Neurobiological Models Research Articles

Toward neuromarkers for tailored smoking cessation treatments

Neurobiological models of addiction attribute vulnerability to compulsive drug use to dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that (a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and (b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and could pave the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that cannot optimally assess individual differences in the motivational salience of drug-related cues and in the ability to control drug-related decisions, hindering the identification of clinically relevant neuromarkers. Here we show that (a) accounting for neuroaffective reactivity to non-drug-related motivationally relevant stimuli when measuring the attribution of motivational salience to drug-related cues, and (b) assessing brain activity while participants make drug-related decisions with immediate consequences, yield replicable neuromarkers with potential clinical relevance. While we use tobacco use disorder as a model, we also show that the methodological issues highlighted here are relevant to other disorders characterized by maladaptive appetitive behaviors.

From cones to color vision: a neurobiological model that explains the unique hues.

The irreducible unique hues-red, green, blue, and yellow-remain one of the great mysteries of vision science. Attempts to create a physiologically parsimonious model that can predict the spectral locations of the unique hues all rely on at least one post hoc adjustment to produce appropriate loci for unique green and unique red, and struggle to explain the non-linearity of the Blue/Yellow system. We propose a neurobiological color vision model that overcomes these challenges by using physiological cone ratios, cone-opponent normalization to equal-energy white, and a simple adaptation mechanism to produce color-opponent mechanisms that accurately predict the spectral locations and variability of the unique hues.

Dynamical Models in Neuroscience From a Closed-Loop Control Perspective.

Modifying neural activity is a substantial goal in neuroscience that facilitates the understanding of brain functions and the development of medical therapies. Neurobiological models play an essential role, contributing to the understanding of the underlying brain dynamics. In this context, control systems represent a fundamental tool to provide a correct articulation between model stimulus (system inputs) and outcomes (system outputs). However, throughout the literature there is a lack of discussions on neurobiological models, from the formal control perspective. In general, existing control proposals applied to this family of systems, are developed empirically, without theoretical and rigorous framework. Thus, the existing control solutions, present clear and significant limitations. The focus of this work is to survey dynamical neurobiological models that could serve for closed-loop control schemes or for simulation analysis. Consequently, this paper provides a comprehensive guide to discuss and analyze control-oriented neurobiological models. It also provides a potential framework to adequately tackle control problems that could modify the behavior of single neurons or networks. Thus, this study constitutes a key element in the upcoming discussions and studies regarding control methodologies applied to neurobiological systems, to extend the present research and understanding horizon for this field.

Integrative Theoretical Framework of Consciousness: Towards a Higher-Order Theory

The Intelligent Principle of the Universe is a beginningless and endless entity considered a fundamental property of the universe. It is in the energetic intimacy of the Psychosoma, its unquestionable “morphogenetic field” that the cells are aggregated to finally model your future physical body. On the other hand, the mind, seat of Consciousness is, therefore, the non-material brain of Consciousness where all the informational content of the human being is stored, since forever. Undoubtedly, the mind is the psychophysical basis of all mind/brain/body phenomena, that is, the mind allows experiences to be created in an interactive and participatory way. The mind, then, is a subtle form of field, an information-processing agent involving the brain’s physical system. The mental domain, as well as the material, is complementary aspects of the same reality. In fact, the existence of a “body image” has been demonstrated, certainly a “biological organizer” agent, a three-dimensional image of the physical body different from the perceived body that forms the energetic anatomical structures. He is portrayed here as Psychosoma. In fact, we propose an integrative framework of Consciousness, mind and matter based on information, seen as one of the most fundamental entities in nature to describe reality. It is an integrative theoretical framework and a neurobiological model based on an informational field involving various theories such as Shannon’s information theory, quantum holographic theory, communication theory, complexity theory, quantum field theory and other information theories. In addition, we introduce concepts of stochastic electrodynamics, a theory derived from quantum field theory more suitable to explain the mechanisms by which living beings relate to nature in order to create a healthy life and a more lasting and sustainable interrelationship. This approach was described as follows: 1) Basic notions about information theories and stochastic electrodynamics; 2) Conscience: intelligent organizing principle of life; 3) Mind: non-material brain; 4) Psychosoma: organizing model of biological life; 5) Consciousness and information; 6) Action of consciousness on matter; 7) Consciousness and physical body; 8) Consciousness and neuronal connection.

