Neurobiological Evidence Research Articles

The Difference between Developmental Dyslexia and Dysgraphia: Recent Neurobiological Evidence

Developmental dyslexia and developmental dysgraphia are considered to be distinct learning difficulties that affect the child's ability to learn. Dyslexia affects all aspects of written language, while the symptoms of dysgraphia appear to be confined to difficulties in writing. However, the distinction between the two learning difficulties is often obscured by the similar learning cognitive deficits manifested by individuals diagnosed with these difficulties. The aim of this review is to summarize and evaluate research concerning the neurobiological basis of the two difficulties with a view to assist researchers and practitioners in their classification of individuals with resembling deficits. In so doing, we bring together the findings of studies that have utilized powerful neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI). The evidence suggests that while individuals with dyslexia and dysgraphia share a left-hemisphere processing limitation resulted from the absence of a scanning mechanism for disembedding, encoding, and rehearsing visual patterns (e.g., words), there are important neurological differences that distinguish the two groups. Specifically, recent neurobiological studies have shown that children with developmental dysgraphia differ from their dyslexic counterparts in white matter integrity, functional connectivity revealed by fMRI, and white matter-gray matter correlations. These differences in the brain between children with developmental dyslexia and children with dysgraphia confirm the neurobiological distinction between these two special learning difficulties. Based on these neurobiological differences researchers and practitioners in the field should exercise special care not to treat the two disorders as the same in their research or professional practice.

Abstractness of human speech sound representations

We argue, based on a study of brain responses to speech sound differences in Japanese, that memory encoding of functional speech sounds—phonemes—are highly abstract. As an example, we provide evidence for a theory where the consonants/p t k b d ɡ/ are not only made up of symbolic features but are underspecified with respect to voicing or laryngeal features, and that languages differ with respect to which feature value is underspecified. In a previous study we showed that voiced stops are underspecified in English [Hestvik, A., & Durvasula, K. (2016). Neurobiological evidence for voicing underspecification in English. Brain and Language], as shown by asymmetries in Mismatch Negativity responses to /t/ and /d/. In the current study, we test the prediction that the opposite asymmetry should be observed in Japanese, if voiceless stops are underspecified in that language. Our results confirm this prediction. This matches a linguistic architecture where phonemes are highly abstract and do not encode actual physical characteristics of the corresponding speech sounds, but rather different subsets of abstract distinctive features.

Exploring the Structural and Strategic Bases of Autism Spectrum Disorders With Deep Learning

Deep learning models are applied in clinical research in order to diagnose disease. However, diagnosing autism spectrum disorders (ASD) remains challenging due to its complex psychiatric symptoms as well as a generally insufficient amount of neurobiological evidence. We investigated the structural and strategic bases of ASD using 14 different types of models, including convolutional and recurrent neural networks. Using an open source autism dataset consisting of more than 1000 MRI scan images and a high-resolution structural MRI dataset, we demonstrated how deep neural networks could be used as tools for diagnosing and analyzing psychiatric disorders. We trained 3D convolutional neural networks to visualize combinations of brain regions, thus representing the most referred-to regions used by the model whilst classifying the images. We also implemented recurrent neural networks to classify the sequence of brain regions efficiently. We found emphatic structural and strategic evidence on which the model heavily relies during the classification process. For instance, we observed that the structural and strategic evidence tends to be associated with subcortical structures, including the basal ganglia (BG). Our work identifies the distinct brain structures that characterize a complex psychiatric disorder while streamlining the deductive reasoning that clinicians can use to ensure an economical and time-efficient diagnosis process.

