scholarly journals Peripheral BDNF: a candidate biomarker of healthy neural activity during learning is disrupted in schizophrenia

2014 ◽  
Vol 45 (4) ◽  
pp. 841-854 ◽  
Author(s):  
A. J. Skilleter ◽  
C. S. Weickert ◽  
A. Vercammen ◽  
R. Lenroot ◽  
T. W. Weickert

Background.Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia.Method.Twenty-five healthy adults and 17 people with schizophrenia or schizo-affective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA).Results.We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant diagnostic difference.Conclusions.This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.

2019 ◽  
Author(s):  
Arian Ashourvan ◽  
Sérgio Pequito ◽  
Maxwell Bertolero ◽  
Jason Z. Kim ◽  
Danielle S. Bassett ◽  
...  

ABSTRACTA fundamental challenge in neuroscience is to uncover the principles governing complex interactions between the brain and its external environment. Over the past few decades, the development of functional neuroimaging techniques and tools from graph theory, network science, and computational neuroscience have markedly expanded opportunities to study the intrinsic organization of brain activity. However, many current computational models are fundamentally limited by little to no explicit assessment of the brain’s interactions with external stimuli. To address this limitation, we propose a simple scheme that jointly estimates the intrinsic organization of brain activity and extrinsic stimuli. Specifically, we adopt a linear dynamical model (intrinsic activity) under unknown exogenous inputs (e.g., sensory stimuli), and jointly estimate the model parameters and exogenous inputs. First, we demonstrate the utility of this scheme by accurately estimating unknown external stimuli in a synthetic example. Next, we examine brain activity at rest and task for 99 subjects from the Human Connectome Project, and find significant task-related changes in the identified system, and task-related increases in the estimated external inputs showing high similarity to known task regressors. Finally, through detailed examination of fluctuations in the spatial distribution of the oscillatory modes of the estimated system during the resting state, we find an apparent non-stationarity in the profile of modes that span several brain regions including the visual and the dorsal attention systems. The results suggest that these brain structures display a time-varying relationship, or alternatively, receive non-stationary exogenous inputs that can lead to apparent system non-stationarities. Together, our embodied model of brain activity provides an avenue to gain deeper insight into the relationship between cortical functional dynamics and their drivers.


2018 ◽  
Vol 2 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Taylor Bolt ◽  
Michael L. Anderson ◽  
Lucina Q. Uddin

Contemporary functional neuroimaging research has increasingly focused on characterization of intrinsic or “spontaneous” brain activity. Analysis of intrinsic activity is often contrasted with analysis of task-evoked activity that has traditionally been the focus of cognitive neuroscience. But does this evoked/intrinsic dichotomy adequately characterize human brain function? Based on empirical data demonstrating a close functional interdependence between intrinsic and task-evoked activity, we argue that the dichotomy between intrinsic and task-evoked activity as unobserved contributions to brain activity is artificial. We present an alternative picture of brain function in which the brain’s spatiotemporal dynamics do not consist of separable intrinsic and task-evoked components, but reflect the enaction of a system of mutual constraints to move the brain into and out of task-appropriate functional configurations. According to this alternative picture, cognitive neuroscientists are tasked with describing both the temporal trajectory of brain activity patterns across time, and the modulation of this trajectory by task states, without separating this process into intrinsic and task-evoked components. We argue that this alternative picture of brain function is best captured in a novel explanatory framework called enabling constraint. Overall, these insights call for a reconceptualization of functional brain activity, and should drive future methodological and empirical efforts.


2010 ◽  
Vol 24 (2) ◽  
pp. 76-82 ◽  
Author(s):  
Martin M. Monti ◽  
Adrian M. Owen

Recent evidence has suggested that functional neuroimaging may play a crucial role in assessing residual cognition and awareness in brain injury survivors. In particular, brain insults that compromise the patient’s ability to produce motor output may render standard clinical testing ineffective. Indeed, if patients were aware but unable to signal so via motor behavior, they would be impossible to distinguish, at the bedside, from vegetative patients. Considering the alarming rate with which minimally conscious patients are misdiagnosed as vegetative, and the severe medical, legal, and ethical implications of such decisions, novel tools are urgently required to complement current clinical-assessment protocols. Functional neuroimaging may be particularly suited to this aim by providing a window on brain function without requiring patients to produce any motor output. Specifically, the possibility of detecting signs of willful behavior by directly observing brain activity (i.e., “brain behavior”), rather than motoric output, allows this approach to reach beyond what is observable at the bedside with standard clinical assessments. In addition, several neuroimaging studies have already highlighted neuroimaging protocols that can distinguish automatic brain responses from willful brain activity, making it possible to employ willful brain activations as an index of awareness. Certainly, neuroimaging in patient populations faces some theoretical and experimental difficulties, but willful, task-dependent, brain activation may be the only way to discriminate the conscious, but immobile, patient from the unconscious one.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gonzalo Rivera-Lillo ◽  
Emmanuel A. Stamatakis ◽  
Tristan A. Bekinschtein ◽  
David K. Menon ◽  
Srivas Chennu