The gradient model of brain organization in decisions involving "empathy for pain".

Influential models of cortical organization propose a close relationship between heteromodal association areas and highly connected hubs in the default mode network. The "gradient model" of cortical organization proposes a close relationship between these areas and highly connected hubs in the default mode network, a set of cortical areas deactivated by demanding tasks. Here, we used a decision-making task and representational similarity analysis with classic "empathy for pain" stimuli to probe the relationship between high-level representations of imminent pain in others and these areas. High-level representations were colocalized with task deactivations or the transitions from activations to deactivations. These loci belonged to 2 groups: those that loaded on the high end of the principal cortical gradient and were associated by meta-analytic decoding with the default mode network, and those that appeared to accompany functional repurposing of somatosensory cortex in the presence of visual stimuli. These findings suggest that task deactivations may set out cortical areas that host high-level representations. We anticipate that an increased understanding of the cortical correlates of high-level representations may improve neurobiological models of social interactions and psychopathology.

Rapid Interactions of Widespread Brain Networks Characterize Semantic Cognition.

Language comprehension requires the rapid retrieval and integration of contextually appropriate concepts ("semantic cognition"). Current neurobiological models of semantic cognition are limited by the spatial and temporal restrictions of single-modality neuroimaging and lesion approaches. This is a major impediment given the rapid sequence of processing steps that have to be coordinated to accurately comprehend language. Through the use of fused functional magnetic resonance imaging and electroencephalography analysis in humans (n = 26 adults; 15 females), we elucidate a temporally and spatially specific neurobiological model for real-time semantic cognition. We find that semantic cognition in the context of language comprehension is supported by trade-offs between widespread neural networks over the course of milliseconds. Incorporation of spatial and temporal characteristics, as well as behavioral measures, provide convergent evidence for the following progression: a hippocampal/anterior temporal phonological semantic retrieval network (peaking at ∼300 ms after the sentence final word); a frontotemporal thematic semantic network (∼400 ms); a hippocampal memory update network (∼500 ms); an inferior frontal semantic syntactic reappraisal network (∼600 ms); and nodes of the default mode network associated with conceptual coherence (∼750 ms). Additionally, in typical adults, mediatory relationships among these networks are significantly predictive of language comprehension ability. These findings provide a conceptual and methodological framework for the examination of speech and language disorders, with additional implications for the characterization of cognitive processes and clinical populations in other cognitive domains.SIGNIFICANCE STATEMENT The present study identifies a real-time neurobiological model of the meaning processes required during language comprehension (i.e., "semantic cognition"). Using a novel application of fused magnetic resonance imaging and electroencephalography in humans, we found that semantic cognition during language comprehension is supported by a rapid progression of widespread neural networks related to meaning, meaning integration, memory, reappraisal, and conceptual cohesion. Relationships among these systems were predictive of individuals' language comprehension efficiency. Our findings are the first to use fused neuroimaging analysis to elucidate language processes. In so doing, this study provides a new conceptual and methodological framework in which to characterize language processes and guide the treatment of speech and language deficits/disorders.

Some theoretical models of addictive disorder are used for behavioral transformation

Existential, neurobiological and cognitive models of addictive behavior are considered as a theoretical basis for transformational therapy of addictive disorders. The NMDA receptor antagonist ketamine, which has neurotrophic, modulatory and psychedelic effects, demonstrates the universal properties of a transforming agent for any of the presented concepts of addictive behavior. Since persistent mental and behavioral changes essentially are psychobiological changes, the substrate that determines the effectiveness of the intervention is synaptic plasticity and neural network remodeling.

RF22 | PMON06 The Contraceptive Synthetic-Progesterone Levonorgestrel (LNG) Significantly Accelerates Fetal Hypothalamic Neuronal Development (Neuroendogenesis) in the Zebrafish (Danio rerio).