Vertical Lobes of the Mushroom Bodies are Essential for View-Based Navigation in Australian Bull Ants

For many animals, visual landmarks provide information about their location in space and the direction to a goal. Insects acquire this visual information through a series of well-choreographed walks or flights of learning carried out prior to leaving home. Views acquired during learning walks are sufficient for pinpointing goals both when in their vicinity and when animals are at locations they have not visited previously. It is presumed that animals returning home match the memorised views to their current view for successful view-based navigation. While view-based navigation strategies have been incorporated in a wide variety of navigation models used in robotics, we still know very little about how view-based navigation is performed by the insect brain. We investigated the role of the mushroom bodies in view-based navigation in a visually oriented Australian bull ant Myrmecia midas. We targeted the mushroom body vertical lobes (VL) because they are innervated by the visual input regions of the mushroom body and are known to be involved in learning and memory. To ensure that ants in our experiments could navigate using only visual landmarks, we captured experienced foragers close to their nest when they were returning home. For our treatment group, we selectively inhibited neural activity in the VL of the mushroom bodies using the anesthetic procaine and compared their behaviour with three groups: untreated control, VL saline injected, and off-target (antennal lobe) procaine injected groups. Ants were then released at their familiar foraging tree, their subsequent paths were filmed, and their final destinations were determined. While all groups exhibited similar walking speeds, we found significant differences in their orientation and the ability of ants to successfully return home. Untreated control and off-target procaine injected ants were well directed and the most successful at returning home. Animals with procaine-inactivated VL had tortuous paths with multiple loops and were unable to find their nest. We analysed their walking speed relative to gaze direction and found that untreated animals accelerated when their gaze was directed toward home. This behaviour was eliminated by anaesthetizing the VL. Our data show that a simple and effective view-based navigation strategy – accelerate whenever a homeward view is in the frontal visual field – is mediated by the VL of the ant brain. We therefore provide neurobiological evidence that view-based navigation requires functional mushroom bodies.

History of withdrawal modulates drug- and food-cue reactivity in cocaine dependent participants

While the centrality of withdrawal in the diagnosis of addiction has been decreasing with each successive edition of the Diagnostic and Statistical Manual of Mental Disorders, psychometric and neurobiological evidence provides withdrawal a central role in the development and maintenance of addiction. The current study offers insight into these conflicting positions by using secondary analyses to assess how a history of DSM-assessed withdrawal influences the magnitude of bias in neural reactivity to drug- and/or food-related reward cues. To this end, we separated an existing sample of cocaine-dependent participants (Denomme et al., 2018) into those with (WD) and without (N-WD) a history of withdrawal, and compared food- and drug-cue reactivity between these groups, and to a non-dependent control group (ND). Analyses indicated that biases in neural reactivity towards drug- versus food-related cues only occurred among the WD participants (within: left dorsomedial prefrontal cortex, left anterior cingulate cortex, left orbitofrontal cortex, left caudate nucleus, and right ventrolateral prefrontal cortex). Thus, withdrawal status may be an important factor to consider when interpreting dependence-related biases in neural reactivity following reward-related cues. Interestingly, while N-WD participants did not show these broad biases in neural reactivity, the magnitude of their bias correlated positively with years of lifetime substance use history, particularly when psychopathic traits were low. It may be that for individuals who’s addiction has not yet reached a compulsive state (see Wise and Koob, 2014), the magnitude of their drug > food bias could serve as a valuable biomarker of addiction severity.

