Fear memories in visual cortex: inter-individual differences related to reflex physiology and genetic variants

AbstractObjectivesThe underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain.MethodsIn total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test.ResultsNo significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia).ConclusionsThe selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments.

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The interplay of genotype and environment in the development of fear and anxiety

e-Neuroforum ◽

10.1007/s13295-013-0045-1 ◽

2013 ◽

Vol 19 (3) ◽

Author(s):

N. Sachser ◽

K.-P. Lesch

Keyword(s):

Individual Differences ◽

Environmental Factors ◽

Anxiety Disorders ◽

Candidate Gene ◽

Early Development ◽

Genetic Variants ◽

External Influences ◽

Postnatal Environment ◽

Fear And Anxiety

AbstractIndividual differences in fear, anxiety, and the etiology of anxiety disorders develop during ontogeny. They are due to both genetic and environmental factors. With regard to the role of the environment, the organism is most susceptible to external influences during early development. Accordingly, stressors that impinge on the maternal organism during pregnancy evoke high levels of anxiety in the offspring later in life, as does an adverse early postnatal environment. However, anxiety-related circuits in the central nervous system retain their plasticity in adulthood, i.e., levels of anxiety can also be modified by experience across the entire successive lifespan. Notably, the effects of external stressors on the individual’s level of anxiety are modulated by genotype. Such genotype-by-environment interactions are particularly well studied in relation to genetic variants that modulate the function of the serotonin transporter. Thus, this review focuses on this candidate gene to elucidate the interplay of genotype and environment in the development of fear and anxiety.

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Associations Between Variants Near a Monoaminergic Pathways Gene (PHOX2B) and Amygdala Reactivity: A Genome-Wide Functional Imaging Study

Twin Research and Human Genetics ◽

10.1017/thg.2012.5 ◽

2012 ◽

Vol 15 (3) ◽

pp. 273-285 ◽

Cited By ~ 18

Author(s):

Olga Therese Ousdal ◽

Andrew Anand Brown ◽

Jimmy Jensen ◽

Per H. Nakstad ◽

Ingrid Melle ◽

...

Keyword(s):

Individual Differences ◽

Signaling Pathways ◽

Functional Imaging ◽

Genetic Variants ◽

Regulatory Region ◽

Phox2b Gene ◽

Genome Wide ◽

A Genome ◽

Genome Wide Data ◽

Amygdala Activity

As the amygdala is part of the phylogenetic old brain, and its anatomical and functional properties are conserved across species, it is reasonable to assume genetic influence on its activity. A large corpus of candidate gene studies indicate that individual differences in amygdala activity may be caused by genetic variants within monoaminergic signaling pathways such as dopamine, serotonin, and norepinephrine. However, to our knowledge, the use of genome-wide data to discover genetic variants underlying individual differences in adult amygdala activity is novel. In the present study, the combination of genome-wide data and functional imaging phenotypes from an emotional faces task yielded a significant association between rs10014254 and the amygdala using a region of interest approach. This single nucleotide polymorphism is located in a regulatory region upstream of the Paired-like homeobox 2b (PHOX2B) gene; therefore it could affect the expression of this gene. PHOX2B regulates the expression of enzymes necessary for the synthesis of several monoamines and is essential for the development of the autonomic nervous system. However, an attempt to replicate the finding in an independent sample from North America did not succeed. The synthesis of functional magnetic resonance imaging (fMRI) and genome-wide data takes a hypothesis-free approach as to which genetic variants are of interest. Therefore, we believe that an undirected finding within such a plausible region is of interest, and that our results add further support to the hypothesis that monoaminergic signaling pathways play a central role in regulating amygdala activity.

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Integrating pharmacogenomics panel testing for supportive care medications in patients with solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e24114 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e24114-e24114

Author(s):

Adrijana Kekic ◽

Mahesh Seetharam ◽

Parminder Singh ◽

Katie Kunze ◽

Michael A Golafshar ◽

...