Abstract The fetal brain has a known vulnerability to exogenous influences due to its plasticity and high volume of replicating and differentiating cells. It is particularly susceptible to a group of environmental molecules classified as endocrine disrupting chemicals (EDCs). Previous vertebrate studies have provided supportive evidence that steroid mimicking EDCs might stimulate hypothalamic progenitor cell differentiation to neurons (neuroendogenesis). Changing the normal timing of neuroendogenesis could play a role in establishing an alternative developmental timeline leading to disruptions in key endocrine regulated process, like pubertal onset. Levonorgestrel (LNG), a synthetic progestin used in contraceptive pills, has been found at physiologically relevant levels in water sources worldwide. Therefore, we investigated the effect LNG had on neuroendogenesis in zebrafish (Danio rerio), an established comparative neurobiological animal model. Fertilized zebrafish embryos were collected (in-house breeding) and individually placed in 96-well plates. Starting at 3 hours post fertilization (hpf), embryos were exposed to either 5 ng of LNG (previously established physiologically relevant dose), 100ng of estradiol (E2, positive control) or a vehicle control for 5 days (5 dpf); covering the duration of neurogenesis. LNG had no effect on fertilization ratios, hatching or morphology compared to controls. On 5 dpf, larvae were paraffin-processed, slides were serially sectioned at (3-4 um) and prepped for immunohistochemistry (IHC). Brain tissue s were stained with hematoxylin and eosin (H&E) to identify regions of the brain including the hypothalamus and thalamus. Brain sections were also stained for the immunofluorescent (IF) neuronal marker α-HUC and/or estrogen receptor (ER) and imaged on a confocal microscope. The number of total cells, positive stained cells and negative stained cells were counted in the preoptic area (POA), rostral hypothalamus (RH) and thalamus, comparisons were made between groups. Interestingly, LNG significantly (p<0.001) increased the number of positive cells expressing α-HUC in the hypothalamus compared to controls. Similar results were observed in the POA (p< 0.01) and RH (p <0.001) compared to their respective controls. Furthermore, we observed no significant changes in α-HUC expression in the thalamus due to LNG treatment comparted to controls. Our data suggests that LNG selectively targets hypothalamic neuronal development, accelerating neuroendogenesis increasing the number of endocrine-regulating neurons in the brain. This is the first study to show that exposure to low environmentally relevant levels of LNG increases neurons in the hypothalamus, thus, highlighting the possibility that LNG may target the brain to potentiate subsequent health issues later in life. Presentation: No date and time listed

The left inferior frontal gyrus and the resolution of unimodal vs. cross-modal interference in speech production: A transcranial direct current stimulation study

Most neurobiological models of spoken word production propose that multiple lexical candidates are activated in left posterior temporal cortex during word retrieval. Some accounts also propose a role for the left inferior frontal gyrus (LIFG) in selecting the correct word from among these candidates. Evidence for both proposals has come from the picture-word interference (PWI) paradigm, in which participants name pictures (e.g., RABBIT) while ignoring a distractor word. Categorically related distractors (e.g., horse -RABBIT) slow naming latencies compared to unrelated words (e.g., violin -RABBIT), an effect known as semantic interference, whereas congruent distractors (e.g., rabbit -RABBIT) facilitate naming, but the precise conditions in which these effects occur remain a matter of debate. Although the neuroimaging evidence for left temporal cortex engagement in this paradigm is robust, the evidence for LIFG involvement is more equivocal, particularly for semantic interference. A key factor distinguishing LIFG involvement in neuroimaging studies is distractor modality , i.e., activity is more consistently reported for auditory distractors. We therefore applied online anodal transcranial Direct Current Stimulation (atDCS) to LIFG and left posterior temporal cortex in a three-way, cross-over, sham-controlled PWI paradigm involving either written (Experiment 1) or auditory (Experiment 2) distractors. Surprisingly, compared to sham, atDCS over posterior temporal cortex significantly slowed the congruent facilitation effect with written distractors, but did not modulate the semantic interference effect, while atDCS to LIFG did not significantly influence either effect. We also failed to observe any significant modulatory effects of atDCS with auditory distractors. The present results only partially support left temporal lobe engagement during PWI and provide no evidence for LIFG involvement. We recommend future PWI studies systematically investigate different electrode montages in tDCS protocols. • Stimulation to left posterior middle temporal gyrus modulated picture naming with written congruent distractor words. • Stimulation to left posterior middle temporal gyrus did not modulate picture naming with auditory distractors. • Stimulation to left inferior frontal gyrus did not modulate picture naming with written or auditory distractors.

Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice.