Use of Neuroscience in Criminal Law Doctrine and Criminal Sentencing

Modern neuroscience has long expanded beyond the framework of traditional biological and medical sciences that study the central nervous system and human brain. Nowadays researchers aim at exploring the links between the biological processes in the brain and human behavior. There is a growing number of research on social neuroscience investigating the neural basis of social behavior. The progress of such studies is facilitated by application of non-invasive neuroimaging techniques (magnetic resonance imaging, functional magnetic resonance imaging, positron emission tomography, etc.), which provide the data on brain structure and activity in the form of visual images. The task of criminal law is to conceptualize the results of brain studies used as evidence in criminal courts in a number of countries that have also revived discussions about free will and criminal responsibility. According to foreign authors, neurobiological evidence, including the results of brain imaging, is used in courts at various stages of the process, in particular when determining the defendant’s competency to stand trial and in insanity defense. However, more often they appear in criminal cases of serious violent and sexual crimes in order to confirm the diagnosis of a mental or neurological disorder and/ or brain damage of the defendant and thereby justify the mitigation of punishment. Such evidence is often combined with results of other expert examinations and appear to be a part of a wider picture describing the defendant. International studies also show that the courts are cautious in decisions concerning admissibility of brain scan evidence because of uncertainty about its scientific validity, reliability and relevance to the case. Moreover, the very practice of the presence of such evidence in courts is considered as ambiguous. The opponents refer to insufficient validity and reliability of such evidence and the subjectivity of experts while interpreting the results of brain imaging. There are also problems of reliability of expert conclusions when the group data is applied to the individual case considered in court. The opponents also refer to the complexity and interconnectedness of the human brain, the inability to link complex human behavior to a specific brain area not to mention a causal relationship between specific brain area and specific behavior. The progress of neuroscience has also given an impulse to a new wave of discussions on key issues of legal philosophy and criminal law doctrine. The results of some studies are interpreted as evidence on lack of voluntary nature of human actions and the illusion of free will, since the brain sends a signal to act before a person realizes it. In combination with findings concerning links between specific brain structures and aggression, impulsiveness and the ability to control one’s behavior, these data are used as the ground to justify the revision of traditional doctrinal ideas about guilt and criminal responsibility. However, majority of experts who analyze the use of the results of neurobiological studies in criminal law doctrine and practice disagree with these claims. They acknowledge that such research can contribute to a better understanding of the mechanisms of human behavior and influence the doctrinal understanding of legal categories, such as guilt and insanity, but they do object against identification of the mind with the brain. The concepts of free will and responsibility are social constructs, and neurosciences are not able to convince society to abandon them.

Functional connectivity within the salience network differentiates autogenous- from reactive-type obsessive-compulsive disorder

BackgroundObsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. To better understand and treat patients, symptomatology of OCD has been categorized into more homogenous symptom dimensions. The autogenous-reactive classification model has proven helpful in the elucidation of the neurobiological substrates for clinical heterogeneity in OCD. The purpose of the current study was to systematically compare regional and network functional alterations between OCD subtypes based on the autogenous-reactive model. MethodsAutogenous-type OCD patients (OCD-AO, n = 40), reactive-type patients (OCD-RO, n = 42), and healthy controls (HC, n = 70) underwent functional magnetic resonance imaging (fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were compared among subjects. Areas of abnormal local spontaneous brain activity that differentiated OCD-AO and OCD-RO patients were identified and entered as seeds in functional connectivity (FC) analysis. ResultsCompared to OCD-RO patients and HC participants, OCD-AO patients showed increased ALFF in the left anterior insula (AI), increased ReHo in the right AI, and hyperconnectivity between bilateral AI and anterior cingulate cortex (ACC). Both OCD-AO and OCD-RO patients shared regional function deficits in several areas within the prefrontal cortex, and stronger FC between bilateral AI and major nodes of the default mode network (DMN) compared to healthy controls. ConclusionThe current results suggest that aberrant functional interaction between the salience network (SN) and the DMN may represent a common substrate in the pathophysiology of OCD, while impaired functional coupling within the SN is distinct to autogenous-type OCD patients. These findings provide further neurobiological evidence to support the autogenous-reactive classification model and contribute to the understanding of the neurobiological basis for clinical heterogeneity in OCD.

Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia.

Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM. RA patients with concomitant FM and those without FM (FM+ and FM-, respectively; n = 27 per group) underwent functional connectivity magnetic resonance imaging. Seed-to-whole-brain functional connectivity analyses were conducted using seeds from the left mid/posterior insula and left inferior parietal lobule (IPL), which are regions that have been previously linked to FM symptoms and inflammation, respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each group separately, followed by post hoc analyses to test for interaction effects. Cluster-level, family-wise error (FWE) rates were considered significant if the P value was less than 0.05. The group of RA patients with FM and those without FM did not differ by age, sex, or ESR (P > 0.2). In FM+ RA patients, increased functional connectivity of the insula-left IPL, left IPL-dorsal anterior cingulate, and left IPL-medial prefrontal cortex regions correlated with higher levels of ESR (all FWE-corrected P < 0.05). Post hoc interaction analyses largely confirmed the relationship between ESR and connectivity changes as FM scores increased. We report the first neurobiologic evidence that FM in RA may be linked to peripheral inflammation via pronociceptive patterns of brain connectivity. In patients with such "bottom-up" pain centralization, concomitant symptoms may partially respond to antiinflammatory treatments.

