Nouchine Hadjikhani

Harvard Medical School | HMS · Athinoula A. Martinos Center for Biomedical Imaging

Migraine is a ubiquitous neurologic disease that afflicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experim...

Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite...

Background Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating patterns without shape or weight concerns, leading to nutritional deficits and psychosocial impairment. Three distinct phenotypes have been described that can co-occur: 1) sensory sensitivity, 2) lack of interest in eating or food, and 3) food avoida...

Background: When looking at faces, we tend to attend more to the left visual field (corresponding to the right side of the person's face). This phenomenon is called the left visual field bias (LVF) and is presumed to reflect the brain's right-sided dominance for face processing. Whether alterations in hemispheric dominance are present in dyslexia,...

The limited availability of large image datasets, mainly due to data privacy and differences in acquisition protocols or hardware, is a significant issue in the development of accurate and generalizable machine learning methods in medicine. This is especially the case for Magnetic Resonance (MR) images, where different MR scanners introduce a bias...

Many so-called “high functioning” autistic individuals struggle with daily living skills, and have poorer than expected adult outcomes in employment, relationships, and quality of life. Significant discrepancies between non-verbal intelligence and emotional processing can be observed in autism, but the role of the magnitude of this gap in achieving...

An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross‐sectional data from clinical samples of small size. This study aimed to extend previous research by using prospecti...

The role of the trigeminal system in facial and dural sensitivity has been recognized for a long time. More recently, the trigeminal system has also been considered a prominent actor in brain nociceptive innervation. It is the anatomical substrate of several frequent conditions, such as primary or secondary headaches, trigeminal neuralgia, and othe...

Background and Objectives The choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, t...

While the neural correlates of migraine have been widely studied, it remains unclear whether glial cells contribute to neuroinflammation in migraine. One marker of glial activation is the presence of elevated levels of 18 kDa translocator protein (TSPO), and earlier studies have shown that individuals suffering from migraine with aura (MWA) exhibit...

Migraine is a highly prevalent chronic pain disorder that is characterized by sensitization and dysregulation of the central autonomic nervous system. Interoception is the sensing of signals originating from within the body, and is altered in chronic pain conditions including episodic migraine. The relationship between brain mechanisms of interocep...

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation...

Dyslexia is a neurodevelopmental difficulty affecting reading, but recent data in adults suggest that difficulties also extend to face processing. Here, we tested face processing in school children with and without dyslexia, using eye-tracking and neuropsychological tests. Children with dyslexia didn't differ significantly from controls in face gaz...

Gaze patterns during face perception have been shown to relate to psychiatric symptoms. Standard analysis of gaze behavior includes calculating fixations within arbitrarily predetermined areas of interest. In contrast to this approach, we present an objective, data-driven method for the analysis of gaze patterns and their relation to diagnostic tes...

Many individuals with autism report that eye contact makes them stressed or uncomfortable. Besides expressing their right to respect for neurodiverse ways of nonverbal communication, some autistic individuals also express the wish to improve their capacity to tolerate eye contact. In the current study, five autistic adults completed a 21- to 28-day...

Background: An overrepresentation of neurodevelopmental disorders (NDDs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDDs are limited to cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using pr...

Limited availability of large image datasets is a major issue in the development of accurate and generalizable machine learning methods in medicine. The limitations in the amount of data are mainly due to the use of different acquisition protocols, different hardware, and data privacy. At the same time, training a classification model on a small da...

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening...

Background The impact of COVID-19 on human health extends beyond the morbidity and death toll directly caused by the SARS-CoV-2 virus. In fact, accumulating evidence indicates a global increase in the incidence of fatigue, brain fog and depression, including among non-infected, since the pandemic onset. Motivated by previous evidence linking those...

There are currently no biomarkers for autism spectrum disorder (ASD). This neurodevelopmental condition has previously been associated with histopathological findings, including increased neuronal packing density in the amygdala, abnormal laminar cytoarchitecture and increased average neuronal density in the prefrontal cortex. The present study exa...

What role does the presence of facial speech play for children with dyslexia? Current literature proposes two distinctive claims. One claim states that children with dyslexia make less use of visual information from the mouth during speech processing due to a deficit in recruitment of audiovisual areas. An opposing claim suggests that children with...

