Neuroimaging in Psychiatric Disorders: A Bibliometric Analysis of The 100 Most Highly Cited Articles

Neuroimaging in Psychiatric Disorders: A Bibliometric Analysis
of the 100 Most Highly Cited Articles

Bo Gong , Sadiq Naveed, Dawood M. Hafeez, Khalid I. Afzal, Salman Majeed, Jonathan Abele, Savvas Nicolaou,
Faisal Khosa
From the MD Undergraduate Program, University of British Columbia, Vancouver, British Columbia, Canada (BG); Child and Adolescent Psychiatry, KVC Hospitals, Kansas
City, KS (SN); Capital Medical University, Beijing, China (DMH); Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL (KIA); Department
of Psychiatry, Penn State Hershey Medical Center, Hershey, PA (SM); Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
(JA); and Department of Radiology, Vancouver General Hospital, Vancouver, British Columbia, Canada (SN, FK).
ABSTRACT
BACKGROUND AND PURPOSE: Extensive research has been conducted to find neuroimaging biomarkers for psychiatric
disorders. This study aimed at identifying trends of the 100 most highly cited articles on neuroimaging in primary psychiatric
disorders.
METHODS: The most highly cited original research articles were identified and analyzed, following searches of MEDLINE and
Web of Science All Databases.
RESULTS: The top 100 articles ranked by yearly citation (from 137.5 to 31.1) were published between 1989 and 2017.
Depressive disorders (30 articles), schizophrenia spectrum and other psychotic disorders (27), autism spectrum disorder (17),
substance-related and addictive disorders (7), and post-traumatic stress disorder (7) were among the most studied conditions.
Functional magnetic resonance imaging (42), structural magnetic resonance imaging (30), and positron emission tomography
(22) were the most utilized neuroimaging modalities. While 85 articles investigated the pathophysiology of psychiatric disorders
(including 7 focusing on developmental changes and 1 on genetic susceptibility), 15 articles studied the impact of treatment,
including antidepressants (6), deep brain stimulation (4), antipsychotics (3), behavior therapy (3), and exercise (1). The analysis
also identified the most contributing authors, countries (the United States: 71 articles, the United Kingdom: 8, Canada: 5, and
China: 5), and journals (JAMA Psychiatry: 20 articles and Biological Psychiatry: 17). Ninety-eight studies were prospective, and
two were retrospective. The sample size ranged from 3 to 1,188 (median: 21).
CONCLUSIONS: Our study identified intellectual milestones in the utility of neuroimaging in investigating primary psychiatric
disorders. The historic trends could help guide future research in this field.
Keywords: Neuroimaging, mental disorders, psychiatry, bibliometrics.

Acceptance: Received August 28, 2018, and in revised form September 25, 2018. Accepted for publication September 26, 2018.
Correspondence: Address correspondence to Faisal Khosa, MD, MBA, FFRRCSI, FRCPC, DABR, Department of Emergency and Trauma Radiology,
Vancouver General Hospital, 899 West 12th Avenue, Vancouver, BC V5Z 1M9, Canada. E-mail: fkhosa@hotmail.com
Acknowledgments and Disclosure: The authors would like to thank medical student Joshua Lee for critical reading of the manuscript. This research did
not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The Department of Radiology, Vancouver General
Hospital has a Master Research Agreement with Siemens Healthcare, Forcheim, Germany. Dr. Khosa is the recipient of the Canadian Association of
Radiologists/Canadian Radiological Foundation Leadership Scholarship (2017). The abstract of this manuscript has been accepted to be presented at
the 2018 Annual Conference of the Canadian Psychiatric Association (September 27–29, 2018 in Toronto, Canada).
J Neuroimaging 2018;0:1-20.
DOI: 10.1111/jon.12570
Introduction of psychiatric disorders, identify at-risk populations, develop

Assessment of primary psychiatric disorders traditionally pharmaceutical drugs, and provide etiology-based treatments.5
depends on the evaluation of patients’ psychological symp- In 1976, the newly invented computer tomography (CT)
toms and behaviors.1 Diagnoses are mapped according to was used to study enlarged cerebral ventricles in schizophrenic
the Diagnostic and Statistical Manual of Mental Disorders patients, providing hope that neuroimaging would be an
(DSM)-52 and the International Classification of Diseases effective tool to identify reliable biomarkers for psychiatry.4,6
(ICD)-10.3 Although such diagnostic guidelines have proved In the following decades, research interest and output in
their practical function in routine psychiatric practice, many this field have grown exponentially, made possible by rapid
agree that the same diagnosis often corresponds to disruption emergence of new and improved neuroimaging modalities,
of heterogeneous neuronal networks, which could in turn particularly the positron emission tomography (PET, first use
be caused by diverse etiologies.4 This misalignment between in psychiatry in 19797 ), structural (sMRI, first use in psychiatry
etiologies and diagnoses is problematic. To improve the in 19838 ), and functional magnetic resonance imaging (fMRI,
diagnosis and treatment of primary psychiatric disorders, first use in psychiatry in 19949 ).10 A substantial body of
efforts have been made to search for reliable biomarkers neuroimaging evidence at both structural and functional
that would help elucidate the neurobiological mechanisms levels has now accumulated regarding many major primary
◦ 2018 by the American Society of Neuroimaging

C 1
psychiatric disorders, such as depressive disorders, schizophre- (exp personality disorders/) or (exp "schizophrenia spectrum
nia spectrum and other psychotic disorders, autism spectrum and other psychotic disorders"/) or (exp sexual dysfunctions,
disorder (ASD), post-traumatic stress disorder (PTSD), and psychological/) or (exp sleep wake disorders/) or (exp so-
attention-deficit/hyperactivity disorder (ADHD).11 Although matoform disorders/) or (exp substance-related disorders/) or
significant challenges remain, many are optimistic that, in the (exp "trauma and stressor related disorders"/)), with the results
near future, the adoption of innovative multivariable analytic limited to human and English language.
methods, development of artificial intelligence technology, and Web of Science databases (Clarivate Analytics, Philadel-
integration with genetic research would allow neuroimaging phia, United States), which include the MEDLINE database,
modalities to achieve sufficient diagnostic accuracy to be used cover more than 8,850 journals from a broad range of disci-
in routine clinical practice of psychiatry.4,12–14 plines and contain references dated back to 1900.30 Web of
With thousands of articles already published, neuroimaging Science All Databases were queried using the following search
was identified as one of the four main foci in psychiatry re- term: (("neuroimaging" or "computed tomography" or "CT" or
search (other three foci were: child and adolescent psychiatry, "magnetic resonance imaging" or "MRI" or "diffusion tensor
diagnostic and classification criteria, and molecular genetics).15 imaging" or "positron emission tomography" or "PET" or "sin-
The large amount of existing literature, combined with its gle photon emission computed tomography" or "SPECT" or
interdisciplinary nature, makes it challenging to identify the "magnetic resonance spectroscopy" or "MRS" or "voxel based
most significant research in this field, especially for students, morphometry") and ("psychiatric disorder$" or "mental disor-
residents, and researchers new to the field. Citation-based der$" or "behavioural disorder$" or "anxiety" or "depression"
bibliometric analysis involves quantitative and qualitative or "depressive disorder$" or "MDD" or "depressive episode" or
analysis of research literature to highlight articles of the most "paranoi*" or "mania" or "hypomania" or "bipolar" or "person-
significance and impact.16,17 It can thus be used to analyze ality disorder$" or "impulse disorder$" or "identity disorder$"
historical trends, reveal emerging novel approaches and topics, or "mood disorder$" or "*phobia$" or "panic disorder$" or "ad-
and guide future directions in a particular field of research.18 justment disorder$" or "stress disorder$" or "stress reaction" or
Furthermore, it also provides an objective measurement of "eating disorder$" or "anorexia nervosa" or "bulimia nervosa"
productivity of individual researchers and organizations, and or "sleep disorder$" or "dissociative disorder$" or "conversion
helps identify leaders in the field.19 As a result, citation-based disorder$" or "affective disorder$" or "psychosis" or "psy-
analysis and lists of most-cited articles have been published chotic" or "schizophrenia" or "delusion*" or "schizoaffective"
for many areas of medicine,20–26 including separate analyses or "schizophreniform" or "schizotypal" or "autism" or "ASD"
conducted on psychiatry27 and neuroimaging,28 respectively. or "neurotic" or "somatoform" or "somatization" or "addiction"
However, according to our literature search in English lan- or "substance" or "attention deficit hyperactivity disorder" or
guage indexed journals, no bibliometric analysis has focused "ADHD" or "post-traumatic stress disorder" or "PTSD" or
specifically on the role of neuroimaging in psychiatry. To fill "obsessive compulsive disorder" or "OCD" or "dyslexia" or
this void, we conducted a bibliometric analysis of original re- "language disorder$" or "asperger" or "conduct disorder$")).
search articles that used neuroimaging modalities to investigate The search results from the MEDLINE database were repop-
the pathophysiology, classification, diagnosis, and treatment ulated in the Web of Science by using PubMed ID as identifier,
of primary psychiatric disorders, for an understanding of the and were then merged with the original search results from the
utility trend of neuroimaging in psychiatry. Web of Science All Databases.
Screening of Original Research Articles

