener, P L; Koelch, M G; Groen, G; Abler, B

2017-02-01

Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT). 38 adolescents (30 female; 19 patients; 13-18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II). Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents. Sample size and missing long-term follow-up limit the interpretability. Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive Communication Impairments: A Family-Focused Viewpoint.

ERIC Educational Resources Information Center

DePompei, Roberta; And Others

1988-01-01

An active role is recommended for family members involved in rehabilitation of cognitive communicative impairments of head-injured individuals. The paper discusses family systems theory, dysfunctional family reactions to the cognitive communicative behaviors of the head-injured member, and methods of assisting the family to develop the…

Role of fruits, nuts, and vegetables in maintaining cognitive health

USDA-ARS?s Scientific Manuscript database

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; howev...

Language Networks as Models of Cognition: Understanding Cognition through Language

NASA Astrophysics Data System (ADS)

Beckage, Nicole M.; Colunga, Eliana

Language is inherently cognitive and distinctly human. Separating the object of language from the human mind that processes and creates language fails to capture the full language system. Linguistics traditionally has focused on the study of language as a static representation, removed from the human mind. Network analysis has traditionally been focused on the properties and structure that emerge from network representations. Both disciplines could gain from looking at language as a cognitive process. In contrast, psycholinguistic research has focused on the process of language without committing to a representation. However, by considering language networks as approximations of the cognitive system we can take the strength of each of these approaches to study human performance and cognition as related to language. This paper reviews research showcasing the contributions of network science to the study of language. Specifically, we focus on the interplay of cognition and language as captured by a network representation. To this end, we review different types of language network representations before considering the influence of global level network features. We continue by considering human performance in relation to network structure and conclude with theoretical network models that offer potential and testable explanations of cognitive and linguistic phenomena.

Development and validation of 26-item dysfunctional attitude scale.

PubMed

Ebrahimi, Amrollah; Samouei, Rahele; Mousavii, Sayyed Ghafour; Bornamanesh, Ali Reza

2013-06-01

Dysfunctional Attitude Scale is one of the most common instruments used to assess cognitive vulnerability. This study aimed to develop and validate a short form of Dysfunctional Attitude Scale appropriate for an Iranian clinical population. Participants were 160 psychiatric patients from medical centers affiliated with Isfahan Medical University, as well as 160 non-patients. Research instruments were clinical interviews based on the Diagnostic and Statistical Manual-IV-TR, Dysfunctional Attitude Scale and General Heath Questionnaire (GHQ-28). Data was analyzed using multicorrelation calculations and factor analysis. Based on the results of factor analysis and item-total correlation, 14 items were judged candidates for omission. Analysis of the 26-item Dysfunctional Attitude Scale (DAS-26) revealed a Cronbach's alpha of 0.92. Evidence for the concurrent criterion validity was obtained through calculating the correlation between the Dysfunctional Attitude Scale and psychiatric diagnosis (r = 0.55), GHQ -28 (r = 0.56) and somatization, anxiety, social dysfunction, and depression subscales (0.45,0.53,0.48, and 0.57, respectively). Factor analysis deemed a four-factor structure the best. The factors were labeled as success-perfectionism, need for approval, need for satisfying others, and vulnerability-performance evaluation. The results showed that the Iranian version of the Dysfunctional Attitude Scale (DAS-26) bears satisfactory psychometric properties suggesting that this cognitive instrument is appropriate for use in an Iranian cultural context. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

PubMed

Ferrazzoli, Davide; Ortelli, Paola; Madeo, Graziella; Giladi, Nir; Petzinger, Giselle M; Frazzitta, Giuseppe

2018-07-01

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Review: Cerebral microvascular pathology in aging and neurodegeneration

PubMed Central

Brown, William R.; Thore, Clara R.

2010-01-01

This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density, and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase (AP). This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in aging, Alzheimer’s disease (AD), and leukoaraiosis (LA), and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow (CBF) is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in LA, and CBF is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in AD, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals, and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation. PMID:20946471

Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment.

PubMed

Murphy, Kelly J; Troyer, Angela K; Levine, Brian; Moscovitch, Morris

2008-11-01

Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66-84 years) and 17 aMCI (age 66-84 years) participants described a personal event from each of the five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial temporal lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

PubMed

Hshieh, Tammy T; Jung, Wooram F; Grande, Laura J; Chen, Jiaying; Stone, Richard M; Soiffer, Robert J; Driver, Jane A; Abel, Gregory A

2018-05-01

As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

The role of social relationships in the link between olfactory dysfunction and mortality.

PubMed

Leschak, Carrianne J; Eisenberger, Naomi I

2018-01-01

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Child, parent and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children.

PubMed

Kazdin, A E

1995-03-01

The present study examined factors that predicted favorable treatment outcomes among clinically referred conduct problem children (N = 105, ages 7-13) who received cognitive-behavioral treatment. Three domains (severity and breadth of child impairment, parent stress and psychopathology and family dysfunction) assessed at pretreatment were predicted to affect treatment outcome. The results only partially supported the prediction. Less dysfunction in each of the domains predicted who responded favorably to treatment on parent ratings of deviance and prosocial functioning but not on teacher ratings of these outcomes. The findings have implications for identifying youths who respond to available treatments. The results also underscore fundamental questions about the assessment of treatment effects and the criteria for evaluating outcome.

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment.

PubMed

Chen, Jiu; Shu, Hao; Wang, Zan; Zhan, Yafeng; Liu, Duan; Liao, Wenxiang; Xu, Lin; Liu, Yong; Zhang, Zhijun

2016-10-01

Both remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. We used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). A reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)-control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN-CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)].