How Spirituality May Mitigate Against Stress and Related Mental Disorders: a Review and Preliminary Neurobiological Evidence

This article aims to review recent research on the relationship between spirituality and stress and how spirituality may protect against stress-related mental disorders. Preliminary data on neural mechanisms by which spirituality may influence stress processing are also presented. Recent neuroscientific research on stress implicates widespread corticostriatal-limbic neural circuitry that includes the salience and the default-mode networks. Acute and chronic stress represents a significant etiological factor for a range of mental disorders, and research suggests that specific brain mechanisms of acute stress in healthy states overlap with mechanisms of psychopathology. Recent studies also indicate that spirituality protects against stress and its adverse consequences. Functional magnetic resonance imaging (fMRI) data are presented in a proof-of-concept manner that suggest potential brain mechanisms for how spirituality may influence stress processing. Brain regions identified have been implicated in stress responsiveness, emotional and cognitive processing, and self-referential processing. Research indicates that spirituality represents an important resilience factor for stress and its sequelae. Furthermore, preliminary fMRI data suggest a role for how spirituality may operate to attenuate neural responses to stress responsivity, regulate emotion during exposure to stress, and prevent and reduce stress-related psychopathology.

17.2 INSIGHTS INTO ALCOHOL USE INITIATION IN ADOLESCENTS USING A LARGE DATA SET

Neurobiological evidence points to a cortical and behavioral co-development, deviations from which are posited to be associated with elevated substance use behavior in adolescents. However, it is not clear whether these deviations are neurobiological predispositions for developing substance use or if they are associated with severity of such behavior. To fill this knowledge gap, the current large-cohort longitudinal study assesses impulsivity and neural reward processing in drug-naïve adolescents who go on to develop alcohol use with varying severity 2 years later.

反社会人格障碍的神经生物学基础及其司法启示

反社会人格障碍的神经生物学基础及其司法启示

Challenging the neurobiological link between number sense and symbolic numerical abilities.

A significant body of research links individual differences in symbolic numerical abilities, such as arithmetic, to number sense, the neurobiological system used to approximate and manipulate quantities without language or symbols. However, recent findings from cognitive neuroscience challenge this influential theory. Our current review presents an overview of evidence for the number sense account of symbolic numerical abilities and then reviews recent studies that challenge this account, organized around the following four assertions. (1) There is no number sense as traditionally conceived. (2) Neural substrates of number sense are more widely distributed than common consensus asserts, complicating the neurobiological evidence linking number sense to numerical abilities. (3) The most common measures of number sense are confounded by other cognitive demands, which drive key correlations. (4) Number sense and symbolic number systems (Arabic digits, number words, and so on) rely on distinct neural mechanisms and follow independent developmental trajectories. The review follows each assertion with comments on future directions that may bring resolution to these issues.

Addressing Evidence Linking Secondary Alexithymia to Aberrant Humor Processing.

In this review, we explore current literature and assess evidence linking secondary (acquired) alexithymia to aberrant humor processing, in terms of their neurobiological underpinnings. In addition, we suggest a possible common neuropathological substrate between secondary alexithymia and deficits in humor appreciation, by drawing on neurophysiologic and neuroradiological evidence, as well as on a recent and unique single-case study showing the cooccurrence of secondary alexithymia and deficit in humor appreciation. In summary, what emerges from the literature is that the cortical midline structures, in particular the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the insular cortex, seem to play a crucial role in the expression of both alexithymia and defective humor processing, while though to a lesser extent, a right hemisphere and bilateral frontoparietal contribution becomes evident. Neurobiological evidence of secondary alexithymia and aberrant humor processing points to the putative role of ACC/mPFC and the insular cortex in representing crucial processing nodes whose damage may produce both the above clinical conditions. We believe that the association of secondary alexithymia and aberrant humor processing, especially humor appreciation deficit, and their correlation with specific brain regions, mainly ACG/mPFC, as emerged from the literature, may be of some heuristic importance. Increased awareness on this topic may be of aid for neurosurgeons when accessing emotion-relevant structures, as well as for neuropsychologists to intensify their efforts to plan evidence-based neurorehabilitative interventions to alleviate the deleterious effects of such interpersonal communication deficits.