Decisions that favor one's own interest versus the interest of another individual depend on context and the relationships between individuals. The neurobiology underlying selfish choices or choices that benefit others is not understood. We developed a two-choice social decision-making task in which mice can decide whether to share a reward with their conspecifics. Preference for altruistic choices was modulated by familiarity, sex, social contact, hunger, hierarchical status and emotional state matching. Fiber photometry recordings and chemogenetic manipulations demonstrated that basolateral amygdala (BLA) neurons are involved in the establishment of prosocial decisions. In particular, BLA neurons projecting to the prelimbic (PL) region of the prefrontal cortex mediated the development of a preference for altruistic choices, whereas PL projections to the BLA modulated self-interest motives for decision-making. This provides a neurobiological model of altruistic and selfish choices with relevance to pathologies associated with dysfunctions in social decision-making.

Deconstructing dissociation: a triple network model of trauma-related dissociation and its subtypes.

Trauma-related pathological dissociation is characterized by disruptions in one's sense of self, perceptual, and affective experience. Dissociation and its trauma-related antecedents disproportionately impact women. However, despite the gender-related prevalence and high individual and societal costs, dissociation remains widely underappreciated in clinical practice. Moreover, dissociation lacks a synthesized neurobiological model across its subtypes. Leveraging the Triple Network Model of psychopathology, we sought to parse heterogeneity in dissociative experience by examining functional connectivity of three core neurocognitive networks as related to: (1) the dimensional dissociation subtypes of depersonalization/derealization and partially-dissociated intrusions; and, (2) the diagnostic category of dissociative identity disorder (DID). Participants were 91 women with and without: a history of childhood trauma, current posttraumatic stress disorder (PTSD), and varied levels of dissociation. Participants provided clinical data about dissociation, PTSD symptoms, childhood maltreatment history, and completed a resting-state functional magnetic resonance imaging scan. We used a novel statistical approach to assess both overlapping and unique contributions of dissociation subtypes. Covarying for age, childhood maltreatment and PTSD severity, we found dissociation was linked to hyperconnectivity within central executive (CEN), default (DN), and salience networks (SN), and decreased connectivity of CEN and SN with other areas. Moreover, we isolated unique connectivity markers associated with depersonalization/derealization in CEN and DN, to partially-dissociated intrusions in CEN, and to DID in CEN. This suggests dissociation subtypes have robust functional connectivity signatures that may serve as targets for PTSD/DID treatment engagement. Our findings underscore dissociation assessment as crucial in clinical care, in particular, to reduce gender-related health disparities.

Neurobiology of Sex and Pornography Addictions: A Primer

Contrary to the earlier notion that addiction is predominantly a substance dependency, research now suggests that any source or experience capable of stimulating an individual has addictive potential. This has led to a paradigm shift in the psychiatric understanding of behavioural addictions. These can refer to a range of behaviors such as gambling, video gaming, and sexual practices. Hypersexual behavior and pornography addiction come to the fore when the behavior becomes intensive, out of the individual’s control, and persists in that pattern despite harmful consequences and risk of harm to one’s emotional and/or physical health. The ongoing Coronavirus disease 2019 pandemic with its’ social distancing norms has further turned sexual practices to digital platforms with increase in pornography use, and hence addictions and unhealthy use of technology. There are several overlapping lines between these dimensions, and there are both components of compulsivity and impulsivity involved. Substantial evidence of neurobiological and psychological models has been used to conceptualize sex and pornography addictions. However, there is no academic consensus or operational criteria that can aid in diagnosing these conditions or estimating their impact. Moreover, the body of evidence on effective treatments is limited. With this background, this descriptive review looks at the various neurophysiological, genetic, and imaging markers of sex and pornography addictions including their possible evidence-based neuroplastic effects on the brain functioning and sexual behavior, and the neurobiological intersections with substance-abuse disorders, and finally outlines the future directions of related research.

Structural covariance predictors of clinical improvement at 2-year follow-up in first-episode psychosis

