Distinct Effects of D9-tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
P. Fusar-Poli

Aims:Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.Method:Fifteen healthy English-native right-handed men were studied on three separate occasions using an event-related fMRI paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10mg of D-9-THC, 600mg of CBD, or a placebo, in a double-blind, randomised, placebo controlled design. Electrodermal activity (Skin Conductance Response, SCR) and objective and subjective ratings of anxiety were recorded durign the scanning.Results:D-9THC increased anxiety, as well as levels of intoxication, sedation and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of D-9THC but decreased following administration of CBD. CBD attenuated the BOLD signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and posterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. D-9-THC mainly modulated activation in frontal and parietal areas.Conclusions:D-9-THC and CBD had clearly distinct effects on the neural, eclectrodermal and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of D-9-THC may be related to effects in other brain regions.

2021 ◽  
Vol 15 ◽  
Author(s):  
Zoe R. Guttman ◽  
Dara G. Ghahremani ◽  
Jean-Baptiste Pochon ◽  
Andy C. Dean ◽  
Edythe D. London

Decision-making strategies shift during normal aging and can profoundly affect wellbeing. Although overweighing losses compared to gains, termed “loss aversion,” plays an important role in choice selection, the age trajectory of this effect and how it may be influenced by associated changes in brain structure remain unclear. We therefore investigated the relationship between age and loss aversion, and tested for its mediation by cortical thinning in brain regions that are susceptible to age-related declines and are implicated in loss aversion — the insular, orbitofrontal, and anterior and posterior cingulate cortices. Healthy participants (n = 106, 17–54 years) performed the Loss Aversion Task. A subgroup (n = 78) provided structural magnetic resonance imaging scans. Loss aversion followed a curvilinear trajectory, declining in young adulthood and increasing in middle-age, and thinning of the posterior cingulate cortex mediated this trajectory. The findings suggest that beyond a threshold in middle adulthood, atrophy of the posterior cingulate cortex influences loss aversion.


2019 ◽  
Vol 16 (11) ◽  
pp. 1055-1062
Author(s):  
Xi Sun ◽  
Binbin Nie ◽  
Shujun Zhao ◽  
Qian Chen ◽  
Panlong Li ◽  
...  

Background: Visuospatial dysfunction is one predominant symptom in many atypical Alzheimer’s disease (AD) patients, however, until now its neural correlates still remain unclear. For the accumulation of intracellular hyperphosphorylated tau proteins is a major pathogenic factor in neurodegeneration of AD, the distributional pattern of tau could highlight the affected brain regions associated with specific cognitive deficits. Objective: We investigated the brain regions particularly affected by tau accumulation in patients with visuospatial dysfunction to explore its neural correlates. Methods: Using 18F-AV-1451 tau positron emission tomography (PET), voxel-wise two-sample t-tests were performed between AD patients with obvious visuospatial dysfunction (VS-AD) and cognitively normal subjects, AD patients with little-to-no visuospatial dysfunction (non VS-AD) and cognitively normal subjects, respectively. Results: Results showed increased tau accumulations mainly located in occipitoparietal cortex, posterior cingulate cortex, precuneus, inferior and medial temporal cortex in VS-AD patients, while increased tau accumulations mainly occurred in the inferior and medial temporal cortex in non VS-AD patients. Conclusion: These findings suggested that occipitoparietal cortex, posterior cingulate cortex and precuneus, which were particularly affected by increased tau accumulation in VS-AD patients, may associate with visuospatial dysfunction of AD.


2020 ◽  
pp. 1-9
Author(s):  
Ian S. Penton-Voak ◽  
Sally Adams ◽  
Katherine S. Button ◽  
Meg Fluharty ◽  
Michael Dalili ◽  
...  

Abstract Background There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need. Methods We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up. Results In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups. Conclusions CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
S. Borgwardt ◽  
P. Allen ◽  
S. Bhattacharyya ◽  
P. Fusar-Poli ◽  
J.A. Crippa ◽  
...  

Background:This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.Methods:Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.Results:Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.Conclusions:These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.


2015 ◽  
Vol 112 (29) ◽  
pp. E3940-E3949 ◽  
Author(s):  
Farshad A. Mansouri ◽  
Mark J. Buckley ◽  
Majid Mahboubi ◽  
Keiji Tanaka

Frontal pole cortex (FPC) and posterior cingulate cortex (PCC) have close neuroanatomical connections, and imaging studies have shown coactivation or codeactivation of these brain regions during performance of certain tasks. However, they are among the least well-understood regions of the primate brain. One reason for this is that the consequences of selective bilateral lesions to either structure have not previously been studied in any primate species. We studied the effects of circumscribed bilateral lesions to FPC or PCC on monkeys’ ability to perform an analog of Wisconsin Card Sorting Test (WCST) and related tasks. In contrast to lesions in other prefrontal regions, neither posttraining FPC nor PCC lesions impaired animals’ abilities to follow the rule switches that frequently occurred within the WCST task. However, FPC lesions were not without effect, because they augmented the ability of animals to adjust cognitive control after experiencing high levels of conflict (whereas PCC lesions did not have any effect). In addition, FPC-lesioned monkeys were more successful than controls or PCC-lesioned animals at remembering the relevant rule across experimentally imposed distractions involving either an intervening secondary task or a surprising delivery of free reward. Although prefrontal cortex posterior to FPC is specialized for mediating efficient goal-directed behavior to maximally exploit reward opportunities from ongoing tasks, our data led us to suggest that FPC is, instead, specialized for disengaging executive control from the current task and redistributing it to novel sources of reward to explore new opportunities/goals.


2018 ◽  
Author(s):  
Vaidehi S. Natu ◽  
Jui-Jui Lin ◽  
Alexis Burks ◽  
Akshay Arora ◽  
Michael D. Rugg ◽  
...  