The prevalence of Avoidant/Restrictive Food Intake Disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening...

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a...

Migraine, the most frequent neurological ailment, affects visual processing during and between attacks. Most visual disturbances associated with migraine can be explained by increased neural hyperexcitability, as suggested by clinical, physiological and neuroimaging evidence. Here, we review how simple (e.g., patterns, color) visual functions can b...

A Correction to this paper has been published: https://doi.org/10.3758/s13415-021-00898-6

To identify newborns at risk of developing ASD and to detect ASD biomarkers early after birth, we compared retrospectively ultrasound and biological measurements of babies diagnosed later with ASD or neurotypical (NT) that are collected routinely during pregnancy and birth. We used a supervised machine learning algorithm with a cross-validation tec...

Judgment of trustworthiness is an important social ability. Many studies show neural activation differences to variations in face trustworthiness in brain reward regions. A previously published analysis of the present fMRI data showed that older adults’ (OA) reward region activation responded significantly to trustworthiness in a set of older and y...

Purpose of review: This review covers several aspects our understanding of episodic manifestations and unusual symptoms that may be associated with migraine aura. Recent findings: The episodic manifestation of migraine aura is typically visual in nature, although five other types are currently recognized: sensory, speech and/or language, motor,...

Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisat...

Supratentorial sensory perception, including pain, is subserved by the trigeminal nerve, in particular, by the branches of its ophthalmic division, which provide an extensive innervation of the dura mater and of the major brain blood vessels. In addition, contrary to previous assumptions, studies on awake patients during surgery have demonstrated t...

Individuals with Autism Spectrum Disorder (ASD) have difficulties recognizing and understanding others’ actions. The goal of the present study was to determine whether children with and without ASD show differences in the way they process stimuli depicting Biological Motion (BM). Thirty‐two children aged 7–16 (16 ASD and 16 typically developing (TD...

Objectives: Individual anatomical biomarkers have limited power for the classification of autism. The present study introduces a multivariate classification approach using structural magnetic resonance imaging data from individuals with and without autism. Methods: The classifier utilizes z-normalization, parameter weighting, and interindividual...

Attempts to extract early biomarkers and expedite detection of Autism Spectrum Disorder (ASD) have been centered on postnatal measures of babies at familial risk. Here, we suggest that it might be possible to do these tasks already at birth relying on ultrasound and biological measurements routinely collected from pregnant mothers and fetuses durin...

Background: Anorexia nervosa (AN) and autism spectrum disorder (ASD) may be phenotypically and etiologically linked. However, due to the absence of prospective studies, it remains unclear whether the elevation of autistic traits in AN is evident in early childhood. Here, we prospectively investigated autistic traits before and after the first diag...

Oxytocin (OXT), shown to decrease food intake in animal models and men, is a promising novel treatment for obesity. We have shown that in men with overweight and obesity, intranasal (IN) OXT reduced the functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent signal in the ventral tegmental area (VTA), the origin of the mesoli...

Background Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain‐meninges‐bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response. Accordingly, this study examines the upregulation of an inflammatory marker i...

In a wide range of brain disorders, experimental observations suggest a rise of intracellular chloride levels leading to a loss of the GABAergic inhibitory drive and even a polarity shift with GABA exerting excitatory actions. These observations suggest that drugs capable of restoring the inhibitory drive of GABA might be useful in a clinical persp...

Background Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown. Methods We investigated if there is similar etiology in (a) the continuous distribution of the...

Most of human genome is present in two copies (maternal and paternal). However, segments of the genome can be deleted or duplicated, and many of these genomic variations (known as Copy Number Variants) are associated with psychiatric disorders. 16p11.2 copy number variants (breakpoint 4-5) confer high risk for neurodevelopmental disorders and are a...

Typically, developing humans innately place subjective value on social information and orient attention to it. This can be shown through tracking of gaze patterns and pupil size, the latter of which taps into an individual’s cognitive engagement and affective arousal. People with Autism Spectrum Disorder (ASD) present with atypical social, communic...

Poster link: https://insar.confex.com/insar/2019/webprogram/Paper31097.html

Background: The hypothalamic neurohormone oxytocin (OXT), shown to decrease food intake in animal models and men, is a promising novel treatment for obesity. The mechanisms underlying OXT effects on caloric intake in humans are not well understood. We previously showed that in overweight and obese men, 24 IU intranasal (IN) OXT reduced fMRI activat...