Methods
This study involved retrospective analysis of publicly available The combined results were downloaded to a local database. In
research literature, and thus did not require ethics approval. the descending order of yearly citation (the total citation count
divided by the year difference between publication year and
Literature Search 2018), two board certified radiologists screened the search re-
sults against selection criteria, until the 100 most highly cited
The MEDLINE (OVID) and Web of Science All Databases
articles were identified. In case of disagreement, a third radiol-
were searched on February 6, 2018. The MEDLINE database
ogist was consulted to reach consensus. Included in the analysis
(the U.S. National Library of Medicine, Bethesda, United
were original research articles that used neuroimaging modali-
States) indexes more than 5,200 journals and contains more
ties to investigate the pathophysiology, classification, diagnosis,
than 25 million references in life sciences and medicine since
and treatment of primary psychiatric disorders. Excluded from
1966.29 Its unique index system (Medical Subject Headings,
the analysis were: (1) case reports, meta-analyses, and reviews;
MeSH) offers the advantage to conduct comprehensive
(2) conference abstracts; (3) nonhuman studies; (4) studies in-
searches that cover the majority of psychiatric disorders.29 The
vestigating diseases of primarily neurological etiologies, such
MEDLINE (OVID) database was queried with the following
as Alzheimer’s disease, Parkinson’s disease, frontotemporal de-
search term: (exp Diagnostic Imaging/) and ((psychiatric dis-
mentia, etc; (5) post-mortem histological studies; and (6) studies
order?.mp.) or (mental disorders/) or (exp anxiety disorders/)
investigating psychological processes that were not in the con-
or (exp "bipolar and related disorders"/) or (exp "disruptive,
text of a psychiatric disorder.
impulse control, and conduct disorders"/) or (exp dissociative
disorders/) or (exp elimination disorders/) or (exp "feeding
Data Analysis
and eating disorders"/) or (exp mood disorders/) or (exp
motor disorders/) or (exp neurodevelopmental disorders/) For each article included in the final analysis, the following
or (exp neurotic disorders/) or (exp paraphilic disorders/) or information was collected: the yearly citation, the psychiatric
2 Journal of Neuroimaging Vol 0 No 0 October 2018

condition studied, the brain areas studied, the neuroimaging high soft tissue contrast resolution, which made it a widely used
modality and examination method used, the topic of study, the modality for anatomical examination of the brain.
country and affiliated department of the first author, and the Thirty of the most highly cited articles utilized sMRI.
sample size. The DSM-5 was used to classify the psychiatric Common measurements included the global brain volume,
disorders. white/gray matter volume, cortical thickness, hippocampal vol-
For descriptive analysis, the maximum, minimum, average, ume, or volumes of specific brain structures such as the amyg-
and median were provided. The Pearson product moment test dala and cingulate cortex. Structural abnormalities were found
was used to examine the correlation between the publication in many psychiatric conditions, such as schizophrenia spectrum
year and author count. A P < .05 was considered statistically and other psychotic disorders (10 articles), ASD (6 articles), de-
significant. pressive disorders (6 articles), ADHD (3 articles), and PTSD
(3 articles). Notably, 13 articles examined the hippocampal vol-
ume, with a volume reduction in major depressive disorder,32–36
Results
schizophrenia,37–39 and PTSD,40–42 and a volume enlargement
The MEDLINE (OVID) search returned 41,188 articles; the
in ASD.43
Web of Science All Databases search returned 110,464 articles.
An overlap existed between these two sets of results, because the Diffusion Tensor Imaging
Web of Science All Databases contain the MEDLINE database.
The final merged set of results contained 139,898 articles, which Proposed in the 1990s, diffusion tensor imaging (DTI) is a rela-
were then screened against the inclusion criteria in descending tively new MRI technique that identifies white matter tracts
order of yearly citation. A total of 263 articles were screened to in the brain, by following paths of water diffusion.44 Thus,
reach the 100th most highly cited article. DTI supplements the role of sMRI by providing structural in-
formation of the white matter tracts. Six of the most highly
Top 100 Highly Cited Articles cited articles used DTI to demonstrate structural abnormality
of white matter in ASD,45–47 schizophrenia,48,49 and stimulant
Shown in Table 1 are these 100 most highly cited original re-
drug addiction.50
search articles that used neuroimaging modalities to investigate
the pathophysiology, classification, diagnosis, and treatment of fMRI
primary psychiatric disorders. For each article, the diagnostic
group of the studied psychiatric disorder, the neuroimaging fMRI measures blood flow in the brain, taking advantage of
modality, the studied brain areas, and the main neuroimag- the difference in magnetic properties between oxyhemoglobin
ing findings were listed. The yearly citation count ranged from and deoxyhemoglobin.11 Based on the notion that an increased
137.46/year to 31.09/year (median: 40.43/year). The total cita- brain blood flow directly corresponds to enhanced brain activi-
tion count ranged from 1,793 to 32 (median: 559.5). ties, fMRI has been used since 1991 for real-time measurements
of brain’s level of function.51
Psychiatric Conditions Studied In the 100 most highly cited articles, fMRI was used to
A wide range of psychiatric conditions, as classified by DSM-5, investigate all identified psychiatric conditions except antisocial
were studied in these most highly cited articles. The major- personality disorder. Two-thirds of the fMRI articles involved
ity of the articles (97) focused on one psychiatric condition, brain function measurements with the participants performing
whereas two articles studied two conditions and one article tasks related to the investigated condition. One-third of the
studied three conditions. As shown in Table 2, the most studied fMRI articles measured brain function at resting state, a more
psychiatric conditions were depressive disorders (30 articles), recent technique that allowed evaluation of connectivity and
schizophrenia spectrum and other psychotic disorders (27 arti- whole-brain functional integrity.13
cles), and ASD (17 articles). Also studied were substance-related
Magnetization Transfer Ratio and Magnetic Resonance Spectroscopy
and addictive disorders (seven articles), PTSD (seven articles),
ADHD (five articles), obsessive compulsive disorder (three ar- Magnetization transfer ratio (MTR) and magnetic resonance
ticles), bipolar disorders (three articles), anxiety disorders (two spectroscopy (MRS) are two specialized MRI imaging
articles), specific learning disorder (two articles), and antisocial techniques. MTR improves imaging contrast in MRI,52 and
personality disorder (one article). was used in one article to measure the strength of white matter
connection in schizophrenic patients as defined as the level
Neuroimaging Modalities of myelination.49 MRS allows noninvasive measurements of
Table 3 lists the neuroimaging modalities that were used in the metabolite levels in the brain,11 and was used in one article
100 most highly cited articles. Four articles used two modal- to measure levels of neurotransmitters (glutamate, gamma-
ities, and the rest used one modality. The most used three aminobutyric acid) in patients with major depressive disorder.53
modalities were fMRI (42 articles), sMRI (30 articles), and PET
(22 articles). PET and Single-Photon Emission Computed Tomography
PET and single-photon emission computed tomography

sMRI
(SPECT) are both nuclear medicine modalities that assess
Developed in the 1970s, MRI makes use of inherent magnetic brain functional levels by measuring emitted radiation from
properties of materials to produce tissue contrast to visualize short half-life radiopharmaceuticals.11 In PET, the radiophar-
structures in the body.31 In sMRI, tissues can be differentiated maceuticals emit positrons, which collide with and annihilate
by the difference of signal from hydrogen nuclei under an exter- electrons. Photon pairs (511 keV) emitted in opposite directions
nal magnetic field.11 Without ionizing radiation, MRI achieves are then recorded and analyzed to localize the origin of the
Gong et al: Neuroimaging in Psychiatric Disorders 3

4
Table 1. The Most Highly Cited 100 Original Research Articles that Used Neuroimaging Modalities to Investigate the Pathophysiology, Classification, Diagnosis, and Treatment of Psychiatric Disorders,
Ranked by Yearly Average Citation
Psychiatric Neuro-imaging Main Brain Areas Yearly Citation