Neuroimaging experiments implicate the posterior cingulate cortex (PCC) in episodic memory processing, making it a potential target for responsive neuromodulation strategies outside of the hippocampal network. However, causal evidence for the role PCC plays in memory encoding is lacking. In patients undergoing seizure mapping, we investigated functional properties of the PCC using deep brain stimulation (DBS) and stereotactic electroencephalography (stereo EEG). These techniques allow precise targeting of deep cortical structures including the PCC, and simultaneous acquisition of oscillatory recordings from neighboring regions such as the hippocampus. We used a free recall experiment in which PCC was stimulated during item encoding period of half of the study lists, while no stimulation was applied during encoding period of the remaining lists. We evaluated if stimulation affected memory and/or modulated hippocampal activity. Results revealed four main findings. (i) Stimulation during encoding impaired memory for early items on the study lists. (ii) Stimulation increased hippocampal gamma band power. (iii) Stimulation-induced gamma power predicted memory impairment. (iv) Functional connectivity between the hippocampus and PCC predicted the degree of stimulation effect on memory. Our findings offer the first causal evidence implicating the PCC in episodic memory encoding. Importantly, results highlight that stimulation targeted outside of the temporal lobe can modulate hippocampal activity with implications on behavior. Furthermore, a-priori measures of connectivity between brain regions within a functional network can be informative in predicting behavioral effects of stimulation. Our findings have significant implications for developing therapies to treat diseases of memory loss and cognitive impairment using DBS.


2020 ◽  
Author(s):  
Laurie Bayet ◽  
Katherine L. Perdue ◽  
Hannah F. Behrendt ◽  
John E. Richards ◽  
Alissa Westerlund ◽  
...  

AbstractFacial emotion processing is an important social skill that develops throughout infancy and early childhood. Here we investigate the neural underpinnings of the ability to process facial emotion across changes in facial identity in cross-sectional groups of 5- and 7-month-old infants. We simultaneously measured neural metabolic, behavioral, and autonomic responses to happy, fearful, and angry faces of different female models using functional near-infrared spectroscopy (fNIRS), eye-tracking, and heart rate measures. We observed significant neural activation to these facial emotions in a distributed set of frontal and temporal brain regions, and longer looking to the mouth region of angry faces compared to happy and fearful faces. No differences in looking behavior or neural activations were observed between 5- and 7-month-olds, although several exploratory, age-independent associations between neural activations and looking behavior were noted. Overall, these findings suggest more developmental stability than previously thought in responses to emotional facial expressions of varying identities between 5- and 7-months of age.


2017 ◽  
Author(s):  
Henrique M. Fernandes ◽  
Joana Cabral ◽  
Tim J. Van Hartevelt ◽  
Louis-David Lord ◽  
Carsten Gleesborg ◽  
...  

AbstractBipolar disorder (BD) has been linked to disrupted structural and functional connectivity between prefrontal networks and limbic brain regions. Studies of patients with pediatric bipolar disorder (PBD) can help elucidate the developmental origins of altered structural connectivity underlying BD and provide novel insights into the aetiology of BD. Here we compare the network properties of whole-brain structural connectomes of PBD patients with psychosis and euthymic matched healthy controls. Our results show widespread changes in the structural connectivity of PBD patients in both cortical and subcortical networks, notably affecting the orbitofrontal cortex, frontal gyrus, amygdala, hippocampus and basal ganglia. Graph theoretical analysis revealed that PBD connectomes have fewer hubs, weaker rich club organization, different modular fingerprint and inter-modular communication, compared to healthy participants. The relationship between network features and neurocognitive and psychotic scores was also assessed. Patients’ IQ and psychotic symptoms significantly correlated with the local efficiency of the orbitofrontal cortex. Our findings reveal that PBD is associated with significant widespread changes in structural network topology, thus strengthening the hypothesis of a reduced capacity for integrative processing of information across brain regions. Localised network changes involve core regions for emotional processing and regulation, as well as memory and executive function, some of which correlate with neurocognitive faculties and symptoms. Together, our findings provide the first comprehensive characterisation of the alterations in local and global structural brain connectivity and network topology, which may contribute to the deficits in cognition and emotion processing and regulation found in PBD.


2019 ◽  
Author(s):  
Roman Trepp ◽  
Raphaela Muri ◽  
Lenka Bosanska ◽  
Stephanie Abgottspon ◽  
Michel Hochuli ◽  
...  

Abstract Background The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood Phe levels in adults outside pregnancy is discussed controversially. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional and neurometabolic parameters of the brain. Methods The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week phenylalanine (Phe) load on cognition and cerebral parameters in 30 adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, non-inferiority trial. The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance in adults with early-treated PKU. As secondary objective, the PICO Study will elucidate cerebral and neurometabolic mechanisms, which accompany changes in Phe concentration using advanced neuroimaging methods. In addition to the intervention study, cognition, structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls, who will be comparable with regard to age, gender and education level. Advanced MR-techniques will be used to investigate intensity of neural activation during the working memory task (fMRI), strength of functional connectivity between brain regions related to performance in working memory (rsfMRI), white matter integrity (DTI), cerebral blood flow (ASL) and brain Phe concentrations (MRS). Discussion Using a combination of neuropsychological and neuroimaging data, the PICO study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed.


2011 ◽  
Vol 41 (11) ◽  
pp. 2253-2264 ◽  
Author(s):  
L. R. Demenescu ◽  
R. Renken ◽  
R. Kortekaas ◽  
M.-J. van Tol ◽  
J. B. C. Marsman ◽  
...  

BackgroundDepression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients.MethodAn event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.ResultsFacial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.ConclusionsWe suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.


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