Behavioral and emotional dysregulation trajectories marked by prefrontal–amygdala function in symptomatic youth

BackgroundNeuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging.MethodA total of 61 youth (9–17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy.ResultsThere were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n = 22) and low and decreasing (LowD; n = 39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p < 0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's < 0.001, corrected).ConclusionsPatterns of function in lateral prefrontal cortical–amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

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The Role of Primate Prefrontal Cortex in Bias and Shift Between Visual Dimensions

Cerebral Cortex ◽

10.1093/cercor/bhz072 ◽

2019 ◽

Vol 30 (1) ◽

pp. 85-99 ◽

Cited By ~ 5

Author(s):

Farshad A Mansouri ◽

Mark J Buckley ◽

Daniel J Fehring ◽

Keiji Tanaka

Keyword(s):

Prefrontal Cortex ◽

Anterior Cingulate ◽

Top Down ◽

Attentional Processes ◽

Prefrontal Cortical ◽

Frontopolar Cortex ◽

Dorsolateral Prefrontal ◽

Cortical Regions ◽

Visual Cortical ◽

Bilateral Lesions

Abstract Imaging and neural activity recording studies have shown activation in the primate prefrontal cortex when shifting attention between visual dimensions is necessary to achieve goals. A fundamental unanswered question is whether representations of these dimensions emerge from top-down attentional processes mediated by prefrontal regions or from bottom-up processes within visual cortical regions. We hypothesized a causative link between prefrontal cortical regions and dimension-based behavior. In large cohorts of humans and macaque monkeys, performing the same attention shifting task, we found that both species successfully shifted between visual dimensions, but both species also showed a significant behavioral advantage/bias to a particular dimension; however, these biases were in opposite directions in humans (bias to color) versus monkeys (bias to shape). Monkeys’ bias remained after selective bilateral lesions within the anterior cingulate cortex (ACC), frontopolar cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), or superior, lateral prefrontal cortex. However, lesions within certain regions (ACC, DLPFC, or OFC) impaired monkeys’ ability to shift between these dimensions. We conclude that goal-directed processing of a particular dimension for the executive control of behavior depends on the integrity of prefrontal cortex; however, representation of competing dimensions and bias toward them does not depend on top-down prefrontal-mediated processes.

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Regional cerebral perfusion correlates with anxiety in neuropsychiatric SLE: evidence for a mechanism distinct from depression

Lupus ◽

10.1177/0961203319887793 ◽

2019 ◽

Vol 28 (14) ◽

pp. 1678-1689 ◽

Cited By ~ 2

Author(s):

E Papadaki ◽

E Kavroulakis ◽

G Bertsias ◽

A Fanouriakis ◽

D Karageorgou ◽

...

Keyword(s):

Blood Flow ◽

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Cerebral Blood Volume ◽

Ventromedial Prefrontal Cortex ◽

Anterior Cingulate ◽

Anxiety And Depression ◽

Healthy Controls ◽

Dorsolateral Prefrontal ◽

Depression Symptomatology

The study examined the hypothesis that hypoperfusion in brain areas known to be involved in emotional disturbances in primary psychiatric disorders is also linked to emotional difficulties in systemic lupus erythematosus (SLE) and that these are not secondary to the physical and social burden incurred by the disease. Nineteen SLE patients without overt neuropsychiatric manifestations (non-NPSLE), 31 NPSLE patients, and 23 healthy controls were examined. Dynamic susceptibility contrast MRI was used and cerebral blood flow and cerebral blood volume values were estimated in six manually selected regions of interest of brain regions suspected to play a role in anxiety and depression (dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate cortex, hippocampi, caudate nuclei and putamen). NPSLE patients reported high rates of anxiety and depression symptomatology. Significantly reduced cerebral blood flow and cerebral blood volume values were detected in the NPSLE group compared to healthy controls in the dorsolateral prefrontal cortex and ventromedial prefrontal cortex, bilaterally. Within the NPSLE group, anxiety symptomatology was significantly associated with lower perfusion in frontostriatal regions and in the right anterior cingulate gyrus. Importantly, the latter associations appeared to be specific to anxiety symptoms, as they persisted after controlling for depression symptomatology and independent of the presence of visible lesions on conventional MRI. In conclusion, hypoperfusion in specific limbic and frontostriatal regions is associated with more severe anxiety symptoms in the context of widespread haemodynamic disturbances in NPSLE.