Rank Article Condition Modality Studied Main Neuroimaging Findings (Total)
1 Mayberg HS, Lozano AM, Voon V, et al. Deep Depression PET Subgenual cingulate Electrical stimulation of the subgenual 137.46
brain stimulation for treatment-resistant region cingulate white matter reverses (1,787)
depression. Neuron 2005;45:651-60 symptoms in patients with
treatment-resistant depression
2 Egan MF, Goldberg TE, Kolachana BS, et al. Schizophrenia/ fMRI-TB Prefrontal lobe COMT Val allele increases risk for 105.47
Effect of COMT Val108/158 Met genotype on psychosis schizophrenia by impairing prefrontal (1,793)
frontal lobe function and risk for physiology
schizophrenia. Proc Natl Acad Sci USA
2001;98:6917-22
3 Greicius MD, Flores BH, Menon V, et al. Depression fMRI-RS Subgenual cingulate Increased resting-state subgenual 96.82
Resting-state functional connectivity in major region, thalamus cingulate and thalamic functional (1,065)
depression: abnormally increased connectivity in patients with depression
contributions from subgenual cingulate cortex
and thalamus. Biol Psychiatry 2007; 62:429-37
4 Drevets WC, Price JL, Simpson JR, Jr, et al. Depression; PET Subgenual Decreased brain activity and reduced 77.00
Journal of Neuroimaging Vol 0 No 0 October 2018

Subgenual prefrontal cortex abnormalities in bipolar sMRI prefrontal cortex cortical volume in the subgenual (1,617)
mood disorders. Nature 1997;386:824-7 prefrontal cortex in patients with
bipolar or unipolar depression
5 Zang YF, He Y, Zhu CZ, et al. Altered baseline ADHD fMRI-RS Multiple cortical Changed spontaneous neuronal activity of 74.45
brain activity in children with ADHD revealed regions, cerebellum, the studied brain regions in children (819)
by resting-state functional MRI. Brain Dev brainstem with ADHD
2007;29:83-91
6 Whitfield-Gabrieli S, Thermenos HW, Milanovic Schizophrenia/ fMRI-TB Medial and Hyperactivation and hypoconnectivity in 73.44
S, et al. Hyperactivity and hyperconnectivity psychosis dorsolateral the default network in patients with (661)
of the default network in schizophrenia and in prefrontal cortex, schizophrenia
first-degree relatives of persons with posterior cingulate
schizophrenia. Proc Natl Acad Sci USA cortex
2009;106:1279-84
7 Dapretto M, Davies MS, Pfeifer JH, et al. ASD fMRI-TB Inferior frontal Impaired mirror neuron activity in the 66.92
Understanding emotions in others: mirror gyrus inferior frontal gyrus in children with (803)
neuron dysfunction in children with autism autism
spectrum disorders. Nat Neurosci
2006;9:28-30
8 Di Martino A, Yan CG, Li Q, et al. The autism ASD fMRI-RS Whole brain Establishment of a brain imaging data 65.25
brain imaging data exchange: towards a exchange platform for autism studies (261)
large-scale evaluation of the intrinsic brain
architecture in autism. Mol Psychiatry
2014;19:659-67
(continued)
Table 1. Continued
Neuro-
Psychiatric imaging Main Brain Areas Yearly Citation
9 Ho BC, Andreasen NC, Ziebell S, Pierson R, Schizophrenia/ sMRI Whole brain Use of antipsychotics causes brain volume 64.29
Magnotta V. Long-term antipsychotic psychosis loss in patients with schizophrenia (450)
treatment and brain volumes: a longitudinal
study of first-episode schizophrenia. Arch Gen
Psychiatry 2011;68:128-37
10 Lynall ME, Bassett DS, Kerwin R, et al. Schizophrenia/ fMRI-RS Seventy-two Decreased functional connectivity but 64.25
Functional connectivity and brain networks in psychosis cerebral regions increased robustness in patients with (514)
schizophrenia. J Neurosci 2010;30:9477-87 schizophrenia
11 Shaw P, Eckstrand K, Sharp W, et al. ADHD sMRI Whole brain Delayed regional cortical maturation in 61.73
Attention-deficit/hyperactivity disorder is children with ADHD (679)
characterized by a delay in cortical maturation.
Proc Natl Acad Sci USA 2007;104:19649-54
12 Dalton KM, Nacewicz BM, Johnstone T, et al. ASD fMRI-TB Fusiform gyrus, Positive correlation between fusiform 59.69
Gaze fixation and the neural circuitry of face amygdala gyrus and amygdala activation and gaze (776)
processing in autism. Nat Neurosci fixation in patients with autism
2005;8:519-26
13 Sheline YI, Wang PW, Gado MH, Csernansky Depression sMRI Hippocampus Decreased hippocampal volume in 59.68
JG, Vannier MW. Hippocampal atrophy in patients with depression (1313)
recurrent major depression. Proc Natl Acad
Sci USA 1996;93:3908-13
14 Liu Y, Liang M, Zhou Y, et al. Disrupted Schizophrenia/ fMRI-RS Ninety cortical and Disrupted small-world network properties 58.40
small-world networks in schizophrenia. Brain psychosis subcortical in patients with schizophrenia (584)
2008;131:945-61 regions
15 Just MA, Cherkassky VL, Keller TA, Minshew ASD fMRI-TB Multiple cortical Decreased cortical functional connectivity 58.29
NJ. Cortical activation and synchronization regions in patients with autism (816)
during sentence comprehension in
high-functioning autism: evidence of
underconnectivity. Brain 2004;127:1811-21
16 Garrity AG, Pearlson GD, McKiernan K, Lloyd Schizophrenia/ fMRI-TB Default mode Altered temporal frequency and spatial 57.64
D, Kiehl KA, Calhoun VD. Aberrant "default psychosis network location of the default mode network in (634)
mode" functional connectivity in patients with schizophrenia
schizophrenia. Am J Psychiatry
2007;164:450-7
17 Sheline YI, Price JL, Yan Z, Mintun MA. Depression fMRI-RS Cognitive control, Increased connectivity of the studied 56.50
Resting-state functional MRI in depression default mode, and networks to the bilateral dorsal medial (452)
unmasks increased connectivity between affective networks prefrontal cortex in patients with
networks via the dorsal nexus. Proc Natl Acad depression
Sci USA 2010;107:11020-5
(continued)
Gong et al: Neuroimaging in Psychiatric Disorders

5
6
Table 1. Continued
Neuro-
18 Bassett DS, Bullmore E, Verchinski BA, Mattay Schizophrenia/ sMRI Multimodal network Abnormal multimodal network 55.90
VS, Weinberger DR, Meyer-Lindenberg A. psychosis organization in patients with (559)
Hierarchical organization of human cortical schizophrenia
networks in health and schizophrenia. J
Neurosci 2008;28:9239-48
19 Pantelis C, Velakoulis D, McGorry PD, et al. Schizophrenia/ sMRI Multiple cortical Gray-matter abnormalities in different 55.00
Neuroanatomical abnormalities before and psychosis regions cortical regions can appear before or at (825)
after onset of psychosis: a cross-sectional and the onset of psychosis
longitudinal MRI comparison. Lancet
2003;361:281-8
20 Castellanos FX, Lee PP, Sharp W, et al. ADHD sMRI Whole brain Roughly parallel development trajectories 54.81
Developmental trajectories of brain volume for many brain structures in ADHD (877)
abnormalities in children and adolescents with patients and controls during childhood
attention-deficit/hyperactivity disorder. JAMA and adolescence
2002;288:1740-8
21 Sheline YI, Barch DM, Price JL, et al. The Depression fMRI-TB Default mode Increased stimulus-induced activity and 54.56