Challenge and Threat: A Critical Review of the Literature and an Alternative Conceptualization.

In this article, the authors describe a new theory, the Evaluative Space Approach to Challenge and Threat (ESACT). Prompted by the Biopsychosocial model of challenge and threat (BPS: Blascovich and Tomaka, 1996) and the development of the Theory of Challenge and Threat States in Athletes (Jones et al., 2009), recent years have witnessed a considerable increase in research examining challenge and threat in sport. This manuscript provides a critical review of the literature examining challenge and threat in sport, tracing its historical development and some of the current empirical ambiguities. To reconcile some of these ambiguities, and utilizing neurobiological evidence associated with approach and avoidance motivation (c.f. Elliot and Covington, 2001), this paper draws upon the Evaluative Space Model (ESM; Cacioppo et al., 1997) and considers the implications for understanding challenge and threat in sport. For example, rather than see challenge and threat as opposite ends of a single bipolar continuum, the ESM implies that individuals could be (1) challenged, (2) threatened, (3) challenged and threatened, or (4) neither challenged or threatened by a particular stimulus. From this perspective, it could be argued that the appraisal of some sport situations as both challenging and threatening could be advantageous, whereas the current literature seems to imply that the appraisal of stress as a threat is maladaptive for performance. The ESACT provides several testable hypotheses for advancing understanding of challenge and threat (in sport) and we describe a number of measures that can be used to examine these hypotheses. In sum, this paper provides a significant theoretical, empirical, and practical contribution to our understanding of challenge and threat (in sport).

Event boundaries do not cause the immediate extinction deficit after Pavlovian fear conditioning in rats

Recent work reveals that the extinction of conditioned fear depends upon the interval between conditioning and extinction. Extinction training that takes place within minutes to hours after fear conditioning fails to produce a long-term extinction memory, a phenomenon known as the immediate extinction deficit (IED). Neurobiological evidence suggests that the IED results from stress-induced dysregulation of prefrontal cortical circuits involved in extinction learning. However, a recent study in humans suggests that an “event boundary” between fear conditioning and extinction protects the conditioning memory from interference by the extinction memory, resulting in high levels of fear during a retrieval test. Here, we contrast these hypotheses in rats by arranging extinction trials to follow conditioning trials with or without an event boundary; in both cases, extinction trials are delivered in proximity to shock-elicited stress. After fear conditioning, rats either received extinction trials 60-sec after the last conditioning trial (continuous, no event boundary) or 15-minutes after conditioning (segmented, a standard “immediate” extinction procedure associated with an event boundary). Both groups of animals showed decreases in conditional freezing to the auditory conditioned stimulus (CS) during extinction and exhibited an equivalent IED relative to non-extinguished controls when tested 48 hours later. Thus, eliminating the event boundary between conditioning and extinction with the continuous extinction procedure did not prevent the IED. These data suggest that the IED is the result of shock-induced stress, rather than boundary-induced reductions in memory interference.