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Leukocyte and brain DDR1 hypermethylation is altered in psychosis and is correlated with stress and inflammatory markers

Epigenomics ◽

10.2217/epi-2019-0191 ◽

2020 ◽

Vol 12 (3) ◽

pp. 251-265 ◽

Cited By ~ 1

Author(s):

Beatriz Garcia-Ruiz ◽

Lorena Moreno ◽

Gerard Muntané ◽

Vanessa Sánchez-Gistau ◽

Alfonso Gutiérrez-Zotes ◽

...

Keyword(s):

Prefrontal Cortex ◽

Psychological Stress ◽

Inflammatory Markers ◽

Dorsolateral Prefrontal Cortex ◽

Healthy Controls ◽

Blood Neutrophil ◽

Psychological Variables ◽

Cpg Sites ◽

Stress Markers ◽

Dorsolateral Prefrontal

Aim: To investigate DDR1 methylation in blood and brain DNA in psychosis and its relationship with stress markers. Materials & methods: Saliva cortisol, blood neutrophil and lymphocyte counts, leukocyte DNA and psychological variables were collected from 60 patients with nonaffective psychosis and 40 healthy controls (HC). Brain dorsolateral prefrontal cortex DNA from 35 patients with schizophrenia and 34 HC was studied. DDR1 methylation at 43 CpG sites was measured using the MassARRAY EpiTYPER platform. Results: We describe leukocyte DDR1 hypermethylation in patients with psychosis compared with HC; this hypermethylation is associated with psychological stress, neutrophil-to-lymphocyte ratios, and, in the dorsolateral prefrontal cortex, DDR1 methylation correlated with DDR1 isoform expression. Conclusion: We confirmed a relationship between stress and blood and brain DDR1 methylation in psychosis.

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Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

Neuropsychopharmacology ◽

10.1038/s41386-019-0583-5 ◽

2019 ◽

Vol 45 (4) ◽

pp. 694-702 ◽

Cited By ~ 4

Author(s):

Nicholas L. Balderston ◽

Emily M. Beydler ◽

Camille Roberts ◽

Zhi-De Deng ◽

Thomas Radman ◽

...

Keyword(s):

Prefrontal Cortex ◽

Transcranial Magnetic Stimulation ◽

Healthy Subjects ◽

Magnetic Stimulation ◽

Dorsolateral Prefrontal Cortex ◽

Subcortical Structures ◽

Prefrontal Cortical ◽

Dorsolateral Prefrontal ◽

Before And After ◽

The Right

AbstractMuch of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.

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Developmental trajectories of abuse – An hypothesis for the effects of early childhood maltreatment on dorsolateral prefrontal cortical development

Medical Hypotheses ◽

10.1016/j.mehy.2013.09.006 ◽

2013 ◽

Vol 81 (5) ◽

pp. 826-829 ◽

Cited By ~ 7

Author(s):

Caley Burrus

Keyword(s):

Early Childhood ◽

Childhood Maltreatment ◽

Developmental Trajectories ◽

Cortical Development ◽

Prefrontal Cortical ◽

Dorsolateral Prefrontal

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Metabolic abnormality in the right dorsolateral prefrontal cortex in patients with obsessive–compulsive disorder: proton magnetic resonance spectroscopy

Acta Neuropsychiatrica ◽

10.1017/neu.2016.48 ◽

2016 ◽

Vol 29 (3) ◽

pp. 164-169 ◽

Cited By ~ 7

Author(s):

Shin-Eui Park ◽

Nam-Gil Choi ◽

Gwang-Woo Jeong

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Resonance Spectroscopy ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Dorsolateral Prefrontal ◽

The Right

ObjectiveProton magnetic resonance spectroscopy (1H-MRS) was used to evaluate metabolic changes in the dorsolateral prefrontal cortex (DLPFC) in patients with obsessive–compulsive disorder (OCD).MethodsIn total, 14 OCD patients (mean age 28.9±7.2 years) and 14 healthy controls (mean age 32.6±7.1 years) with no history of neurological and psychiatric illness participated in this study. Brain metabolite concentrations were measured from a localised voxel on the right DLPFC using a 3-Tesla 1H-MRS.ResultsThe metabolic concentration of myo-inositol in patients with OCD increased significantly by 52% compared with the healthy controls, whereas glutamine/glutamate was decreased by 11%. However, there were no significant differences in N-acetylaspartate, choline, lactate and lipid between the two groups.ConclusionThese findings would be helpful to understand the pathophysiology of OCD associated with the brain metabolic abnormalities in the right DLPFC.