default mode network and self-referential network decreased downregulation in the (491)
processes in depression. Proc Natl Acad Sci default mode network in patients with
USA 2009;106:1942-7 depression
22 Bremner JD, Narayan M, Anderson ER, Staib Depression sMRI Hippocampus Decreased left hippocampal volume in 54.39
LH, Miller HL, Charney DS. Hippocampal patients with depression (979)
volume reduction in major depression. Am J
23 Milad MR, Pitman RK, Ellis CB, et al. PTSD fMRI-TB Amygdala, Dysfunctional activation of the studied 54.33
Neurobiological basis of failure to recall hippocampus, brain structures in patients with PTSD (489)
extinction memory in posttraumatic stress ventromedial
disorder. Biol Psychiatry 2009;66:1075-82 prefrontal and
dorsal anterior
cingulate cortices
24 Volkow ND, Wang GJ, Telang F, et al. Cocaine Addiction PET Dorsal and ventral Decreased dopamine level in the dorsal 50.42
cues and dopamine in dorsal striatum: striatum striatum during craving in cocaine (605)
mechanism of craving in cocaine addiction. J addiction
Neurosci 2006;26:6583-8
25 Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression sMRI Hippocampus, Decreased bilateral hippocampal and 49.68
Depression duration but not age predicts amygdala amygdala core nuclei volumes in (944)
hippocampal volume loss in medically healthy patients with recurrent major
women with recurrent major depression. J depression
Neurosci 1999;19:5034-43
(continued)
Table 1. Continued
Neuro-
26 Johnstone T, van Reekum CM, Urry HL, Kalin Depression fMRI-TB Prefrontal cortex, Altered prefrontal cortical activation in 49.55
NH, Davidson RJ. Failure to regulate: amygdala response to negative stimuli in patients (545)
counterproductive recruitment of top-down with depression
prefrontal-subcortical circuitry in major
depression. J Neurosci 2007;27:8877-84
27 Sheline YI, Gado MH, Kraemer HC. Untreated Depression sMRI Hippocampus Increased hippocampal volume loss in 49.07
depression and hippocampal volume loss. Am patients with longer durations of (736)
J Psychiatry 2003;160:1516-8 untreated depression
28 Gilbertson MW, Shenton ME, Ciszewski A, et al. PTSD sMRI Hippocampus Negative correlation between PTSD 48.88
Smaller hippocampal volume predicts disorder severity and hippocampal (782)
pathologic vulnerability to psychological volume in monozygotic twins with
trauma. Nat Neurosci 2002;5:1242-7 discordant trauma exposure
29 Just MA, Cherkassky VL, Keller TA, Kana RK, ASD fMRI-TB Frontal and parietal Cortical underconnectivity in patients 48.55
Minshew NJ. Functional and anatomical cortices, corpus with autism (534)
cortical underconnectivity in autism: evidence callosum
from an FMRI study of an executive function
task and corpus callosum morphometry.
Cereb Cortex 2007;17:951-61
30 Castelli F, Frith C, Happe F, Frith U. Autism, ASD PET Medial prefrontal Altered activation pattern of the 48.00
Asperger syndrome and brain mechanisms for cortex, superior mentalizing network in patients with (768)
the attribution of mental states to animated temporal sulcus, autism and Asperger syndrome
shapes. Brain 2002;125:1839-49 extrastriate cortex
31 Courchesne E, Karns CM, Davis HR, et al. ASD sMRI Whole brain Early overgrowth and subsequent 47.88
Unusual brain growth patterns in early life in abnormally slowed growth in young (814)
patients with autistic disorder: an MRI study. patients with autism
Neurology 2001;57:245-54
32 Lozano AM, Mayberg HS, Giacobbe P, Hamani Depression PET Limbic and cortical Altered metabolic activity in the limbic 47.00
C, Craddock RC, Kennedy SH. Subcallosal regions and cortical regions following deep (470)
cingulate gyrus deep brain stimulation for brain stimulation of the subcallosal
treatment-resistant depression. Biol Psychiatry cingulate gyrus in patients with
2008;64:461-7 treatment-resistant depression
33 Schlaepfer TE, Cohen MX, Frick C, et al. Deep Depression PET Fronto-striatal Altered metabolic activity in the 45.40
brain stimulation to reward circuitry alleviates networks fronto-striatal networks following deep (454)
anhedonia in refractory major depression. brain stimulation of the nucleus
Neuropsychopharmacology 2008;33:368-77 accumbens in patients with refractory
depression
(continued)

7
8
Table 1. Continued
Neuro-
34 Baron-Cohen S, Ring HA, Wheelwright S, et al. ASD fMRI-TB Superior temporal Activation of fronto-temporal regions 45.37
Social intelligence in the normal and autistic gyrus, amygdala, instead of amygdala in a social (862)
brain: an fMRI study. Eur J Neurosci prefrontal cortex intelligence test in patients with autism
1999;11:1891-8 or Asperger syndrome
35 Jafri MJ, Pearlson GD, Stevens M, Calhoun VD. Schizophrenia/ fMRI-RS Seven resting state Increased functional connectivity in 45.20
A method for functional network connectivity psychosis networks several resting state networks in (452)
among spatially independent resting-state patients with schizophrenia
components in schizophrenia. Neuroimage
2008;39:1666-81
36 Drysdale AT, Grosenick L, Downar J, et al. Depression fMRI-RS Limbic and Classification of four neurophysiological 45.00
Resting-state connectivity biomarkers define frontostriatal subtypes of depression based on (45)
neurophysiological subtypes of depression. networks distinct dysfunctional connectivity in
Nat Med 2017;23:28-38 the limbic and frontostriatal networks
37 Castellanos FX, Margulies DS, Kelly C, et al. ADHD fMRI-RS Anterior cingulate Decreased long-range connections linking 44.50
Cingulate-precuneus interactions: a new locus cortex, posterior the dorsal anterior cingulate to the (445)
of dysfunction in adult cingulate cortex, posterior cingulate and precuneus in
attention-deficit/hyperactivity disorder. Biol precuneus patients with ADHD

37 Bloomfield PS, Selvaraj S, Veronese M, et al. Schizophrenia/ PET Whole brain Increased microglial activity in patients 44.50
Microglial activity in people at ultra high risk psychosis with schizophrenia or at ultra high risk (89)
of psychosis and in schizophrenia: an of psychosis
[(11)C]PBR28 PET Brain Imaging Study. Am J
39 Siegle GJ, Thompson W, Carter CS, Steinhauer Depression fMRI-TB Amygdala, Increased amygdala and decreased 44.36
SR, Thase ME. Increased amygdala and dorsolateral dorsolateral prefrontal activity in (488)
decreased dorsolateral prefrontal BOLD prefrontal cortex patients with depression
responses in unipolar depression: related and
independent features. Biol Psychiatry
2007;61:198-209
40 Sheline YI, Barch DM, Donnelly JM, Ollinger Depression fMRI-TB Amygdala Increased amygdala activity in response 44.35
JM, Snyder AZ, Mintun MA. Increased to masked emotional faces in patients (754)
amygdala response to masked emotional faces with depression, which was normalized
in depressed subjects resolves with with antidepressant treatment
antidepressant treatment: an fMRI study. Biol
41 Farde L, Nordstrom AL, Wiesel FA, Pauli S, Schizophrenia/ PET Basal ganglia Distinct D1 and D2 dopamine receptor 43.15
Halldin C, Sedvall G. Positron emission psychosis occupancy patterns following treatment (1122)
tomographic analysis of central D1 and D2 with classic neuroleptics and clozapine,
dopamine receptor occupancy in patients and the correlation with extrapyramidal
treated with classical neuroleptics and side effects, in patients with
clozapine. Relation to extrapyramidal side schizophrenia
effects. Arch Gen Psychiatry 1992;49:538-44
(continued)
Table 1. Continued
Neuro-
41 Shin LM, Wright CI, Cannistraro PA, et al. A PTSD fMRI-TB Amygdala, medial Increased amygdala and decreased medial 43.15
functional magnetic resonance imaging study prefrontal cortex prefrontal cortex activity in response to (561)
of amygdala and medial prefrontal cortex fearful faces in patients with PTSD
responses to overtly presented fearful faces in
posttraumatic stress disorder. Arch Gen
43 Zeng LL, Shen H, Liu L, et al. Identifying major Depression fMRI-RS Whole brain Altered whole-brain resting-state 42.67
depression using whole-brain functional functional connectivity in patients with (256)
connectivity: a multivariate pattern analysis. depression
Brain 2012;135:1498-507
44 Bewernick BH, Hurlemann R, Matusch A, et al. Depression PET Subgenual cingulate, Decreased metabolism in the subgenual 42.63
Nucleus accumbens deep brain stimulation prefrontal regions cingulate and prefrontal regions (341)
decreases ratings of depression and anxiety in following deep brain stimulation of the
treatment-resistant depression. Biol Psychiatry nucleus accumbens in patients with
2010;67:110-6 treatment-resistant depression
45 Zhang J, Wang J, Wu Q, et al. Disrupted brain Depression fMRI-RS Ninety brain regions Disruptions of the topological 42.57
connectivity networks in drug-naive, organizations of functional brain (298)
first-episode major depressive disorder. Biol networks in patients with depression
46 Goldin PR, Gross JJ. Effects of Anxiety fMRI-TB Multiple brain Decreased amygdala activity and 42.13
mindfulness-based stress reduction (MBSR) on regions increased activity in brain regions (337)
emotion regulation in social anxiety disorder. implicated in attentional deployment
Emotion 2010;10:83-91 during MBSR in patients with social
anxiety disorder
47 Setiawan E, Wilson AA, Mizrahi R, et al. Role of Depression PET Prefrontal cortex, Increased microglial activation in the 42.00
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49 Wolff JJ, Gu H, Gerig G, et al. Differences in ASD DTI White matter tracts Aberrant development of white matter 41.67
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Am J Psychiatry 2012;169:589-600 the first year of life
(continued)