The relationship between structural brain alterations and prediction of clinical improvement in first-episode psychosis (FEP) has been scarcely studied. We investigated whether structural covariance, a well-established approach to identify abnormal patterns of volumetric correlation across distant brain regions, which allows incorporating network-level information to structural assessments, is associated with longitudinal clinical course.We assessed a sample of 74 individuals from a multicenter study. Magnetic resonance imaging scans were acquired at baseline, and clinical assessments at baseline and at a 2-year follow-up. Participants were split in two groups as a function of their clinical improvement after 2 years (i.e., ≥ < 40% reduction in psychotic symptom severity, (n = 29, n = 45)). We performed a seed-based approach and focused our analyses on 3 cortical and 4 subcortical regions of interest to identify alterations in cortical and cortico-subcortical networks.Improvers presented an increased correlation between the volumes of the right posterior cingulate cortex (PCC) and the left precentral gyrus, and between the left PCC and the left middle occipital gyrus. They also showed an increased correlation between right posterior hippocampus and left angular gyrus volumes.Our study provides a novel mean to identify structural correlates of clinical improvement in FEP, describing clinically-relevant anatomical differences in terms of large-scale brain networks, which is better aligned with prevailing neurobiological models of psychosis. The results involve brain regions considered to participate in the multisensory processing of bodily signals and the construction of bodily self-consciousness, which resonates with recent theoretical accounts in psychosis research.

Supramodal Sentence Processing in the Human Brain: fMRI Evidence for the Influence of Syntactic Complexity in More Than 200 Participants.

This study investigated two questions. One is: To what degree is sentence processing beyond single words independent of the input modality (speech vs. reading)? The second question is: Which parts of the network recruited by both modalities is sensitive to syntactic complexity? These questions were investigated by having more than 200 participants read or listen to well-formed sentences or series of unconnected words. A largely left-hemisphere frontotemporoparietal network was found to be supramodal in nature, i.e., independent of input modality. In addition, the left inferior frontal gyrus (LIFG) and the left posterior middle temporal gyrus (LpMTG) were most clearly associated with left-branching complexity. The left anterior temporal lobe showed the greatest sensitivity to sentences that differed in right-branching complexity. Moreover, activity in LIFG and LpMTG increased from sentence onset to end, in parallel with an increase of the left-branching complexity. While LIFG, bilateral anterior temporal lobe, posterior MTG, and left inferior parietal lobe all contribute to the supramodal unification processes, the results suggest that these regions differ in their respective contributions to syntactic complexity related processing. The consequences of these findings for neurobiological models of language processing are discussed.

Emotion Words in Spanish: Lexical Selection, Affective Dimensions, Sex and Age Differences

Abstract This study proposes a method for selection and analysis of words that refer to emotions. A comparison of 380 synonyms corresponding to the six basic emotions in 15 Spanish thesauri resulted in 43 terms. Respondents of an online survey (n = 980) stated whether they recognized and used each word and how often they experienced the designated emotion, which resulted in 23 terms. The correlation matrix for the selected terms frequencies and a multivariate analysis of the data revealed three affective dimensions: anger, fear, and satisfaction. The frequency for the terms was higher for women, who reported more panic and irritation than men. In both, the frequency of the negative emotions of fear and sadness decrease with age, while pleasure, satisfaction, and indignation increase. The results suggest the existence of three affective dimensions (anger/repulsion, fear/sorrow, and satisfaction/admiration), which have been recognized in neurobiological, ecological, ethological, and evolutionary models.

Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0.0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = 0.162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

Streamlining Culture Conditions for the Neuroblastoma Cell Line SH-SY5Y: A Prerequisite for Functional Studies.

The neuroblastoma cell line SH-SY5Y has been a well-established and very popular in vitro model in neuroscience for decades, especially focusing on neurodevelopmental disorders, such as Parkinson’s disease. The ability of this cell type to differentiate compared with other models in neurobiology makes it one of the few suitable models without having to rely on a primary culture of neuronal cells. Over the years, various, partly contradictory, methods of cultivation have been reported. This study is intended to provide a comprehensive guide to the in vitro cultivation of undifferentiated SH-SY5Y cells. For this purpose, the morphology of the cell line and the differentiation of the individual subtypes are described, and instructions for cell culture practice and long-term cryoconservation are provided. We describe the key growth characteristics of this cell line, including proliferation and confluency data, optimal initial seeding cell numbers, and a comparison of different culture media and cell viability during cultivation. Furthermore, applying an optimized protocol in a long-term cultivation over 60 days, we show that cumulative population doubling (CPD) is constant over time and does not decrease with incremental passage, enabling stable cultivation, for example, for recurrent differentiation to achieve the highest possible reproducibility in subsequent analyses. Therefore, we provide a solid guidance for future research that employs the neuroblastoma cell line SH-SY5Y.