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Reduced subcortical glutamate/glutamine in adults with autism spectrum disorders: a [1H]MRS study

Translational Psychiatry ◽

10.1038/tp.2013.53 ◽

2013 ◽

Vol 3 (7) ◽

pp. e279-e279 ◽

Cited By ~ 68

Author(s):

J Horder ◽

T Lavender ◽

M A Mendez ◽

R O'Gorman ◽

E Daly ◽

...

Keyword(s):

Prefrontal Cortex ◽

Basal Ganglia ◽

Control Region ◽

Dorsolateral Prefrontal Cortex ◽

Autism Spectrum ◽

Resonance Spectroscopy ◽

Healthy Controls ◽

Glutamatergic Neurotransmission ◽

Broader Phenotype ◽

Dorsolateral Prefrontal

Abstract Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (ASD). However, relatively few studies have directly measured brain glutamate in ASD adults, or related variation in glutamate to clinical phenotype. We therefore set out to investigate brain glutamate levels in adults with an ASD, comparing these to healthy controls and also comparing results between individuals at different points on the spectrum of symptom severity. We recruited 28 adults with ASD and 14 matched healthy controls. Of those with ASD, 15 fulfilled the ‘narrowly’ defined criteria for typical autism, whereas 13 met the ‘broader phenotype’. We measured the concentration of the combined glutamate and glutamine signal (Glx), and other important metabolites, using proton magnetic resonance spectroscopy in two brain regions implicated in ASD—the basal ganglia (including the head of caudate and the anterior putamen) and the dorsolateral prefrontal cortex—as well as in a parietal cortex ‘control’ region. Individuals with ASD had a significant decrease (P<0.001) in concentration of Glx in the basal ganglia, and this was true in both the ‘narrow’ and ‘broader’ phenotype. Also, within the ASD sample, reduced basal ganglia Glx was significantly correlated with increased impairment in social communication (P=0.013). In addition, there was a significant reduction in the concentration of other metabolites such as choline, creatine (Cr) and N-acetylaspartate (NAA) in the basal ganglia. In the dorsolateral prefrontal cortex, Cr and NAA were reduced (P<0.05), although Glx was not. There were no detectable differences in Glx, or any other metabolite, in the parietal lobe control region. There were no significant between-group differences in age, gender, IQ, voxel composition or data quality. In conclusion, individuals across the spectrum of ASD have regionally specific abnormalities in subcortical glutamatergic neurotransmission that are associated with variation in social development.

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Prefrontal cortex activity in people with schizophrenia and control subjects

The British Journal of Psychiatry ◽

10.1192/bjp.172.4.316 ◽

1998 ◽

Vol 172 (4) ◽

pp. 316-323 ◽

Cited By ~ 77

Author(s):

Sean A. Spence ◽

Steven R. Hirsch ◽

David J. Brooks ◽

Paul M. Grasby

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Symptomatic Improvement ◽

Emission Tomography ◽

Cortical Function ◽

Control Subjects ◽

Prefrontal Cortical ◽

Positron Emission ◽

Dorsolateral Prefrontal ◽

And Control

BackgroundHypo-activation of the left dorsolateral prefrontal cortex is inconsistently found in neuroimaging studies of schizophrenia. As the left dorsolateral prefrontal cortex is involved in the generation of action, disordered function in this region may be implicated in schizophrenic symptomatology.MethodWe used H215O positron emission tomography to study dorsolateral prefrontal cortical function in men with schizophrenia (n=13) and male control subjects (n=6) performing joystick movements on two occasions, 4–6 weeks apart. The patients were initially in relapse. To clarify dorsolateral prefrontal cortical function we also scanned another group of control subjects (n=5) performing mouth movements.ResultsThe control subjects performing hand or mouth movements activated the left dorsolateral prefrontal cortex to a maximum when the movements were self-selected. The men with relapsed schizophrenia exhibited left dorsolateral prefrontal cortical hypo-activation, which remitted with symptomatic improvement.ConclusionsHypofrontality in these patients is a dynamic phenomenon across time, possibly related to current symptomatology. The most appropriate question about the presence of hypofrontality in schizophrenia may be when, rather than whether, it will occur.

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