9
10
Table 1. Continued
Neuro-
50 Breiter HC, Gollub RL, Weisskoff RM, et al. Addiction fMRI-TB Multiple brain Altered brain network activities in 40.52
Acute effects of cocaine on human brain regions patients with cocaine dependence (851)
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51 Zhu X, Wang X, Xiao J, et al. Evidence of a Depression fMRI-RS Anterior medial Altered functional activity (increased in 40.33
dissociation pattern in resting-state default cortex, posterior the anterior medial cortex and (242)
mode network connectivity in first-episode, medial cortex decreased in the posterior medial
treatment-naive major depression patients. cortex) in patients with depression
Biol Psychiatry 2012;71:611-7
52 Laruelle M, Abi-Dargham A, van Dyck CH, Schizophrenia/ SPECT Striatum Increased amphetamine-induced striatal 39.64
et al. Single photon emission computerized psychosis dopamine in patients with (872)
tomography imaging of amphetamine-induced schizophrenia
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53 MacQueen GM, Campbell S, McEwen BS, et al. Depression sMRI Hippocampus Positive correlation between hippocampal 39.53

Course of illness, hippocampal function, and volume reduction and illness duration (593)
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53 Ersche KD, Jones PS, Williams GB, Turton AJ, Addiction DTI Frontostriatal region Abnormalities in frontostriatal brain 39.33
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56 Breier A, Su TP, Saunders R, et al. Schizophrenia/ PET Striatum Increased striatal synaptic dopamine 38.71
Schizophrenia is associated with elevated psychosis concentration in patients with (813)
amphetamine-induced synaptic dopamine schizophrenia
concentrations: evidence from a novel
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57 Howes OD, Montgomery AJ, Asselin MC, et al. Schizophrenia/ PET Striatum Dopamine overactivity in the associative 38.33
Elevated striatal dopamine function linked to psychosis striatum predates the onset of (345)
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Psychiatry 2009;66:13-20 symptom severity
(continued)
Table 1. Continued
Neuro-
58 Cannon TD, Chung Y, He G, et al. Progressive Schizophrenia/ sMRI Cerebral cortex Increased gray matter loss in multiple 38.00
reduction in cortical thickness as psychosis psychosis cortical regions in patients at high risk (114)
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59 Courchesne E, Carper R, Akshoomoff N. ASD sMRI Cerebral cortex Abnormally increased brain growth rate 37.80
Evidence of brain overgrowth in the first year in the first year corresponds to greater (567)
of life in autism. JAMA 2003;290:337-44 cerebral gray matter volume at 2–5
years in patients with autism
60 Clementz BA, Sweeney JA, Hamm JP, et al. Schizophrenia/ sMRI Whole brain Biotype-based classification of psychosis 37.50
Identification of distinct psychosis biotypes psychosis; using multiple biomarkers, including (75)
using brain-based biomarkers. Am J Psychiatry bipolar neuroimaging findings
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61 Robinson D, Woerner MG, Alvir JM, et al. Schizophrenia/ sMRI Whole brain Identification of predictors of relapse, 37.47
Predictors of relapse following response from a psychosis including neuroimaging features, in (712)
first episode of schizophrenia or schizoaffective patients with schizophrenia or
disorder. Arch Gen Psychiatry 1999;56:241-7 schizoaffective disorder
62 Rauch SL, Whalen PJ, Shin LM, et al. PTSD fMRI-TB Amygdala Increased amygdala responses to masked 37.33
Exaggerated amygdala response to masked facial stimuli in patients with PTSD (672)
facial stimuli in posttraumatic stress disorder: a
functional MRI study. Biol Psychiatry
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63 Kapur S, Zipursky R, Jones C, Remington G, Schizophrenia/ PET Striatum, Association between dopamine D2 36.83
Houle S. Relationship between dopamine D(2) psychosis cerebellum receptor occupancy and clinical (663)
occupancy, clinical response, and side effects: response/side effects in schizophrenic
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64 Fu CH, Williams SC, Cleare AJ, et al. Depression fMRI-TB Amygdala, striatum, Decreased activation capacity in the left 36.50
Attenuation of the neural response to sad faces frontoparietal limbic, subcortical and neocortical (511)
in major depression by antidepressant cortex, pregenual areas, and increased dynamic range in
treatment: a prospective, event-related cingulate cortex the left prefrontal cortex in depression
functional magnetic resonance imaging study. patients undergoing antidepressant
Arch Gen Psychiatry 2004;61:877-89 treatment
65 Hasler G, van der Veen JW, Tumonis T, Meyers Depression MRS Dorsomedial and Reduced glutamate/glutamine and 36.45
N, Shen J, Drevets WC. Reduced prefrontal dorsal gamma-aminobutyric acid levels in the (401)
glutamate/glutamine and anterolateral studied brain regions in patients with
gamma-aminobutyric acid levels in major prefrontal cortices depression
depression determined using proton magnetic
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2007;64:193-200

(continued)
11
12
Table 1. Continued
Neuro-
66 Shenton ME, Kikinis R, Jolesz FA, et al. Schizophrenia/ sMRI Left temporal lobe Localized reduction in the gray matter of 36.38
Abnormalities of the left temporal lobe and psychosis the left temporal lobe in patients with (946)
thought disorder in schizophrenia. A schizophrenia
quantitative magnetic resonance imaging
study. N Engl J Med 1992;327:604-12
67 Mataix-Cols D, Wooderson S, Lawrence N, OCD fMRI-TB Multiple brain Increased activation in the studied brain 36.07
Brammer MJ, Speckens A, Phillips ML. regions regions in patients with OCD (505)
Distinct neural correlates of washing,
checking, and hoarding symptom dimensions
in obsessive-compulsive disorder. Arch Gen
68 Hamilton JP, Furman DJ, Chang C, Thomason Depression fMRI-RS Default-mode Altered activity in the default-mode and 35.71
ME, Dennis E, Gotlib IH. Default-mode and network, task-positive networks in patients with (250)
task-positive network activity in major task-positive depression
depressive disorder: implications for adaptive network, right

and maladaptive rumination. Biol Psychiatry fronto-insular
2011;70:327-33 cortex
69 Drevets WC, Videen TO, Price JL, Preskorn SH, Depression PET Prefrontal cortex, Altered activity in the prefrontal cortex 35.46
Carmichael ST, Raichle ME. A functional amygdala and amygdala in patients with familial (922)
anatomical study of unipolar depression. J pure depressive disease
Neurosci 1992;12:3628-41
70 Courchesne E, Campbell K, Solso S. Brain ASD sMRI Whole brain Early overgrowth in infancy and toddler 35.43
growth across the life span in autism: years and increased decline in brain (248)
age-specific changes in anatomical pathology. size in adolescence to late middle age in
Brain Res 2011;1380:138-45 patients with autism
71 van den Heuvel MP, Mandl RC, Stam CJ, Kahn Schizophrenia/ DTI Frontal and Longer node-specific path lengths in 35.25
RS, Hulshoff Pol HE. Aberrant frontal and psychosis MTR temporal regions frontal and temporal regions in patients (282)
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Neurosci 2010;30:15915-26
72 Volkow ND, Chang L, Wang GJ, et al. Addiction PET Striatum Decreased striatal dopamine transporter 35.00
Association of dopamine transporter reduction level in methamphetamine users (595)
with psychomotor impairment in
methamphetamine abusers. Am J Psychiatry
2001;158:377-82
(continued)
Table 1. Continued
Neuro-
73 Siegle GJ, Steinhauer SR, Thase ME, Stenger Depression fMRI-TB Amygdala Prolonged amygdala activity in response 34.81
VA, Carter CS. Can’t shake that feeling: to emotional information in patients (557)
event-related fMRI assessment of sustained with depression
amygdala activity in response to emotional
information in depressed individuals. Biol
Psychiatry 2002;51:693-707
74 Baxter LR, Jr., Schwartz JM, Phelps ME, et al. Depression; PET Left dorsal Altered activity in the left dorsal 34.66
Reduction of prefrontal cortex glucose bipolar; anterolateral anterolateral prefrontal cortex in (1005)
metabolism common to three types of OCD prefrontal cortex patients with unipolar, bipolar
depression. Arch Gen Psychiatry depression and OCD
1989;46:243-50
75 Castellanos FX, Giedd JN, Marsh WL, et al. ADHD sMRI Multiple brain Altered activity in the studied brain 34.64
Quantitative brain magnetic resonance regions regions consistent with dysfunction of (762)
imaging in attention-deficit hyperactivity right-sided prefrontal-striatal systems in
disorder. Arch Gen Psychiatry 1996;53:607-16 patients with ADHD
76 Bremner JD, Randall P, Vermetten E, et al. PTSD sMRI Hippocampus Decreased left hippocampal volume in 34.62
Magnetic resonance imaging-based PTSD patients with a history of (727)
measurement of hippocampal volume in childhood abuse
posttraumatic stress disorder related to
childhood physical and sexual abuse–a
preliminary report. Biol Psychiatry
1997;41:23-32
77 Velakoulis D, Wood SJ, Wong MT, et al. Schizophrenia/ sMRI Hippocampus, Distinct medial temporal structural 34.50
Hippocampal and amygdala volumes psychosis amygdala change patterns in patients with (414)
according to psychosis stage and diagnosis: a different types of psychosis (chronic
magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis,
schizophrenia, first-episode psychosis, and or ultra-high-risk individuals)
ultra-high-risk individuals. Arch Gen
78 Paulesu E, Demonet JF, Fazio F, et al. Dyslexia: Specific learning PET Left hemisphere Decreased activity level in left 34.41
cultural diversity and biological unity. Science disorder hemisphere regions in dyslexia patients (585)
2001;291:2165-7 in three countries
79 Mayberg HS, Brannan SK, Mahurin RK, et al. Depression PET Rostral anterior Hypometabolism in the rostral anterior 34.38
Cingulate function in depression: a potential cingulate region cingulate region in depression patients (722)
predictor of treatment response. Neuroreport not responding to antidepressant
1997;8:1057-61 treatment
80 Monk CS, Telzer EH, Mogg K, et al. Amygdala Anxiety fMRI-TB Amygdala, Increased right amygdala activation and 34.20
and ventrolateral prefrontal cortex activation ventrolateral strong negative connectivity to the right (342)
to masked angry faces in children and prefrontal cortex ventrolateral prefrontal cortex in
adolescents with generalized anxiety disorder. response to masked angry faces in
Arch Gen Psychiatry 2008;65:568-76 pediatric patients with generalized
anxiety disorder
80 van den Heuvel MP, Sporns O, Collin G, et al. Schizophrenia/ DTI Whole brain Selective disruption of brain connectivity 34.20