Keyword(s):

Individual Differences ◽

Supportive Care ◽

Solid Tumors ◽

Solid Tumor ◽

Genetic Variants ◽

Medication Management ◽

Drug Effects ◽

Dose Selection ◽

Pain Medications ◽

Increased Risk

e24114 Background: Pharmacogenomics (PGx) testing is used increasingly in cancer supportive care for drug and dose selection, and side effects prediction with antidepressants, antiemetics, and pain medications. Genetic variants in genes that encode for drug metabolizing enzymes (CYPs), transporters (SLC6A4) and drug receptors (HTR2A, OPRM1, etc) are well known for these medications. They contribute to inter-individual differences in medication safety and efficacy. We report on their frequency and effect on supportive care drugs in patients with solid tumors. Methods: Between 06/06/19 and 12/18/19, solid tumor cancer patients at Mayo Clinic Arizona were enrolled in a PGx prospective study. They were genotyped using a multi-gene panel, OneOme RightMed. The panel assessed 27 genes, including CYP2C9, CYP2C19, CYP2D6, CYP3A4, COMT, OPRM1, GRIK4, HTR2A, SLC6A4, associated with pain medications, antidepressants, and antiemetics. PGx pharmacist provided medication recommendations and dose adjustments based on PGx test results and concurrent medications. Results: 200 patients were swabbed and 196 patients were genotyped. The results were available within 5 days. All patients were also assessed for pheno-conversion (drug-drug-gene interactions) by a pharmacist. Recommendations were made based on predicted phenotype. Various solid tumor types were represented, including prostate (19.9%), colorectal (17.9%), melanoma (14.8%), and others (47.4%). Median age was 65 with 59.2% patients being male and 40.85% female. All had at least one actionable polymorphism related to these medications. The most significant findings were related to CYP2C19 and CYP2D6 genes. Of 196 patients, a total of 132 (67.3%) had other than normal CYP2D6 metabolizer phenotype and 112 (57.1%) had other than normal CYP2C19 metabolizer phenotype. Based on these genotypes, alternatives to pain medications were recommended for 37 patients, to ondansetron in 9 patients, and to anti-depressants in 51 patients. Conclusions: Genetic variants were commonly found that affect supportive care medications used in oncology practice and contribute to inter-individual differences associated with increased risk of adverse drug effects and reduced efficacy. PGx guided recommendation may help physicians in individualizing medication treatment outcomes for patients with different cancer types and with polypharmacy. PGx trained pharmacist can serve as a valuable asset in optimizing personalized medication management.

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Cortical suppression in human primary visual cortex predicts individual differences in illusory tilt perception

Journal of Vision ◽

10.1167/18.11.3 ◽

2018 ◽

Vol 18 (11) ◽

pp. 3 ◽

Cited By ~ 1

Author(s):

Kiley J. Seymour ◽

Timo Stein ◽

Colin W. G. Clifford ◽

Philipp Sterzer

Keyword(s):

Visual Cortex ◽

Individual Differences ◽

Primary Visual Cortex

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Neural Dissociation of Number from Letter Recognition and Its Relationship to Parietal Numerical Processing

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00085 ◽

2012 ◽

Vol 24 (1) ◽

pp. 39-50 ◽

Cited By ~ 56

Author(s):

Joonkoo Park ◽

Andrew Hebrank ◽

Thad A. Polk ◽

Denise C. Park

Keyword(s):

Visual Cortex ◽

Individual Differences ◽

Parietal Cortex ◽

Visual Recognition ◽

Higher Order ◽

Letter Recognition ◽

Numerical Processing ◽

Double Dissociation ◽

Neural Organization ◽

Number Recognition

The visual recognition of letters dissociates from the recognition of numbers at both the behavioral and neural level. In this article, using fMRI, we investigate whether the visual recognition of numbers dissociates from letters, thereby establishing a double dissociation. In Experiment 1, participants viewed strings of consonants and Arabic numerals. We found that letters activated the left midfusiform and inferior temporal gyri more than numbers, replicating previous studies, whereas numbers activated a right lateral occipital area more than letters at the group level. Because the distinction between letters and numbers is culturally defined and relatively arbitrary, this double dissociation provides some of the strongest evidence to date that a neural dissociation can emerge as a result of experience. We then investigated a potential source of the observed neural dissociation. Specifically, we tested the hypothesis that lateralization of visual number recognition depends on lateralization of higher-order numerical processing. In Experiment 2, the same participants performed addition, subtraction, and counting on arrays of nonsymbolic stimuli varying in numerosity, which produced neural activity in and around the intraparietal sulcus, a region associated with higher-order numerical processing. We found that individual differences in the lateralization of number activity in visual cortex could be explained by individual differences in the lateralization of numerical processing in parietal cortex, suggesting a functional relationship between the two regions. Together, these results demonstrate a neural double dissociation between letter and number recognition and suggest that higher-level numerical processing in parietal cortex may influence the neural organization of number processing in visual cortex.

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Common Genetic Variants in FOXP2 Are Not Associated with Individual Differences in Language Development

PLoS ONE ◽

10.1371/journal.pone.0152576 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0152576 ◽

Cited By ~ 11

Author(s):

Kathryn L. Mueller ◽

Jeffrey C. Murray ◽

Jacob J. Michaelson ◽

Morten H. Christiansen ◽

Sheena Reilly ◽

...