Increased tactile sensitivity and deficient feed-forward inhibition in pathological hair pulling and skin picking

An increasing body of evidence has linked pathological body-focused repetitive behaviors (BFRBs) to excessive sensory sensitivity and difficulty modulating sensory inputs. Likewise, neurobiological evidence points to deficits in feed-forward inhibition and sensory habituation in conditions with similar symptomatology. There is currently little evidence regarding potential physiological sensory abnormalities in BFRBs. The current study compared 46 adults with pathological hair pulling and/or skin picking to 46 age-matched healthy control participants on a series of self-report measures and objective psychophysical tests of neurophysiological sensory functions. Persons in the BFRB group reported increased scores on the Sensory Gating Inventory (U = 320.50, p < .001) and all of its subscales (all p-values < .001), reflecting abnormal sensory experiences. The BFRB group also showed decreased tactile thresholds (increased sensitivity) (F[1, 76] = 10.65, p = .002, ηp2 = .12) and deficient feed-forward inhibition (F[1, 76] = 5.18, p = .026, ηp2 = .064), but no abnormalities in quickly-adapting sensory habituation were detected on an amplitude discrimination task. Performance on objective psychophysical tests was not associated with self-reported sensory gating symptoms or symptom severity. Implications of these results for the pathophysiology of BFRBs and related disorders are discussed.

Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications.

Pain can be both a cause and a consequence of sleep deficiency. This bidirectional relationship between sleep and pain has important implications for clinical management of patients, but also for chronic pain prevention and public health more broadly. The review that follows will provide an overview of the neurobiological evidence of mechanisms thought to be involved in the modulation of pain by sleep deficiency, including the opioid, monoaminergic, orexinergic, immune, melatonin, and endocannabinoid systems; the hypothalamus-pituitary-adrenal axis; and adenosine and nitric oxide signaling. In addition, it will provide a broad overview of pharmacological and non-pharmacological approaches for the management of chronic pain comorbid with sleep disturbances and for the management of postoperative pain, as well as discuss the effects of sleep-disturbing medications on pain amplification.

Superior colliculus encodes visual saliency during smooth pursuit eye movements.

The saliency map has played a long-standing role in models and theories of visual attention, and it is now supported by neurobiological evidence from several cortical and subcortical brain areas. While visual saliency is computed during moments of active fixation, it is not known whether the same is true while engaged in smooth pursuit of a moving stimulus, which is very common in real-world vision. Here, we examined extrafoveal saliency coding in the superior colliculus, a midbrain area associated with attention and gaze, during smooth pursuit eye movements. We found that SC neurons from the superficial visual layers showed a robust representation of peripheral saliency evoked by a conspicuous stimulus embedded in a wide-field array of goal-irrelevant stimuli. In contrast, visuomotor neurons from the intermediate saccade-related layers showed a poor saliency representation, even though most of these neurons were visually responsive during smooth pursuit. These results confirm and extend previous findings that place the SCs in a unique role as a saliency map that monitors peripheral vision during foveation of stationary and now moving objects.

Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders.

Many neuropsychiatric and neurodevelopmental disorders commonly share genetic risk factors. To date, the mechanisms driving the pathogenesis of these disorders, particularly how genetic variations affect the function of risk genes and contribute to disease symptoms, remain largely unknown. Neurexins are a family of synaptic adhesion molecules, which play important roles in the formation and establishment of synaptic structure, as well as maintenance of synaptic function. Accumulating genomic findings reveal that genetic variations within genes encoding neurexins are associated with a variety of psychiatric conditions such as schizophrenia, autism spectrum disorder, and some developmental abnormalities. In this review, we focus on NRXN1, one of the most compelling psychiatric risk genes of the neurexin family. We performed a comprehensive survey and analysis of current genetic and molecular data including both common and rare alleles within NRXN1 associated with psychiatric illnesses, thus providing insights into the genetic risk conferred by NRXN1. We also summarized the neurobiological evidences, supporting the function of NRXN1 and its protein products in synaptic formation, organization, transmission and plasticity, as well as disease-relevant behaviors, and assessed the mechanistic link between the mutations of NRXN1 and synaptic and behavioral pathology in neuropsychiatric disorders.

Privacy Decision Making: The Brain Approach

Functional magnetic resonance imaging tools develop neurobiological evidence of human brain reactions to privacy risks. Our results indicate that privacy decisions are more affective cognitive than purely cognitive, as assumed in the existing affective-computing models for privacy decision making.