Abnormal rich club organization and psychosis fMRI-RS among central hub regions in patients (171)
functional brain dynamics in schizophrenia. with schizophrenia
JAMA Psychiatry 2013;70:783-92
13
(continued)
Table 1. Continued
14
Neuro- Yearly
Psychiatric imaging Main Brain Areas Citation
82 Raine A, Lencz T, Bihrle S, LaCasse L, Colletti P. Antisocial sMRI Prefrontal cortex Decreased prefrontal gray matter 34.00
Reduced prefrontal gray matter volume and volume in patients with (612)
reduced autonomic activity in antisocial antisocial personality disorder
personality disorder. Arch Gen Psychiatry
2000;57:119-27
83 Shaywitz BA, Shaywitz SE, Pugh KR, et al. Specific fMRI-TB Posterior brain Disruption in the posterior brain 33.56
Disruption of posterior brain systems for reading learning regions regions in children with (537)
in children with developmental dyslexia. Biol disorder developmental dyslexia
84 Garavan H, Pankiewicz J, Bloom A, et al. Addiction fMRI-TB Thirteen brain Activation of multiple brain 33.17
Cue-induced cocaine craving: neuroanatomical regions regions in association with (597)
specificity for drug users and drug stimuli. Am J cocaine craving
Psychiatry 2000;157:1789-98
85 Baxter LR, Jr., Schwartz JM, Bergman KS, et al. OCD PET Right caudate Decreased right caudate nucleus 33.12
Caudate glucose metabolic rate changes with both nucleus activity in OCD patients (861)
drug and behavior therapy for undergoing drug or behavior
obsessive-compulsive disorder. Arch Gen therapy
86 Abi-Dargham A, Rodenhiser J, Printz D, et al. Schizophrenia/ SPECT Striatum Increased striatal stimulation of D2 33.00

Increased baseline occupancy of D2 receptors by psychosis receptor by dopamine in (594)
dopamine in schizophrenia. Proc Natl Acad Sci patients with schizophrenia
USA 2000;97:8104-9
87 Barnea-Goraly N, Kwon H, Menon V, Eliez S, ASD DTI White matter tracts Disruption of the white matter 32.29
Lotspeich L, Reiss AL. White matter structure in tracts between the studied (452)
autism: preliminary evidence from diffusion regions in patients with autism
tensor imaging. Biol Psychiatry 2004;55:323-6
88 Alexander AL, Lee JE, Lazar M, et al. Diffusion ASD DTI Corpus callosum Altered microstructure of the 32.09
tensor imaging of the corpus callosum in Autism. corpus callosum in patients with (353)
Neuroimage 2007;34:61-73 autism
89 Callicott JH, Mattay VS, Verchinski BA, Marenco S, Schizophrenia/ fMRI-TB Dorsolateral Prefrontal cortical dysfunction in 32.00
Egan MF, Weinberger DR. Complexity of psychosis prefrontal cortex patients with schizophrenia (480)
prefrontal cortical dysfunction in schizophrenia:
more than up or down. Am J Psychiatry
2003;160:2209-15
89 Hazlett HC, Gu H, Munsell BC, et al. Early brain ASD sMRI Whole brain Hyper-expansion of cortical 32.00
development in infants at high risk for autism surface area between 6 and 12 (32)
spectrum disorder. Nature 2017;542:348-51 months of age predicts autism
diagnosis at 24 months in
high-risk infants
91 Shin LM, Orr SP, Carson MA, et al. Regional PTSD PET Amygdala, medial Complex pattern of changes in 31.86
cerebral blood flow in the amygdala and medial prefrontal cortex medial prefrontal cortex and (446)
prefrontal cortex during traumatic imagery in amygdala activity in patients
male and female Vietnam veterans with PTSD. with PTSD
Arch Gen Psychiatry 2004;61:168-76
(continued)
Table 1. Continued
Neuro-
92 McGrath CL, Kelley ME, Holtzheimer PE, et al. Depression PET Six limbic and Insula activity level predicts response to 31.80
Toward a neuroimaging treatment selection cortical regions escitalopram or behavior therapy in (159)
biomarker for major depressive disorder. patients with depression
JAMA Psychiatry 2013;70:821-9
93 Sparks BF, Friedman SD, Shaw DW, et al. Brain ASD sMRI Cerebrum, Abnormal volume changes of the studied 31.75
structural abnormalities in young children with cerebellum, regions in young children with autism (508)
autism spectrum disorder. Neurology amygdala,
2002;59:184-92 hippocampus
94 Pajonk FG, Wobrock T, Gruber O, et al. Schizophrenia/ sMRI Hippocampus Increased hippocampal volume following 31.63
Hippocampal plasticity in response to exercise psychosis aerobic exercise in patients with (253)
in schizophrenia. Arch Gen Psychiatry schizophrenia
2010;67:133-43
95 Surguladze S, Brammer MJ, Keedwell P, et al. A Depression fMRI-TB Multiple brain Increased neural responses to sad but not 31.62
differential pattern of neural response toward regions happy facial expressions in the studied (411)
sad versus happy facial expressions in major regions in patients with depression
depressive disorder. Biol Psychiatry
2005;57:201-9
96 Pierce K, Muller RA, Ambrose J, Allen G, ASD fMRI-TB Fusiform gyrus, Individual-specific, scattered activation of 31.59
Courchesne E. Face processing occurs outside inferior temporal brain regions outside fusiform face area (537)
the fusiform ‘face area’ in autism: evidence gyrus, middle during a face perception task in patients
from functional MRI. Brain 2001;124:2059-73 temporal gyrus, with autism
amygdala
97 Ko CH, Liu GC, Hsiao S, et al. Brain activities Addiction fMRI-TB Multiple brain Activation of the studied regions during a 31.44
associated with gaming urge of online gaming regions gaming urge/craving test in patients (283)
addiction. J Psychiatr Res 2009;43:739-47 with online game addiction
98 Schumann CM, Bloss CS, Barnes CC, et al. ASD sMRI Whole brain Abnormal growth rate in multiple brain 31.25
Longitudinal magnetic resonance imaging regions by 2.5 years of age in young (250)
study of cortical development through early children with autism
childhood in autism. J Neurosci
2010;30:4419-27
99 Callicott JH, Bertolino A, Mattay VS, et al. Schizophrenia/ fMRI-TB Dorsolateral Exaggerated and inefficient cortical 31.11
Physiological dysfunction of the dorsolateral psychosis prefrontal cortex activity in the dorsolateral prefrontal (560)
prefrontal cortex in schizophrenia revisited. cortex in patients with schizophrenia
Cereb Cortex 2000;10:1078-92
100 Grant S, London ED, Newlin DB, et al. Addiction PET Cortical and limbic Activation of a distributed neural network 31.09
Activation of memory circuits during regions in cue-elicited craving in cocaine users (684)
cue-elicited cocaine craving. Proc Natl Acad
Sci USA 1996;93:12040-5
ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OCD = obsessive compulsive disorder; PTSD = post-traumatic stress disorder; sMRI = structural MRI; fMRI-RS = functional MRI – resting state;