PubMed

Ichikawa, Hiroo

2016-02-01

Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels.

Perceptual Anomalies in Schizophrenia: Integrating Phenomenology and Cognitive Neuroscience

PubMed Central

Uhlhaas, Peter J.; Mishara, Aaron L.

2007-01-01

From phenomenological and experimental perspectives, research in schizophrenia has emphasized deficits in “higher” cognitive functions, including attention, executive function, as well as memory. In contrast, general consensus has viewed dysfunctions in basic perceptual processes to be relatively unimportant in the explanation of more complex aspects of the disorder, including changes in self-experience and the development of symptoms such as delusions. We present evidence from phenomenology and cognitive neuroscience that changes in the perceptual field in schizophrenia may represent a core impairment. After introducing the phenomenological approach to perception (Husserl, the Gestalt School), we discuss the views of Paul Matussek, Klaus Conrad, Ludwig Binswanger, and Wolfgang Blankenburg on perception in schizophrenia. These 4 psychiatrists describe changes in perception and automatic processes that are related to the altered experience of self. The altered self-experience, in turn, may be responsible for the emergence of delusions. The phenomenological data are compatible with current research that conceptualizes dysfunctions in perceptual processing as a deficit in the ability to combine stimulus elements into coherent object representations. Relationships of deficits in perceptual organization to cognitive and social dysfunction as well as the possible neurobiological mechanisms are discussed. PMID:17118973

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder

PubMed Central

Schulz, Kurt P.; Bédard, Anne-Claude V.; Fan, Jin; Clerkin, Suzanne M.; Dima, Danai; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD. PMID:24918067

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder.

PubMed

Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; Newcorn, Jeffrey H; Halperin, Jeffrey M

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD.

Social cognition and self-other distinctions in neuropsychiatry: Insights from schizophrenia and Tourette syndrome.

PubMed

Eddy, Clare M

2018-03-02

Impairments in social cognition may reflect dysfunction of disorder specific or disorder general mechanisms. Although cross-disorder comparison may prove insightful, few studies have compared social cognition in different neuropsychiatric disorders. Parallel investigation of schizophrenia and Tourette syndrome (TS) is encouraged by similarities including the presence of problematic social behavior, echophenomena, emotional dysregulation and dopamine dysfunction. Focusing on tests of social cognition administered in both disorders, this review aims to summarize behavioral, neurophysiological and neuroimaging findings, before exploring how these may contribute to clinical symptoms. Studies investigating social cognition (imitation, emotion recognition, and understanding of beliefs or intentions) in patients with schizophrenia or TS were identified through Web of Science and PubMed searches. Although findings indicate that social cognitive deficits are more apparent in schizophrenia, adults with TS can exhibit similar task performance to patients with paranoia. In both disorders, behavioral and neuroimaging findings raise the possibility of increased internal simulation of others' actions and emotions, in combination with a relative under-application of mentalizing. More specifically, dysfunction in neurobiological substrates such as temporo-parietal junction and inferior frontal gyrus may underlie problems with self-other distinctions in both schizophrenia and TS. Difficulties in distinguishing between actions and mental states linked to the self and other may contribute to a range of psychiatric symptoms, including emotional dysregulation, paranoia, social anhedonia and socially disruptive urges. Comparing different patient populations could therefore reveal common neuro-cognitive risk factors for the development of problematic social behaviors, in addition to markers of resilience, coping strategies and potential neuro-compensation mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

PubMed Central

Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

2016-01-01

Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered purine metabolism and astrogliosis, thereby linking the importance of adenosine homeostasis in the brain to radiation injury. PMID:27375429

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.

PubMed

Durstewitz, Daniel; Seamans, Jeremy K

2008-11-01

There is now general consensus that at least some of the cognitive deficits in schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1- and D2-class receptors are highly complex, often apparently opposing, and hence difficult to understand with regard to their functional implications. Biophysically realistic computational models have provided valuable insights into how the effects of DA on PFC neurons and synaptic currents as measured in vitro link up to the neural network and cognitive levels. They suggest the existence of two discrete dynamical regimes, a D1-dominated state characterized by a high energy barrier among different network patterns that favors robust online maintenance of information and a D2-dominated state characterized by a low energy barrier that is beneficial for flexible and fast switching among representational states. These predictions are consistent with a variety of electrophysiological, neuroimaging, and behavioral results in humans and nonhuman species. Moreover, these biophysically based models predict that imbalanced D1:D2 receptor activation causing extremely low or extremely high energy barriers among activity states could lead to the emergence of cognitive, positive, and negative symptoms observed in schizophrenia. Thus, combined experimental and computational approaches hold the promise of allowing a detailed mechanistic understanding of how DA alters information processing in normal and pathological conditions, thereby potentially providing new routes for the development of pharmacological treatments for schizophrenia.

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

PubMed Central

Parihar, Vipan K; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2013-01-01

Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI. PMID:23807240

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A.; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M.; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS. PMID:29209169

Exploring neural dysfunction in 'clinical high risk' for psychosis: a quantitative review of fMRI studies.

PubMed

Dutt, Anirban; Tseng, Huai-Hsuan; Fonville, Leon; Drakesmith, Mark; Su, Liang; Evans, John; Zammit, Stanley; Jones, Derek; Lewis, Glyn; David, Anthony S

2015-02-01

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations. Copyright © 2014. Published by Elsevier Ltd.