Profiling 26,000 Aplysia californica neurons by single cell mass spectrometry reveals neuronal populations with distinct neuropeptide profiles

Neuropeptides are a chemically diverse class of cell-to-cell signaling molecules that are widely expressed throughout the central nervous system, often in a cell-specific manner. While cell-to-cell differences in neuropeptides is expected, it is often unclear how exactly neuropeptide expression varies among neurons. Here we created a microscopy-guided, high-throughput single cell matrix-assisted laser desorption/ionization mass spectrometry approach to investigate the neuropeptide heterogeneity of individual neurons in the central nervous system of the neurobiological model Aplysia californica, the California sea hare. In all, we analyzed more than 26,000 neurons from 18 animals and assigned 866 peptides from 66 prohormones by mass matching against an in silico peptide library generated from known Aplysia prohormones retrieved from the UniProt database. Louvain–Jaccard (LJ) clustering of mass spectra from individual neurons revealed 40 unique neuronal populations, or LJ clusters, each with a distinct neuropeptide profile. Prohormones and their related peptides were generally found in single cells from ganglia consistent with the prohormones’ previously known ganglion localizations. Several LJ clusters also revealed the cellular colocalization of behaviorally related prohormones, such as an LJ cluster exhibiting achatin and neuropeptide Y, which are involved in feeding, and another cluster characterized by urotensin II, small cardiac peptide, sensorin A, and FRFa, which have shown activity in the feeding network or are present in the feeding musculature. This mass spectrometry–based approach enables the robust categorization of large cell populations based on single cell neuropeptide content and is readily adaptable to the study of a range of animals and tissue types.

Brain responses in aggression-prone individuals: A systematic review and meta-analysis of functional magnetic resonance imaging (fMRI) studies of anger- and aggression-eliciting tasks

Reactive aggression in response to perceived threat or provocation is part of humans' adaptive behavioral repertoire. However, high levels of aggression can lead to the violation of social and legal norms. Understanding brain function in individuals with high levels of aggression as they process anger- and aggression-eliciting stimuli is critical for refining explanatory models of aggression and thereby improving interventions. Three neurobiological models of reactive aggression – the limbic hyperactivity, prefrontal hypoactivity, and dysregulated limbic-prefrontal connectivity models – have been proposed. However, these models are based on neuroimaging studies involving mainly non-aggressive individuals, leaving it unclear which model best describes brain function in those with a history of aggression.We conducted a systematic literature search (PubMed and Psycinfo) and Multilevel Kernel Density meta-analysis (MKDA) of nine functional magnetic resonance imaging (fMRI) studies (eight included in the between-group analysis [i.e., aggression vs. control groups], five in the within-group analysis). Studies examined brain responses to tasks putatively eliciting anger and aggression in individuals with a history of aggression alone and relative to controls.Individuals with a history of aggression exhibited greater activity in the superior temporal gyrus and in regions comprising the cognitive control and default mode networks (right posterior cingulate cortex, precentral gyrus, precuneus, right inferior frontal gyrus) during reactive aggression relative to baseline conditions. Compared to controls, individuals with a history of aggression exhibited increased activity in limbic regions (left hippocampus, left amygdala, left parahippocampal gyrus) and temporal regions (superior, middle, inferior temporal gyrus), and reduced activity in occipital regions (left occipital cortex, left calcarine cortex).These findings lend support to the limbic hyperactivity model in individuals with a history of aggression, and further indicate altered temporal and occipital activity in anger- and aggression-eliciting conditions involving face and speech processing.

Neural Correlates of Cue Reactivity and the Regulation of Craving in Substance Use Disorders

Abstract. Theoretical background: Considerable progress has been made in illuminating the neural basis of the compulsive use patterns characterizing substance use disorders. It has been suggested to utilize these findings to alleviate the health burden associated with substance use. Objective: We address how neuroimaging research can provide these benefits. Methods: Based on neurobiological models of addiction, we highlight neuroimaging research elucidating neural predictors of relapse and how treatments modify these markers. Results: With the focus on cue reactivity, brain activity related to the motivational salience of drugs and automatized use behaviors can predict relapse. Cue reactivity changes with abstinence, and it remains to be determined whether such changes confer periods of critical relapse susceptibility. Conclusions: Several established and emerging interventions modulate brain activity associated with drug value. However, executive deficits in addiction may compromise interventions targeting control-related prefrontal brain areas. Lastly, it remains more difficult to change the brain responses mediating habitual behaviors.