fMRI-TB = functional MRI – task based; DTI = diffusion tensor imaging; MTR = magnetization transfer ratio; MRS = magnetic resonance spectroscopy; SPECT = single-photon emission computed tomography.
15
Table 2. The Psychiatric Conditions Studied in the 100 Most Highly
Cited Articles
Psychiatric Condition Article Count
Depressive disorders 30
Schizophrenia spectrum and other psychotic disorders 27
Autism spectrum disorder 17
Substance-related and addictive disorders 7
Post-traumatic stress disorder 7
Attention-deficit/hyperactivity disorder 5
Obsessive compulsive disorder 3
Bipolar disorders 3
Anxiety disorders 2
Specific learning disorder 2
Antisocial personality disorder 1
radiopharmaceutical activity. Among the most highly cited

articles using PET, different radiopharmaceuticals were used
for various functional measurements, including measurements
of regional cerebral blood flow using [15 O]-H2 O (nine articles),
brain glucose metabolism using [18 F]-fluorodeoxyglucose
(seven articles), dopamine receptor occupancy using ra- Fig 1. Historic trends of article count and utilized neuroimaging
diolabeled dopamine receptor ligands [11 C]-raclopride or modality in the 100 most highly cited articles. sMRI = structural MRI;
[11 C]-SCH23390, microglia activation using [18 F]-FEPPA or SPECT = single-photon emission computed tomography; fMRI-TB
= functional MRI – task based; DTI = diffusion tensor imaging; MRS
[11 C]-PBR28 (two articles), dopamine transporter level using
= magnetic resonance spectroscopy; fMRI-RS = functional MRI –
[11 C]-D-threo-methylphenidate, and dopaminergic function resting state; MTR = magnetization transfer imaging.
by [18 F]-fluoro-L-DOPA uptake (one article). In SPECT,
radiopharmaceuticals emitting lower energy gamma rays
Table 3. The Neuroimaging Modalities Used in the 100 Most Highly
(typically 140 or 159 keV) are used. Among the most highly Cited Articles
cited articles, two articles used SPECT to measure dopamine
receptor occupancy levels using [123 I]-IBZM. Modality Article Count
Functional MRI 42
Historic Trends: Publication Count and Utilized Neuroimaging
-Task-based (28)
Modalities -Resting-sate (14)
The 100 most highly cited articles were published between 1989 Structural MRI 30
and 2017, with 85% of the articles published within the last 20 -Involving hippocampal volume measurement (13)
years. Figure 1 illustrates the yearly trends of the most highly Positron emission tomography 22
cited articles, with the number of articles utilizing different neu- -Regional cerebral blood flow (9)
roimaging modalities also plotted against the publication year. -Brain glucose metabolism (7)
-Dopamine receptor occupancy (4)
The results show that highly cited articles using sMRI and PET
-Neuroinflammation (microglia activation) (2)
modalities appeared early (around 1990) and persisted through -Dopamine transporter level (1)
2017. Task-based fMRI articles appeared later (1997-2010 pe- -Dopaminergic function (L-DOPA uptake) (1)
riod). Resting-state fMRI articles emerged the latest (2007) and
Diffusion tensor imaging 6
persisted to 2017.
Single-photon emission computed tomography 2
Most Used Neuroimaging Modalities for Main Psychiatric Conditions -Dopamine receptor occupancy (2)
Magnetization transfer ratio 1
A detailed breakdown of the neuroimaging modalities used
to investigate depressive disorders, schizophrenia spectrum Magnetic resonance spectroscopy 1
and other psychotic disorders, and ASD is provided in Ta- -Neurotransmitter level (1)
ble 4. While these conditions were all investigated by vari-
ous neuroimaging modalities, the utilization patterns differed.
The most used modality for depressive disorders was PET. For
schizophrenia spectrum and other psychotic disorders, it was including seven articles describing developmental changes,
sMRI. For ASD, both sMRI and task-based fMRI were equally one genetic susceptibility, one disease classification, and one
utilized. highlighting the development of a data exchange platform.
Fifteen articles investigated the treatment of psychiatric con-
Topic of the Study
ditions (with two articles investigating two treatment options),
Table 5 summarizes the topics of the 100 most highly cited including antidepressants in six articles, deep brain stimulation
articles. The majority of the articles (85) focused on various in four, antipsychotics in three, behavioral therapy in three,
aspects of the pathophysiology of psychiatric conditions, and exercise in one.

Table 4. The Most Utilized Neuroimaging Modalities for Depressive Disorders, Schizophrenia Spectrum/Psychotic Disorders, and Autism
Spectrum Disorder
(Article Count) PET sMRI fMRI-TB fMRI-RS DTI SPECT MTR MRS
Depression 10 6 7 7 1
Schizophrenia/psychosis 5 10 5 4 2 2 1
ASD 1 6 6 1 3
ASD = autism spectrum disorder; sMRI = structural MRI; fMRI-TB = functional MRI – task based; fMRI-RS = functional MRI – resting state; DTI = diffusion tensor
imaging; SPECT = single-photon emission computed tomography; MTR = magnetization transfer ratio; MRS = magnetic resonance spectroscopy.
Table 5. Topics of the 100 Most Highly Cited Articles nal. The journals that published the most articles were JAMA
Topic Article Count
Psychiatry (20 articles, previously titled: Archives of General
Psychiatry), Biological Psychiatry (17 articles), American Journal of
Pathophysiology 85 Psychiatry (11 articles), and Proceedings of the National Academy
-Developmental changes (7) of Sciences of the United States of America (11 articles). A full list
-Genetic susceptibility (1)
of articles and their most recent impact factors is provided in
-Disease classification (1)
-Data exchange platform (1) Table 8.
Treatment 15 Study Design
-Antidepressants (6)
-Deep brain stimulation (4) The majority of the most highly cited articles were prospective
-Antipsychotics (3) (98 articles), and two articles were retrospective. The sample
-Behavioral therapy (3) sizes ranged from 3 to 1,188, with a median of 21 and average
-Exercise (1) of 63.2.
Discussion
Authors In this study, we conducted a bibliometric analysis of the 100
most highly cited original research articles that depicted the
Each of the 100 most highly cited articles had 2–42 authors. roles of neuroimaging in the investigation of the pathophysi-
Although the Pearson correlation test only showed a weak pos- ology, classification, diagnosis, and treatment of primary psy-
itive correlation between the publication year and author count chiatric disorders. By analyzing the most commonly used neu-
(correlation coefficient: .221, P = .0273), there seems to be a roimaging modalities, the most commonly studied psychiatric
trend of an increasing number of authors in more recent arti- disorders, and the most productive authors/countries/journals,
cles. The four articles with the fewest authors (2-3 authors) were we illustrated the historic trends of this highly active field that
published between 2003 and 2011. In contrast, the four articles may help guide future research. Our results can be important
with the most authors (20-42 authors) were published between not only for students and researchers new to this field, but
2014 and 2017. also for established researchers to identify innovative research
The total author count of the 100 articles was 944. Among ideas and approaches. In particular, by informing both psychia-
745 unique authors, the majority (607 authors, 81.5%) con- trists and radiologists, this study could be valuable for fostering
tributed to one article, 104 authors (14.0%) contributed to two collaboration between these two specialties in the context of
articles, 16 authors (2.1%) contributed to three articles, and 11 potential emergence of a new interdisciplinary clinical field of
authors (1.5%) contributed to four articles. Among the seven re- psychoradiology.13
searchers contributing five or six articles, six authors are from Our results reveal that multiple neuroimaging modalities
the United States. Their contributions and research focus are were utilized in psychiatric research, with the modalities com-
listed in Table 6. plementing each other to offer information about psychiatric
Among the 100 first authors, the majority were affiliated disorders at both structural and functional levels. For exam-
with the psychiatry (69), neuroscience (10), or psychology (7) ple, studies involving sMRI offered volumetric information of
departments. A minority of the authors were affiliated with global or regional brain structures, while the DTI studies of-
the radiology (seven), engineering (three), or medical physics fered complementary structural information of the white mat-
(one) departments. Other affiliations included neurology (one), ter tracts. These results can then be correlated with functional
neurosurgery (one), and pediatrics (one). information provided by fMRI and PET. Several PET, SPECT,
When analyzing the country of affiliation of the first authors, and MRS articles even involved functional studies at a molecu-
the majority of the articles originated from the United States lar level. The diversity of the utilized neuroimaging approaches
(71). Other major countries of origin included the United King- and the results highlights the need and value of innovative mul-
dom (eight), Canada (five), China (five), and Germany (three). tivariable analytical methods to make use of results from mul-
A full list of the countries of origin is provided in Table 7. tiple modalities to achieve higher diagnostic accuracy, which
could be a critical step for neuroimaging to fully enter the clin-
Journals
ical realm of psychiatry.4
The 100 most highly cited articles were published in 25 jour- Our results support the previous finding that neuroimaging
nals, including 12 neuroscience/neurology journals, 7 general research was one of the major research foci in psychiatry.15 The
medicine journals, 5 psychiatry journals, and 1 radiology jour- 100 most highly cited original articles all yielded an average