Abstract While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiolog...

Objective: To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions. Methods: Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [11C]PBR28, a radioliga...

Objective To examine Facial Emotion Recognition (FER) and visual scanning behavior (eye‐tracking) during FER in women long‐term recovered from teenage‐onset anorexia nervosa (recAN) with and without autism spectrum disorder (±ASD) and age‐matched comparison women (COMP), using a sensitive design with facial emotion expressions at varying intensitie...

Cambridge Core - Psychiatry - Autism and Pervasive Developmental Disorders - edited by Fred R. Volkmar

Autism and Pervasive Developmental Disorders - edited by Fred R. Volkmar January 2019

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory‐based gain control of network excitation. Th...

Pupillary contagion is an involuntary change in the observer's pupil size in response to the pupil size of another person. This effect, presumed to be an important adaption for individuals living in groups, has been documented in both typical infants and adults. Here, for the first time, we report pupillary contagion in individuals with autism, a d...

The extent to which affective empathy is impaired in Autism Spectrum Disorder (ASD) remains unclear, as some ‐but not all ‐ previous neuroimaging studies investigating empathy for pain in ASD have shown similar levels to those of neurotypicals individuals. These inconsistent results could be due to the use of different empathy‐eliciting stimuli. Wh...

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations, and their suppression by strong excitatory drive may stem from inhibitory-based gain control of network excitation. Individual variations in the gamma suppression may therefore reflect efficiency of gain control and subjective sensit...

Gamma-band oscillations arise from the interplay between neural excitation (E) and inhibition (I) and may provide a non-invasive window into the state of cortical circuitry. A bell-shaped modulation of gamma response power by increasing the intensity of sensory input was observed in animals and is thought to reflect neural gain control. Here we sou...

Gamma-band oscillations arise from the interplay between neural excitation (E) and inhibition (I) and may provide a non-invasive window into the state of cortical circuitry. A bell-shaped modulation of gamma response power by increasing the intensity of sensory input was observed in animals and is thought to reflect neural gain control. Here we sou...

The circumstances under which empathy is altered in ASD remain unclear, as previous studies did not systematically find differences in brain activation between ASD and controls in empathy-eliciting paradigms, and did not always monitor whether differences were primarily due to ASD “per se”, or to conditions overlapping with ASD, such as alexithymia...

Research demonstrating responsiveness of the neural reward network to face trustworthiness has not assessed whether the effects are mediated by dopaminergic function. We filled this gap in the literature by investigating whether dietary dopamine depletion would blunt the sensitivity of neural activation to faces varying in trustworthiness across re...

Supplementary data: Description of ARX expression in the developing human brain; Supplementary Table 1: Age and cause of death of selected autopsy cases.

The ARX (Aristaless Related homeoboX) gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the ARX gene, a du...

Background 16p11.2 BP4-BP5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, language and cognitive impairment. In this multi-site study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. Methods Using voxel- and surface-based brain morphometric methods, we analyzed structural m...

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contac...

We examined older adult (OA) and younger adult (YA) neural sensitivity to face trustworthiness in reward circuit regions, previously found to respond to trustworthiness in YA. Interactions of face trustworthiness with age revealed effects exclusive to OA in the amygdala and caudate, and an effect that was not moderated by age in the dorsal anterior...

Objective: Anorexia nervosa is associated with social-emotional functioning deficits and low levels of the social neurohormone oxytocin, even after weight gain. The relationship between low oxytocin levels and social-emotional functioning impairment has not been studied. Method: We performed a cross-sectional study of 79 women (19 who were less...

In his book “Die Geschichte von dem Zappel-Philipp,” the German psychiatrist Heinrich Hoffmann (1809–1894) offers a clinical vignette which raises the question of the description of a disobedient child or presenting hyperactivity symptoms. This article describes the historical context and the biographical aspects related to this interesting approac...

Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutra...

Objective: The ARX (Aristaless Related homeoboX) gene encodes a transcription factor which mutations have been associated with syndromes ranging from severe neuronal migration defects such as lissencephaly, to mild or moderate forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent ARX mutation (c.429_...