Keyword(s):

Individual Differences ◽

Language Development ◽

Genetic Variants ◽

Common Genetic Variants

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Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic

International Journal of Molecular Sciences ◽

10.3390/ijms22179489 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9489

Author(s):

Jin Kim ◽

Ji Young Lee ◽

Han Gil Kim ◽

Min Woo Kwak ◽

Tae Hyun Kang

Keyword(s):

Signal Transduction ◽

Endothelial Cells ◽

Individual Differences ◽

Genetic Variants ◽

Promoter Region ◽

Control Point ◽

Protective Function ◽

Effector Functions ◽

Antibody Therapeutics ◽

Antibody Function

The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc–FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.

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Individual differences in reading comprehension and off-task thought relate to perceptually-coupled and decoupled cognition

10.1101/387035 ◽

2018 ◽

Author(s):

Meichao Zhang ◽

Nicola Savill ◽

Daniel S. Margulies ◽

Jonathan Smallwood ◽

Elizabeth Jefferies

Keyword(s):

Reading Comprehension ◽

Visual Cortex ◽

Individual Differences ◽

Task Performance ◽

Default Mode Network ◽

Expository Text ◽

External Input ◽

Middle Temporal Gyrus ◽

Middle Temporal ◽

Intrinsic Connectivity

AbstractAlthough the default mode network (DMN) is associated with off-task states, recent evidence shows it can support tasks. This raises the question of how DMN activity can be both beneficial and detrimental to task performance. The decoupling hypothesis proposes that these opposing states occur because DMN supports modes of cognition driven by external input, as well as retrieval states unrelated to input. To test this account, we capitalised on the fact that during reading, regions in DMN are thought to represent the meaning of words through their coupling with visual cortex; the absence of visual coupling should occur when the attention drifts off from the text. We examined individual differences in reading comprehension and off-task thought while participants read an expository text in the laboratory, and related variation in these measures to (i) the neural response during reading in the scanner (Experiment 1), and (ii) patterns of intrinsic connectivity measured in the absence of a task (Experiment 2). The responsiveness of a region of DMN in middle temporal gyrus (MTG) to orthographic inputs during reading predicted good comprehension, while intrinsic decoupling of the same site from visual cortex at rest predicted more frequent off-task thought. In addition, good comprehension was associated with greater intrinsic connectivity between MTG and medial prefrontal regions also within DMN, demonstrating that DMN coupling can support task performance, not only off-task states. These findings indicate that the opposing roles of DMN in cognition reflect its capacity to support both perceptually-coupled and decoupled cognition.

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Task-Related Modulation of Visual Cortex

Journal of Neurophysiology ◽

10.1152/jn.2000.83.6.3525 ◽

2000 ◽

Vol 83 (6) ◽

pp. 3525-3536 ◽

Cited By ~ 92

Author(s):

Alexander C. Huk ◽

David J. Heeger

Keyword(s):

Visual Cortex ◽

Individual Differences ◽

Task Performance ◽

Discrimination Task ◽

Threshold Level ◽

Cortical Activity ◽

Repeated Measurements ◽

Visual Areas ◽

Speed Discrimination ◽

Contrast Discrimination

We performed a series of experiments to quantify the effects of task performance on cortical activity in early visual areas. Functional magnetic resonance imaging (fMRI) was used to measure cortical activity in several cortical visual areas including primary visual cortex (V1) and the MT complex (MT+) as subjects performed a variety of threshold-level visual psychophysical tasks. Performing speed, direction, and contrast discrimination tasks produced strong modulations of cortical activity. For example, one experiment tested for selective modulations of MT+ activity as subjects alternated between performing contrast and speed discrimination tasks. MT+ responses modulated in phase with the periods of time during which subjects performed the speed discrimination task; that is, MT+ activity was higher during speed discrimination than during contrast discrimination. Task-related modulations were consistent across repeated measurements in each subject; however, significant individual differences were observed between subjects. Together, the results suggest 1) that specific changes in the cognitive/behavioral state of a subject can exert selective and reliable modulations of cortical activity in early visual cortex, even in V1; 2) that there are significant individual differences in these modulations; and 3) that visual areas and pathways that are highly sensitive to small changes in a given stimulus feature (such as contrast or speed) are selectively modulated during discrimination judgments on that feature. Increasing the gain of the relevant neuronal signals in this way may improve their signal-to-noise to help optimize task performance.

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