Table 6. The Most Productive Researchers among the Authors of the 100 Most Highly Cited Articles
Researcher Article# Article Rank Current Affiliation Research Focus
Bullmore, Edward T. 6 10, 18, 19, 34, 53, 64 Department of Psychiatry, Schizophrenia/psychosis (sMRI,
(MB, PhD) University of Cambridge, fMRI-RS);
Cambridge, UK ASD (fMRI-TB);
addiction (sMRI, DTI); depression
(fMRI-TB)
Sheline, Yvette I. (MD) 6 13, 17, 21, 25, 27, 40 Department of Psychiatry, Depression
University of Pennsylvania, (sMRI, fMRI-TB, fMRI-RB)
Philadelphia, USA
Mayberg, Helen S. 5 1, 32, 36, 79, 92 Center for Advanced Circuit Depression
(MD) Therapeutics, Icahn School of (fMRI-RS, PET)
Medicine at Mount Sinai, New
York, USA
Weinberger, Daniel R. 5 2, 18, 56, 89, 99 Lieber Institute for Brain Schizophrenia/psychosis
(MD) Development; Department of (sMRI, fMRI-TB, PET)
Psychiatry, Johns Hopkins
University, Baltimore, USA
Lasko, Natasha B. (PhD) 5 23, 28, 41, 62, 91 Department of Psychiatry, PTSD
Harvard Medical School, (sMRI, fMRI-TB, PET)
Boston, USA
Orr, Scott P. (PhD) 5 23, 28, 41, 62, 91 Department of Psychiatry, PTSD
Harvard Medical School, (sMRI, fMRI-TB, PET)
Boston, USA
Courchesne, Eric (PhD) 5 31, 59, 70, 96, 98 Department of Neurosciences, ASD
University of California, San (sMRI, fMRI-TB)
Diego, USA
sMRI = structural MRI; fMRI-RS = functional MRI – resting state; fMRI-TB = functional MRI – task based; DTI = diffusion tensor imaging.
Table 7. Countries of Origin of the 100 Most Highly Cited Articles, ment (deep brain stimulation in four and antidepressant in two).
Defined as the Country of Affiliation of the First Author Ten schizophrenia/psychosis articles used sMRI and two used
Country Article Count DTI, possibly reflecting a strong interest in identifying struc-
tural abnormalities in schizophrenia spectrum and other psy-
United States 71 chotic disorders. In ASD studies, there were similar number of
United Kingdom 8
sMRI/DTI and fMRI articles, reflecting a comparable research
Canada 5
China, People’s Republic 5 interest in investigating the disease at both structural and func-
Germany 3 tional levels.
Australia 2 Nevertheless, for each condition, there was a common theme
The Netherlands 2 of utilizing multiple imaging modalities at both structural and
China, Republic 1 functional levels, as also evidenced by the research focus and
Italy 1
approaches of the seven most productive authors. The accumu-
Sweden 1
Switzerland 1
lated evidence provided by multiple imaging modalities could
prompt new multivariable analytic methods, which have the
potential of overcoming the low sensitivity in single modality re-
search due to overlapping results between the disorder and con-
trol populations.4 This process could potentially be facilitated
yearly citation of at least 30, indicating a high level of research by the development and commercialization of multimodality
activity. The historic trends of neuroimaging modalities also imaging techniques, such as combined PET/MRI scanners that
show a rapid utilization of newly available imaging techniques. integrate the unique features of both modalities.54 The rapid im-
The versatile nature of many imaging modalities was fully har- provement in artificial intelligence algorithms could also further
nessed, as evidenced by the various types of radioligands and refine such multivariable analytic methods to identify and max-
tests used for PET imaging and the various disorder-related imize the most significant neuroimaging findings.55–57 Further-
tasks examined in the fMRI studies. These findings reflect ac- more, the versatile nature of the multivariable analysis can al-
tive efforts of the field to keep expanding the scope of research. low inclusion of nonimaging information gathered from genetic
These most highly cited articles primarily focused on ma- and pharmacological studies.12 Such integration may prove to
jor psychiatric conditions like depressive disorders, schizophre- be critical for the eventual adoption of neuroimaging in the
nia spectrum and other psychotic disorders, and ASD. As we clinical practice of psychiatry.
have shown, each psychiatric condition had a unique utilization
Limitations
pattern of neuroimaging modalities, which could be attributed
to different research focus in these conditions. For example, In this study, we searched two databases, the MEDLINE and
in articles investigating depressive disorders, six articles used Web of Science All Databases, to make use of the exhaustive
PET to examine the functional improvement following treat- MeSH index system of the former, and the comprehensive

Table 8. Journals that Published the 100 Most Highly Cited Articles
Journal Article Count 2017 Impact Factor (Clarivate Analytics)
JAMA Psychiatry (Previously: Archives of General Psychiatry) 20 16.642

Biological Psychiatry 17 11.982
American Journal of Psychiatry 11 13.391
Proceedings of the National Academy of Sciences of the United States of America 11 9.504
Journal of Neuroscience 8 5.970
Brain 5 10.840
Nature Neuroscience 3 19.912
JAMA-Journal of the American Medical Association 2 47.661
Nature 2 41.577
Science 2 41.058
Neuron 2 14.318
Neurology 2 7.609
Cerebral Cortex 2 6.308
Neuroimage 2 5.426
New England Journal of Medicine 1 79.258
Lancet 1 53.254
Nature Medicine 1 32.621
Journal of Psychiatric Research 1 4.000
Molecular Psychiatry 1 11.640
Neuropsychopharmacology 1 6.544
Brain Research 1 3.125
Emotion 1 3.039
European Journal of Neuroscience 1 2.832
Brain & Development 1 1.544
Neuroreport 1 1.266
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of the 100 Most Highly Cited Articles

Keywords: Neuroimaging, mental disorders, psychiatry, bibliometrics.

Introduction of psychiatric disorders, identify at-risk populations, develop

◦ 2018 by the American Society of Neuroimaging

Screening of Original Research Articles

2 Journal of Neuroimaging Vol 0 No 0 October 2018

PET and single-photon emission computed tomography

Gong et al: Neuroimaging in Psychiatric Disorders 3

Psychiatric Neuro-imaging Main Brain Areas Yearly Citation

Journal of Neuroimaging Vol 0 No 0 October 2018

Gong et al: Neuroimaging in Psychiatric Disorders

Journal of Neuroimaging Vol 0 No 0 October 2018

Gong et al: Neuroimaging in Psychiatric Disorders

Journal of Neuroimaging Vol 0 No 0 October 2018

Gong et al: Neuroimaging in Psychiatric Disorders

Journal of Neuroimaging Vol 0 No 0 October 2018

Gong et al: Neuroimaging in Psychiatric Disorders

Journal of Neuroimaging Vol 0 No 0 October 2018

Gong et al: Neuroimaging in Psychiatric Disorders

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Gong et al: Neuroimaging in Psychiatric Disorders

Psychiatric Condition Article Count

radiopharmaceutical activity. Among the most highly cited

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Gong et al: Neuroimaging in Psychiatric Disorders 17

Researcher Article# Article Rank Current Affiliation Research Focus

18 Journal of Neuroimaging Vol 0 No 0 October 2018

Journal Article Count 2017 Impact Factor (Clarivate Analytics)

JAMA Psychiatry (Previously: Archives of General Psychiatry) 20 16.642

Gong et al: Neuroimaging in Psychiatric Disorders 19

20 Journal of Neuroimaging Vol 0 No 0 October 2018

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