AbstractThe overt or covert ability to follow commands in patients with disorders of consciousness is considered a sign of awareness and has recently been defined as cortically mediated behaviour. Despite its clinical relevance, the brain signatures of the perceptual processing supporting command following have been elusive. This multimodal study investigates the temporal spectral pattern of electrical brain activity to identify features that differentiated healthy controls from patients both able and unable to follow commands. We combined evidence from behavioural assessment, functional neuroimaging during mental imagery and high-density electroencephalography collected during auditory prediction, from 21 patients and 10 controls. We used a penalised regression model to identify command following using features from electroencephalography. We identified seven well-defined spatiotemporal signatures in the delta, theta and alpha bands that together contribute to identify DoC subjects with and without the ability to follow command, and further distinguished these groups of patients from controls. A fine-grained analysis of these seven signatures enabled us to determine that increased delta modulation at the frontal sensors was the main feature in command following patients. In contrast, higher frequency theta and alpha modulations differentiated controls from both groups of patients. Our findings highlight a key role of spatiotemporally specific delta modulation in supporting cortically mediated behaviour including the ability to follow command. However, patients able to follow commands nevertheless have marked differences in brain activity in comparison with healthy volunteers.


PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0176610 ◽  
Author(s):  
Min Sheng ◽  
Peiying Liu ◽  
Deng Mao ◽  
Yulin Ge ◽  
Hanzhang Lu

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jizheng Zhao ◽  
Dardo Tomasi ◽  
Corinde E. Wiers ◽  
Ehsan Shokri-Kojori ◽  
Şükrü B. Demiral ◽  
...  

Negative urgency (NU) and positive urgency (PU) are implicated in several high-risk behaviors, such as eating disorders, substance use disorders, and nonsuicidal self-injury behavior. The current study aimed to explore the possible link between trait of urgency and brain activity at rest. We assessed the amplitude of low-frequency fluctuations (ALFF) of the resting-state functional magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate, and posterior cingulate cortex/precuneus. In addition, trait urgency measures showed significant correlations with the functional connectivity of the posterior cingulate cortex/precuneus seed with the thalamus and midbrain region. These findings suggest an association between intrinsic brain activity and impulsive behaviors in healthy humans.


2021 ◽  
pp. 1-22
Author(s):  
Jenny R. Rieck ◽  
Giulia Baracchini ◽  
Cheryl L. Grady

Cognitive control involves the flexible allocation of mental resources during goal-directed behavior and comprises three correlated but distinct domains—inhibition, shifting, and working memory. The work of Don Stuss and others has demonstrated that frontal and parietal cortices are crucial to cognitive control, particularly in normal aging, which is characterized by reduced control mechanisms. However, the structure–function relationships specific to each domain and subsequent impact on performance are not well understood. In the current study, we examined both age and individual differences in functional activity associated with core domains of cognitive control in relation to fronto-parietal structure and task performance. Participants ( N = 140, aged 20–86 years) completed three fMRI tasks: go/no-go (inhibition), task switching (shifting), and n-back (working memory), in addition to structural and diffusion imaging. All three tasks engaged a common set of fronto-parietal regions; however, the contributions of age, brain structure, and task performance to functional activity were unique to each domain. Aging was associated with differences in functional activity for all tasks, largely in regions outside common fronto-parietal control regions. Shifting and inhibition showed greater contributions of structure to overall decreases in brain activity, suggesting that more intact fronto-parietal structure may serve as a scaffold for efficient functional response. Working memory showed no contribution of structure to functional activity but had strong effects of age and task performance. Together, these results provide a comprehensive and novel examination of the joint contributions of aging, performance, and brain structure to functional activity across multiple domains of cognitive control.


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